Bio

Bio


Sarah S. Donaldson is the Catharine and Howard Avery Professor in the Department of Radiation Oncology at Stanford University School of Medicine. She is also Associate Director of the residency program at Stanford’s Department of Radiation Oncology and Chief of the Radiation Oncology service at the Packard Children’s Hospital in Stanford, California. She is a member of the National Academy of Medicine/Institute of Medicine and a fellow of AAAS, ASTRO, ACR, and ASCO.

Dr. Donaldson has broad expertise in Radiation Oncology with particular interest in Pediatrics, Breast, CNS, Sarcoma Lymphoma, and rare tumors.

She is widely regarded as an authority in pediatric radiation oncology having served as a founding member as the Children’s Oncology Group and the Childhood Cancer Survivor’s Study. She has served as principal investigator on Pediatric Hodgkins Lymphoma, Rhabdomyosarcoma, and Ewings Sarcoma clinical trials.

Clinical Focus


  • Cancer > Cutaneous (Dermatologic) Oncology
  • Cancer > Lymphoma
  • Cancer > Radiation Oncology
  • Sarcomas - Radiation Oncology
  • Bone Cancer
  • Basal / Squamous Cell Carcinomas - Radiation Oncology
  • Brain / Central Nervous System Tumors
  • Brain / Central Nervous System Tumors - Radiation Oncology
  • Breast Cancer
  • Breast Cancer - Radiation Oncology
  • Burkitt's Lymphoma
  • Burkitt's Lymphoma - Radiation Oncology
  • Childhood Cancers
  • Eye / Orbital Cancer
  • Eye / Orbital Cancer - Benign
  • Eye / Orbital Cancer - Malignancies
  • Germ Cell Tumors
  • Germ Cell Tumors - Radiation Oncology
  • Hodgkin's Disease
  • Hodgkin's Disease - Radiation Oncology
  • Leukemia
  • Leukemia - Radiation Oncology
  • Lymphoma
  • Melanoma
  • Melanoma - Radiation Oncology
  • Multiple Myeloma
  • Multiple Myeloma - Radiation Oncology
  • Non-Hodgkin's Lymphoma
  • Non-Hodgkin's Lymphoma - Radiation Oncology
  • Osteosarcoma
  • Pediatric Cancers
  • Pigmented Skin Lesions
  • Pigmented Skin Lesions - Radiation Oncology
  • Pituitary Adenomas
  • Pituitary Adenomas - Radiation Oncology
  • Radiation Oncology
  • Sarcomas - Bone
  • Sarcomas - Bone - Radiation Oncology
  • Sarcomas - Soft Tissue
  • Sarcomas - Soft Tissue - Radiation Oncology
  • Skin Cancer
  • Skin Cancer - Radiation Oncology
  • Therapeutic Radiology
  • Thyroid Cancers
  • Thyroid Cancers - Radiation Oncology
  • sarcoma

Administrative Appointments


  • Associate Chair, Stanford University School of Medicine - Radiation Oncology (1997 - 2011)
  • Chief, Radiation Oncology Service, Lucile Packard Children's Hospital, Stanford Hospital and Clinics (1991 - Present)
  • Associate Residency Program Director, Department of Radiation Oncology (2009 - Present)

Honors & Awards


  • Women Who Conquer Cancer Mentorship Award, Conquer Cancer Foundation of ASCO (2016)
  • Distinguished Career Achievement Award, Dartmouth Geisel School of Medicine (2015)
  • Ho Hung Chiu Medical Education Foundation Lecturer, Ho Hung Chiu Medical Education Foundation (2015)
  • Honorary Member, European Society of Radiology (2014)
  • Honorary Member, French Society of Radiology (SFR) (2014)
  • Honorary Member, American Association of Physicists in Medicine (2014)
  • Medal of the French Society of Radiotherapy, French Society of Radiotherapy (2014)
  • Medical Staff Distinguished Service Award, Lucile Packard Children’s Hospital at Stanford (2014)
  • Radiology Leadership Institute, Leadership Luminary Award, The American College of Radiology (2014)
  • Albion Walter Hewlett Award, Department of Medicine Stanford University (2013)
  • Fellow, American Society of Clinical Oncology (2012)
  • Fellow, American Association for the Advancement of Science (2012)
  • Richard T. Hoppe Leadership Award, Department Radiation Oncology (2012)
  • The Dean’s Medal, Stanford University School of Medicine (2012)
  • John H. Wineman Lecture, University of Michigan (2010)
  • Inaugural Lecture, Pediatric Radiation Oncology Society (2009)
  • ASCO Pediatric Oncology Award, American Society of Clinical Oncology (2007)
  • ASCO Statesman Award, American Society of Clinical Oncology (2007)
  • Gold Medal, American College of Radiology (2007)
  • Pediatric Oncology Award, American Society of Clinical Oncology (2007)
  • Fellow, American Society of Therapeutic Radiology and Oncology (2006)
  • Morton M. Kligerman Lecturer and Award, University of Pennsylvania (2006)
  • Elizabeth Blackwell Award, American Medical Women's Association (2005)
  • Ira J. Spiro Visiting Professor and Memorial Lecturer, Massachusetts General Hospital (2005)
  • Honorary Member, National Council on Radiation Protection and Measurements (2004)
  • Mark Nesbit lecturer, University of Minnesota (2002)
  • W.W. Sutow lecturer and Gold Medal, M.D. Anderson Cancer Center (2002)
  • Juan A. del Regato Foundation Lecturer and Gold Medal, del Regato Foundation (2001)
  • Gold medal, American Society of Therapeutic Radiology and Oncology (2000)
  • Janeway lecturer and Gold medal recipient, American Radium Society (1999)
  • Member, Institute of Medicine (1999)
  • Marie Curie Award, American Association for Women Radiologists (1998)
  • Radiation Oncology Orator, Radiological Society of North America (1995)

Boards, Advisory Committees, Professional Organizations


  • Member, International Society of Pediatric Oncology (1973 - Present)
  • Member, Radiological Society of North America (1993 - Present)
  • Member, American Association for Women Radiologists (1993 - Present)
  • Member, American College of Radiology (1981 - Present)
  • Diplomat, American Board of Radiology (1973 - Present)
  • Member, American Society for Radiology Oncology (1973 - Present)
  • Member, American Society for Clinical Oncology (1973 - Present)
  • RSNA Representative, Academy of Radiology Research (2011 - Present)
  • Steering Committee Member, NCI Pediatric and Adolescent Solid Tumor Steering Committee Coordinating Center for Clinical Trials (2010 - Present)

Professional Education


  • Fellowship:MD Anderson Cancer Center (1971) TX
  • Internship:University of Washington School of Medicine (1969) WA
  • Board Certification: Therapeutic Radiology, American Board of Radiology (1974)
  • Fellowship:Institut Gustave-Roussy (1973) France
  • Residency:Stanford University Medical Center (1972) CA
  • Medical Education:Harvard Medical School (1968) MA
  • M.D., Harvard Medical School (1968)

Research & Scholarship

Current Research and Scholarly Interests


Combined Modality Treatment of Cancer
Late Effects of Treatment
Genetic Effects of Cancer
Rhabdomyosarcoma
Hodgkins Disease
Pediatric Radiation Oncolgy
Pediatric Oncolgy
Breast Cancer
Conformal Radiotherapy/IMRT
Radiotherapy for Benign Diseases

Clinical Trials


  • Dakin's Solution in Preventing Radiation Dermatitis in Patients With Breast Cancer Undergoing Radiation Therapy Recruiting

    This pilot clinical trial studies Dakin's solution in preventing radiation dermatitis in patients with breast cancer undergoing radiation therapy. Radiation dermatitis is a skin condition in which the affected skin becomes painful, red, itchy, and blistered. Dakin's solution may help reduce dermatitis caused by radiation therapy.

    View full details

  • Adcetris (Brentuximab Vedotin), Combination Chemotherapy, and Radiation Therapy in Treating Younger Patients With Stage IIB, IIIB and IV Hodgkin Lymphoma Recruiting

    This pilot phase II trial studies how well giving brentuximab vedotin, combination chemotherapy, and radiation therapy works in treating younger patients with stage IIB, IIIB or IV Hodgkin lymphoma. Monoclonal antibodies, such as brentuximab vedotin, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer killing substances to them. Drugs used in chemotherapy, such as etoposide, prednisone, doxorubicin hydrochloride, cyclophosphamide, and dacarbazine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill cancer cells. Giving brentuximab vedotin with combination chemotherapy may kill more cancer cells and reduce the need for radiation therapy.

    View full details

  • Feasibility Neurocognitive Outcome After Transplant Recruiting

    This pilot study will primarily be evaluated by feasibility and adherence to an iPad-based neurocognitive intervention program. It will secondarily be evaluated by performance on the neurocognitive testing post-transplant and change in performance in subsequent years.

    View full details

Teaching

2015-16 Courses


Publications

All Publications


  • Radiation-Related New Primary Solid Cancers in the Childhood Cancer Survivor Study: Comparative Radiation Dose Response and Modification of Treatment Effects INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Inskip, P. D., Sigurdson, A. J., Veiga, L., Bhatti, P., Ronckers, C., Rajaraman, P., Boukheris, H., Stovall, M., Smith, S., Hammond, S., Henderson, T. O., Watt, T. C., Mertens, A. C., Leisenring, W., Stratton, K., Whitton, J., Donaldson, S. S., Armstrong, G. T., Robison, L. L., Neglia, J. P. 2016; 94 (4): 800-807

    Abstract

    The majority of childhood cancer patients now achieve long-term survival, but the treatments that cured their malignancy often put them at risk of adverse health outcomes years later. New cancers are among the most serious of these late effects. The aims of this review are to compare and contrast radiation dose-response relationships for new solid cancers in a large cohort of childhood cancer survivors and to discuss interactions among treatment and host factors.This review is based on previously published site-specific analyses for subsequent primary cancers of the brain, breast, thyroid gland, bone and soft tissue, salivary glands, and skin among 12,268 5-year childhood cancer survivors in the Childhood Cancer Survivor Study. Analyses included tumor site-specific, individual radiation dose reconstruction based on radiation therapy records. Radiation-related second cancer risks were estimated using conditional logistic or Poisson regression models for excess relative risk (ERR).Linear dose-response relationships over a wide range of radiation dose (0-50 Gy) were seen for all cancer sites except the thyroid gland. The steepest slopes occurred for sarcoma, meningioma, and nonmelanoma skin cancer (ERR/Gy > 1.00), with glioma and cancers of the breast and salivary glands forming a second group (ERR/Gy = 0.27-0.36). The relative risk for thyroid cancer increased up to 15-20 Gy and then decreased with increasing dose. The risk of thyroid cancer also was positively associated with chemotherapy, but the chemotherapy effect was not seen among those who also received very high doses of radiation to the thyroid. The excess risk of radiation-related breast cancer was sharply reduced among women who received 5 Gy or more to the ovaries.The results suggest that the effect of high-dose irradiation is consistent with a linear dose-response for most organs, but they also reveal important organ-specific and host-specific differences in susceptibility and interactions between different aspects of treatment.

    View details for DOI 10.1016/j.ijrobp.2015.11.046

    View details for Web of Science ID 000371581900021

    View details for PubMedID 26972653

  • Local Control for Intermediate-Risk Rhabdomyosarcoma: Results From D9803 According to Histology, Group, Site, and Size: A Report From the Children's Oncology Group INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Wolden, S. L., Lyden, E. R., Arndt, C. A., Hawkins, D. S., Anderson, J. R., Rodeberg, D. A., Morris, C. D., Donaldson, S. S. 2015; 93 (5): 1071-1076
  • Delayed primary excision with subsequent modification of radiotherapy dose for intermediate-risk rhabdomyosarcoma: A report from the Children's Oncology Group Soft Tissue Sarcoma Committee INTERNATIONAL JOURNAL OF CANCER Rodeberg, D. A., Wharam, M. D., Lyden, E. R., Stoner, J. A., Brown, K., Wolden, S. L., Paidas, C. N., Donaldson, S. S., Hawkins, D. S., Spunt, S. L., Arndt, C. A. 2015; 137 (1): 204-211

    Abstract

    The majority of intermediate-risk rhabdomyosarcoma (RMS) patients have gross residual disease (Group III) after their first operative procedure. It is currently not known if local control rates can be maintained when, following induction chemotherapy, the radiation therapy (RT) dose is decreased after a delayed primary excision (DPE). To answer this question we evaluated patients enrolled on COG D9803 (1999-2005) who had Group III tumors of the bladder dome, extremity or trunk (thorax, abdomen and pelvis) were candidates for DPE at Week 12 if the primary tumor appeared resectable. RT dose was then adjusted by the completeness of DPE: no evidence of disease 36 Gy, microscopic residual 41.4 Gy and gross residual disease (GRD) 50.4 Gy. A total of 161 Group III patients were evaluated (24 bladder dome, 63 extremity and 74 trunk). Seventy-three patients (45%) underwent DPE which achieved removal of all gross disease in 61 (84%) who were then eligible for reduced RT dose (43/73 received 36 Gy, 19/73 received 41.4 Gy). The local 5-year failure rate (0% for bladder dome, 7% for extremity and 20% for trunk) was similar to IRS-IV, which did not encourage DPE and did not allow for DPE adapted RT dose reduction. In conclusion, DPE was performed in 45% of Group III RMS patients with tumors at select anatomic sites (bladder dome, extremity and trunk) and 84% of those who had DPE were eligible for RT dose reduction. Local control outcomes were similar to historic results with RT alone.

    View details for DOI 10.1002/ijc.29351

    View details for Web of Science ID 000353297600020

    View details for PubMedID 25418440

  • Management of Nodular Lymphocyte Predominant Hodgkin Lymphoma in the Modern Era INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS King, M. T., Donaldson, S. S., Link, M. P., Natkunam, Y., Advani, R. H., Hoppe, R. T. 2015; 92 (1): 67-75

    Abstract

    To analyze treatment outcomes for nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) at a single institution.Patients with newly diagnosed NLPHL between 1996 and 2013 were reviewed retrospectively. Patients treated before 1996 were excluded because the majority received extended field radiation therapy (RT) alone.Fifty-five patients (22 ≤ 21 years old) were identified. The median follow-up time was 6.8 years. Among 37 patients with limited-stage (I-II) disease, treatments included involved field RT at a median dose of 36 Gy (n=9), rituximab monotherapy (n=9), observation (n=3), and response-adaptive therapy (n=16), in which the RT dose was reduced from 25.5 Gy to 15 Gy or was eliminated based on interim imaging after chemotherapy. The 5-year progression-free survival (PFS) was 76.4% (95% confidence interval [CI], 63.1-92.4). Nine patients experienced progression, including 5 receiving rituximab, 2 undergoing observation, and 2 receiving response-adaptive therapy. Rituximab was associated with an inferior PFS compared with RT alone (P=.02). The difference in PFS between response-adaptive therapy and RT alone was not statistically significant (P=.39). Among 18 patients with advanced-stage (III-IV) disease, treatments included chemotherapy alone (n=3), combined modality therapy (CMT) (n=2), response-adaptive therapy (n=2), rituximab (n=7), and observation (n=4). The 5-year PFS was 29.9% (CI, 13.3-67.4). Twelve patients experienced progression, including 1 receiving chemotherapy, 1 receiving CMT, 6 receiving rituximab, and 4 undergoing observation. There was no significant PFS difference between rituximab and non-rituximab therapies (P=.19) within the caveat of small sample sizes. In the entire cohort, 9 patients (3 with limited disease, 6 with advanced disease) experienced large cell transformation (LCT). Seven patients died; of those, 5 died with LCT.For limited disease, response-adaptive therapy demonstrated comparable outcomes with RT alone. Rituximab monotherapy resulted in inferior outcomes for limited disease and a high relapse rate for advanced disease.

    View details for DOI 10.1016/j.ijrobp.2015.02.001

    View details for Web of Science ID 000353988200011

  • Improved Outcomes after Autologous Bone Marrow Transplantation for Children with Relapsed or Refractory Hodgkin Lymphoma: Twenty Years Experience at a Single Institution BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Garfin, P. M., Link, M. P., Donaldson, S. S., Advani, R. H., Luna-Fineman, S., Kharbanda, S., Porteus, M., Weinberg, K. I., Agarwal-Hashmi, R. 2015; 21 (2): 326-334

    Abstract

    The purpose of this study is to evaluate the survival of pediatric patients undergoing autologous bone marrow transplantation (auBMT) for relapsed or refractory Hodgkin lymphoma (rrHL) and to identify factors that might contribute to their outcome. We reviewed the records and clinical course of 89 consecutive rrHL patients ≤ 21 years old who underwent auBMT at Stanford Hospitals and Clinics and the Lucile Packard Children's Hospital, Stanford between 1989 and 2012. We investigated, by multiple analyses, patient, disease, and treatment characteristics associated with outcome. Endpoints were 5-year overall and event-free survival. Our findings include that cyclophosphamide, carmustine, and etoposide (CBV) as a conditioning regimen for auBMT is effective for most patients ≤ 21 years old with rrHL (5-year overall survival, 71%). Transplantation after the year 2001 was associated with significantly improved overall survival compared with our earlier experience (80% compared with 65%). Patients with multiply relapsed disease or with disease not responsive to initial therapy fared less well compared with those with response to initial therapy or after first relapse. Administration of post-auBMT consolidative radiotherapy (cRT) also appears to contribute to improved survival. We are able to conclude that high-dose chemotherapy with CBV followed by auBMT is effective for the treatment of rrHL in children and adolescents. Survival for patients who undergo auBMT for rrHL has improved significantly. This improvement may be because of patient selection and improvements in utilization of radiotherapy rather than improvements in chemotherapy. Further investigation is needed to describe the role of auBMT across the entire spectrum of patients with rrHL and to identify the most appropriate preparative regimen with or without cRT therapy in the treatment of rrHL in young patients.

    View details for DOI 10.1016/j.bbmt.2014.10.020

    View details for Web of Science ID 000348632700018

  • Comparative Evaluation of Local Control Strategies in Localized Ewing Sarcoma of Bone A Report From the Children's Oncology Group CANCER DuBois, S. G., Krailo, M. D., Gebhardt, M. C., Donaldson, S. S., Marcus, K. J., Dormans, J., Shamberger, R. C., Sailer, S., Nicholas, R. W., Healey, J. H., Tarbell, N. J., Randall, R. L., Devidas, M., Meyer, J. S., Granowetter, L., Womer, R. B., Bernstein, M., Marina, N., Grier, H. E. 2015; 121 (3): 467-475

    Abstract

    Patients with Ewing sarcoma require local primary tumor control with surgery, radiation, or both. The optimal choice of local control for overall and local disease control remains unclear.Patients with localized Ewing sarcoma of bone who were treated on 3 consecutive protocols with standard-dose, 5-drug chemotherapy every 3 weeks were included (n=465). Propensity scores were used to control for differences between local control groups by constructing multivariate models to assess the impact of local control type on clinical endpoints (event-free survival [EFS], overall survival, local failure, and distant failure) independent of differences in their propensity to receive each local control type.Patients who underwent surgery were younger (P=.02) and had more appendicular tumors (P<.001). Compared with surgery, radiation had higher unadjusted risks of any event (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.18-2.44), death (HR, 1.84; 95% CI, 1.18-2.85), and local failure (HR, 2.57; 95% CI, 1.37-4.83). On multivariate analysis, compared with surgery, radiation had a higher risk of local failure (HR, 2.41; 95% CI, 1.24-4.68), although there were no significant differences in EFS (HR, 1.42; 95% CI, 0.94-2.14), overall survival (HR, 1.37; 95% CI, 0.83-2.26), or distant failure (HR, 1.13; 95% CI, 0.70-1.84) between local control groups.In this large group of similarly treated patients, choice of the mode of local control was not related significantly to EFS, overall survival, or distant failure, although the risk of local failure was greater for radiation compared with surgery. These data support surgical resection when appropriate, whereas radiotherapy remains a reasonable alternative in selected patients. Cancer 2015;121:467-475. © 2014 American Cancer Society.

    View details for DOI 10.1002/cncr.29065

    View details for Web of Science ID 000349394900021

    View details for PubMedID 25251206

  • Recent advances in understanding and managing rhabdomyosarcoma. F1000prime reports Hiniker, S. M., Donaldson, S. S. 2015; 7: 59-?

    Abstract

    Rhabdomyosarcoma is the most common childhood soft tissue sarcoma and the fourth most common pediatric solid tumor. For most patients, treatment consists of a multimodality approach, including chemotherapy, surgery, and/or radiotherapy. To guide treatment, patients with rhabdomyosarcoma are risk stratified based on a number of factors. These factors include clinical group, which depends largely on the extent of resection and nodal involvement, and stage, which takes into account tumor size, invasion, nodal involvement, and disease site. Histology of the tumor and age at diagnosis are also factored into risk stratification. Recent advances in understanding the biology of the disease have allowed for the further sub-classification of rhabdomyosarcoma. In addition, elucidation of additional clinical features associated with poor prognosis has allowed for better understanding of risk and provides more clarity regarding those patients who require more intensive therapy. Many areas of active investigation are ongoing, including the following: further delineation of the biological underpinnings of the various disease subtypes with the possibility of molecularly targeted therapy; a better understanding of clinical risk factors, including the evaluation and management of potentially involved lymph nodes; determination of the appropriate role of post-treatment imaging and assessment of response to therapy; and incorporation of advanced radiotherapeutic techniques, including conformal intensity-modulated photon and proton therapy.

    View details for DOI 10.12703/P7-59

    View details for PubMedID 26097732

  • Age-related Toxicity in Patients With Rhabdomyosarcoma: A Report From the Children's Oncology Group JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Altaf, S., Enders, F., Lyden, E., Donaldson, S. S., Rodeberg, D., Arndt, C. 2014; 36 (8): 599-604
  • Quality of life outcomes in proton and photon treated pediatric brain tumor survivors RADIOTHERAPY AND ONCOLOGY Yock, T. I., Bhat, S., Szymonifka, J., Yeap, B. Y., Delahaye, J., Donaldson, S. S., MacDonald, S. M., Pulsifer, M. B., Hill, K. S., DeLaney, T. F., Ebb, D., Huang, M., Tarbell, N. J., Fisher, P. G., Kuhlthau, K. A. 2014; 113 (1): 89-94

    Abstract

    Radiotherapy can impair Health Related Quality of Life (HRQoL) in survivors of childhood brain tumors, but proton radiotherapy (PRT) may mitigate this effect. This study compares HRQoL in PRT and photon (XRT) pediatric brain tumor survivors.HRQoL data were prospectively collected on PRT-treated patients aged 2-18 treated at Massachusetts General Hospital (MGH). Cross-sectional PedsQL data from XRT treated Lucile Packard Children's Hospital (LPCH) patients provided the comparison data.Parent proxy HRQoL scores were reported at 3 years for the PRT cohort (PRT-C) and 2.9 years (median) for the XRT cohort (XRT-C). The total core HRQoL score for the PRT-C, XRT-C, and normative population differed from one another and was 75.9, 65.4 and 80.9 respectively (p=0.002; p=0.024; p<0.001). The PRT-C scored 10.3 and 10.5 points higher than the XRT-C in the physical (PhSD) and psychosocial (PsSD) summary domains of the total core score (TCS, p=0.015; p=0.001). The PRT-C showed no difference in PhSD compared with the normative population, but scored 6.1 points less in the PsSD (p=0.003). Compared to healthy controls, the XRT-C scored lower in all domains (p<0.001).The HRQoL of pediatric brain tumor survivors treated with PRT compare favorably to those treated with XRT and similar to healthy controls in the PhSD.

    View details for DOI 10.1016/j.radonc.2014.08.017

    View details for Web of Science ID 000347604800015

    View details for PubMedID 25304720

  • Successful Treatment with Temozolomide Combined with Chemoradiotherapy and Surgery of a Metastatic Undifferentiated Soft Tissue Sarcoma with Relapse in the Central Nervous System of a Young Adult JOURNAL OF ADOLESCENT AND YOUNG ADULT ONCOLOGY Hsu, C. H., Daldrup-Link, H. E., Yeom, K. W., Donaldson, S. S., Million, L., Hazard, F. K., Rangaswami, A. 2014; 3 (2): 100-103
  • Survival and Neurocognitive Outcomes After Cranial or Craniospinal Irradiation Plus Total-Body Irradiation Before Stem Cell Transplantation in Pediatric Leukemia Patients With Central Nervous System Involvement INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hiniker, S. M., Agarwal, R., Modlin, L. A., Gray, C. C., Harris, J. P., Million, L., Kiamanesh, E. F., Donaldson, S. S. 2014; 89 (1): 67-74

    Abstract

    To evaluate survival and neurocognitive outcomes in pediatric acute lymphoblastic leukemia (ALL) patients with central nervous system (CNS) involvement treated according to an institutional protocol with stem cell transplantation (SCT) and a component of craniospinal irradiation (CSI) in addition to total-body irradiation (TBI) as preparative regimen.Forty-one pediatric ALL patients underwent SCT with TBI and received additional cranial irradiation or CSI because of CNS leukemic involvement. Prospective neurocognitive testing was performed before and after SCT in a subset of patients. Cox regression models were used to determine associations of patient and disease characteristics and treatment methods with outcomes.All patients received a cranial radiation boost; median total cranial dose was 24 Gy. Eighteen patients (44%) received a spinal boost; median total spinal dose for these patients was 18 Gy. Five-year disease-free survival (DFS) for all patients was 67%. Those receiving CSI had a trend toward superior DFS compared with those receiving a cranial boost alone (hazard ratio 3.23, P=.14). Patients with isolated CNS disease before SCT had a trend toward superior DFS (hazard ratio 3.64, P=.11, 5-year DFS 74%) compared with those with combined CNS and bone marrow disease (5-year DFS 59%). Neurocognitive testing revealed a mean post-SCT overall intelligence quotient of 103.7 at 4.4 years. Relative deficiencies in processing speed and/or working memory were noted in 6 of 16 tested patients (38%). Pre- and post-SCT neurocognitive testing revealed no significant change in intelligence quotient (mean increase +4.7 points). At a mean of 12.5 years after transplant, 11 of 13 long-term survivors (85%) had completed at least some coursework at a 2- or 4-year college.The addition of CSI to TBI before SCT in pediatric ALL with CNS involvement is effective and well-tolerated. Craniospinal irradiation plus TBI is worthy of further protocol investigation in children with CNS leukemia.

    View details for DOI 10.1016/j.ijrobp.2014.01.056

    View details for Web of Science ID 000334590500011

    View details for PubMedID 24725690

  • Histologic subtypes of breast cancer following radiotherapy for Hodgkin lymphoma ANNALS OF ONCOLOGY Horst, K. C., Hancock, S. L., OGNIBENE, G., Chen, C., Advani, R. H., Rosenberg, S. A., Donaldson, S. S., Hoppe, R. T. 2014; 25 (4): 848-851

    Abstract

    The purpose of the study was to determine whether breast cancers (BCs) that develop in women previously irradiated for Hodgkin lymphoma (HL) are biologically similar to sporadic BC.We retrospectively reviewed the charts of patients who developed BC after radiotherapy (RT) for HL. Tumors were classified as ductal carcinoma in situ (DCIS) or invasive carcinoma. Invasive carcinomas were further characterized according to the subtype: hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)-, HR+/HER2+, HR-/HER2+, and HR-/HER2-. BCs after HL were compared with four age-matched sporadic, non-breast cancer (BRCA) I or II mutated BCs.One hundred forty-seven HL patients who were treated with RT between 1966 and 1999 and subsequently developed BCs were identified. Of these, 65 patients with 71 BCs had complete pathologic information. The median age at HL diagnosis was 23 (range, 10-48). The median age at BC diagnosis was 44 (range, 28-66). The median time to developing BC was 20 years. Twenty cancers (28%) were DCIS and 51 (72%) were invasive. Of the 51 invasive cancers, 24 (47%) were HR+/HER2-, 2 (4%) were HR+/HER2+, 5 (10%) were HR-/HER2+, and 20 (39%) were HR-/HER2-. There were no differences in BC histologic subtype according to the age at which patients were exposed to RT, the use of chemotherapy for HL treatment, or the time from RT exposure to the development of BC. In a 4 : 1 age-matched comparison to sporadic BCs, BCs after HL were more likely to be HR-/HER2- (39% versus 14%) and less likely to be HR+/HER2- (47% versus 61%) or HR+/HER2+ (4% versus 14%) (P = 0.0003).BCs arising in previously irradiated breast tissue were more likely to be triple negative compared with age-matched sporadic invasive cancers and less likely to be HR positive. Further studies will be important to determine the molecular pathways of carcinogenesis in breast tissue that is exposed to RT.

    View details for DOI 10.1093/annonc/mdu017

    View details for Web of Science ID 000334077000014

  • Pulmonary Outcomes in Survivors of Childhood Central Nervous System Malignancies: A Report From the Childhood Cancer Survivor Study PEDIATRIC BLOOD & CANCER Huang, T. T., Chen, Y., Dietz, A. C., Yasui, Y., Donaldson, S. S., Stokes, D. C., Stovall, M., Leisenring, W. M., Sklar, C. A., Diller, L. R., Mertens, A. C., Armstrong, G. T., Green, D. M., Robison, L. L., Ness, K. K. 2014; 61 (2): 319-325

    Abstract

    Adult survivors of childhood central nervous system (CNS) tumors may be at risk for pulmonary dysfunction. This study enumerates the incidence of pulmonary dysfunction and explores associations between craniospinal irradiation (CSI) and pulmonary dysfunction among survivors of childhood CNS tumors.Participants included Childhood Cancer Survivor Study (CCSS) cohort members treated for CNS malignancies when 3.0 for asthma, chronic cough and need for extra oxygen. Rates of fibrosis (RR 2.0, 95% CI 1.0-3.9), chest wall abnormalities (RR 19.0, 95% CI 4.2-85.7), chronic cough (RR 1.6, 95% CI 1.2-2.1) and need for supplemental oxygen (RR 2.5, 95% CI 1.9-3.3) were higher among survivors than among siblings. Survivors treated with CSI were 10.4 (95% CI 7.6-14.4) times more likely than those not exposed to report chest wall deformity.Adult survivors of CNS malignancy have high rates of pulmonary dysfunction 5+ years after diagnosis. Survivors treated with CSI should be monitored for pulmonary disease to permit early interventions.

    View details for DOI 10.1002/pbc.24819

    View details for Web of Science ID 000328694300031

    View details for PubMedID 24127436

  • The Cyclophosphamide Equivalent Dose as an Approach for Quantifying Alkylating Agent Exposure: A Report From the Childhood Cancer Survivor Study PEDIATRIC BLOOD & CANCER Green, D. M., Nolan, V. G., Goodman, P. J., Whitton, J. A., Srivastava, D., Leisenring, W. M., Neglia, J. P., Sklar, C. A., Kaste, S. C., Hudson, M. M., Diller, L. R., Stovall, M., Donaldson, S. S., Robison, L. L. 2014; 61 (1): 53-67

    Abstract

    Estimation of the risk of adverse long-term outcomes such as second malignant neoplasms and infertility often requires reproducible quantification of exposures. The method for quantification should be easily utilized and valid across different study populations. The widely used Alkylating Agent Dose (AAD) score is derived from the drug dose distribution of the study population and thus cannot be used for comparisons across populations as each will have a unique distribution of drug doses.We compared the performance of the Cyclophosphamide Equivalent Dose (CED), a unit for quantifying alkylating agent exposure independent of study population, to the AAD. Comparisons included associations from three Childhood Cancer Survivor Study (CCSS) outcome analyses, receiver operator characteristic (ROC) curves and goodness of fit based on the Akaike's Information Criterion (AIC).The CED and AAD performed essentially identically in analyses of risk for pregnancy among the partners of male CCSS participants, risk for adverse dental outcomes among all CCSS participants and risk for premature menopause among female CCSS participants, based on similar associations, lack of statistically significant differences between the areas under the ROC curves and similar model fit values for the AIC between models including the two measures of exposure.The CED is easily calculated, facilitating its use for patient counseling. It is independent of the drug dose distribution of a particular patient population, a characteristic that will allow direct comparisons of outcomes among epidemiological cohorts. We recommend the use of the CED in future research assessing cumulative alkylating agent exposure.

    View details for DOI 10.1002/pbc.24679

    View details for Web of Science ID 000326765100011

    View details for PubMedID 23940101

  • The Effect of Radiation Timing on Patients With High-Risk Features of Parameningeal Rhabdomyosarcoma: An Analysis of IRS-IV and D9803 INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Spalding, A. C., Hawkins, D. S., Donaldson, S. S., Anderson, J. R., Lyden, E., Laurie, F., Wolden, S. L., Arndt, C. A., Michalski, J. M. 2013; 87 (3): 512-516

    Abstract

    Radiation therapy remains an essential treatment for patients with parameningeal rhabdomyosarcoma (PMRMS), and early radiation therapy may improve local control for patients with intracranial extension (ICE).To address the role of radiation therapy timing in PMRMS in the current era, we reviewed the outcome from 2 recent clinical trials for intermediate-risk RMS: Intergroup Rhabdomyosarcoma Study (IRS)-IV and Children's Oncology Group (COG) D9803. The PMRMS patients on IRS-IV with any high-risk features (cranial nerve palsy [CNP], cranial base bony erosion [CBBE], or ICE) were treated immediately at day 0, and PMRMS patients without any of these 3 features received week 6-9 radiation therapy. The D9803 PMRMS patients with ICE received day 0 X-Ray Therapy (XRT) as well; however, those with either CNP or CBBE had XRT at week 12.Compared with the 198 PMRMS patients from IRS-IV, the 192 PMRMS patients from D9803 had no difference (P<.05) in 5-year local failure (19% vs 19%), failure-free-survival (70% vs 67%), or overall survival (75% vs 73%) in aggregate. The 5-year local failure rates by subset did not differ when patients were classified as having no risk features (None, 15% vs 19%, P=.25), cranial nerve palsy/cranial base of skull erosion (CNP/CBBE, 15% vs 28%, P=.22), or intracranial extension (ICE, 21% vs 15%, P=.27). The D9083 patients were more likely to have received initial staging by magnetic resonance imaging (71% vs 53%).These data support that a delay in radiation therapy for high-risk PMRMS features of CNP/CBBE does not compromise clinical outcomes.

    View details for DOI 10.1016/j.ijrobp.2013.07.003

    View details for Web of Science ID 000325165300021

    View details for PubMedID 24074925

  • Relapse after treatment of pediatric hodgkin lymphoma: Outcome and role of surveillance after end of therapy PEDIATRIC BLOOD & CANCER Friedmann, A. M., Wolfson, J. A., Hudson, M. M., Weinstein, H. J., Link, M. P., Billett, A., Larsen, E. C., Yock, T., Donaldson, S. S., Marcus, K., Krasin, M. J., Howard, S. C., Metzger, M. L. 2013; 60 (9): 1458-1463

    Abstract

    The outcome of treatment for pediatric Hodgkin lymphoma (HL) is excellent using chemotherapy and radiation. However, a minority of patients will relapse after treatment, but additional therapy achieves durable second remission in many cases. The optimal surveillance strategy after modern therapy for HL has not been well defined.We reviewed the outcomes of pediatric patients with HL treated between 1990 and 2006 to determine the primary event that led to the detection of relapse. We determined the probability of relapse detection by routine follow-up procedures, including history, physical examination, laboratory tests, and imaging, and determined the impact of each of these screening methods on the likelihood of survival after relapse.Relapse occurred in 64 of 402 evaluable patients (15.9%) at a median of 1.7 years from the time of diagnosis. The majority of relapses (60%) were diagnosed at a routine visit, and patient complaint was the most common initial finding that led to a diagnosis of relapse (47% of relapses). An abnormal finding on physical examination was the primary event in another 17% of relapses, and imaging abnormalities led to the diagnosis in the remaining 36%. Laboratory abnormalities were never the primary finding. The method of detection of relapse and timing (whether detected at a routine visit or an extra visit) did not impact survival.In pediatric HL, most relapses are identified through history and physical examination. Frequent imaging of asymptomatic patients does not appear to impact survival and is probably not warranted.

    View details for DOI 10.1002/pbc.24568

    View details for Web of Science ID 000321703900078

  • Low-dose radiation therapy (2 Gy × 2) in the treatment of orbital lymphoma. International journal of radiation oncology, biology, physics Fasola, C. E., Jones, J. C., Huang, D. D., Le, Q., Hoppe, R. T., Donaldson, S. S. 2013; 86 (5): 930-935

    Abstract

    PURPOSE: Low-dose radiation has become increasingly used in the management of indolent non-Hodgkin lymphoma (NHL), but has not been studied specifically for cases of ocular adnexal involvement. The objective of this study is to investigate the effectiveness of low-dose radiation in the treatment of NHL of the ocular adnexa. METHODS AND MATERIALS: We reviewed the records of 20 NHL patients with 27 sites of ocular adnexal involvement treated with low-dose radiation consisting of 2 successive fractions of 2 Gy at our institution between 2005 and 2011. The primary endpoint of this study is freedom from local relapse (FFLR). RESULTS: At a median follow-up time of 26 months (range 7-92), the overall response rate for the 27 treated sites was 96%, with a complete response (CR) rate of 85% (n=23) and a partial response rate of 11% (n=3). Among all treated sites with CR, the 2-year FFLR was 100%, with no in-treatment field relapses. The 2-year freedom from regional relapse rate was 96% with 1 case of relapse within the ipsilateral orbit (outside of the treatment field). This patient underwent additional treatment with low-dose radiation of 4 Gy to the area of relapse achieving a CR and no evidence of disease at an additional 42 months of follow-up. Orbital radiation was well tolerated with only mild acute side effects (dry eye, conjunctivitis, transient periorbital edema) in 30% of treated sites without any reports of long-term toxicity. CONCLUSIONS: Low-dose radiation with 2 Gy × 2 is effective and well tolerated in the treatment of indolent NHL of the ocular adnexa with high response rates and durable local control with the option of reirradiation in the case of locoregional relapse.

    View details for DOI 10.1016/j.ijrobp.2013.04.035

    View details for PubMedID 23726002

  • Low-Dose Radiation Therapy (2 Gy x 2) in the Treatment of Orbital Lymphoma INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Fasola, C. E., Jones, J. C., Huang, D. D., Quynh-Thu Le, Q. T., Hoppe, R. T., Donaldson, S. S. 2013; 86 (5): 930-935
  • Changes in Health Status Among Aging Survivors of Pediatric Upper and Lower Extremity Sarcoma: A Report From the Childhood Cancer Survivor Study ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION Marina, N., Hudson, M. M., Jones, K. E., Mulrooney, D. A., Avedian, R., Donaldson, S. S., Popat, R., West, D. W., Fisher, P., Leisenring, W., Stovall, M., Robison, L. L., Ness, K. K. 2013; 94 (6): 1062-1073

    Abstract

    To evaluate health status and participation restrictions in survivors of childhood extremity sarcomas.Members of the Childhood Cancer Survivor Study cohort with extremity sarcomas who completed questionnaires in 1995, 2003, or 2007 were included.Cohort study of survivors of extremity sarcomas.Childhood extremity sarcoma survivors (N=1094; median age at diagnosis, 13y (range, 0-20y); current age, 33y (range, 10-53y); 49% male; 87.5% white; 75% had lower extremity tumors) who received their diagnosis and treatment between 1970 and 1986.Not applicable.Prevalence rates for poor health status in 6 domains and 5 suboptimal social participation categories were compared by tumor location and treatment exposure with generalized estimating equations adjusted for demographic/personal factors and time/age.In adjusted models, when compared with upper extremity survivors, lower extremity survivors had an increased risk of activity limitations but a lower risk of not completing college. Compared with those who did not have surgery, those with limb-sparing (LS) and upper extremity amputations (UEAs) were 1.6 times more likely to report functional impairment, while those with an above-the-knee amputation (AKA) were 1.9 times more likely to report functional impairment. Survivors treated with LS were 1.5 times more likely to report activity limitations. Survivors undergoing LS were more likely to report inactivity, incomes <$20,000, unemployment, and no college degree. Those with UEAs more likely reported inactivity, unmarried status, and no college degree. Those with AKA more likely reported no college degree. Treatment with abdominal irradiation was associated with an increased risk of poor mental health, functional impairment, and activity limitation.Treatment of lower extremity sarcomas is associated with a 50% increased risk for activity limitations; upper extremity survivors are at a 10% higher risk for not completing college. The type of local control influences health status and participation restrictions. Both of these outcomes decline with age.

    View details for DOI 10.1016/j.apmr.2013.01.013

    View details for Web of Science ID 000319954400008

  • Risk of Salivary Gland Cancer After Childhood Cancer: A Report From the Childhood Cancer Survivor Study INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Boukheris, H., Stovall, M., Gilbert, E. S., Stratton, K. L., Smith, S. A., Weathers, R., Hammond, S., Mertens, A. C., Donaldson, S. S., Armstrong, G. T., Robison, L. L., Neglia, J. P., Inskip, P. D. 2013; 85 (3): 776-783

    Abstract

    To evaluate effects of radiation therapy, chemotherapy, cigarette smoking, and alcohol consumption on the risk of second primary salivary gland cancer (SGC) in the Childhood Cancer Survivor Study (CCSS).Standardized incidence ratios (SIR) and excess absolute risks (EAR) of SGC in the CCSS were calculated using incidence rates from Surveillance, Epidemiology, and End Results population-based cancer registries. Radiation dose to the salivary glands was estimated based on medical records. Poisson regression was used to assess risks with respect to radiation dose, chemotherapy, smoking, and alcohol consumption.During the time period of the study, 23 cases of SGC were diagnosed among 14,135 childhood cancer survivors. The mean age at diagnosis of the first primary cancer was 8.3 years, and the mean age at SGC diagnosis was 24.8 years. The incidence of SGC was 39-fold higher in the cohort than in the general population (SIR = 39.4; 95% CI = 25.4-57.8). The EAR was 9.8 per 100,000 person-years. Risk increased linearly with radiation dose (excess relative risk = 0.36/Gy; 95% CI = 0.06-2.5) and remained elevated after 20 years. There was no significant trend of increasing risk with increasing dose of chemotherapeutic agents, pack-years of cigarette smoking, or alcohol intake.Although the cumulative incidence of SGC was low, childhood cancer survivors treated with radiation experienced significantly increased risk for at least 2 decades after exposure, and risk was positively associated with radiation dose. Results underscore the importance of long-term follow up of childhood cancer survivors for the development of new malignancies.

    View details for DOI 10.1016/j.ijrobp.2012.06.006

    View details for Web of Science ID 000314687000044

    View details for PubMedID 22836059

  • Absolute Risk Prediction of Second Primary Thyroid Cancer Among 5-Year Survivors of Childhood Cancer JOURNAL OF CLINICAL ONCOLOGY Kovalchik, S. A., Ronckers, C. M., Veiga, L. H., Sigurdson, A. J., Inskip, P. D., de Vathaire, F., Sklar, C. A., Donaldson, S. S., Anderson, H., Bhatti, P., Hammond, S., Leisenring, W. M., Mertens, A. C., Smith, S. A., Stovall, M., Tucker, M. A., Weathers, R. E., Robison, L. L., Pfeiffer, R. M. 2013; 31 (1): 119-127

    Abstract

    We developed three absolute risk models for second primary thyroid cancer to assist with long-term clinical monitoring of childhood cancer survivors.We used data from the Childhood Cancer Survivor Study (CCSS) and two nested case-control studies (Nordic CCSS; Late Effects Study Group). Model M1 included self-reported risk factors, model M2 added basic radiation and chemotherapy treatment information abstracted from medical records, and model M3 refined M2 by incorporating reconstructed radiation absorbed dose to the thyroid. All models were validated in an independent cohort of French childhood cancer survivors.M1 included birth year, initial cancer type, age at diagnosis, sex, and past thyroid nodule diagnosis. M2 added radiation (yes/no), radiation to the neck (yes/no), and alkylating agent (yes/no). Past thyroid nodule was consistently the strongest risk factor (M1 relative risk [RR], 10.8; M2 RR, 6.8; M3 RR, 8.2). In the validation cohort, 20-year absolute risk predictions for second primary thyroid cancer ranged from 0.04% to 7.4% for M2. Expected events agreed well with observed events for each model, indicating good calibration. All models had good discriminatory ability (M1 area under the receiver operating characteristics curve [AUC], 0.71; 95% CI, 0.64 to 0.77; M2 AUC, 0.80; 95% CI, 0.73 to 0.86; M3 AUC, 0.75; 95% CI, 0.69 to 0.82).We developed and validated three absolute risk models for second primary thyroid cancer. Model M2, with basic prior treatment information, could be useful for monitoring thyroid cancer risk in childhood cancer survivors.

    View details for DOI 10.1200/JCO.2012.41.8996

    View details for Web of Science ID 000312911900025

    View details for PubMedID 23169509

  • Finding the Balance in Pediatric Hodgkin's Lymphoma JOURNAL OF CLINICAL ONCOLOGY Donaldson, S. S. 2012; 30 (26): 3158-3159

    View details for DOI 10.1200/JCO.2012.42.6890

    View details for Web of Science ID 000308707100009

    View details for PubMedID 22649142

  • Association Between Radiotherapy vs No Radiotherapy Based on Early Response to VAMP Chemotherapy and Survival Among Children With Favorable-Risk Hodgkin Lymphoma JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Metzger, M. L., Weinstein, H. J., Hudson, M. M., Billett, A. L., Larsen, E. C., Friedmann, A., Howard, S. C., Donaldson, S. S., Krasin, M. J., Kun, L. E., Marcus, K. J., Yock, T. I., Tarbell, N., Billups, C. A., Wu, J., Link, M. P. 2012; 307 (24): 2609-2616

    Abstract

    More than 90% of children with favorable-risk Hodgkin lymphoma can achieve long-term survival, yet many will experience toxic effects from radiation therapy. Pediatric oncologists strive for maintaining excellent cure rates while minimizing toxic effects.To evaluate the efficacy of 4 cycles of vinblastine, Adriamycin (doxorubicin), methotrexate, and prednisone (VAMP) in patients with favorable-risk Hodgkin lymphoma who achieve a complete response after 2 cycles and do not receive radiotherapy.Multi-institutional, unblinded, nonrandomized single group phase 2 clinical trial to assess the need for radiotherapy based on early response to chemotherapy. Eighty-eight eligible patients with Hodgkin lymphoma stage I and II (<3 nodal sites, no B symptoms, mediastinal bulk, or extranodal extension) enrolled between March 3, 2000, and December 9, 2008. Follow-up data are current to March 12, 2012.The 47 patients who achieved a complete response after 2 cycles received no radiotherapy, and the 41 with less than a complete response were given 25.5 Gy-involved-field radiotherapy.Two-year event-free survival was the primary outcome measure. A 2-year event-free survival of greater than 90% was desired, and 80% was considered to be unacceptably low.Two-year event-free survival was 90.8% (95% CI, 84.7%-96.9%). For patients who did not require radiotherapy, it was 89.4% (95% CI, 80.8%-98.0%) compared with 92.5% (95% CI, 84.5%-100%) for those who did (P = .61). Most common acute adverse effects were neuropathic pain (2% of patients), nausea or vomiting (3% of patients), neutropenia (32% of cycles), and febrile neutropenia (2% of patients). Nine patients (10%) were hospitalized 11 times (3% of cycles) for febrile neutropenia or nonneutropenic infection. Long-term adverse effects after radiotherapy were asymptomatic compensated hypothyroidism in 9 patients (10%), osteonecrosis and moderate osteopenia in 2 patients each (2%), subclinical pulmonary dysfunction in 12 patients (14%), and asymptomatic left ventricular dysfunction in 4 patients (5%). No second malignant neoplasms were observed.Among patients with favorable-risk Hodgkin lymphoma and a complete early response to chemotherapy, the use of limited radiotherapy resulted in a high rate of 2-year event-free survival.clinicaltrials.gov Identifier: NCT00145600.

    View details for Web of Science ID 000305692600029

    View details for PubMedID 22735430

  • Local Control With Reduced-Dose Radiotherapy for Low-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group D9602 Study INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Breneman, J., Meza, J., Donaldson, S. S., Raney, R. B., Wolden, S., Michalski, J., Laurie, F., Rodeberg, D. A., Meyer, W., Walterhouse, D., Hawkins, D. S. 2012; 83 (2): 720-726

    Abstract

    To analyze the effect of reduced-dose radiotherapy on local control in children with low-risk rhabdomyosarcoma (RMS) treated in the Children's Oncology Group D9602 study.Patients with low-risk RMS were nonrandomly assigned to receive radiotherapy doses dependent on the completeness of surgical resection of the primary tumor (clinical group) and the presence of involved regional lymph nodes. After resection, most patients with microscopic residual and uninvolved nodes received 36 Gy, those with involved nodes received 41.4 to 50.4 Gy, and those with orbital primary tumors received 45 Gy. All patients received vincristine and dactinomycin, with cyclophosphamide added for patient subsets with a higher risk of relapse in Intergroup Rhabdomyosarcoma Study Group III and IV studies.Three hundred forty-two patients were eligible for analysis; 172 received radiotherapy as part of their treatment. The cumulative incidence of local/regional failure was 15% in patients with microscopic involved margins when cyclophosphamide was not part of the treatment regimen and 0% when cyclophosphamide was included. The cumulative incidence of local/regional failure was 14% in patients with orbital tumors. Protocol-specified omission of radiotherapy in girls with Group IIA vaginal tumors (n = 5) resulted in three failures for this group.In comparison with Intergroup Rhabdomyosarcoma Study Group III and IV results, reduced-dose radiotherapy does not compromise local control for patients with microscopic tumor after surgical resection or with orbital primary tumors when cyclophosphamide is added to the treatment program. Girls with unresected nonbladder genitourinary tumors require radiotherapy for postsurgical residual tumor for optimal local control to be achieved.

    View details for DOI 10.1016/j.ijrobp.2011.06.2011

    View details for Web of Science ID 000303920800058

    View details for PubMedID 22104356

  • Evaluation of local control strategies in patients with localized Ewing sarcoma of bone: A report from the Children's Oncology Group. DuBois, S. G., Krailo, M. D., Gebhardt, M. C., Donaldson, S. S., Marcus, K. C., Dormans, J. P., Shamberger, R. C., Sailer, S. L., Nicholas, R. W., Healey, J. H., Tarbell, N., Devidas, M., Meyer, J. S., Granowetter, L., Womer, R., Bernstein, M. L., Marina, N., Grier, H. E. AMER SOC CLINICAL ONCOLOGY. 2012
  • Stanford V chemotherapy and involved field radiotherapy for children and adolescents with unfavorable risk Hodgkin lymphoma: Results of a multi-institutional prospective clinical trial Metzger, M., Billett, A., Friedmann, A. M., Krasin, M. J., Howard, S. C., Weinstein, H. J., Larsen, E., Marcus, K. C., Billups, C., Wu, J., Donaldson, S. S., Link, M. P., Hudson, M. M. AMER SOC CLINICAL ONCOLOGY. 2012
  • A Tribute to Malcolm A. Bagshaw-An Innovative Physician Who Soared to Success INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hoppe, R. T., Donaldson, S. S. 2012; 83 (1): 6-7

    View details for DOI 10.1016/j.ijrobp.2012.02.010

    View details for Web of Science ID 000302993900023

    View details for PubMedID 22516381

  • EFFECT OF RADIOTHERAPY TECHNIQUES (IMRT VS. 3D-CRT) ON OUTCOME IN PATIENTS WITH INTERMEDIATE-RISK RHABDOMYOSARCOMA ENROLLED IN COG D9803-A REPORT FROM THE CHILDREN'S ONCOLOGY GROUP INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Lin, C., Donaldson, S. S., Meza, J. L., Anderson, J. R., Lyden, E. R., Brown, C. K., Morano, K., Laurie, F., Arndt, C. A., Enke, C. A., Breneman, J. C. 2012; 82 (5): 1764-1770

    Abstract

    To compare the dosimetric parameters of intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) in patients with intermediate-risk rhabdomyosarcoma and to analyze their effect on locoregional control and failure-free survival (FFS).The study population consisted of 375 patients enrolled in the Children's Oncology Group protocol D9803 study, receiving IMRT or 3D-CRT. Dosimetric data were collected from 179 patients with an available composite plan. The chi-square test or Fisher's exact test was used to compare the patient characteristics and radiotherapy parameters between the two groups. The interval-to-event outcomes were estimated using the Kaplan-Meier method and compared using log-rank tests. Cox proportional hazards regression analysis was used to examine the effect of the treatment technique on FFS after adjusting for primary site and risk group.The median follow-up time was 5.7 and 4.2 years for patients receiving 3D-CRT and IMRT, respectively. No differences in the 5-year failure of locoregional control (18% vs. 15%) or FFS (72% vs. 76%) rates were noted between the two groups. Multivariate analysis revealed no association between the two techniques and FFS. Patients with primary tumors in parameningeal sites were more likely to receive IMRT than 3D-CRT. IMRT became more common during the later years of the study. Patients receiving IMRT were more likely to receive >50 Gy, photon energy of ?6 MV, and >5 radiation fields than those who received 3D-CRT. The coverage of the IMRT planning target volume by the prescription dose was improved compared with the coverage using 3D-CRT with similar target dose heterogeneity.IMRT improved the target dose coverage compared with 3D-CRT, although an improvement in locoregional control or FFS could not be demonstrated in this population. Future studies comparing the integral dose to nontarget tissue and late radiation toxicity between the two groups are warranted.

    View details for DOI 10.1016/j.ijrobp.2011.01.036

    View details for Web of Science ID 000301891300045

    View details for PubMedID 21470795

  • Risk Factors for Obesity in Adult Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study JOURNAL OF CLINICAL ONCOLOGY Green, D. M., Cox, C. L., Zhu, L., Krull, K. R., Srivastava, D. K., Stovall, M., Nolan, V. G., Ness, K. K., Donaldson, S. S., Oeffinger, K. C., Meacham, L. R., Sklar, C. A., Armstrong, G. T., Robison, L. L. 2012; 30 (3): 246-255

    Abstract

    Many Childhood Cancer Survivor Study (CCSS) participants are at increased risk for obesity. The etiology of their obesity is likely multifactorial but not well understood.We evaluated the potential contribution of demographic, lifestyle, treatment, and intrapersonal factors and self-reported pharmaceutical use to obesity (body mass index ? 30 kg/m2) among 9,284 adult (> 18 years of age) CCSS participants. Independent predictors were identified using multivariable regression models. Interrelationships were determined using structural equation modeling (SEM).Independent risk factors for obesity included cancer diagnosed at 5 to 9 years of age (relative risk [RR], 1.12; 95% CI, 1.01 to 1.24; P = .03), abnormal Short Form-36 physical function (RR, 1.19; 95% CI, 1.06 to 1.33; P < .001), hypothalamic/pituitary radiation doses of 20 to 30 Gy (RR, 1.17; 95% CI, 1.05 to 1.30; P = .01), and paroxetine use (RR, 1.29; 95% CI, 1.08 to 1.54; P = .01). Meeting US Centers for Disease Control and Prevention guidelines for vigorous physical activity (RR, 0.90; 95% CI, 0.82 to 0.97; P = .01) and a medium amount of anxiety (RR, 0.86; 95% CI, 0.75 to 0.99; P = .04) reduced the risk of obesity. Results of SEM (N = 8,244; comparative fit index = 0.999; Tucker Lewis index = 0.999; root mean square error of approximation = 0.014; weighted root mean square residual = 0.749) described the hierarchical impact of the direct predictors, moderators, and mediators of obesity.Treatment, lifestyle, and intrapersonal factors, as well as the use of specific antidepressants, may contribute to obesity among survivors. A multifaceted intervention, including alternative drug and other therapies for depression and anxiety, may be required to reduce risk.

    View details for DOI 10.1200/JCO.2010.34.4267

    View details for Web of Science ID 000302620200011

    View details for PubMedID 22184380

  • Resectable pediatric nonrhabdomyosarcoma soft tissue sarcoma: which patients benefit from adjuvant radiation therapy and how much? ISRN oncology Million, L., Donaldson, S. S. 2012; 2012: 341408-?

    Abstract

    It remains unclear which children and adolescents with resected nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) benefit from radiation therapy, as well as the optimal dose, volume, and timing of radiotherapy when used with primary surgical resection. This paper reviews the sparse literature from clinical trials and retrospective studies of resected pediatric NRSTS to discern local recurrence rates in relationship to the use of radiation therapy.

    View details for DOI 10.5402/2012/341408

    View details for PubMedID 22523704

  • Chemotherapy and Thyroid Cancer Risk: a Report from the Childhood Cancer Survivor Study CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Veiga, L. H., Bhatti, P., Ronckers, C. M., Sigurdson, A. J., Stovall, M., Smith, S. A., Weathers, R., Leisenring, W., Mertens, A. C., Hammond, S., Neglia, J. P., Meadows, A. T., Donaldson, S. S., Sklar, C. A., Friedman, D. L., Robison, L. L., Inskip, P. D. 2012; 21 (1): 92-101

    Abstract

    Although ionizing radiation is an established environmental risk factor for thyroid cancer, the effect of chemotherapy drugs on thyroid cancer risk remains unclear. We evaluated the chemotherapy-related risk of thyroid cancer in childhood cancer survivors and the possible joint effects of chemotherapy and radiotherapy.The study included 12,547 five-year survivors of childhood cancer diagnosed during 1970 through 1986. Chemotherapy and radiotherapy information was obtained from medical records, and radiation dose was estimated to the thyroid gland. Cumulative incidence and relative risks were calculated with life-table methods and Poisson regression. Chemotherapy-related risks were evaluated separately by categories of radiation dose.Histologically confirmed thyroid cancer occurred in 119 patients. Thirty years after the first childhood cancer treatment, the cumulative incidence of thyroid cancer was 1.3% (95% CI, 1.0-1.6) for females and 0.6% (0.4-0.8) for males. Among patients with thyroid radiation doses of 20 Gy or less, treatment with alkylating agents was associated with a significant 2.4-fold increased risk of thyroid cancer (95% CI, 1.3-4.5; P = 0.002). Chemotherapy risks decreased as radiation dose increased, with a significant decrease for patients treated with alkylating agents (P(trend) = 0.03). No chemotherapy-related risk was evident for thyroid radiation doses more than 20 Gy.Treatments with alkylating agents increased thyroid cancer risk, but only in the radiation dose range less than 20 Gy, in which cell sparing likely predominates over cell killing.Our study adds to the evidence for chemotherapy agent-specific increased risks of thyroid cancer, which to date, were mainly thought to be related to prior radiotherapy.

    View details for DOI 10.1158/1055-9965.EPI-11-0576

    View details for Web of Science ID 000299051500010

    View details for PubMedID 22028399

  • Controversies in radiotherapy for pediatric Hodgkin's lymphoma EXPERT REVIEW OF ANTICANCER THERAPY Wiegner, E. A., Donaldson, S. S. 2011; 11 (9): 1357-1366

    Abstract

    Cure rates for pediatric Hodgkin's lymphoma remain among the highest in pediatric oncology. Research efforts are currently focused on minimizing treatment-related toxicity without compromising outcomes. For children with early stage/favorable Hodgkin's lymphoma, the standard treatment includes 2-4 cycles of combination chemotherapy, generally followed by low-dose involved-field radiotherapy. Children with advanced stage/unfavorable disease require more intense treatment than those with favorable disease. The standard treatment for advanced stage/unfavorable disease is 4–6 cycles of intense multiagent non-cross-resistant chemotherapy and involved-field radiotherapy. Response-adapted therapy is emerging as a promising strategy to attenuate therapy and thereby reduce toxicity in children with an excellent prognosis and intensify therapy in those children at higher risk of progression or relapse.

    View details for DOI 10.1586/ERA.10.91

    View details for Web of Science ID 000296034500013

    View details for PubMedID 22029056

  • Rhabdomyosarcoma in Infants Younger Than 1 Year A Report From the Children's Oncology Group CANCER Malempati, S., Rodeberg, D. A., Donaldson, S. S., Lyden, E. R., Anderson, J. R., Hawkins, D. S., Arndt, C. A. 2011; 117 (15): 3493-3501

    Abstract

    Rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in children, occurs less commonly in infants. Historically, poorer outcomes have been reported for infants diagnosed with RMS than for older children.The authors analyzed the characteristics, treatment administered, outcomes, and patterns of failure for infants aged < 1 year with nonmetastatic RMS who received multimodal therapy on Intergroup Rhabdomyosarcoma Study (IRS) protocols IRS-IV, D9602, and D9803.Seventy-six infants with nonmetastatic RMS were treated on the 3 protocols from 1991 to 2005. Their median age was 7.4 months (range, 0.1-12 months). Tumor histology included embryonal (57%), alveolar (21%), and undifferentiated sarcoma/other (22%). A parameningeal primary tumor site was less common in this infant cohort (3%) than in all patients who were treated on IRS-IV (25%). The estimated 5-year failure-free survival and overall survival rates (95% confidence interval [CI]) were 57% (95% CI, 44%-67%) and 76% (95% CI, 65%-85%), respectively, for infants compared with 81% (95% CI, 79%-83%) and 87% (95% CI, 85%-89%), respectively, for children ages 1 to 9 years. Twenty-three of 32 infants with treatment failure had local recurrence/progression with distant failure (n = 3) or without distant failure (n = 20). The overall local failure rate was 30%. The median time to treatment failure was 13 months. The failure-free survival rate was worse for infants who had IRS Group III tumors and for those who received less than protocol-recommended radiation therapy.Infants with RMS appeared to have worse outcomes than older patients, in part because of high rates of local failure. The authors concluded that concerns regarding morbidity in infants and reluctance to use aggressive local control measures may lead to higher rates of local failure.

    View details for DOI 10.1002/cncr.25887

    View details for Web of Science ID 000293103800023

    View details for PubMedID 21264837

  • REGIONAL NODAL INVOLVEMENT AND PATTERNS OF SPREAD ALONG IN-TRANSIT PATHWAYS IN CHILDREN WITH RHABDOMYOSARCOMA OF THE EXTREMITY: A REPORT FROM THE CHILDREN'S ONCOLOGY GROUP INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS La, T. H., Wolden, S. L., Rodeberg, D. A., Hawkins, D. S., Brown, K. L., Anderson, J. R., Donaldson, S. S. 2011; 80 (4): 1151-1157

    Abstract

    To evaluate the incidence and prognostic factors for regional failure, with attention to the in-transit pathways of spread, in children with nonmetastatic rhabdomyosarcoma of the extremity.The Intergroup rhabdomyosarcoma studies III, IV-Pilot, and IV enrolled 226 children with rhabdomyosarcoma of the extremity. Failure at the in-transit (epitrochlear/brachial and popliteal) and proximal (axillary/infraclavicular and inguinal/femoral) lymph nodes was evaluated. The median follow-up for the surviving patients was 10.4 years.Of the 226 children, 55 (24%) had clinical or pathologic evidence of either in-transit and/or proximal lymph node involvement at diagnosis. The actuarial 5-year risk of regional failure was 12%. The prognostic factors for poor regional control were female gender and lymph node involvement at diagnosis. In the 116 patients with a distal extremity primary tumor, 5% had in-transit lymph node involvement at diagnosis. The estimated 5-year incidences of in-transit and proximal nodal failure was 12% and 8%, respectively. The in-transit failure rate was 0% for patients who underwent radiotherapy and/or underwent lymph node sampling of the in-transit nodal site but was 15% for those who did not (p = .07). However, the 5-year event-free survival rate did not differ between these two groups (64% vs. 55%, respectively, p = .47).The high incidence of regional involvement necessitates aggressive identification and treatment of regional lymph nodes in patients with rhabdomyosarcoma of the extremity. In patients with distal extremity tumors, in-transit failures were as common as failures in more proximal regional sites. Patients who underwent complete lymph node staging with appropriate radiotherapy to the in-transit nodal site, if indicated, were at a slightly lower risk of in-transit failure.

    View details for DOI 10.1016/j.ijrobp.2010.03.050

    View details for Web of Science ID 000292486200027

    View details for PubMedID 20542386

  • Local Control and Outcome in Children With Localized Vaginal Rhabdomyosarcoma: A Report From the Soft Tissue Sarcoma Committee of the Children's Oncology Group PEDIATRIC BLOOD & CANCER Walterhouse, D. O., Meza, J. L., Breneman, J. C., Donaldson, S. S., Hayes-Jordan, A., Pappo, A. S., Arndt, C., Raney, R. B., Meyer, W. H., Hawkins, D. S. 2011; 57 (1): 76-83

    Abstract

    The local control approach for girls with non-resected vaginal rhabdomyosarcoma (RMS) enrolled onto Intergroup RMS Study Group (IRSG)/Children's Oncology Group (COG) studies has differed from that used at other primary sites by delaying or eliminating radiotherapy (RT) based on response achieved with chemotherapy and delayed primary resection.We reviewed locoregional treatment and outcome for patients with localized RMS of the vagina on the two most recent COG low-risk RMS studies.Forty-one patients with localized vaginal RMS were enrolled: 25 onto D9602 and 16 onto Subset 2 of ARST0331. Only four of the 39 with non-resected tumors received RT. The 5-year cumulative incidence of local recurrence was 26% on D9602, and the 2-year cumulative incidence of local recurrence was 43% on ARST0331. Increased local failure rates appeared to correlate with chemotherapy regimens that incorporated lower cumulative doses of cyclophosphamide. Estimated 5-year and 2-year failure free survival rates were 70% (95% CI: 46%, 84%) on D9602 and 42% (95% CI: 11%, 70%) on ARST0331, respectively.To prevent local recurrence, we recommend a local control approach for patients with non-resected RMS of the vagina that is similar to that used for other primary sites and includes RT. We recognize that potential long-term effects of RT are sometimes unacceptable, especially for children less than 24 months of age. However, when making the decision to eliminate RT, the risk of local recurrence must be considered especially when using a chemotherapy regimen with a total cumulative cyclophosphamide dose of ? 4.8 g/m².

    View details for DOI 10.1002/pbc.22928

    View details for Web of Science ID 000290452400014

    View details for PubMedID 21298768

  • INFLUENCE OF NONCOMPLIANCE WITH RADIATION THERAPY PROTOCOL GUIDELINES AND OPERATIVE BED RECURRENCES FOR CHILDREN WITH RHABDOMYOSARCOMA AND MICROSCOPIC RESIDUAL DISEASE: A REPORT FROM THE CHILDREN'S ONCOLOGY GROUP INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Million, L., Anderson, J., Breneman, J., Hawkins, D. S., Laurie, F., Michalski, J., Rodeberg, D., Wharam, M., Wolden, S., Donaldson, S. S. 2011; 80 (2): 333-338

    Abstract

    Postoperative radiation therapy (RT) is recommended for patients with rhabdomyosarcoma having microscopic disease. Sometimes RT dose/volume is reduced or omitted in an attempt to avoid late effects, particularly in young children. We reviewed operative bed recurrences to determine if noncompliance with RT protocol guidelines influenced local-regional control.All operative bed recurrences among 695 Group II rhabdomyosarcoma patients in Intergroup Rhabdomyosarcoma Study Group (IRS) I through IV were reviewed for deviation from RT protocol. Major/minor dose deviation was defined as >10% or 6-10% of the prescribed dose (40-60 Gy), respectively. Major/minor volume deviation was defined as tumor excluded from the RT field or treatment volume not covered by the specified margin (preoperative tumor volume and 2- to 5-cm margin), respectively. No RT was a major deviation.Forty-six of 83 (55%) patients with operative bed recurrences did not receive the intended RT (39 major and 7 minor deviations). RT omission was the most frequent RT protocol deviation (19/46, 41%), followed by dose (17/46, 37%), volume (9/46, 20%), and dose and volume deviation (1/46, 2%). Only 7 operative bed recurrences occurred in IRS IV (5% local-regional failure) with only 3 RT protocol deviations. Sixty-three (76%) patients with recurrence died of disease despite retrieval therapy, including 13 of 19 nonirradiated children.Over half of the operative bed recurrences were associated with noncompliance; omission of RT was the most common protocol deviation. Three fourths of children die when local-regional disease is not controlled, emphasizing the importance of RT in Group II rhabdomyosarcoma.

    View details for DOI 10.1016/j.ijrobp.2010.01.058

    View details for Web of Science ID 000290837100003

    View details for PubMedID 20646841

  • LOCAL THERAPY FOR RHABDOMYOSARCOMA OF THE HANDS AND FEET: IS AMPUTATION NECESSARY? A REPORT FROM THE CHILDREN'S ONCOLOGY GROUP INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS La, T. H., Wolden, S. L., Su, Z., Linardic, C., Randall, R. L., Hawkins, D. S., Donaldson, S. S. 2011; 80 (1): 206-212

    Abstract

    To evaluate the outcome of children with rhabdomyosarcoma (RMS) of the hand or foot treated with surgery and/or local radiotherapy (RT).Forty-eight patients with nonmetastatic RMS of the hand or foot were enrolled on Intergroup Rhabdomyosarcoma Study III, IV-Pilot, and IV. Patients received multiagent chemotherapy with surgery and/or RT. Twenty-four patients (50%) underwent surgery without local RT, of whom 4 had complete resection and 20 had an amputation. The remaining 24 patients (50%) underwent local RT, of whom 2 required RT for microscopic residual disease after prior amputation. Median follow-up for surviving patients was 9.7 years.Actuarial 10-year local control was 100%; 10-year event-free survival and overall survival rates were 62% and 63%, respectively. Poor prognostic factors for recurrence included gross residual (Group III) disease and nodal involvement (p = 0.01 and 0.05, respectively). More patients in the RT group had alveolar histology, Group III disease, and nodal involvement, as compared with the surgery group. There was no difference in 10-year event-free survival (57% vs. 66%) or overall survival (63% vs. 63%) between patients who underwent surgery or local RT. Among relapsing patients, there were no long-term survivors. No secondary malignancies have been observed.Despite having high-risk features, patients treated with local RT achieved excellent local control. Complete surgical resection without amputation is difficult to achieve in the hand or foot. Therefore, we recommend either definitive RT or surgical resection that maintains form and function as primary local therapy rather than amputation in patients with hand or foot RMS.

    View details for DOI 10.1016/j.ijrobp.2010.01.053

    View details for Web of Science ID 000290006300030

    View details for PubMedID 20646853

  • Decreased fertility among female childhood cancer survivors who received 22-27 Gy hypothalamic/pituitary irradiation: a report from the Childhood Cancer Survivor Study FERTILITY AND STERILITY Green, D. M., Nolan, V. G., Kawashima, T., Stovall, M., Donaldson, S. S., Srivastava, D., Leisenring, W., Robison, L. L., Sklar, C. A. 2011; 95 (6): 1922-U76

    Abstract

    To evaluate the effect of hypothalamic/pituitary radiation (HPT RT) dose on the occurrence of first pregnancy.Retrospective cohort study of childhood cancer 5-year survivors (CCS) diagnosed between 1970 and 1986 before 21 years of age at one of 26 North American pediatric cancer treatment centers.Self-administered questionnaire.A total of 3,619 female CCS who participated in the Childhood Cancer Survivor Study and received no or scatter (?0.1 Gy) radiation to the ovaries and 2,081 female siblings (Sibs) of the participants.None.Self-reported pregnancy events.As a group, CCS were as likely to report being pregnant as Sibs (hazard ratio 1.07, 95% confidence interval 0.97-1.19). Multivariable models showed a significant decrease in the risk of pregnancy with HPT RT doses?22 Gy compared with those CCS receiving no HPT RT.These results support the hypothesis that exposures of 22-27 Gy HPT RT may be a contributing factor to infertility among female CCS.

    View details for DOI 10.1016/j.fertnstert.2011.02.002

    View details for Web of Science ID 000289620900016

    View details for PubMedID 21376314

  • Prognostic Significance and Tumor Biology of Regional Lymph Node Disease in Patients With Rhabdomyosarcoma: A Report From the Children's Oncology Group JOURNAL OF CLINICAL ONCOLOGY Rodeberg, D. A., Garcia-Henriquez, N., Lyden, E. R., Davicioni, E., Parham, D. M., Skapek, S. X., Hayes-Jordan, A. A., Donaldson, S. S., Brown, K. L., Triche, T. J., Meyer, W. H., Hawkins, D. S. 2011; 29 (10): 1304-1311

    Abstract

    Regional lymph node disease (RLND) is a component of the risk-based treatment stratification in rhabdomyosarcoma (RMS). The purpose of this study was to determine the contribution of RLND to prognosis for patients with RMS.Patient characteristics and survival outcomes for patients enrolled onto Intergroup Rhabdomyosarcoma Study IV (N = 898, 1991 to 1997) were evaluated among the following three patient groups: nonmetastatic patients with clinical or pathologic negative nodes (N0, 696 patients); patients with clinical or pathologic positive nodes (N1, 125 patients); and patients with a single site of metastatic disease (77 patients).Outcomes for patients with nonmetastatic alveolar N0 RMS were significantly better than for patients with N1 RMS (5-year failure-free survival [FFS], 73% v 43%, respectively; 5-year overall survival [OS], 80% v 46%, respectively; P < .001). Patients with a single site of alveolar metastasis had even worse FFS and OS (23% FFS and OS, P = .01) when compared with patients with N1 RMS; however, the differences was not as large as the differences between patients with N0 RMS and N1 RMS. For embryonal RMS, there was no statistically significant difference in FFS or OS (P = .41 and P = .77, respectively) for patients with N1 versus N0 RMS. Gene array analysis of primary tumor specimens identified that genes associated with the immune system and antigen presentation were significantly increased in N1 versus N0 alveolar RMS.RLND alters prognosis for alveolar but not embryonal RMS. For patients with N1 disease and alveolar histology, outcomes were more similar to distant metastatic disease rather than local disease. Current data suggest that more aggressive therapy for patients with alveolar N1 RMS may be warranted.

    View details for DOI 10.1200/JCO.2010.29.4611

    View details for Web of Science ID 000288990100027

    View details for PubMedID 21357792

  • Significance of Indeterminate Pulmonary Nodules Identified on Chest Computed-tomography in Adult Patients with Newly Diagnosed Sarcoma Wiegner, E. A., Minn, A. Y., Abelson, D., Murphy, J. D., Jacobs, C., Donaldson, S. S., Kapp, D. S. ELSEVIER SCIENCE INC. 2011: S689-S689
  • Risk of Second Primary Thyroid Cancer after Radiotherapy for a Childhood Cancer in a Large Cohort Study: An Update from the Childhood Cancer Survivor Study RADIATION RESEARCH Bhatti, P., Veiga, L. H., Ronckers, C. M., Sigurdson, A. J., Stovall, M., Smith, S. A., Weathers, R., Leisenring, W., Mertens, A. C., Hammond, S., Friedman, D. L., Neglia, J. P., Meadows, A. T., Donaldson, S. S., Sklar, C. A., Robison, L. L., Inskip, P. D. 2010; 174 (6): 741-752

    Abstract

    Previous studies have indicated that thyroid cancer risk after a first childhood malignancy is curvilinear with radiation dose, increasing at low to moderate doses and decreasing at high doses. Understanding factors that modify the radiation dose response over the entire therapeutic dose range is challenging and requires large numbers of subjects. We quantified the long-term risk of thyroid cancer associated with radiation treatment among 12,547 5-year survivors of a childhood cancer (leukemia, Hodgkin lymphoma and non-Hodgkin lymphoma, central nervous system cancer, soft tissue sarcoma, kidney cancer, bone cancer, neuroblastoma) diagnosed between 1970 and 1986 in the Childhood Cancer Survivor Study using the most current cohort follow-up to 2005. There were 119 subsequent pathologically confirmed thyroid cancer cases, and individual radiation doses to the thyroid gland were estimated for the entire cohort. This cohort study builds on the previous case-control study in this population (69 thyroid cancer cases with follow-up to 2000) by allowing the evaluation of both relative and absolute risks. Poisson regression analyses were used to calculate standardized incidence ratios (SIR), excess relative risks (ERR) and excess absolute risks (EAR) of thyroid cancer associated with radiation dose. Other factors such as sex, type of first cancer, attained age, age at exposure to radiation, time since exposure to radiation, and chemotherapy (yes/no) were assessed for their effect on the linear and exponential quadratic terms describing the dose-response relationship. Similar to the previous analysis, thyroid cancer risk increased linearly with radiation dose up to approximately 20 Gy, where the relative risk peaked at 14.6-fold (95% CI, 6.8-31.5). At thyroid radiation doses >20 Gy, a downturn in the dose-response relationship was observed. The ERR model that best fit the data was linear-exponential quadratic. We found that age at exposure modified the ERR linear dose term (higher radiation risk with younger age) (P < 0.001) and that sex (higher radiation risk among females) (P  =  0.008) and time since exposure (higher radiation risk with longer time) (P < 0.001) modified the EAR linear dose term. None of these factors modified the exponential quadratic (high dose) term. Sex, age at exposure and time since exposure were found to be significant modifiers of the radiation-related risk of thyroid cancer and as such are important factors to account for in clinical follow-up and thyroid cancer risk estimation among childhood cancer survivors.

    View details for DOI 10.1667/RR2240.1

    View details for Web of Science ID 000285031500009

    View details for PubMedID 21128798

  • Randomized Phase II Window Trial of Two Schedules of Irinotecan With Vincristine in Patients With First Relapse or Progression of Rhabdomyosarcoma: A Report From the Children's Oncology Group Mascarenhas, L., Lyden, E. R., Breitfeld, P. P., Walterhouse, D. O., Donaldson, S. S., Paidas, C. N., Parham, D. M., Anderson, J. R., Meyer, W. H., Hawkins, D. S. AMER SOC CLINICAL ONCOLOGY. 2010: 4658-4663

    Abstract

    To compare response rates for two schedules of irinotecan with vincristine in patients with rhabdomyosarcoma at first relapse or disease progression.Patients with first relapse or progression of rhabdomyosarcoma and an unfavorable prognosis were randomly assigned to one of two treatment schedules of irinotecan with vincristine: regimen 1A included irinotecan 20 mg/m(2)/d intravenously for 5 days at weeks 1, 2, 4, and 5 with vincristine 1.5 mg/m(2) administered intravenously on day 1 of weeks 1, 2, 4, and 5; regimen 1B included irinotecan 50 mg/m(2)/d intravenously for 5 days at weeks 1 and 4 with vincristine as in regimen 1A. Disease response was assessed at week 6. Those with responsive disease continued to receive 44 weeks of multiagent chemotherapy that incorporated the assigned irinotecan-vincristine regimen.Ninety-two eligible patients were randomly assigned (1A, 45; 1B, 47). Response could be assessed in 89 patients (1A, 42; 1B, 47). There were five complete responses and six partial responses on regimen 1A (response rate, 26%; 95% CI, 16% to 42%) and 17 partial responses on regimen 1B (response rate, 37%; 95% CI, 25% to 51%; P = .36). Neutropenia was less common on regimen 1A (P = .04). One-year failure-free and overall survival rates for regimen 1A were 37% (95% CI, 23% to 51%) and 55% (95% CI, 39% to 69%), respectively, and for 1B, they were 38% (95% CI, 25% to 53%) and 60% (95% CI, 44% to 72%).There was no difference in the response rates between the two irinotecan-vincristine schedules. We recommend the shorter, more convenient regimen (1B) for further investigation.

    View details for DOI 10.1200/JCO.2010.29.7390

    View details for Web of Science ID 000283056400036

    View details for PubMedID 20837952

  • Treatment Results for Patients With Localized, Completely Resected (Group I) Alveolar Rhabdomyosarcoma on Intergroup Rhabdomyosarcoma Study Group (IRSG) Protocols III and IV, 1984-1997: A Report From the Children's Oncology Group PEDIATRIC BLOOD & CANCER Raney, R. B., Anderson, J. R., Brown, K. L., Huh, W. W., Maurer, H. M., Meyer, W. H., Parham, D. M., Rodeberg, D. A., Wolden, S. L., Donaldson, S. S. 2010; 55 (4): 612-616

    Abstract

    To assess local control, event-free survival (EFS), and overall survival (OS) rates in 71 patients with localized, completely resected (Group I) alveolar rhabdomyosarcoma (ALV RMS) and their relation to radiation therapy (RT) on IRSG Protocols III and IV, 1984-1997.Chart review and standard statistical procedures. PATIENTS AND TUMORS: Patients were 1-18 years at diagnosis (median, 6 years). Primary tumor sites were extremity/trunk (N = 54), head/neck (N = 9), genitourinary tract (N = 7), and perineum (N = 1). Thirty patients received VA +/- C with RT; 41 received VA +/- C alone. RT was assigned, not randomized.Fifty-four patients had Stage 1 (favorable site, any size) or Stage 2 (unfavorable site, < or = 5 cm) tumors. Eight-year EFS was 90%, with 100% local control for 17 patients given RT. Eight-year EFS was 88%, with 92% local control for 37 patients without RT; P = 0.52 for EFS comparisons, 0.3 for local control comparisons. In 17 Stage 3 patients (unfavorable site, tumors >5 cm, N0), 8-year EFS was 84% with 100% local control in 13 patients given RT; 8-year EFS was only 25% and local control 50% in 4 patients without RT. Local recurrence was the most common site of first failure in non-irradiated patients.Patients with Stage 1-2 ALV RMS had slightly but statistically insignificantly improved local control, EFS, and OS rates when local RT was given. The need for local RT in Stage 1-2 patients deserves evaluation in a randomized study. Local control, EFS, and OS rates were significantly improved in Stage 3 patients receiving local RT.

    View details for DOI 10.1002/pbc.22520

    View details for Web of Science ID 000281542900007

    View details for PubMedID 20806360

  • Early Treatment Failure in Intermediate-Risk Rhabdomyosarcoma: Results From IRS-IV and D9803-A Report From the Children's Oncology Group JOURNAL OF CLINICAL ONCOLOGY Minn, A. Y., Lyden, E. R., Anderson, J. R., Million, L., Arndt, C. A., Brown, K., Hawkins, D. S., Donaldson, S. S. 2010; 28 (27): 4228-4232

    Abstract

    The goal of this study was to determine the frequency and clinical features of early treatment failure during induction chemotherapy before protocol radiation therapy for children with intermediate-risk rhabdomyosarcoma (RMS).Patients with intermediate-risk RMS enrolled onto the Intergroup Rhabdomyosarcoma Study-IV and the Children's Oncology Group D9803 study were reviewed for an early treatment failure. Early failure was defined as failure caused by progressive disease, death as a result of progressive disease, or death as a result of other causes occurring fewer than 120 days from study entry. Patients with parameningeal site RMS with high-risk features who received radiation therapy at week 1 were excluded from analysis. Overall survival (OS) was estimated using the Kaplan-Meier method. Fisher's exact test was used to compare differences between groups. Cumulative incidence of progression was estimated.Of 916 patients, 20 (2.2%) were found to have an early disease progression and did not receive planned protocol radiotherapy. Three additional early failures resulted from treatment-related death without progression. Median time to failure was 48 days (range, 7 to 106 days). Nineteen (95%) of the 20 patients experienced progression at their primary site. Five-year OS was 32% (95% CI, 12% to 54%) for patients experiencing an early progression.A small proportion of patients with intermediate-risk RMS suffer an early failure as a result of early progression (2.2%) or treatment-related mortality (0.3%). The majority of patients with early progression had a local failure. Earlier radiotherapy could potentially improve outcome by preventing early local progression.

    View details for DOI 10.1200/JCO.2010.29.0247

    View details for Web of Science ID 000281909700020

    View details for PubMedID 20713850

  • Subsequent Neoplasms in 5-Year Survivors of Childhood Cancer: The Childhood Cancer Survivor Study JOURNAL OF THE NATIONAL CANCER INSTITUTE Friedman, D. L., Whitton, J., Leisenring, W., Mertens, A. C., Hammond, S., Stovall, M., Donaldson, S. S., Meadows, A. T., Robison, L. L., Neglia, J. P. 2010; 102 (14): 1083-1095

    Abstract

    The occurrence of subsequent neoplasms has direct impact on the quantity and quality of life in cancer survivors. We have expanded our analysis of these events in the Childhood Cancer Survivor Study (CCSS) to better understand the occurrence of these events as the survivor population ages.The incidence of and risk for subsequent neoplasms occurring 5 years or more after the childhood cancer diagnosis were determined among 14,359 5-year survivors in the CCSS who were treated from 1970 through 1986 and who were at a median age of 30 years (range = 5-56 years) for this analysis. At 30 years after childhood cancer diagnosis, we calculated cumulative incidence at 30 years of subsequent neoplasms and calculated standardized incidence ratios (SIRs), excess absolute risks (EARs) for invasive second malignant neoplasms, and relative risks for subsequent neoplasms by use of multivariable Poisson regression.Among 14,359 5-year survivors, 1402 subsequently developed 2703 neoplasms. Cumulative incidence at 30 years after the childhood cancer diagnosis was 20.5% (95% confidence interval [CI] = 19.1% to 21.8%) for all subsequent neoplasms, 7.9% (95% CI = 7.2% to 8.5%) for second malignant neoplasms (excluding nonmelanoma skin cancer), 9.1% (95% CI = 8.1% to 10.1%) for nonmelanoma skin cancer, and 3.1% (95% CI = 2.5% to 3.8%) for meningioma. Excess risk was evident for all primary diagnoses (EAR = 2.6 per 1000 person-years, 95% CI = 2.4 to 2.9 per 1000 person-years; SIR = 6.0, 95% CI = 5.5 to 6.4), with the highest being for Hodgkin lymphoma (SIR = 8.7, 95% CI = 7.7 to 9.8) and Ewing sarcoma (SIR = 8.5, 95% CI = 6.2 to 11.7). In the Poisson multivariable analysis, female sex, older age at diagnosis, earlier treatment era, diagnosis of Hodgkin lymphoma, and treatment with radiation therapy were associated with increased risk of subsequent neoplasm.As childhood cancer survivors progress through adulthood, risk of subsequent neoplasms increases. Patients surviving Hodgkin lymphoma are at greatest risk. There is no evidence of risk reduction with increasing duration of follow-up.

    View details for DOI 10.1093/jnci/djq238

    View details for Web of Science ID 000280269400013

    View details for PubMedID 20634481

  • Second Malignant Neoplasms in Survivors of Pediatric Hodgkin's Lymphoma Treated With Low-Dose Radiation and Chemotherapy JOURNAL OF CLINICAL ONCOLOGY O'Brien, M. M., Donaldson, S. S., Balise, R. R., Whittemore, A. S., Link, M. P. 2010; 28 (7): 1232-1239

    Abstract

    Survivors of childhood Hodgkin's lymphoma (HL) are at risk for second malignant neoplasms (SMNs). It is theorized that this risk may be attenuated in patients treated with lower doses of radiation. We report the first long-term outcomes of a cohort of pediatric survivors of HL treated with chemotherapy and low-dose radiation.Pediatric patients with HL (n = 112) treated at Stanford from 1970 to 1990 on two combined modality treatment protocols were identified. Treatment included six cycles of chemotherapy with 15 to 25.5 Gy involved-field radiation with optional 10 Gy boosts to bulky sites. Follow-up through September 1, 2007, was obtained from retrospective chart review and patient questionnaires.One hundred ten children completed HL therapy; median follow-up was 20.6 years. Eighteen patients developed one or more SMNs, including four leukemias, five thyroid carcinomas, six breast carcinomas, and four sarcomas. Cumulative incidence of first SMN was 17% (95% CI, 10.5 to 26.7) at 20 years after HL diagnosis. The standard incidence ratio for any SMN was 22.9 (95% CI, 14.2 to 35) with an absolute excess risk of 93.7 cases per 10,000 person-years. All four secondary leukemias were fatal. For those with second solid tumors, the mean (+/- SE) 5-year disease-free and overall survival were 76% +/- 12% and 85% +/- 10% with median follow-up 5 years from SMN diagnosis.Despite treatment with low-dose radiation, children treated for HL remain at significant risk for SMN. Sarcomas, breast and thyroid carcinomas occurred with similar frequency and latency as found in studies of children with HL who received high-dose radiation.

    View details for DOI 10.1200/JCO.2009.24.8062

    View details for Web of Science ID 000274892500025

    View details for PubMedID 20124178

  • Fertility of Male Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study JOURNAL OF CLINICAL ONCOLOGY Green, D. M., Kawashima, T., Stovall, M., Leisenring, W., Sklar, C. A., Mertens, A. C., Donaldson, S. S., Byrne, J., Robison, L. L. 2010; 28 (2): 332-339

    Abstract

    This study was undertaken to determine the effect of treatment for childhood cancer on male fertility.We reviewed the fertility of male Childhood Cancer Survivor Study survivor and sibling cohorts who completed a questionnaire. We abstracted the chemotherapeutic agents administered, the cumulative dose of drug administered for selected drugs, and the doses and volumes of all radiation therapy from medical records. Risk factors for siring a pregnancy were evaluated using Cox proportional hazards models.The 6,224 survivors age 15 to 44 years who were not surgically sterile were less likely to sire a pregnancy than siblings (hazard ratio [HR], 0.56; 95% CI, -0.49 to 0.63). Among survivors, the HR of siring a pregnancy was decreased by radiation therapy of more than 7.5 Gy to the testes (HR, 0.12; 95% CI, -0.02 to 0.64), higher cumulative alkylating agent dose (AAD) score or treatment with cyclophosphamide (third tertile HR, 0.42; 95% CI, -0.31 to 0.57) or procarbazine (second tertile HR, 0.48; 95% CI, -0.26 to 0.87; third tertile HR, 0.17; 95% CI, -0.07 to 0.41). Compared with siblings, the HR for ever siring a pregnancy for survivors who had an AAD score = 0, a hypothalamic/pituitary radiation dose = 0 Gy, and a testes radiation dose = 0 Gy was 0.91 (95% CI, 0.73 to 1.14; P = .41).This large study identified risk factors for decreased fertility that may be used for counseling male cancer patients.

    View details for DOI 10.1200/JCO.2009.24.9037

    View details for Web of Science ID 000273418000025

    View details for PubMedID 19949008

  • Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort BRITISH MEDICAL JOURNAL Mulrooney, D. A., Yeazel, M. W., Kawashima, T., Mertens, A. C., Mitby, P., Stovall, M., Donaldson, S. S., Green, D. M., Sklar, C. A., Robison, L. L., Leisenring, W. M. 2009; 339

    Abstract

    To assess the incidence of and risks for congestive heart failure, myocardial infarction, pericardial disease, and valvular abnormalities among adult survivors of childhood and adolescent cancers.Retrospective cohort study.26 institutions that participated in the Childhood Cancer Survivor Study.14,358 five year survivors of cancer diagnosed under the age of 21 with leukaemia, brain cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, kidney cancer, neuroblastoma, soft tissue sarcoma, or bone cancer between 1970 and 1986. Comparison group included 3899 siblings of cancer survivors.Participants or their parents (in participants aged less than 18 years) completed a questionnaire collecting information on demographic characteristics, height, weight, health habits, medical conditions, and surgical procedures occurring since diagnosis. The main outcome measures were the incidence of and risk factors for congestive heart failure, myocardial infarction, pericardial disease, and valvular abnormalities in survivors of cancer compared with siblings.Survivors of cancer were significantly more likely than siblings to report congestive heart failure (hazard ratio (HR) 5.9, 95% confidence interval 3.4 to 9.6; P<0.001), myocardial infarction (HR 5.0, 95% CI 2.3 to 10.4; P<0.001), pericardial disease (HR 6.3, 95% CI 3.3 to 11.9; P<0.001), or valvular abnormalities (HR 4.8, 95% CI 3.0 to 7.6; P<0.001). Exposure to 250 mg/m(2) or more of anthracyclines increased the relative hazard of congestive heart failure, pericardial disease, and valvular abnormalities by two to five times compared with survivors who had not been exposed to anthracyclines. Cardiac radiation exposure of 1500 centigray or more increased the relative hazard of congestive heart failure, myocardial infarction, pericardial disease, and valvular abnormalities by twofold to sixfold compared to non-irradiated survivors. The cumulative incidence of adverse cardiac outcomes in cancer survivors continued to increase up to 30 years after diagnosis.Survivors of childhood and adolescent cancer are at substantial risk for cardiovascular disease. Healthcare professionals must be aware of these risks when caring for this growing population.

    View details for DOI 10.1136/bmj.b4606

    View details for Web of Science ID 000272697300001

    View details for PubMedID 19996459

  • Vincristine, Actinomycin, and Cyclophosphamide Compared With Vincristine, Actinomycin, and Cyclophosphamide Alternating With Vincristine, Topotecan, and Cyclophosphamide for Intermediate-Risk Rhabdomyosarcoma: Children's Oncology Group Study D9803 JOURNAL OF CLINICAL ONCOLOGY Arndt, C. A., Stoner, J. A., Hawkins, D. S., Rodeberg, D. A., Hayes-Jordan, A. A., Paidas, C. N., Parham, D. M., Teot, L. A., Wharam, M. D., Breneman, J. C., Donaldson, S. S., Anderson, J. R., Meyer, W. H. 2009; 27 (31): 5182-5188

    Abstract

    The purpose of this study was to compare the outcome of patients with intermediate-risk rhabdomyosarcoma (RMS) treated with standard VAC (vincristine, dactinomycin, and cyclophosphamide) chemotherapy to that of patients treated with VAC alternating with vincristine, topotecan, and cyclophosphamide (VAC/VTC).Patients were randomly assigned to 39 weeks of VAC versus VAC/VTC; local therapy began after week 12. Patients with parameningeal RMS with intracranial extension (PME) were treated with VAC and immediate x-ray therapy. The primary study end point was failure-free survival (FFS). The study was designed with 80% power (5% two-sided alpha level) to detect an increase in 5-year FFS from 64% to 75% with VAC/VTC.A total of 617 eligible patients were entered onto the study: 264 were randomly assigned to VAC and 252 to VAC/VTC; 101 PME patients were nonrandomly treated with VAC. Treatment strata were embryonal RMS, stage 2/3, group III (33%); embryonal RMS, group IV, less than age 10 years (7%); alveolar RMS or undifferentiated sarcoma (UDS), stage 1 or group I (17%); alveolar RMS/UDS (27%); and PME (16%). At a median follow-up of 4.3 years, 4-year FFS was 73% with VAC and 68% with VAC/VTC (P = .3). There was no difference in effect of VAC versus VAC/VTC across risk groups. The frequency of second malignancies was similar between the two treatment groups.For intermediate-risk RMS, VAC/VTC does not significantly improve FFS compared with VAC.

    View details for DOI 10.1200/JCO.2009.22.3768

    View details for Web of Science ID 000271274300013

    View details for PubMedID 19770373

  • Neurocognitive Status in Long-Term Survivors of Childhood CNS Malignancies: A Report From the Childhood Cancer Survivor Study NEUROPSYCHOLOGY Ellenberg, L., Liu, Q., Gioia, G., Yasui, Y., Packer, R. J., Mertens, A., Donaldson, S. S., Stovall, M., Kadan-Lottick, N., Armstrong, G., Robison, L. L., Zeltzer, L. K. 2009; 23 (6): 705-717

    Abstract

    To assess neurocognitive functioning in adult survivors of childhood Central Nervous System (CNS) malignancy, a large group of CNS malignancy survivors were compared to survivors of non-CNS malignancy and siblings without cancer on a self-report instrument (CCSS-NCQ) assessing four factors, Task Efficiency, Emotional Regulation, Organization and Memory. Additional multiple linear regressions were used to assess the contribution of demographic, illness, and treatment variables to reported neurocognitive functioning in CNS malignancy survivors and the relationship of reported neurocognitive functioning to socioeconomic indicators. Survivors of CNS malignancy reported significantly greater neurocognitive impairment on all CCSS-NCQ factors than non-CNS cancer survivors or siblings (p < .01). Within the CNS malignancy group, medical complications (hearing deficits, paralysis and cerebrovascular incidents) resulted in a greater likelihood of reported deficits on all CCSS-NCQ factors. Total or partial brain irradiation and ventriculoperitoneal (VP) shunt placement was associated with greater impairment on Task Efficiency and Memory. Female gender was associated with a greater likelihood of impaired scores on Task Efficiency and Emotional Regulation, while diagnosis before age 2 years resulted in less likelihood of reported impairment on the Memory factor. CNS malignancy survivors with more impaired CCSS-NCQ scores demonstrated significantly lower educational attainment (p < .01), less household income (p < .001), less full time employment (p < .001), and fewer marriages (p < .001). Survivors of childhood CNS malignancy were found to be at significant risk for neurocognitive impairment that continues to adulthood and is correlated with lower socioeconomic achievement.

    View details for DOI 10.1037/a0016674

    View details for Web of Science ID 000271689300003

    View details for PubMedID 19899829

  • EXTERNAL BEAM RADIATION THERAPY ENHANCES LOCAL CONTROL IN PIGMENTED VILLONODULAR SYNOVITIS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Horoschak, M., Tran, P. T., Bachireddy, P., West, R. B., Mohler, D., Beaulieu, C. F., Kapp, D. S., Donaldson, S. S. 2009; 75 (1): 183-187

    Abstract

    Pigmented villonodular synovitis (PVNS) is a rare proliferative disorder of the synovium with locally aggressive behavior. We reviewed our experience using radiation therapy in the treatment of PVNS.Seventeen patients with 18 sites of PVNS were treated with radiation between 1993 and 2007. Cases were retrospectively reviewed for patient information, treatment parameters, complications, and outcome. Seven sites were primary presentations and 11 were recurrent with an average of 2.5 prior surgical interventions. The most common location was the knee joint (67%). Cytoreductive surgery was performed before radiation therapy in 16/18 sites with all having proven or suspected residual disease. Radiation was delivered using 4-15 MV photons with an average total dose 34 Gy (range, 20-36 Gy). Seventeen of 18 sites (94%) had postradiotherapy imaging.With average follow-up of 46 months (range, 8-181 months), initial local control was achieved in 75% (12/16) of the sites with prior cytoreductive surgery (mean time to recurrence, 38 months). Ultimate local control was 100% after repeat resection (mean follow-up, 61 months). Two additional sites without prior cytoreductive surgery showed growth after radiotherapy (mean time to documented growth, 10.5 months). Seventeen of the 18 involved joints (94%) were scored as excellent or good PVNS-related function, one site (5%) as fair function, and no site with poor function. No patient required amputation; and there were no Grade 3/4 treatment-related complications.Postoperative external beam radiation is effective in preventing disease recurrence and should be offered following maximal cytoreduction to enhance local control in PVNS.

    View details for DOI 10.1016/j.ijrobp.2008.10.058

    View details for Web of Science ID 000269328700031

    View details for PubMedID 19211195

  • Radiation Dose and Breast Cancer Risk in the Childhood Cancer Survivor Study JOURNAL OF CLINICAL ONCOLOGY Inskip, P. D., Robison, L. L., Stovall, M., Smith, S. A., Hammond, S., Mertens, A. C., Whitton, J. A., Diller, L., Kenney, L., Donaldson, S. S., Meadows, A. T., Neglia, J. P. 2009; 27 (24): 3901-3907

    Abstract

    The purpose of this study was to quantify the risk of breast cancer in relation to radiation dose and chemotherapy among survivors of childhood cancer.We conducted a case-control study of breast cancer in a cohort of 6,647 women who were 5-year survivors of childhood cancer and who were treated during 1970 through 1986. One hundred twenty patients with histologically confirmed breast cancer were identified and were individually matched to four selected controls on age at initial cancer and time since initial cancer. Medical physicists estimated radiation dose to the breast tumor site and ovaries on the basis of medical records.The odds ratio for breast cancer increased linearly with radiation dose, and it reached 11-fold for local breast doses of approximately 40 Gy relative to no radiation (P for trend < .0001). Risk associated with breast irradiation was sharply reduced among women who received 5 Gy or more to the ovaries (P = .002). The excess odds ratio per Gy was 0.36 for those who received ovarian doses less than 5 Gy and was 0.06 for those who received higher doses. Radiation-related risk did not vary significantly by age at exposure. Borderline significantly elevated risks were seen for doxorubicin, dactinomycin, dacarbazine, and carmustine.Results confirm the radiation sensitivity of the breast in girls age 10 to 20 years but do not demonstrate a strong effect of age at exposure within this range. Irradiation of the ovaries at doses greater than 5 Gy seems to lessen the carcinogenic effects of breast irradiation, most likely by reducing exposure of radiation-damaged breast cells to stimulating effects of ovarian hormones.

    View details for DOI 10.1200/JCO.2008.20.7738

    View details for Web of Science ID 000269064300007

    View details for PubMedID 19620485

  • Long-Term Outcomes Among Adult Survivors of Childhood Central Nervous System Malignancies in the Childhood Cancer Survivor Study JOURNAL OF THE NATIONAL CANCER INSTITUTE Armstrong, G. T., Liu, Q., Yasui, Y., Huang, S., Ness, K. K., Leisenring, W., Hudson, M. M., Donaldson, S. S., King, A. A., Stovall, M., Krull, K. R., Robison, L. L., Packer, R. J. 2009; 101 (13): 946-958

    Abstract

    Adult survivors of childhood central nervous system (CNS) malignancies are at high risk for long-term morbidity and late mortality. However, patterns of late mortality, the long-term risks of subsequent neoplasms and debilitating medical conditions, and sociodemographic outcomes have not been comprehensively characterized for individual diagnostic and treatment groups.We collected information on treatment, mortality, chronic medical conditions, and neurocognitive functioning of adult 5-year survivors of CNS malignancies diagnosed between 1970 and 1986 within the Childhood Cancer Survivor Study. Using competing risk framework, we calculated cumulative mortality according to cause of death and cumulative incidence of subsequent neoplasms according to exposure and dose of cranial radiation therapy (RT). Neurocognitive impairment and socioeconomic outcomes were assessed with respect to dose of CNS radiotherapy to specific brain regions. Cumulative incidence of chronic medical conditions was compared between survivors and siblings using Cox regression models. All tests of statistical significance were two-sided.Among all eligible 5-year survivors (n = 2821), cumulative late mortality at 30 years was 25.8% (95% confidence interval [CI] = 23.4% to 28.3%), due primarily to recurrence and/or progression of primary disease. Patients who received cranial RT of 50 Gy or more (n = 813) had a cumulative incidence of a subsequent neoplasm within the CNS of 7.1% (95% CI = 4.5% to 9.6%) at 25 years from diagnosis compared with 1.0% (95% CI = 0% to 2.3%) for patients who had no RT. Survivors had higher risk than siblings of developing new endocrine, neurological, or sensory complications 5 or more years after diagnosis. Neurocognitive impairment was high and proportional to radiation dose for specific tumor types. There was a dose-dependent association between RT to the frontal and/or temporal lobes and lower rates of employment, and marriage.Survivors of childhood CNS malignancies are at high risk for late mortality and for developing subsequent neoplasms and chronic medical conditions. Care providers should be informed of these risks so they can provide risk-directed care and develop screening guidelines.

    View details for DOI 10.1093/jnci/djp148

    View details for Web of Science ID 000267666900012

    View details for PubMedID 19535780

  • Fertility of Female Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study JOURNAL OF CLINICAL ONCOLOGY Green, D. M., Kawashima, T., Stovall, M., Leisenring, W., Sklar, C. A., Mertens, A. C., Donaldson, S. S., Byrne, J., Robison, L. L. 2009; 27 (16): 2677-2685

    Abstract

    This study was undertaken to determine the effect, if any, of treatment for cancer diagnosed during childhood or adolescence on fertility.We reviewed the fertility of female participants in the Childhood Cancer Survivor Study (CCSS), which consisted of 5-year survivors, and a cohort of randomly selected siblings who responded to a questionnaire. Medical records of all members of the cohort were abstracted to obtain chemotherapeutic agents administered; the cumulative dose of drug administered for several drugs of interest; and the doses, volumes, and dates of administration of all radiation therapy.There were 5,149 female CCSS participants, and there were 1,441 female siblings of CCSS participants who were age 15 to 44 years. The relative risk (RR) for survivors of ever being pregnant was 0.81 (95% CI, 0.73 to 0.90; P < .001) compared with female siblings. In multivariate models among survivors only, those who received a hypothalamic/pituitary radiation dose > or = 30 Gy (RR, 0.61; 95% CI, 0.44 to 0.83) or an ovarian/uterine radiation dose greater than 5 Gy were less likely to have ever been pregnant (RR, 0.56 for 5 to 10 Gy; 95% CI, 0.37 to 0.85; RR, 0.18 for > 10 Gy; 95% CI, 0.13 to 0.26). Those with a summed alkylating agent dose (AAD) score of three or four or who were treated with lomustine or cyclophosphamide were less likely to have ever been pregnant.This large study demonstrated that fertility is decreased among female CCSS participants. The risk factors identified may be utilized for pretreatment counseling of patients and their parents.

    View details for DOI 10.1200/JCO.2008.20.1541

    View details for Web of Science ID 000266454600018

    View details for PubMedID 19364965

  • The Childhood Cancer Survivor Study: A National Cancer Institute-Supported Resource for Outcome and Intervention Research JOURNAL OF CLINICAL ONCOLOGY Robison, L. L., Armstrong, G. T., Boice, J. D., Chow, E. J., Davies, S. M., Donaldson, S. S., Green, D. M., Hammond, S., Meadows, A. T., Mertens, A. C., Mulvihill, J. J., Nathan, P. C., Neglia, J. P., Packer, R. J., Rajaraman, P., Sklar, C. A., Stovall, M., Strong, L. C., Yasui, Y., Zeltzer, L. K. 2009; 27 (14): 2308-2318

    Abstract

    Survival for childhood cancer has increased dramatically over the last 40 years with 5-year survival rates now approaching 80%. For many diagnostic groups, rapid increases in survival began in the 1970s with the broader introduction of multimodality approaches, often including combination chemotherapy with or without radiation therapy. With this increase in rates of survivorship has come the recognition that survivors are at risk for adverse health and quality-of-life outcomes, with risk being influenced by host-, disease-, and treatment-related factors. In 1994, the US National Cancer Institute funded the Childhood Cancer Survivor Study, a multi-institutional research initiative designed to establish a large and extensively characterized cohort of more than 14,000 5-year survivors of childhood and adolescent cancer diagnosed between 1970 and 1986. This ongoing study, which reflects the single most comprehensive body of information ever assembled on childhood and adolescent cancer survivors, provides a dynamic framework and resource to investigate current and future questions about childhood cancer survivors.

    View details for DOI 10.1200/JCO.2009.22.3339

    View details for Web of Science ID 000266195200002

    View details for PubMedID 19364948

  • Second Neoplasms in Survivors of Childhood Cancer: Findings From the Childhood Cancer Survivor Study Cohort JOURNAL OF CLINICAL ONCOLOGY Meadows, A. T., Friedman, D. L., Neglia, J. P., Mertens, A. C., Donaldson, S. S., Stovall, M., Hammond, S., Yasui, Y., Inskip, P. D. 2009; 27 (14): 2356-2362

    Abstract

    To review the reports of subsequent neoplasms (SNs) in the Childhood Cancer Survivor Study (CCSS) cohort that were made through January 1, 2006, and published before July 31, 2008, and to discuss the host-, disease-, and therapy-related risk factors associated with SNs.SNs were ascertained by survivor self-reports and subsequently confirmed by pathology findings or medical record review. Cumulative incidence of SNs and standardized incidence ratios for second malignant neoplasms (SMNs) were calculated. The impact of host-, disease-, and therapy-related risk factors was evaluated by Poisson regression.Among 14,358 cohort members, 730 reported 802 SMNs (excluding nonmelanoma skin cancers). This represents a 2.3-fold increase in the number of SMNs over that reported in the first comprehensive analysis of SMNs in the CCSS cohort, which was done 7 years ago. In addition, 66 cases of meningioma and 1,007 cases of nonmelanoma skin cancer were diagnosed. The 30-year cumulative incidence of SMNs was 9.3% and that of nonmelanoma skin cancer was 6.9%. Risk of SNs remains elevated for more than 20 years of follow-up for all primary childhood cancer diagnoses. In multivariate analyses, risks differ by SN subtype, but include radiotherapy, age at diagnosis, sex, family history of cancer, and primary childhood cancer diagnosis. Female survivors whose primary childhood cancer diagnosis was Hodgkin's lymphoma or sarcoma and who received radiotherapy are at particularly increased risk. Analyses of risk associated with radiotherapy demonstrated different dose-response curves for specific SNs.Childhood cancer survivors are at a substantial and increasing risk for SNs, including nonmelanoma skin cancer and meningiomas. Health care professionals should understand the magnitude of these risks to provide individuals with appropriate counseling and follow-up.

    View details for DOI 10.1200/JCO.2008.21.1920

    View details for Web of Science ID 000266195200006

    View details for PubMedID 19255307

  • High-Risk Populations Identified in Childhood Cancer Survivor Study Investigations: Implications for Risk-Based Surveillance JOURNAL OF CLINICAL ONCOLOGY Hudson, M. M., Mulrooney, D. A., Bowers, D. C., Sklar, C. A., Green, D. M., Donaldson, S. S., Oeffinger, K. C., Neglia, J. P., Meadows, A. T., Robison, L. L. 2009; 27 (14): 2405-2414

    Abstract

    Childhood cancer survivors often experience complications related to cancer and its treatment that may adversely affect quality of life and increase the risk of premature death. The purpose of this manuscript is to review how data derived from Childhood Cancer Survivor Study (CCSS) investigations have facilitated identification of childhood cancer survivor populations at high risk for specific organ toxicity and secondary carcinogenesis and how this has informed clinical screening practices. Articles previously published that used the resource of the CCSS to identify risk factors for specific organ toxicity and subsequent cancers were reviewed and results summarized. CCSS investigations have characterized specific groups to be at highest risk of morbidity related to endocrine and reproductive dysfunction, pulmonary toxicity, cerebrovascular injury, neurologic and neurosensory sequelae, and subsequent neoplasms. Factors influencing risk for specific outcomes related to the individual survivor (eg, sex, race/ethnicity, age at diagnosis, attained age), sociodemographic status (eg, education, household income, health insurance) and cancer history (eg, diagnosis, treatment, time from diagnosis) have been consistently identified. These CCSS investigations that clarify risk for treatment complications related to specific treatment modalities, cumulative dose exposures, and sociodemographic factors identify profiles of survivors at high risk for cancer-related morbidity who deserve heightened surveillance to optimize outcomes after treatment for childhood cancer.

    View details for DOI 10.1200/JCO.2008.21.1516

    View details for Web of Science ID 000266195200012

    View details for PubMedID 19289611

  • Medical care in long-term survivors of childhood cancer: A report from the Childhood Cancer Survivor Study JOURNAL OF CLINICAL ONCOLOGY Nathan, P. C., Greenberg, M. L., Ness, K. K., Hudson, M. M., Mertens, A. C., Mahoney, M. C., Gurney, J. G., Donaldson, S. S., Leisenring, W. M., Robison, L. L., Oeffinger, K. C. 2008; 26 (27): 4401-4409

    Abstract

    To evaluate whether childhood cancer survivors receive regular medical care focused on the specific morbidities that can arise from their therapy.We conducted a cross-sectional survey of health care use in 8,522 participants in the Childhood Cancer Survivor Study, a multi-institutional cohort of childhood cancer survivors. We assessed medical visits in the preceding 2 years, whether these visits were related to the prior cancer, whether survivors received advice about how to reduce their long-term risks, and whether screening tests were discussed or ordered. Completion of echocardiograms and mammograms were assessed in patients at high risk for cardiomyopathy or breast cancer. We examined the relationship between demographics, treatment, health status, chronic medical conditions, and health care use.Median age at cancer diagnosis was 6.8 years (range, 0 to 20.9 years) and at interview was 31.4 years (range, 17.5 to 54.1 years). Although 88.8% of survivors reported receiving some form of medical care, only 31.5% reported care that focused on their prior cancer (survivor-focused care), and 17.8% reported survivor-focused care that included advice about risk reduction or discussion or ordering of screening tests. Among survivors who received medical care, those who were black, older at interview, or uninsured were less likely to have received risk-based, survivor-focused care. Among patients at increased risk for cardiomyopathy or breast cancer, 511 (28.2%) of 1,810 and 169 (40.8%) of 414 had undergone a recommended echocardiogram or mammogram, respectively.Despite a significant risk of late effects after cancer therapy, the majority of childhood cancer survivors do not receive recommended risk-based care.

    View details for DOI 10.1200/JCO.2008.16.9607

    View details for Web of Science ID 000259350700009

    View details for PubMedID 18802152

  • Understanding the risk of second malignant tumors in children with Hodgkin's disease INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Donaldson, S. S., O'Brien, M. M. 2008; 72 (1): 4-5

    View details for DOI 10.1016/j.ijrobp.2008.05.007

    View details for Web of Science ID 000258741700002

    View details for PubMedID 18722256

  • Results in patients with cranial parameningeal sarcoma and metastases (stage 4) treated on Intergroup Rhabdomyosarcoma Study Group (IRSG) Protocols II-IV, 1978-1997: Report from the children's oncology group PEDIATRIC BLOOD & CANCER Raney, B., Anderson, J., Breneman, J., Donaldson, S. S., Huh, W., Maurer, H., Michalski, J., Qualman, S., Ullrich, F., Wharam, M., Meyer, W. 2008; 51 (1): 17-22

    Abstract

    Determine outcome of patients with cranial parameningeal sarcoma and concurrent metastases treated on Intergroup Rhabdomyosarcoma Study Group (IRSG) Protocols II-IV.We identified 91 patients in the database, which includes newly diagnosed subjects <21 years old with rhabdomyosarcoma (RMS) and undifferentiated sarcoma, and reviewed their charts in detail.The 54 males and 37 females were <1-19 years at diagnosis. Primary sites were nasopharynx-nasal cavity, middle ear/mastoid and parapharyngeal area ("better" sites, 55%), paranasal sinus and infratemporal-pterygopalatine area ("worse" sites, 42%), and other (3%). Sixty-eight percent of informative patients had direct intracranial extension. Major metastatic sites at diagnosis were lung (63%), bone marrow (33%), and bone (27%). Treatment included vincristine, actinomycin D, and cyclophosphamide (VAC) chemotherapy and radiotherapy to the primary tumor and up to five metastatic sites/tissues.The estimated 10-year failure-free survival (FFS) rate was 32% (95% confidence interval [CI]: 22%, 42%). Sixty patients had progressive disease (N = 49) or death as a first event (N = 11); another developed myelodysplastic syndrome and died. Sites of first progression/relapse were distant (55%), local (12%), CNS extension (8%), mixed (6%), and uncertain (18%). Factors indicating likelihood of 10-year FFS included tumor arising in "better" versus "worse" sites (FFS 46% vs. 18%, P = 0.02) and embryonal versus other histology (FFS 37% vs. 19%, P = 0.06).Cure was possible for some patients with metastatic cranial parameningeal sarcoma. Patients with the best outlook had embryonal RMS located in the nasopharynx/nasal cavity, middle ear/mastoid, or parapharyngeal region. Distant metastases were the most frequent type of recurrence, indicating that more effective systemic agents are needed to eliminate residual disease.

    View details for DOI 10.1002/pbc.21492

    View details for Web of Science ID 000255816800005

    View details for PubMedID 18266224

  • Cause-specific mortality and second cancer incidence after non-Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study BLOOD Bluhm, E. C., Ronckers, C., Hayashi, R. J., Neglia, J. P., Mertens, A. C., Stovall, M., Meadows, A. T., Mitby, P. A., Whitton, J. A., Hammond, S., Barker, J. D., Donaldson, S. S., Robison, L. L., Inskip, P. D. 2008; 111 (8): 4014-4021

    Abstract

    Second primary malignancies and premature death are a concern for patients surviving treatment for childhood lymphomas. We assessed mortality and second malignant neoplasms (SMNs) among 1082 5-year survivors of non-Hodgkin lymphoma (NHL) in the Childhood Cancer Survivor Study, a multi-institutional North American retrospective cohort study of cancer survivors diagnosed from 1970 to 1986. Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) were calculated using US population rates. Relative risks for death and solid tumor SMNs were calculated based on demographic, clinical, and treatment characteristics using Poisson regression models. There were 87 observed deaths (SMR = 4.2; 95% CI, 1.8-4.1) with elevated rates of death from solid tumors, leukemia, cardiac disease, and pneumonia. Risk for death remained elevated beyond 20 years after NHL. Risk factors for death from causes other than NHL included female sex (rate ratio [RR] = 3.4) and cardiac radiation therapy exposure (RR = 1.9). There were 27 solid tumor SMNs (SIR = 3.9; 95% CI, 2.6-5.7) with 3% cumulative incidence between 5 and 20 years after NHL diagnosis. Risk factors were female sex (RR = 3.1), mediastinal NHL disease (RR = 5.2), and breast irradiation (RR = 4.3). Survivors of childhood NHL, particularly those treated with chest RT, are at continued increased risk of early mortality and solid tumor SMNs.

    View details for DOI 10.1182/blood-2007-08-106021

    View details for Web of Science ID 000255134700022

    View details for PubMedID 18258798

  • Treatment of Pediatric Hodgkin Lymphoma CURRENT TREATMENT OPTIONS IN ONCOLOGY Olson, M. R., Donaldson, S. S. 2008; 9 (1): 81-94

    Abstract

    OPINION STATEMENT: We are increasingly successful in the treatment of Hodgkin lymphoma. Current risk adapted trials seek to maintain the excellent efficacy of older therapies, while simultaneously limiting their late toxicities. Current management of early stage/favorable disease involves the use of two to four cycles of tailored chemotherapy, often followed by low-dose, involved field radiation. Those with intermediate and advanced stage disease require more intense chemotherapy and radiation regimens. Functional imaging using [(18)F]-2 fluoro-D-2-deoxyglucose is increasingly used to determine complete vs. partial response and to detect relapse. Given the success of primary therapy, retrieval of patients remains a highly individualized challenge. The majority of children failing combined-modality treatment undergo high-dose chemotherapy followed by autologous hematopoietic stem cell rescue, oftentimes with consolidative radiotherapy.

    View details for DOI 10.1007/s11864-008-0058-0

    View details for Web of Science ID 000262835600007

    View details for PubMedID 18461462

  • Treatment of metastatuc Ewing Sarcoma/Primitive neuroectodermal tumor of bone: Evaluation of increasing the dose intensity of chemotherapy - A report from the children's oncology group PEDIATRIC BLOOD & CANCER Miser, J. S., Goldsby, R. E., Chen, Z., Krailo, M. D., Tarbell, N. J., Link, M. P., Fryer, C. J., Pritchard, D. J., Gebhardt, M. C., Dickman, P. S., Perlman, E. J., Meyers, P. A., Donaldson, S. S., Moore, S. G., Rausen, A. R., Vietti, T. J., Grier, H. E. 2007; 49 (7): 894-900

    Abstract

    The outcome for patients with Ewing sarcoma family of tumors (ESFTs) of bone with metastases at diagnosis remains poor despite new approaches to treatment. We evaluated whether a dose-intensity chemotherapy regimen improved survival for patients with ESFTs of bone with metastases at diagnosis.We entered 60 patients with metastatic ESFTs of bone onto a single arm trial of a new intensive therapy. Treatment consisted of 51-weeks of chemotherapy and local control of the primary with radiation, surgery, or both. The chemotherapeutic protocol included two alternating blocks: one with vincristine (2 mg/m(2)), doxorubicin (90 mg/m(2)), and cyclophosphamide (2,200 mg/m(2)); and the second with ifosfamide (2,800 mg/m(2)/day x 5 days) and etoposide (100 mg/m(2)/day x 5 days).Of the 60 patients with metastatic ESFTs of bone enrolled onto this single arm trial, 12 had metastasis to lung only, 7 to bone marrow or bone only, 38 to multiple sites, 2 in other sites and 3 not specified. There were three toxic deaths. Six patients (6-year cumulative incidence: 9%) developed second malignant neoplasms and died. The 6-year overall event-free survival (EFS) was 28% (standard error (SE) 6%) and survival (S) was 29% (SE 6%).An intensified treatment regimen using higher doses of cyclophosphamide, ifosfamide, and doxorubicin increased toxicity and risk of second malignancy without improving EFS and S.

    View details for DOI 10.1002/pbc.21233

    View details for Web of Science ID 000250487800004

    View details for PubMedID 17584910

  • Fertility of males after treatment for childhood cancer - A preliminary report from the childhood cancer survivor study (CCSS) Green, D., Kawashima, T., Leisenring, W., Stovall, M., Donaldson, S., Sklar, C., Byrne, J., Robison, L. WILEY-BLACKWELL. 2007: 413-413
  • Two consecutive phase II window trials of irinotecan alone or in combination with vincristine for the treatment of metastatic rhabdomyosarcoma: The Children's Oncology Group JOURNAL OF CLINICAL ONCOLOGY Pappo, A. S., Lyden, E., Breitfeld, P., Donaldson, S. S., Wiener, E., Parham, D., Crews, K. R., Houghton, P., Meyer, W. H. 2007; 25 (4): 362-369

    Abstract

    To estimate the antitumor activity and toxicity of irinotecan alone and in combination with vincristine when administered as window therapy and in combination with standard chemotherapy in pediatric patients with newly diagnosed metastatic rhabdomyosarcoma.Nineteen patients younger than age 21 years with newly diagnosed metastatic rhabdomyosarcoma or undifferentiated sarcoma received window therapy with two cycles of irinotecan (20 mg/m2 daily for 5 days, repeated for 2 weeks) and 50 patients received window therapy with vincristine 1.5 mg/m2 (weeks 0, 1, 3, and 4) and two cycles of irinotecan (20 mg/m2 daily for 5 days, repeated for 2 weeks). Patients who achieved a partial response (PR) or complete response (CR) received these agents alternating with vincristine (V; 1.5/mg/m2), dactinomycin (A; 1.5 mg/m2), and cyclophosphamide (C; 2.2 g/m2) during weeks 6 through 41. Nonresponders were treated with VAC alone. Radiotherapy was administered to sites of disease at weeks 15 to 21.The window response rate (PR/CR) for patients who received irinotecan was 42% (95% CI, 38% to 80%) but the high progressive disease (PD) rate of 32% (95% CI, 11% to 52%) prompted closure of the trial. The window CR/PR rate for patients who received vincristine and irinotecan was 70% (95% CI, 57% to 83%), and the PD rate was only 8%. GI toxicities (abdominal pain, diarrhea, dehydration) were the most common adverse effects associated with the administration of irinotecan.The combination of vincristine and irinotecan is highly active in metastatic rhabdomyosarcoma. The different mechanism of action and nonoverlapping toxicity profile with VAC makes this combination an attractive candidate for further testing in intermediate risk patients with rhabdomyosarcoma.

    View details for DOI 10.1200/JCO.2006.07.1720

    View details for Web of Science ID 000244070400004

    View details for PubMedID 17264331

  • Final results of a prospective clinical trial with VAMP and low-dose involved-field radiation for children with low-risk Hodgkin's disease JOURNAL OF CLINICAL ONCOLOGY Donaldson, S. S., Link, M. P., Weinstein, H. J., Rai, S. N., Brain, S., Billett, A. L., Hurwitz, C. A., Krasin, M., Kun, L. E., Marcus, K. C., Tarbell, N. J., Young, J. A., Hudson, M. M. 2007; 25 (3): 332-337

    Abstract

    To evaluate outcome and assess complications in children and adolescents with low-risk Hodgkin's disease treated with vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) chemotherapy and low-dose, involved-field radiation therapy (IFRT).One hundred ten children with low-risk Hodgkin's disease were treated with four cycles of VAMP and 15 Gy IFRT for those who achieved a complete response (CR) or 25.5 Gy for those with a partial response after two cycles of VAMP.With median follow-up of 9.6 years (range, 1.7 to 15.0), 5- and 10-year overall survival were 99.1% and 96.1%, respectively, and 5-and 10-year event-free survival (EFS) were 92.7% and 89.4%. Factors contributing to 10-year EFS were: early CR (P = .02), absence of B symptoms (P = .01), lymphocyte predominant histologic subtype (P = .04), and less than three initial sites of disease (P = .02). Organ toxicity has been limited to correctable hypothyroidism in 42% of irradiated patients, and one case of cardiac dysfunction. Seventeen healthy babies have been born to 106 survivors. There have been two malignant tumors: one thyroid cancer within the radiation therapy field and one Ewing's sarcoma outside the radiation therapy field.Risk-adapted, combined-modality therapy using VAMP chemotherapy with radiation is effective and well tolerated. Pediatric patients with low-risk Hodgkin's disease can be cured with therapy without an alkylating agent, bleomycin, etoposide, or high-dose, extended-field radiotherapy. Thus, these children are expected to retain normal fertility, organ function, and be at low risk of a second malignant tumor.

    View details for DOI 10.1200/JCO.2006.08.4772

    View details for Web of Science ID 000243729200016

    View details for PubMedID 17235049

  • New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the childhood cancer survivor study JOURNAL OF THE NATIONAL CANCER INSTITUTE Neglia, J. P., Robison, L. L., Stovall, M., Liu, Y., Packer, R. J., Hammond, S., Yasui, Y., Kasper, C. E., Mertens, A. C., Donaldson, S. S., Meadows, A. T., Inskip, P. D. 2006; 98 (21): 1528-1537

    Abstract

    Subsequent primary neoplasms of the central nervous system (CNS) have frequently been described as late events following childhood leukemia and brain tumors. However, the details of the dose-response relationships, the expression of excess risk over time, and the modifying effects of other host and treatment factors have not been well defined.Subsequent primary neoplasms of the CNS occurring within a cohort of 14,361 5-year survivors of childhood cancers were ascertained. Each patient was matched with four control subjects by age, sex, and time since original cancer diagnosis. Tumor site-specific radiation dosimetry was performed, and chemotherapy information was abstracted from medical records. Conditional logistic regression was used to estimate odds ratios (ORs), to calculate 95% confidence intervals (CIs), and to model the excess relative risk (ERR) as a function of radiation dose and host factors. For subsequent gliomas, standardized incidence ratios (SIRs) and excess absolute risks (EARs) were calculated based on Surveillance, Epidemiology, and End Results data.Subsequent CNS primary neoplasms were identified in 116 individuals. Gliomas (n = 40) occurred a median of 9 years from original diagnosis; for meningiomas (n = 66), it was 17 years. Radiation exposure was associated with increased risk of subsequent glioma (OR = 6.78, 95% CI = 1.54 to 29.7) and meningioma (OR = 9.94, 95% CI = 2.17 to 45.6). The dose response for the excess relative risk was linear (for glioma, slope = 0.33 [95% CI = 0.07 to 1.71] per Gy, and for meningioma, slope = 1.06 [95% CI = 0.21 to 8.15] per Gy). For glioma, the ERR/Gy was highest among children exposed at less than 5 years of age. After adjustment for radiation dose, neither original cancer diagnosis nor chemotherapy was associated with risk. The overall SIR for glioma was 8.7, and the EAR was 19.3 per 10,000 person-years.Exposure to radiation therapy is the most important risk factor for the development of a new CNS tumor in survivors of childhood cancers. The higher risk of subsequent glioma in children irradiated at a very young age may reflect greater susceptibility of the developing brain to radiation.

    View details for DOI 10.1093/jnci/djj411

    View details for Web of Science ID 000242379600008

    View details for PubMedID 17077355

  • Female survivors of childhood cancer: Preterm birth and low birth weight among their children JOURNAL OF THE NATIONAL CANCER INSTITUTE Signorello, L. B., Cohen, S. S., Bosetti, C., Stovall, M., Kasper, C. E., Weathers, R. E., Whitton, J. A., Green, D. M., Donaldson, S. S., Mertens, A. C., Robison, L. L., Boice, J. D. 2006; 98 (20): 1453-1461

    Abstract

    Improved survival after childhood cancer raises concerns over the possible long-term reproductive health effects of cancer therapies. We investigated whether children of female childhood cancer survivors are at elevated risk of being born preterm or exhibiting restricted fetal growth and evaluated the associations of different cancer treatments on these outcomes.Using data from the Childhood Cancer Survivor Study, a large multicenter cohort of childhood cancer survivors, we studied the singleton live births of female cohort members from 1968 to 2002. Included were 2201 children of 1264 survivors and 1175 children of a comparison group of 601 female siblings. Data from medical records were used to determine cumulative prepregnancy exposures to chemotherapy and radiotherapy. Logistic regression was used to estimate odds ratios (ORs) for the association between quantitative therapy exposures and preterm (<37 weeks) birth, low birth weight (<2.5 kg), and small-for-gestational-age (SGA) (lowest 10th percentile) births. All statistical tests were two-sided.Survivors' children were more likely to be born preterm than the siblings' children (21.1% versus 12.6%; OR = 1.9, 95% confidence interval [CI] = 1.4 to 2.4; P<.001). Compared with the children of survivors who did not receive any radiotherapy, the children of survivors treated with high-dose radiotherapy to the uterus (>500 cGy) had increased risks of being born preterm (50.0% versus 19.6%; OR = 3.5, 95% CI = 1.5 to 8.0; P = .003), low birth weight (36.2% versus 7.6%; OR = 6.8, 95% CI = 2.1 to 22.2; P = .001), and SGA (18.2% versus 7.8%; OR = 4.0, 95% CI = 1.6 to 9.8; P = .003). Increased risks were also apparent at lower uterine radiotherapy doses (starting at 50 cGy for preterm birth and at 250 cGy for low birth weight).Late effects of treatment for female childhood cancer patients may include restricted fetal growth and early births among their offspring, with risks concentrated among women who receive pelvic irradiation.

    View details for DOI 10.1093/jnci/djj394

    View details for Web of Science ID 000241721400009

    View details for PubMedID 17047194

  • Thyroid cancer in childhood cancer survivors: A detailed evaluation of radiation dose response and its modifiers RADIATION RESEARCH Ronckers, C. M., Sigurdson, A. J., Stovall, M., Smith, S. A., Mertens, A. C., Liu, Y., Hammond, S., Land, C. E., Neglia, J. P., Donaldson, S. S., Meadows, A. T., Sklar, C. A., Robison, L. L., Inskip, P. D. 2006; 166 (4): 618-628

    Abstract

    Radiation exposure at a young age is a strong risk factor for thyroid cancer. We conducted a nested case-control study of 69 thyroid cancer cases and 265 controls from a cohort of 14,054 childhood cancer survivors to evaluate the shape of the radiation dose-response relationship, in particular at high doses, and to assess modification of the radiation effects by patient and treatment characteristics. We considered several types of statistical models to estimate the excess relative risk (ERR), mainly guided by radiobiological models. A two-parameter model with a term linear in dose and a negative exponential in dose squared provided the best parsimonious description with an ERR of 1.3 per gray (95% confidence interval 0.4-4.1) at doses below 6 Gy and a relative decrease in ERR of 0.2% per unit dose squared with increasing dose, that is, decreases in the ERR/Gy of 53% at 20 Gy and 95% at 40 Gy. Further analyses using spline models suggested that the significant nonlinearity at high doses was characterized most appropriately as a true downturn rather than a flattening of the dose-response curve. We found no statistically significant modification of the dose-response relationship by patient characteristics; however, the linear parameter (i.e., the ERR/ Gy at doses less than 6 Gy) did decrease consistently and linearly with increasing age at childhood cancer diagnosis, from 4.45 for 0-1-year-olds to 0.48 for 15-20-year-olds. In summary, we applied models derived from radiobiology to describe the radiation dose-response curve for thyroid cancer in an epidemiological study and found convincing evidence for a downturn in risk at high doses.

    View details for Web of Science ID 000240883000007

    View details for PubMedID 17007558

  • Local control in pelvic Ewing sarcoma: Analysis from INT-0091 - A report from the Children's Oncology Group Yock, T. I., Krailo, M., Fryer, C. J., Donaldson, S. S., Miser, J. S., Chen, Z., Bernstein, M., Laurie, F., Gebhardt, M. C., Grier, H. E., Tarbell, N. J. AMER SOC CLINICAL ONCOLOGY. 2006: 3838-3843

    Abstract

    The impact of the modality used for local control of Ewing sarcoma is uncertain. We investigated the relationship between the type of local control modality, surgery, radiation (RT) or both (S + RT), and subsequent risk for local failure (LF) in patients with nonmetastatic pelvic Ewing sarcoma treated on INT-0091.Patients < or = 30 years with Ewing sarcoma, primitive neuroectodermal tumor or primitive sarcoma of bone were randomly assigned to receive chemotherapy with doxorubicin, vincristine, cyclophosphamide, and dactinomycin, (VACA) or with these four drugs alternating with ifosfamide and etoposide (VACA-IE). The local control modality, surgery, RT or both was chosen by the treating physicians. The effect of local control modality was assessed after adjusting for the size of tumor (< 8 cm, > or = 8 cm) and chemotherapy type.Seventy-five patients with pelvic tumors and a median follow-up of 4.4 years (0.6 to 11.4 years) comprised the study population. Twelve underwent surgery, 44 received RT, and 19 received both. The 5-year event-free survival (EFS) and cumulative incidence of LF was 49% and 21% (16%, LF only; 5%, LF and distant failure). There was no significant difference in EFS or LF by tumor size (< 8 cm, > or = 8 cm), local control (LC) modality, or chemotherapy. However, VACA-IE seems to confer an LC benefit (11% v 30%; P = .06).There was no significant effect of local control modality (surgery, RT or S + RT) selected by the treating physicians on rates of local failure or EFS. However, VACA-IE improves LC (11%) compared with previously published results for pelvic Ewing sarcoma.

    View details for DOI 10.1200/JCO.2006.05.9188

    View details for Web of Science ID 000240052300007

    View details for PubMedID 16921035

  • Advances toward an understanding of brainstem gliomas JOURNAL OF CLINICAL ONCOLOGY Donaldson, S. S., Laningham, F., Fisher, P. G. 2006; 24 (8): 1266-1272

    Abstract

    The diagnosis of brainstem glioma was long considered a single entity. However, since the advent of magnetic resonance imaging in the late 1980s, neoplasms within this anatomic region are now recognized to include several tumors of varying behavior and natural history. More recent reports of brainstem tumors include diverse sites such as the cervicomedullary junction, pons, midbrain, or the tectum. Today, these tumors are broadly categorized as either diffuse intrinsic gliomas, most often in the pons, or the nondiffuse brainstem tumors originating at the tectum, focally in the midbrain, dorsal and exophytic to the brainstem, or within the cervicomedullary junction. Although we briefly discuss the nondiffuse tumors, we focus specifically on those diffuse brainstem tumors that regrettably still carry a bleak prognosis.

    View details for DOI 10.1200/JCO.2005.04.6599

    View details for Web of Science ID 000236235700006

    View details for PubMedID 16525181

  • Stroke as a late treatment effect of Hodgkin's disease: A report from the Childhood Cancer Survivor Study JOURNAL OF CLINICAL ONCOLOGY Bowers, D. C., McNeil, D. E., Liu, Y., Yasui, Y., Stovall, M., Gurney, J. G., Hudson, M. M., Donaldson, S. S., Packer, R. J., Mitby, P. A., Kasper, C. E., Robison, L. L., Oeffinger, K. C. 2005; 23 (27): 6508-6515

    Abstract

    The objectives of this report are to examine the incidence of and risk factors for stroke among childhood Hodgkin's disease (HD) survivors.The Childhood Cancer Survivor Study is a multi-institutional cohort study of more than 5-year cancer survivors diagnosed between 1970 and 1986 and a sibling comparison group. Incidence rates of stroke among HD survivors (n = 1,926) and siblings (n = 3,846) were calculated and compared. Cox proportional hazards models were used to estimate the hazard ratios, reported as relative risks (RR), of developing stroke between HD survivors and siblings.Nine siblings reported a stroke, for an incidence of 8.00 per 100,000 person-years (95% CI, 3.85 to 14.43 per 100,000 person-years). Twenty-four HD survivors reported a stroke. The incidence of late-occurring stroke among HD survivors was 83.6 per 100,000 person-years (95% CI, 54.5 to 121.7 per 100,000 person-years). The RR of stroke among HD survivors was 4.32 (95% CI, 2.01 to 9.29; P = .0002). All 24 survivors received mantle radiation exposure (median dose, 40 Gy). The incidence of late-occurring stroke among HD survivors treated with mantle radiation was 109.8 per 100,000 person-years (95% CI, 70.8 to 161.1 per 100,000 person-years). The RR of late-occurring stroke among HD survivors treated with mantle radiation was 5.62 (95% CI, 2.59 to 12.25; P < .0001).Survivors of childhood HD are at increased risk of stroke. Mantle radiation exposure is strongly associated with subsequent stroke. Potential mechanisms may include carotid artery disease or cardiac valvular disease.

    View details for DOI 10.1200/JCO.2005.15.107

    View details for Web of Science ID 000232233100012

    View details for PubMedID 16170160

  • Long-term medical effects of childhood and adolescent rhabdomyosarcoma: A report from the childhood cancer survivor study PEDIATRIC BLOOD & CANCER Punyko, J. A., Mertens, A. C., Gurney, J. G., Yasui, Y., Donaldson, S. S., Rodeberg, D. A., Raney, R. B., Stovall, M., Sklar, C. A., Robison, L. L., Baker, K. S. 2005; 44 (7): 643-653

    Abstract

    This study was conducted to evaluate the incidence of adverse medical conditions and to assess the risk of developing these conditions in a cohort of long-term survivors of rhabdomyosarcoma (RMS) diagnosed before age 21.Using data from the Childhood Cancer Survivor Study (CCSS), we evaluated the incidence of self-reported adverse medical conditions for 606 RMS survivors and 3,701 siblings of cancer survivors. Cancer and treatment data abstracted from medical records were used to evaluate the effects of primary tumor site and combined modality therapy on the risk of developing sequelae in survivors.The relative risk (RR) for developing sequelae among survivors compared with siblings was greatest within 5 years after diagnosis. RR was elevated more than 5 years after diagnosis for several conditions (RR, 95% CI) as follows: eye impairment (cataract: 7.4, 2.9-18.9; visual disturbances: 3.2, 2.0-5.1; very dry eyes: 2.0, 1.2-3.3), endocrine impairment (growth hormone deficiency: 83.9, 33.0-213.6; hypothyroidism: 6.9, 4.1-11.3; need for medications to induce puberty: 90.4, 30.2-270.5), cardiopulmonary impairment (congestive heart failure: 43.0, 12.7-145.5; angina-like symptoms: 2.0, 1.3-2.9), neurosensory impairment (legal blindness: 9.8, 4.8-20.0; abnormal sensations: 1.5, 1.0-2.2), and neuromotor impairment (repeated seizures: 2.3, 1.2-4.4; motor problems: 3.7, 2.2-6.4; problems chewing or swallowing: 3.8, 1.9-7.5).Survivors are at risk for developing sequelae many years after their initial diagnosis and treatment. Continued medical surveillance is necessary to ensure the long-term health and well-being of RMS survivors.

    View details for DOI 10.1002/pbc.20310

    View details for Web of Science ID 000228789300012

    View details for PubMedID 15700252

  • Characteristics and outcomes of rhabdomyosarcoma patients with isolated lung metastases from IRS-IV JOURNAL OF PEDIATRIC SURGERY Rodeberg, D., Arndt, C., Breneman, J., Lyden, E., Donaldson, S., Paidas, C., Andrassy, R., Meyer, W., Wiener, J. 2005; 40 (1): 256-262

    Abstract

    To better understand outcomes in children with rhabdomyosarcoma (RMS) and lung-only metastatic disease, the authors reviewed the experience from Intergroup Rhabdomyosarcoma Studies IV Pilot and IV.Patients with lung-only (n = 46) vs other sites of metastatic disease (n = 234) were reviewed using patient charts and the database of Children's Oncology Group (COG).Sixteen percent of patients with RMS and metastatic disease had isolated lung metastases. Thirty-one (67%) had more than 5 metastatic lung lesions. These were bilateral in 34 (74%). Only 6 patients were biopsied at diagnosis. Sixteen children (35%) did not receive any lung radiotherapy. Patients that received lung radiotherapy had fewer lung recurrences ( P = .04), although this has no significant impact on overall survival (OAS, 47% radiotherapy vs 31% no radiotherapy). Compared with patients with other sites of metastatic disease, patients with lung-only metastases have a greater proportion of favorable histology (67% vs 39%, P = .0017), negative nodal involvement (67% vs 32%, P = .0013), and parameningeal primaries (39% vs 12%) and a smaller proportion of extremity primaries (20% vs 33%, P = .0005 for site of primary tumor). Overall survival at 4 years for lung-only metastases was not significantly different from other single-site metastasis (42% vs 34%). Survival was not improved for unilateral disease or fewer than 5 metastatic lesions. Factors associated with diminished OAS include unfavorable histology (P = .0001) and age >10 years (P = .015).Children with RMS and lung-only metastases usually present with extensive bilateral disease that is frequently not biopsied nor given protocol-recommended radiotherapy (XRT). However, outcome is comparable, although slightly better, than patients with other single-site metastasis.

    View details for DOI 10.1016/j.jpedsurg.2004.09.045

    View details for Web of Science ID 000226927000073

    View details for PubMedID 15868594

  • Risk-adapted, combined-modality therapy with VAMP/COP and response-based, involved-field radiation for unfavorable pediatric Hodgkin's disease JOURNAL OF CLINICAL ONCOLOGY Hudson, M. M., Krasin, M., Link, M. P., Donaldson, S. S., BILLUPS, C., Merchant, T. E., Kun, L., Billet, A. L., Kaste, S., Tarbell, N. J., Howard, S., Friedmann, A. M., Hurwitz, C. A., Young, J. A., Marcus, K. C., Rai, S., Cowan, T., Weinstein, H. J. 2004; 22 (22): 4541-4550

    Abstract

    To evaluate the efficacy of vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) and cyclophosphamide, vincristine, and procarbazine (COP) chemotherapy and response-based, involved-field radiation, a combined-modality regimen that limits doses of alkylating agents, anthracyclines, and radiation, in children with advanced and unfavorable Hodgkin's disease.From 1993 to 2000, 159 children and adolescents with unfavorable Hodgkin's disease received three alternating cycles (total of six cycles) of VAMP/COP chemotherapy followed by response-based, involved-field radiation therapy: 15 Gy was administered to patients achieving a complete response, and 25.5 Gy was administered to those achieving a partial response after the first two cycles of chemotherapy and to all sites of bulky lymphadenopathy. Unfavorable disease was defined as clinical stage I and II with bulky peripheral nodal disease greater than 6 cm, initial bulky mediastinal mass 33% or more of the intrathoracic diameter, and/or "B" symptoms and all stage III and IV.Study enrollment was closed after an interim analysis estimated a 5-year event-free survival (EFS) rate below a predefined level. Disease presentation was localized (stage I/II) in 77 patients (48.4%) and advanced (stage III/IV) in 82 patients (51.6%). At a median follow-up of 5.8 years (range, 1.3 to 10.0 years), 38 patients had events, including relapse/progression (n = 35), second malignancy (n = 2), and accidental death (n = 1); nine relapses (25.7%) occurred greater than 4 years from diagnosis. Five-year survival and EFS estimates are 92.7% +/- 2.5% and 75.6% +/- 4.1%, respectively.Risk-adapted combined-modality therapy with VAMP/COP and response-based, involved-field radiation therapy results in an unsatisfactory outcome for pediatric patients with unfavorable presentations of Hodgkin's disease.

    View details for DOI 10.1200/JCO.2004.02.139

    View details for Web of Science ID 000225175600016

    View details for PubMedID 15542805

  • Genetic effects of radiotherapy for childhood cancer: Gonadal dose reconstruction INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Stovall, M., Donaldson, S. S., Weathers, R. E., Robison, L. L., Mertens, A. C., Winther, J. F., Olsen, J. H., Boice, J. D. 2004; 60 (2): 542-552

    Abstract

    To estimate the doses of radiation to organs of interest during treatment of childhood cancer for use in an epidemiologic study of possible heritable diseases, including birth defects, chromosomal abnormalities, cancer, stillbirth, and neonatal and premature death.The study population was composed of more than 25,000 patients with cancer in Denmark and the United States who were survivors of childhood cancer and subsequently had nearly 6,500 children of their own. Radiation therapy records were sought for the survivors who parented offspring who had adverse pregnancy outcomes (>300 offspring), and for a sample of all survivors in a case-cohort design. The records were imaged and centrally abstracted. Water phantom measurements were made to estimate doses for a wide range of treatments. Mathematical phantoms were used to apply measured results to estimate doses to ovaries, uterus, testes, and pituitary for patients ranging in age from newborn to 25 years. Gonadal shielding, ovarian pinning (oophoropexy), and field blocking were taken into account.Testicular radiation doses ranged from <1 to 700 cGy (median, 7 cGy) and ovarian doses from <1 to >2,500 cGy (median, 13 cGy). Ten percent of the records were incomplete, but sufficient data were available for broad characterizations of gonadal dose. More than 49% of the gonadal doses were >10 cGy and 16% were >100 cGy.Sufficient radiation therapy data exist as far back as 1943 to enable computation of gonadal doses administered for curative therapy for childhood cancer. The range of gonadal doses is broad, and for many cancer survivors, is high and just below the threshold for infertility. Accordingly, the epidemiologic study has >90% power to detect a 1.3-fold risk of an adverse pregnancy outcome associated with radiation exposure to the gonads. This study should provide important information on the genetic consequences of radiation exposure to humans.

    View details for DOI 10.1016/j.ijrobp.2004.03.017

    View details for Web of Science ID 000223966500027

    View details for PubMedID 15380591

  • Cyclophosphamide dose intensification during induction therapy for intermediate-risk pediatric rhabdomyosarcoma is feasible but does not improve outcome: A report from the soft tissue sarcoma committee of the children's oncology group CLINICAL CANCER RESEARCH Spunt, S. L., Smith, L. M., Ruymann, F. B., Qualman, S. J., Donaldson, S. S., Rodeberg, D. A., Anderson, J. R., Crist, W. M., Link, M. P. 2004; 10 (18): 6072-6079

    Abstract

    More than half of pediatric rhabdomyosarcoma cases have intermediate-risk features and suboptimal outcome (3-year failure-free survival estimates, 55 to 76%). Dose intensification of known active agents may improve outcome.This pilot study evaluated the feasibility of dose intensification of cyclophosphamide in previously untreated patients ages < 21 years with intermediate-risk rhabdomyosarcoma. Induction therapy comprised four 3-week cycles of VAC: vincristine (V) 1.5 mg/m2 on days 0, 7, and 14; actinomycin D (A) 1.35 mg/m2 on day 0; and dose-intensified cyclophosphamide (C) on days 0, 1, and 2. The three cyclophosphamide dose levels tested were as follows: (a) 1.2 g/m2/dose; (b) 1.5 g/m2/dose; and (c) 1.8 g/m2/dose. Continuation therapy comprised nine additional cycles of VAC with 2.2 g/m2/cycle of C. Radiotherapy was administered at week 0 (parameningeal tumors with intracranial extension) or week 12 or 15 (all others).Between October 1996 and August 1999, 115 eligible patients were enrolled. Three of 15 patients treated at dose level 2 experienced life-threatening dose-limiting toxicity (typhlitis +/- other severe toxicity). Dose level 1 was the maximum-tolerated dose, and 91 evaluable patients were treated at this level. The 3-year failure-free and overall survival estimates for patients treated at the maximum-tolerated dose were 52% (95% confidence interval, 41-64%) and 67% (95% confidence interval, 56-77%), respectively, at a median follow-up of 3 years.A 64% increase in the standard cyclophosphamide dosage during induction (to 3.6 g/m2/cycle) was tolerated. However, outcomes were similar to those observed at lower dosages, suggesting that alkylator dose intensification does not benefit patients with intermediate-risk rhabdomyosarcoma.

    View details for Web of Science ID 000224080200014

    View details for PubMedID 15447992

  • Late events occurring five years or more after successful therapy for childhood rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group EUROPEAN JOURNAL OF CANCER Sung, L., Anderson, J. R., Donaldson, S. S., Spunt, S. L., Crist, W. M., Pappo, A. S. 2004; 40 (12): 1878-1885

    Abstract

    The aim of our study was to describe late failures in children who initially survived event-free five years from a diagnosis of rhabdomyosarcoma. Charts of children enrolled in the Intergroup Rhabdomyosarcoma Study Group (IRSG) trials III, IV pilot and IV (1984-1997) who survived five years event-free and subsequently experienced an adverse event (disease recurrence, second malignant neoplasm or death from other causes) were reviewed. Of the 2534 enrolled patients, 1160 were event-free at five years and 48 subsequently experienced a late event. The estimated 10-year event rate for the 1160 patients who were alive and event-free at five years was 9% (95% Confidence Interval (CI) 5%, 13%). Patients with both advanced disease (Group III/IV) and large primary tumours at diagnosis (> 5 cm) were at the highest risk for late events (19%; 95% CI 8%, 30%). Late events after successful treatment for rhabdomyosarcoma occur in 9%. Those with advanced disease and large primary tumours have the highest risk of late events.

    View details for DOI 10.1016/j.ejca.2004.04.005

    View details for Web of Science ID 000223456600018

    View details for PubMedID 15288290

  • Influence of radiation therapy parameters on outcome in children treated with radiation therapy for localized parameningeal rhabdomyosarcoma in intergroup rhabdomyosarcoma study group trials II through IV INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Michalski, J. M., Meza, J., Breneman, J. C., Wolden, S. L., Laurie, F., Jodoin, M., Raney, B., Wharam, M. D., Donaldson, S. S. 2004; 59 (4): 1027-1038

    Abstract

    To evaluate the impact of radiation treatment parameters on cancer control outcomes for children with parameningeal rhabdomyosarcoma (PM-RMS) treated on Intergroup Rhabdomyosarcoma Study Group protocols II through IV (including IRS-IV pilot).Radiation therapy (RT) treatment quality was assessed by contemporary review of portal radiographs, simulation films, treatment plans, and, in most cases, cross-sectional diagnostic imaging data for patients treated on Intergroup Rhabdomyosarcoma Study Group protocols II through IV. Five hundred ninety-five patients with PM-RMS were registered on these 4 studies between 1978 and 1997. Most of these patients (95%) had Group III disease. Radiation doses varied over the span of these trials with protocol doses ranging from 40 Gy to 50.4 Gy on IRS-II and IRS-III and 50.4 Gy to 59.4 Gy (hyperfractionated) on IRS-IV pilot and IRS-IV. Patients with high-risk signs of meningeal impingement, including cranial nerve palsy (CNP) or cranial base bone erosion (CBBE) with or without intracranial extension (ICE), were required to start radiotherapy at the time of study entry (Day 0). Among 595 patients reviewed, 385 (65%) had diagnostic images submitted to the Quality Assurance Review Center for assessment of target volume coverage. Only 123 (21%) patients, 49 (40%) of whom were treated on IRS-II, received whole brain RT.The estimated overall survival and failure-free survival rates were 73% and 69% at 5 years, respectively. The estimated 5-year local failure (LF) rate was 17%. The detection of ICE increased from 24% to 41% as more cross-sectional diagnostic images became available. For patients with any sign of meningeal impingement, starting RT <2 weeks after diagnosis (n = 315) had 18% LF compared to 33% LF if started >2 weeks after diagnosis (n = 43) (p = 0.03). For patients with ICE, starting RT <2 weeks after diagnosis (n = 177) resulted in LF in 16% compared to 37% among those who started >2 weeks after (n = 19) (p = 0.07). For patients with CNP and/or CBBE, starting RT <2 weeks after diagnosis (n = 138) resulted in 21% LF compared to 30% among those that started >2 weeks (n = 23) (p = 0.23). In none of these circumstances was the 5-year failure-free survival significantly impacted by this increase in LF. The estimated 3-year survival after local failure was 17% (95% CI, 10%-25%). For patients without signs of meningeal impingement, there was no difference in local control whether they started radiation therapy earlier or later than 10 weeks. Patients with large (> or =5 cm) Group III tumors had an LF rate of 35% if they received less than 47.5 Gy compared to an LF rate of 18% in patients who received less than 47.5 Gy with smaller tumors or a rate of 15% if they received more than 47.5 Gy, irrespective of tumor size (p = 0.14). There was no evidence that whole brain radiation therapy affected LF or reduced central nervous system (CNS) relapse. Multivariate analysis of RT parameters and clinical factors demonstrated that a radiation dose of >47.5 Gy was associated with lower LF. The presence of ICE, CNP, or CBBE and age >10 years at diagnosis were significantly associated with higher rates of local failure.The availability of cross-sectional diagnostic images (CT or MRI) has improved detection of ICE. Starting radiation therapy within 2 weeks of diagnosis for patients with signs of meningeal impingement was associated with lower rates of local failure. When no signs of meningeal impingement were present, delay of radiation therapy for more than 10 weeks did not impact local failure rates. Whole brain radiation therapy is unnecessary in PM-RMS. A dose of at least 47.5 Gy seems to be associated with lower rates of local failure, especially when tumor diameter is > or =5 cm.

    View details for DOI 10.1016/j.ijrobp.2004.02.064

    View details for Web of Science ID 000222541300013

    View details for PubMedID 15234036

  • Treatment of metastatic Ewing's sarcoma or primitive neuroectodermal tumor of bone: Evaluation of combination ifosfamide and etoposide - A children's cancer group and pediatric oncology group study JOURNAL OF CLINICAL ONCOLOGY Miser, J. S., Krailo, M. D., Tarbell, N. J., Link, M. P., Fryer, C. J., Pritchard, D. J., Gebhardt, M. C., Dickman, P. S., Perlman, E. J., Meyers, P. A., Donaldson, S. S., Moore, S., Rausen, A. R., Vietti, T. J., Grier, H. E. 2004; 22 (14): 2873-2876

    Abstract

    One hundred twenty patients with metastatic Ewing's sarcoma or primitive neuroectodermal tumor (PNET) of bone were entered onto a randomized trial evaluating whether the addition of ifosfamide and etoposide to vincristine, doxorubicin, cyclophosphamide, and dactinomycin improved outcomes.Thirty-two patients had metastases to lungs only, 12 patients had metastases to bone marrow or bones only, 64 patients had metastases in multiple sites, and five patients had metastases in other sites; seven patients could not be assessed precisely. Treatment comprised 9 weeks of chemotherapy before local control and 42 weeks of chemotherapy; thereafter, regimen A consisted of vincristine 2 mg/m(2), cyclophosphamide 1,200 mg/m(2), and either doxorubicin 75 mg/m(2) or dactinomycin 1.25 mg/m(2). Regimen B consisted of regimen A alternating every 3 weeks with ifosfamide 1,800 mg/m(2)/d for 5 days and etoposide 100 mg/m(2)/d for 5 days.Patients treated on regimen B did not have significantly better survival than those treated on regimen A. The event-free survival (EFS) and survival (S) at 8 years were 20% (SE, 5%) and 32% (SE, 6%), respectively, for those treated on regimen A and 20% (SE, 6%) and 29% (SE, 6%), respectively, for those treated on regimen B. Patients who had only lung metastases had EFS and S of 32% (SE, 8%) and 41% (SE, 9%), respectively, at 8 years. There were six toxic deaths (5%), four from cardiac toxicity and two from sepsis (four treated on regimen B and two treated on regimen A). Two had second malignant neoplasms.Adding ifosfamide and etoposide to standard therapy does not improve outcomes of patients with Ewing's sarcoma or PNET of bone with metastases at diagnosis.

    View details for DOI 10.1200/JCO.2004.01.041

    View details for Web of Science ID 000222729000017

    View details for PubMedID 15254055

  • Subspecialty training and certification for radiation oncology. Journal of the American College of Radiology Donaldson, S. S., Halperin, E. C. 2004; 1 (7): 488-492

    Abstract

    To address the recurring issues regarding subspecialty training and certification in radiation oncology, and using pediatric radiation oncology as an example, the authors considered the problem of inadequate case material for resident teaching. Potential solutions to the identified problems are addressed, and the roles of oversight committees and regulatory bodies are clarified. The problem of the nonuniform distribution of pediatric case material across residency programs cannot be solved by removing pediatric radiation oncology from the core radiation oncology educational curriculum or by offering fellowship training to those who may select it. As a result, the authors believe that subspecialty training and certification in radiation oncology is not a near-term possibility.

    View details for PubMedID 17411637

  • Results of treatment of fifty-six patients with localized retroperitoneal and pelvic rhabdomyosarcoma: A report from the Intergroup Rhabdomyosarcoma Study-IV, 1991-1997 PEDIATRIC BLOOD & CANCER Raney, R. B., Stoner, J. A., Walterhouse, D. O., Andrassy, R. J., Donaldson, S. S., Laurie, F., Meyer, W. H., Qualman, S. J., Crist, W. A. 2004; 42 (7): 618-625

    Abstract

    We reviewed 56 IRS-IV patients with localized rhabdomyosarcoma [RMS] of the retroperitoneum/pelvis to assess outcome and prognostic factors, including the value of initially excising >or=50% of the tumor (debulking) before chemotherapy.Patients had embryonal RMS [N=38], alveolar RMS [N = 7], RMS not otherwise specified [NOS, N = 7], or undifferentiated sarcoma [N = 4]. Fifteen patients were debulked; 41 patients were biopsied. All received VAC; most received radiotherapy.Estimated 5-year failure-free survival [FFS] and overall survival rates were 70 and 75%, respectively. FFS rates were better for patients <10 years old and those with embryonal RMS compared to alveolar RMS/undifferentiated sarcoma. After adjusting for age and histological differences, FFS was better for patients whose tumor was debulked prior to beginning therapy [P = 0.02].These results are superior to those of previous protocols for patients with RMS of the retroperitoneum/pelvis. Initial excision of >or=50% of the tumor may be associated with increased FFS.

    View details for DOI 10.1002/pbc.20012

    View details for Web of Science ID 000221225800011

    View details for PubMedID 15127417

  • Does bladder preservation (as a surgical principle) lead to retaining bladder function in bladder/prostate rhabdomyosarcoma? Results from Intergroup Rhabdomyosarcoma Study IV JOURNAL OF UROLOGY Arndt, C., Rodeberg, D., Breitfeld, P. P., Raney, R. B., Ullrich, F., Donaldson, S. 2004; 171 (6): 2396-2403

    Abstract

    We determine patient and tumor characteristics, event-free and overall survival, methods of local control, rate of bladder preservation and proportion with normal bladder function for patients with localized bladder/prostate (BP) rhabdomyosarcoma (RMS) treated on the Fourth Intergroup Rhabdomyosarcoma Study (IRS IV).We reviewed the records of 90 patients with nonmetastatic BP RMS enrolled on IRS IV for presenting characteristics, details of therapy and outcome.Of the 90 records 88 had sufficient information for review. Patient age distribution was less than 1 year for 7 patients, 1 to 9 years for 71 and 10 or greater years for 10. Tumors commonly arose in the bladder (70%), had favorable histology (embryonal or botryoid 80%), large (69% greater than 5 cm), unresectable (84% group III) and invasive (56% T2). Local therapy included radiation in 74 patients, and most patients underwent second-look operations after radiation. All patients received alkylating based chemotherapy. With a median followup of 6.1 years there have been 3 second malignancies, 1 toxic death and 18 relapses, for an event-free survival rate of 77%. Bladders were retained without relapse at last contact in 55 patients. Of those 55 patients 36 and of the entire group 40% had normal function determined by history.Of patients with nonmetastatic BP RMS on IRS IV 82% survived 6 years. Bladder function was preserved in 55% (36/66) of event-free survivors. Of all patients entered on study 40% (36 of 88) survive event-free with apparently normal functioning bladders. More precise long-term evaluation of bladder and sexual function will require application of better tools such as urodynamic studies and validated patient surveys.

    View details for DOI 10.1097/01.ju.0000127752.41749.a4

    View details for Web of Science ID 000221510300093

    View details for PubMedID 15126860

  • Failure pattern and factors predictive of local failure in rhabdomyosarcoma: A report of group III patients on the third intergroup rhabdomyosarcoma study JOURNAL OF CLINICAL ONCOLOGY Wharam, M. D., Meza, J., Anderson, J., Breneman, J. C., Donaldson, S. S., Fitzgerald, T. J., Michalski, J., Teot, L. A., Wiener, E. S., Meyer, W. H. 2004; 22 (10): 1902-1908

    Abstract

    To analyze patterns of failure and factors predictive of local treatment failure in children enrolled on the third Intergroup Rhabdomyosarcoma Study who had either biopsy only or subtotal resection of their primary tumor, had no distant metastases, and received radiation therapy for local control.Treatment failure was categorized as local, regional nodal, or distant metastatic. The 5-year cumulative risk of failure was estimated for each category and factors predictive of local failure risk were determined using the Cox model and binary recursive partitioning.The estimated 5-year cumulative incidence rates by failure category were: total local (with or without concurrent regional or distant failure), 19%; total regional nodal, 2%; total distant, 11%; and death from toxicity or unknown recurrence type, 4%. Lymph node involvement at diagnosis was the single factor most predictive of increased total local failure risk (5-year cumulative incidence 32%) compared with children with negative nodes or unknown node status (16%). No significant effect on local failure risk was observed by total radiotherapy dose over the prescribed range of 41.4 Gy to 50.4 Gy. For all patients (N = 405), the estimated 5-year failure-free survival and overall survival were, respectively, 70% and 78%.Local failure after radiotherapy for group III rhabdomyosarcoma patients is the predominant type of relapse. Involved lymph nodes at diagnosis predict a higher risk of local and distant treatment failure compared with patients whose lymph nodes are negative.

    View details for Web of Science ID 000221492600018

    View details for PubMedID 15143083

  • Part of proceedings - Ewing sarcoma: Radiation dose and target volume PEDIATRIC BLOOD & CANCER Donaldson, S. S. 2004; 42 (5): 471-476

    Abstract

    The outcome of children and adolescents with Ewing sarcoma is impacted by many prognostic factors and often measured by estimates of: event-free, relapse-free, disease-free, or overall survival. However, the preferred assessment following radiation therapy is local control.A review of large group experiences over the past several decades was undertaken to assess the optimal radiation dose and volume for patients with localized, osseous Ewing sarcoma. New approaches and techniques to improve local control were also investigated.With multidisciplinary therapy, 5-year overall local control rates range from 58 to 93%. Following definitive irradiation, they are 53-86%. Recommended radiation therapy doses are 55.8-60.0 Gy. In the postoperative setting, gross disease requires 55.8 Gy; microscopic disease requires 45 Gy. Altered fractionation schemes have not improved local control. The appropriate irradiated volume is an involved field to the pretreatment tumor volume plus 2.0-2.5 cm margin, followed by a boost to the post-induction chemotherapy tumor volume with margin. Good radiation quality control with central review improves local control. Use of an involved radiation field requires accuracy in defining tumor volume. Techniques to improve local control include risk-adapted multidisciplinary therapy, intraoperative boost radiation, and high radiation doses as delivered by 3-dimensional conformal radiation. Intensity modulated and proton beam radiotherapy may offer an advantage at special sites.Innovative uses of radiation in the multidisciplinary setting will continue to provide excellent local control, improved function, and quality of life for young patients with localized Ewing sarcoma of bone.

    View details for DOI 10.1002/pbc.10472

    View details for Web of Science ID 000220869100018

  • High-dose Therapy and Autologous Hemapoietic Stem-cell Transplantation for Recurrent or Refractory Pediatric Hodgkin's Disease: Results and Prognostic Indices Journal of Clinical Oncology Lieskovsky YYE, Donaldson SS, Torres MA, Wong RM, Amylon MD, Link MP, Agarwal R 2004; 22: 4532-4540
  • Influence of Radiation Therapy Parameters on Outcome in Children Treated with Radiation Therapy for Localized Parameningeal Rhabdomyosarcoma in the Intergroup Rhabdomyosarcoma Study Group Trials II through IV International Journal of Radiation Oncology, Biology, and Physics Michalski JM, Meza J, Breneman JC, Wolden SL, Laurie F, Jodoin MA, Raney B, Wharam MD, Donaldson SS 2004; 59: 1027-1038
  • Failure Pattern and Factors Predictive of Local Failure in Rhabdomyosarcoma: A Report of Group III Patients on the Third Intergroup Rhabdomyosarcoma Study Journal of Clinical Oncology Wharam MD, Meza J, Anderson J, Breneman JC, Donaldson SS, Fitzgerald TJ, Michalski J, Teot LA, Wiener ES, Meyer WH 2004; 22: 1902-1908
  • Genetic Effects of Radiotherapy for Childhood Cancer: Gonadal Dose Reconstruction International Journal of Radiation Oncology, Biology, and Physics Stovall M, Donaldson S, Weathers RE, Robison LL, Mertens AC, Winther JF, Olsen JH, Boice JD 2004; 60: 542-552
  • Risk-adapted Combined-modality Therapy with VAMP/COP and Response-based Involved-field Radiation for Unfavorable Pediatric Hodgkin's Disease Journal of Clinical Oncology Hudson MM, Krasin M, Link MP, Donaldson SS, Billups C, Merchant TE, Kun L, Billey AL, Kaste S, Tarbell NJ, Howard S, Friedman AM, Hurwitz CA, Young JA, Marcus KC, Rai S, Cowen T, Weinstein HJ 2004; 22: 4541-4550
  • Long-term neurologic and neurosensory sequelae in adult survivors of a childhood brain tumor: Childhood cancer survivor study JOURNAL OF CLINICAL ONCOLOGY Packer, R. J., Gurney, J. G., Punyko, J. A., Donaldson, S. S., Inskip, P. D., Stovall, M., Yasui, Y., Mertens, A. C., Sklar, C. A., Nicholson, H. S., Zeltzer, L. K., Neglia, J. P., Robison, L. L. 2003; 21 (17): 3255-3261

    Abstract

    To describe the neurologic and neurosensory deficits in children with brain tumors (BTs), compare incidence of these deficits with that of a sibling control group, and evaluate the factors associated with the development of these deficits.Detailed questionnaires were completed on 1,607 patients diagnosed between 1970 and 1986 with a primary CNS tumor. Neurosensory and neurologic dysfunctions were assessed and results compared with those of a sibling control group. Medical records on all patients were abstracted, including radiotherapy dose and volume.Seventeen percent of patients developed neurosensory impairment. Relative to the sibling comparison group, patients surviving BTs were at elevated risk for hearing impairments (relative risk [RR], 17.3; P = <.0001), legal blindness in one or both eyes (RR, 14.8; P = <.0001), cataracts (RR, 11.9; P = <.0001), and double vision (RR, 8.8; P = <.0001). Radiation exposure greater than 50 Gy to the posterior fossa was associated with a higher likelihood of developing any hearing impairment. Coordination and motor control problems were reported in 49% and 26%, respectively, of survivors. Children receiving at least 50 Gy to the frontal brain regions had a moderately elevated risk for motor problems (RR, 2.0; P <.05). Seizure disorders were reported in 25% of patients, including 6.5% who had a late first occurrence. Radiation dose of 30 Gy or more to any cortical segment of the brain was associated with a two-fold elevated risk for a late seizure disorder.Children surviving BTs are at significant risk for both early and late neurologic or neurosensory sequelae. These sequelae need to be prospectively monitored.

    View details for DOI 10.1200/JCO.2003.01.202

    View details for Web of Science ID 000185091300014

    View details for PubMedID 12947060

  • Genetic effects of radiotherapy for childhood cancer HEALTH PHYSICS Boice, J. D., Tawn, E. J., Winther, J. F., Donaldson, S. S., Green, D. M., Mertens, A. C., Mulvihill, J. J., Olsen, J. H., Robison, L. L., Stovall, M. 2003; 85 (1): 65-80

    Abstract

    Radiation-induced heritable diseases have not been demonstrated in humans and estimates of genetic risks for protection purposes are based on mouse experiments. The most comprehensive epidemiologic study is of the Japanese atomic bomb survivors and their children, which found little evidence for inherited defects attributable to parental radiation. Studies of workers exposed to occupational radiation or of populations exposed to environmental radiation appear too small and exposures too low to convincingly detect inherited genetic damage. In contrast, survivors of childhood cancer form the largest group of people exposed to high doses of ionizing radiation before reproduction and offer unique advantages for studying trans-generation effects. A wide range of gonadal doses are possible, several comparison groups are readily available (including siblings), and there is a strong willingness among cancer survivors to participate in health studies. Cancer patients also have detailed medical records that facilitate both the accurate estimation of gonadal doses and the assessment of potentially confounding factors, such as intercurrent illness, personal and family medical histories, lifestyle characteristics such as tobacco use, and circumstances at delivery. An international study is nearing completion of over 25,000 survivors of childhood cancer in the United States and Denmark who gave birth to or fathered over 6,000 children. Doses to gonads are being reconstructed from radiotherapy records with 46% over 100 mSv and 16% over 1,000 mSv. Adverse pregnancy outcomes being evaluated include major congenital malformations, cytogenetic abnormalities, stillbirths, miscarriages, neonatal deaths, total deaths, leukemia and childhood cancers, altered sex ratio, and birth weight. The main analyses are based on dose-response evaluations. Blood studies of trios (cancer survivor, spouse or partner and offspring) have been initiated to evaluate mechanistic evidence for the transmission of any radiation-induced genetic damage such as minisatellite mutations. Markers of cancer susceptibility such as chromosomal radiosensitivity and genotype profile will also be examined. In the United States series to date, 4,214 children were born to cancer survivors among whom 157 (3.7%) genetic diseases were reported in contrast to 95 (4.1%) reported conditions among 2,339 children born to sibling controls. In the Denmark series the comparable figures were 82 (6.1%) birth defects among 1,345 children of cancer survivors and 211 (5.0%) among 4,225 children of sibling controls. Coupled with prior studies, these preliminary findings, if sustained by ongoing dose-response analyses, provide reassurance that cancer treatments including radiotherapy do not carry much if any risk for inherited genetic disease in offspring conceived after exposure.

    View details for Web of Science ID 000183603400013

    View details for PubMedID 12852473

  • Radiation therapy for intracranial germ cell tumors INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Haas-Kogan, D. A., Missett, B. T., Wara, W. M., Donaldson, S. S., Lamborn, K. R., Prados, M. D., Fisher, P. G., Huhn, S. L., Fisch, B. M., Berger, M. S., Le, Q. T. 2003; 56 (2): 511-518

    Abstract

    To review the combined experiences of University of California, San Francisco, and Stanford University Medical Center in the treatment of intracranial germ cell tumors (GCT) and to assess the impact of craniospinal radiation (CSI) on patterns of relapse, progression-free survival (PFS), and overall survival (OS).Ninety-three patients received radiation for newly diagnosed intracranial GCTs, including 49 germinomas, 16 nongerminomatous GCTs (NGGCT), and 28 with no biopsy. Median follow-up for surviving patients was 4.5 years (range 0.25-34). Tests for variables correlating with OS and PFS were conducted using Cox proportional hazards model.Five-year PFS and OS rates were 60% +/- 15% and 68% +/- 14% for patients with NGGCT and 88% +/- 5% and 93% +/- 4% for those with germinoma. Of 6 patients with localized NGGCT who did not receive CSI, 1 experienced an isolated spinal recurrence but was salvaged. Of 41 patients with localized germinoma, 6 who received CSI and 35 who did not, no isolated spinal cord relapses occurred. Twenty-one patients with localized germinoma received neither CSI nor whole brain radiation. Of these, none of 18 with ventricular radiation relapsed. One of 3 patients with primary tumor radiation relapsed intracranially but had only received 11 Gy at initial treatment. On multivariate analysis, germinoma histology but not CSI correlated with improved PFS and OS.CSI is not indicated in the treatment of localized germinomas. For patients with localized germinomas treated with radiation alone, we recommend ventricular irradiation followed by primary tumor boost to a total of 45-50 Gy.

    View details for DOI 10.1016/S0360-3016(02)04611-4

    View details for Web of Science ID 000182861500026

    View details for PubMedID 12738328

  • Outcome and local control (LC) for bladder prostate rhabdomyosarcoma (BP RMS) on IRS IV Arndt, C. A., Rodeberg, D. A., Ullrich, F., Donaldson, S. S., Anderson, J. R., Raney, R. B., Breitfeld, P. P. NATURE PUBLISHING GROUP. 2003: 269A-269A
  • Addition of ifosfamide and etoposide to standard chemotherapy for Ewing's sarcoma and primitive neuroectodermal tumor of bone NEW ENGLAND JOURNAL OF MEDICINE Grier, H. E., Krailo, M. D., Tarbell, N. J., Link, M. P., Fryer, C. J., Pritchard, D. J., Gebhardt, M. C., Dickman, P. S., Perlman, E. J., Meyers, P. A., Donaldson, S. S., Moore, S., Rausen, A. R., Vietti, T. J., Miser, J. S. 2003; 348 (8): 694-701

    Abstract

    Ewing's sarcoma and primitive neuroectodermal tumor of bone are closely related, highly malignant tumors of children, adolescents, and young adults. A new drug combination, ifosfamide and etoposide, was highly effective in patients with Ewing's sarcoma or primitive neuroectodermal tumor of bone who had a relapse after standard therapy. We designed a study to test whether the addition of these drugs to a standard regimen would improve the survival of patients with newly diagnosed disease.Patients 30 years old or younger with Ewing's sarcoma, primitive neuroectodermal tumor of bone, or primitive sarcoma of bone were eligible. The patients were randomly assigned to receive 49 weeks of standard chemotherapy with doxorubicin, vincristine, cyclophosphamide, and dactinomycin or experimental therapy with these four drugs alternating with courses of ifosfamide and etoposide.A total of 518 patients met the eligibility requirements. Of 120 patients with metastatic disease, 62 were randomly assigned to the standard-therapy group and 58 to the experimental-therapy group. There was no significant difference in five-year event-free survival between the treatment groups (P=0.81). Among the 398 patients with nonmetastatic disease, the mean (+/-SE) five-year event-free survival among the 198 patients in the experimental-therapy group was 69+/-3 percent, as compared with 54+/-4 percent among the 200 patients in the standard-therapy group (P=0.005). Overall survival was also significantly better among patients in the experimental-therapy group (72+/-3.4 percent vs. 61+/-3.6 percent in the standard-therapy group, P=0.01).The addition of ifosfamide and etoposide to a standard regimen does not affect the outcome for patients with metastatic disease, but it significantly improves the outcome for patients with nonmetastatic Ewing's sarcoma, primitive neuroectodermal tumor of bone, or primitive sarcoma of bone.

    View details for Web of Science ID 000181014400004

    View details for PubMedID 12594313

  • Treatment of localized nonorbital, nonparameningeal head and neck rhabdomyosarcoma: Lessons learned from intergroup rhabdomyosarcoma studies III and IV JOURNAL OF CLINICAL ONCOLOGY Pappo, A. S., Meza, J. L., Donaldson, S. S., Wharam, M. D., Wiener, E. S., Qualman, S. J., Maurer, H. M., Crist, W. M. 2003; 21 (4): 638-645

    Abstract

    The characteristics and clinical outcomes of children and adolescents with localized nonorbital, nonparameningeal head and neck rhabdomyosarcoma (RMS) treated on national protocols from the Intergroup Rhabdomyosarcoma Group are reported.We conducted a retrospective review of 164 children and adolescents enrolled in the third and fourth Intergroup Rhabdomyosarcoma Studies. Variables analyzed included age, sex, primary tumor site, histologic subtype, clinical group, therapy, site and rate of treatment failure, and time to initial recurrence.Localized nonorbital, nonparameningeal RMS accounted for 9% of all cases of RMS. The median age at diagnosis was 5 years; the median follow-up was 6.6 years. Estimated 5-year failure-free survival (FFS) and survival (S) rates were 76% (95% CI, 69% to 83%) and 83% (95% CI, 77% to 89%), respectively. In multivariate analysis, patients with clinically involved regional nodes (N1) had worse FFS (P =.02). For patients with embryonal tumors, FFS was significantly improved, especially among patients with Group I/II without nodal disease clinical Group I, II N0. For patients with alveolar/undifferentiated histology, FFS was significantly worse in children under the age of 1 year. Actuarial estimates of recurrences at 15 years were local (19%), regional (5%), and distant (9%).More than 80% of patients with RMS of the head and neck are cured of their disease using surgery and vincristine, dactinomycin +/- cyclophosphamide with or without radiotherapy. Our results indicate that early, limited exposure to cyclophosphamide might reduce recurrence in low-risk embryonal patients and that reduced dosages might achieve comparable results with improved toxicity profiles. These hypotheses will be tested in the next generation of trials from the Soft Tissue Committee of the Children's Oncology Group.

    View details for DOI 10.1200/JCO.2003.01.032

    View details for Web of Science ID 000181002500012

    View details for PubMedID 12586800

  • Pregnancy outcome of partners of male survivors of childhood cancer: A report from the childhood cancer survivor study JOURNAL OF CLINICAL ONCOLOGY Green, D. M., Whitton, J. A., Stovall, M., Mertens, A. C., Donaldson, S. S., Ruymann, F. B., Pendergrass, T. W., Robison, L. L. 2003; 21 (4): 716-721

    Abstract

    This study was undertaken to determine the effect, if any, on pregnancy loss, live births, and birthweight of treatment for cancer diagnosed during childhood or adolescence.We reviewed pregnancy outcome among sexually active male Childhood Cancer Survivor Study (CCSS) participants who responded to a questionnaire before February 3, 2000. Medical records of all members of the cohort were abstracted to obtain chemotherapeutic agents administered, the cumulative dose of drug administered for several drugs of interest, and the doses, volumes, and dates of administration of all radiotherapy.There were 4,106 sexually active males; 1,227 reported they sired 2,323 pregnancies (69% live births, 1% stillbirths, 13% miscarriages, 13% abortions, 5% unknown or in gestation). The male-to-female ratio of the offspring of the partners of the male survivors was significantly different from that of the offspring of the partners of the male siblings of the survivors (1.0:1.03 v 1.24:1.0) (P =.016). The proportion of pregnancies of the partners of male survivors that ended with a liveborn infant was significantly lower than for the partners of the male siblings of the survivors who were the control group for comparison (relative risk = 0.77, P =.007). There were no significant differences in pregnancy outcome by treatment.This large study did not identify adverse pregnancy outcomes for the partners of male survivors treated with most chemotherapeutic agents. The reversal of the sex ratio and the association observed for procarbazine warrant further investigation.

    View details for DOI 10.1200/JCO.2003.04.085

    View details for Web of Science ID 000181002500023

    View details for PubMedID 12586811

  • A discourse: The 2002 Wataru W. Sutow Lecture - Hodgkin disease in children - Perspectives and progress MEDICAL AND PEDIATRIC ONCOLOGY Donaldson, S. S. 2003; 40 (2): 73-81

    Abstract

    THE PIONEER: Wataru W. Sutow, 1912-1981, was a remarkable and pivotal leader in pediatric oncology. Early in his medical career, he conducted important clinical and anthropometric studies among Japanese and Marshall Island children exposed to atomic radiation. These studies established standards for childhood growth and development still in use today. Dr. Sutow pioneered the multidisciplinary approach to childhood cancer by combining multidrug chemotherapy protocols with surgery and radiotherapy in the common childhood solid tumors. The textbook "Clinical Pediatric Oncology," of which he was the senior editor, served to define the discipline of pediatric oncology and educate a new era of oncologists in the curative treatment for childhood cancer. THE PAST AND PRESENT: The first edition of "Clinical Pediatric Oncology," published in 1973, demonstrated that only children with early-stage localized Hodgkin disease had a realistic opportunity for cure. Soon the use of combined-modality therapy consisting of low-dose, involved-field radiation plus multi-agent chemotherapy emerged, and made the goal of cure realistic for all patients. This approach is now universal. Today, the 5-year relative survival rate for American children with Hodgkin disease, who are under 14 years of age, is 94%, a dramatic and remarkable achievement. FUTURE: Management of children with Hodgkin disease now involves clinical staging and risk-adapted, combined-modality therapy. Clinical and translational research initiatives that hold promise for children with Hodgkin disease in the future include: use of the WHO Classification System combining morphologic and biologic criteria; noninvasive staging procedures with increased sensitivity and specificity; development of a useful prognostic index to define groups for risk-adapted therapy; high-dose therapy with stem cell transplantation; and novel therapies.

    View details for DOI 10.1002/mpo.10219

    View details for Web of Science ID 000179873900001

    View details for PubMedID 12461789

  • A Discourse: The 2002 Wataru W. Sutow Lecture; Hodgkin's Disease in Children: Perspectives and Progress Medical and Pediatric Oncology Donaldson SS 2003; 40: 73-81
  • Prognostic factors and clinical outcomes in children and adolescents with metastatic rhabdomyosarcoma - A report from the intergroup rhabdomyosarcoma study IV JOURNAL OF CLINICAL ONCOLOGY Breneman, J. C., Lyden, E., Pappo, A. S., Link, M. P., Anderson, J. R., Parham, D. M., Qualman, S. J., Wharam, M. D., Donaldson, S. S., Maurer, H. M., Meyer, W. H., Baker, K. S., Paidas, C. N., Crist, W. M. 2003; 21 (1): 78-84

    Abstract

    To identify risk factors associated with outcomes in children with metastatic rhabdomyosarcoma (RMS) treated on the fourth Intergroup Rhabdomyosarcoma Study (IRS-IV).Patients with metastatic RMS were treated with one of two regimens that incorporated a window of either ifosfamide and etoposide (IE) with vincristine, dactinomycin, and cyclophosphamide (VAC) or vincristine, melphalan (VM) and VAC. Study end points were failure-free survival (FFS) and overall survival (OS). Clinical factors including age, histology, sites of primary and metastatic disease, and number of sites of metastatic disease were correlated with those end points.One hundred twenty-seven patients were eligible for analysis. The estimated 3-year OS and FFS for all patients were 39% and 25%, respectively. By univariate analysis, 3-year OS was significantly influenced by histology (47% for embryonal v 34% for all others, P =.026) and increasing number of metastatic sites (P =.028). By multivariate analysis, the presence of two or fewer metastatic sites was the only significant predictor (P =.007 and.006, respectively). The combination of embryonal histology with two or fewer metastatic sites identified a subgroup with 3-year FFS of 40% and OS of 47%.Children with group IV RMS treated on the IRS-IV study had improved OS and FFS if they had two or fewer metastatic sites and embryonal histology. This favorable subset of patients has outcomes approaching those observed in selected patients with localized, nonmetastatic disease. Thus, these patients might not be appropriate candidates for regimens that include experimental agents with substantial toxicities or unproven antitumor activity.

    View details for Web of Science ID 000183281100014

    View details for PubMedID 12506174

  • Genetic Effects of Radiotherapy for Childhood Cancer Health Physics Boice JD, Tawn EJ, Winther JF, Donaldson SS, Green DM, Mertens AC, Mulvihill JJ, Olsen JH, Robison LL, Stovall M 2003; 85 (1): 65-80
  • Prognostic Factors for Children with Hodgkin's Disease Treated with a Combined Modality Therapy Journal of Clinical Oncology Smith RS, Chen Q, Hudson MM, Link MP, Kun L, Weinstein H, Billen A, Marcus KJ, Tarbell NJ, Donaldson SS 2003; 21: 2026-2033
  • Pregnancy outcome of female survivors of childhood cancer: A report from the Childhood Cancer Survivor Study AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Green, D. N., Whitton, J. A., Stovall, M., Mertens, A. C., Donaldson, S. S., Ruymann, F. B., Pendergrass, T. W., Robison, L. L. 2002; 187 (4): 1070-1080

    Abstract

    This study was undertaken to determine the effect, if any, of prior treatment with radiation therapy or chemotherapy for cancer diagnosed during childhood or adolescence on pregnancy loss, live births, and birth weight.We reviewed pregnancy outcome among female participants in the Childhood Cancer Survivor Study (CCSS) who returned a questionnaire. Eligibility for the CCSS included 5-year survivors who were <21 years old at diagnosis and who were diagnosed with an eligible cancer between January 1, 1970, and December 31, 1986, at the 25 participating CCSS institutions. The questionnaire included items regarding attempts to become pregnant, the occurrence of pregnancy, and the outcome of pregnancy (ie, live birth, stillbirth, miscarriage, abortion). Medical records of all members of the cohort were abstracted to obtain chemotherapeutic agents administered, the cumulative dose of drug administered for several drugs of interest, and the doses, anatomic regions, and dates of administration of all radiation therapy.One thousand nine hundred fifteen females reported 4029 pregnancies (63% live births, 1% stillbirths, 15% miscarriages, 17% abortions, 3% unknown or in gestation). There were no significant differences in pregnancy outcome by treatment. A higher, but not statistically significant, risk of miscarriage was present among women whose ovaries were in the radiation therapy field (relative risk [RR] 1.86, P =.14), were near the radiation therapy field (RR 1.64, P =.06), or were shielded (RR 0.90, P =.88). The rate of live birth was not lower for the patients treated with any particular chemotherapeutic agent. The offspring of the patients who received pelvic irradiation were more likely to weigh <2500 g at birth (RR 1.84, P =.03).This large study did not identify adverse pregnancy outcomes for female survivors treated with most chemotherapeutic agents. The offspring of women who received pelvic irradiation are at risk for low birth weight.

    View details for DOI 10.1067/mob.2002.126643

    View details for Web of Science ID 000178709300052

    View details for PubMedID 12389007

  • Pediatric Hodgkin's disease - Up, up, and beyond INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Donaldson, S. S. 2002; 54 (1): 1-8

    Abstract

    Juan A. del Regato, 1909-1999, was a superb clinician-educator who recognized the radiocurability of Hodgkin's disease but questioned treatment without late effects, particularly in children. The remarkable progress in pediatric Hodgkin's disease today is a tribute to this influential pioneer, who served as a role model to many. Combined modality therapy using low-dose, involved-field radiation and multiagent chemotherapy today results in a 5-year relative survival rate of 94% among American children with Hodgkin's disease. However, several areas hold promise for future advances, including a new pathology classification and biology studies that distinguish classic Hodgkin's disease from other lymphomas; new noninvasive staging techniques, including 18F-fluorodeoxyglucose-positron emission tomography; the definition of risk groups to segregate low-, intermediate-, and high-risk groups on the basis of a prognostic index, facilitating risk-adapted therapy; and myeloablative therapy followed by hematopoietic stem cell transplantation. Currently used for children with relapse, it is associated with a 5-year survival of 65% and should be considered as the initial therapy for high-risk groups. Idiopathic diffuse pulmonary toxicity after autologous transplantation is high among children with an atopic history; thus, atopy should be considered when selecting children appropriate for transplantation. Finally, novel therapies, such as the anti-CD20 antibody, rituximab, may be useful for children with CD20+, lymphocyte-predominant Hodgkin's disease. The universal goal of cure without late effects is realistic for almost all children with Hodgkin's disease today.

    View details for Web of Science ID 000177780900001

    View details for PubMedID 12182968

  • VAMP and low-dose, involved-field radiation for children and adolescents with favorable, early-stage Hodgkin's disease: Results of a prospective clinical trial JOURNAL OF CLINICAL ONCOLOGY Donaldson, S. S., Hudson, M. M., Lamborn, K. R., Link, M. P., Kun, L., Billett, A. L., Marcus, K. C., Hurwitz, C. A., Young, J. A., Tarbell, N. J., Weinstein, H. J. 2002; 20 (14): 3081-3087

    Abstract

    To evaluate outcome and assess toxicity of children and adolescents with early-stage, favorable Hodgkin's disease treated with vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) and low-dose, involved-field radiation.One hundred ten patients with clinical stages I and II, favorable (nonbulky) Hodgkin's disease were treated with four cycles of VAMP chemotherapy and 15 Gy involved-field radiation for those who achieved a complete response, or 25.5 Gy for those who achieved a partial response to two cycles of VAMP.With a median follow-up of 5.6 years (range, 1.1 to 10.4 years), the 5-year survival and event-free survival were 99% (lower confidence limit [CL], 97.4%) and 93% (lower CL, 88.6%), respectively. Factors associated with event-free survival of 100% were complete response to two cycles of VAMP and histology other than nodular sclerosing Hodgkin's disease (NSHD). No serious early or late toxicity has been observed. Patients presenting with clinical stages I and IIA, nonbulky disease involving fewer than three nodal sites have a projected survival and event-free survival of 100% and 97% (lower CL, 93%), respectively, at 5 years.Risk-adapted, combined-modality therapy using only four cycles of VAMP chemotherapy with 15 to 25.5 Gy of involved-field radiation for patients with early-stage/favorable Hodgkin's disease is highly effective and without demonstrable late effects. These results indicate that pediatric patients with stages I and II favorable Hodgkin's disease can be cured with limited therapy that does not include an alkylating agent, bleomycin, etoposide, or high-dose, extended-field radiation therapy.

    View details for DOI 10.1200/JCO.2002.12.101

    View details for Web of Science ID 000176920000007

    View details for PubMedID 12118021

  • Treatment of unfavorable childhood Hodgkin's disease with VEPA and low-dose, involved-field radiation JOURNAL OF CLINICAL ONCOLOGY Friedmann, A. M., Hudson, M. M., Weinstein, H. J., Donaldson, S. S., Kun, L., Tarbell, N. J., Link, M. P. 2002; 20 (14): 3088-3094

    Abstract

    Between January 1990 and April 1993, 56 pediatric patients with Hodgkin's disease were treated on a single-arm trial at three institutions with a regimen designed to maintain high cure rates while minimizing the potential late effects of treatment, such as infertility, second malignant neoplasms, and cardiopulmonary injury.The regimen used combined-modality therapy with six cycles of vinblastine, etoposide, prednisone, and doxorubicin (VEPA) chemotherapy and low-dose, involved-field radiation. Unfavorable features comprised bulky presentations of localized (stage I or II) disease or advanced (stage III or IV) Hodgkin's disease.Of 56 patients enrolled, 26 (46%) had unfavorable presentations of stage I/II disease and 30 (54%) had advanced (stage III/IV) disease. Seventy-nine percent of the patients are alive without disease at a median follow-up time of 8.9 years from diagnosis. Nineteen patients had events at a median of 1.5 years (range, 0.4 to 7.9 years) from diagnosis; 17 patients relapsed, one died of cardiomyopathy, and one died of accidental injuries. Survival and event-free survival (EFS) estimates at 5 years for the entire cohort were 81.9% (SE, 5.2%) and 67.8% (SE, 6.3%), respectively. Five-year EFS by stage was 100% for stage I, 79.2% (SE, 8.3%) for stage II, 70% (SE, 14.5%) for stage III, and 49.5% (SE, 11.3%) for stage IV patients.Combined-modality therapy with VEPA chemotherapy and low-dose, involved-field radiation is adequate for disease control of early-stage patients with unfavorable features, but it is inferior to other standard regimens for advanced-stage patients.

    View details for DOI 10.1200/JCO.2002.03.051

    View details for Web of Science ID 000176920000008

    View details for PubMedID 12118022

  • Study design and cohort characteristics of the childhood cancer survivor study: A multi-institutional collaborative project MEDICAL AND PEDIATRIC ONCOLOGY Robison, L. L., Mertens, A. C., Boice, J. D., Breslow, N. E., Donaldson, S. S., Green, D. M., Li, F. P., Meadows, A. T., Mulvihill, J. J., Neglia, J. P., Nesbit, M. E., Packer, R. J., Potter, J. D., Sklar, C. A., Smith, M. A., Stovall, M., Strong, L. C., Yasui, Y., Zeltzer, L. K. 2002; 38 (4): 229-239

    Abstract

    Increased attention has been directed toward the long-term health outcomes of survivors of childhood cancer. To facilitate such research, a multi-institutional consortium established the Childhood Cancer Survivor Study (CCSS), a large, diverse, and well-characterized cohort of 5-year survivors of childhood and adolescent cancer.Eligibility for the CCSS cohort included a selected group of cancer diagnoses prior to age 21 years between 1970-1986 and survival for at least 5 years.A total of 20,276 eligible subjects were identified from the 25 contributing institutions, of whom 15% are considered lost to follow-up. Currently, 14,054 subjects (69.3% of the eligible cohort) have participated by completing a 24-page baseline questionnaire. The distribution of first diagnoses includes leukemia (33%), lymphoma (21%), neuroblastoma (7%), CNS tumor (13%), bone tumor (8%), kidney tumor (9%), and soft-tissue sarcoma (9%). Abstraction of medical records for chemotherapy, radiation therapy, and surgical procedures has been successfully completed for 98% of study participants. Overall, 78% received radiotherapy and 73% chemotherapy.The CCSS represents the largest and most extensively characterized cohort of childhood and adolescent cancer survivors in North America. It serves as a resource for addressing important issues such as risk of second malignancies, endocrine and reproductive outcome, cardiopulmonary complications, and psychosocial implications, among this unique and ever-growing population.

    View details for DOI 10.1002/mpo.1316

    View details for Web of Science ID 000174673100001

    View details for PubMedID 11920786

  • Pediatric Hodgkin's Disease: Up, Up and Beyond International Journal of Radiation Oncology, Biology, and Physics Donaldson SS 2002; 54: 1-8
  • Treatment of children and adolescents with localized parameningeal sarcoma: Experience of the Intergroup Rhabdomyosarcoma Study Group Protocols IRS-II through-IV, 1978-1997 MEDICAL AND PEDIATRIC ONCOLOGY Raney, R. B., Meza, J., Anderson, J. R., Fryer, C. J., Donaldson, S. S., Breneman, J. C., Fitzgerald, T. J., Gehan, E. A., Michalski, J. M., Ortega, J. A., Qualman, S. J., Sandler, E., Wharam, M. D., Wiener, E. S., Maurer, H. M., Crist, W. M. 2002; 38 (1): 22-32

    Abstract

    We reviewed 611 patients with parameningeal sarcoma entered on Intergroup Rhabdomyosarcoma Study Group (IRSG) Protocols-II through IV (1978-1997), to delineate treatment results and evaluate prognostic factors.Primary sites were the middle ear/mastoid (N = 138), nasopharynx/nasal cavity (N = 235), paranasal sinuses (N = 132), parapharyngeal region (N = 29), and the pterygopalatine/infratemporal fossa (N = 77). Treatment was initial biopsy or surgery followed by multiagent chemotherapy and radiation therapy (XRT). Beginning in 1977, patients with cranial nerve palsy, cranial base bony erosion, and/or intracranial extension at diagnosis were considered as having meningeal involvement. They received triple intrathecal medications, whole brain XRT, and then spinal XRT. These treatments were successively eliminated from 1980 to 1991.The 611 patients' overall survival rate at 5 years was 73% (95% confidence interval, 70-77%). Favorable prognostic factors were: age 1-9 years at diagnosis; primary tumor in the nasopharynx/nasal cavity, middle ear/mastoid, or parapharyngeal areas; no meningeal involvement; and non-invasive tumors (T1). Thirty-five of 526 patients (6.7%) with information about presence/absence of meningeal involvement at diagnosis developed central nervous system (CNS) extension at 5-164 weeks (median, 46 weeks) after starting therapy. The estimated 5-year cumulative incidence rate of CNS extension during the study period was 5-7% (P = 0.88).Biopsy, XRT to the target volume, and systemic chemotherapy are successful treatments for the large majority of patients with localized parameningeal sarcoma. Carefully defining and irradiating the initial volume should reduce the risk of CNS failure. Aggressive initial surgical management of these patients is unnecessary.

    View details for Web of Science ID 000173123300004

    View details for PubMedID 11835233

  • VAMP and Low-dose, Involved-field Radiation for Children and Adolescents with Favorable, Early-stage Hodkin's Disease: Results of a Prospective Clinical Trial Journal of Clinical Oncology Donaldson SS, Hudson MM, Lamborn KR, Link MP, Kun L, Billett AL, Marcus KC, Hurwitz CA, Young JA, Tarbell NJ, Weinstein HJ 2002; 20: 3081-3087
  • Study Design and Cohort Characteristics of the Childhood Cancer Survivor Study: A Multi-institutional Collaborative Project Medical and Pediatric Oncology Robinson LL, Mertens AC, Boice JD, Breslow NE, Donaldson SS, Green DM, Li FP, Meadows AT, Mulvihill JJ, Neglia JP, Nesbit ME, Packer RJ, Potter JD, Sklar CA, Smith MA, Stovall M, Strong LC, Yasui Y, Zeltser L 2002; 38: 229-239
  • Rhabdomyosarcoma of the parotid region occurring in childhood and adolescence - A report from the Intergroup Rhabdomyosarcoma Study Group CANCER Walterhouse, D. O., Pappo, A. S., Baker, K. S., Parham, D. M., Anderson, J. R., Donaldson, S. S., Paidas, C. N., Womer, R. B., Crist, W. M. 2001; 92 (12): 3135-3146

    Abstract

    Rhabdomyosarcoma (RMS) of the parotid region is rare and to the authors' knowledge little information is available regarding the site of tumor origin, clinical presentation, and outcome in these patients. Therefore, the authors reviewed the files of all patients with RMS of the parotid region who were registered on the Intergroup Rhabdomyosarcoma Studies (IRS) I-IV.Patient charts and the Intergroup Rhabdomyosarcoma Study Group (IRSG) database were reviewed.Sixty-two patients presenting with a mass in the parotid region were identified. None of the tumors was localized exclusively to the parotid gland, so the primary site was referred to as the "parotid region." The tumor invaded a parameningeal site in 30 patients. These cases have been designated as parameningeal-parotid tumors to distinguish them from 32 cases that did not invade a parameningeal site and were designated as nonparameningeal-parotid tumors. The majority of patients had Group III tumors in both the nonparameningeal-parotid and parameningeal-parotid subgroups. However, although there were 16 patients with Group I or II tumors in the nonparameningeal-parotid subgroup, no patients with Group I or II tumors were found in the parameningeal-parotid subgroup (P = 0.001). Fifty-six of 62 patients (90%) received radiotherapy. The parameningeal primary site designation resulted in intensification of both chemotherapy and radiotherapy for patients with parameningeal-parotid RMS. The 5-year failure-free survival rate was 81% and the 5-year survival rate was 84%. There were no deaths reported among patients with Group I or II tumors. The 5-year failure-free survival did not appear to differ when comparing patients with parameningeal-parotid tumors with patients with nonparameningeal-parotid tumors (P = 0.21).Treatment as defined by the IRS protocols has been reported to be highly effective for patients with RMS of the parotid region. Outcome for the more aggressively treated patients with parameningeal-parotid RMS appears similar to that for patients with nonparameningeal-parotid RMS.

    View details for Web of Science ID 000172757600021

    View details for PubMedID 11753993

  • Results from the IRS-IV randomized trial of hyperfractionated radiotherapy in children with rhabdomyosarcoma - A report from the IRSG INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Donaldson, S. S., Meza, J., Breneman, J. C., Crist, W. M., Laurie, F., Qualman, S. J., Wharam, M. 2001; 51 (3): 718-728

    Abstract

    To evaluate the outcome and toxicity of hyperfractionated radiotherapy (HFRT) vs. conventionally fractionated radiotherapy (CFRT) in children with Group III rhabdomyosarcoma (RMS).Five hundred fifty-nine children were enrolled into the Intergroup Rhabdomyosarcoma Study IV with Group III RMS. Sixty-nine were ineligible for the analysis because of incorrect group or pathologic findings. Of the 490 remaining, 239 were randomized to HFRT (59.4 Gy in 54 1.1-Gy twice daily fractions) and 251 to CFRT (50.4 Gy in 28 1.8-Gy daily fractions). The age range was <1-21 years. All patients received chemotherapy. RT began at Week 9 after induction chemotherapy for all but those with high-risk parameningeal tumors who received RT during induction chemotherapy. The patient groups were equally balanced. The median follow-up was 3.9 years.Analysis by randomized treatment assignment (intent to treat) revealed an estimated 5-year failure-free survival (FFS) rate of 70% and overall survival (OS) of 75%. In the univariate analysis, the factors associated with the best outcome were age 1-9 years at diagnosis; noninvasive tumors; tumor size <5 cm; uninvolved lymph nodes; Stage 1 or 2 disease; primary site in the orbit or head and neck; and embryonal histologic features (p = 0.001 for all factors). No differences in the FFS or OS between the two RT treatment methods and no differences in the FFS or OS between HFRT and CFRT were found when analyzed by age, gender, tumor size, tumor invasiveness, nodal status, histologic features, stage, or primary site. Treatment compliance differed by age. Of the children <5 years, 57% assigned to HFRT received HFRT and 77% assigned to CFRT received CFRT. Of the children >or=5 years, 88% assigned to both HFRT and CFRT received their assigned treatment. The reasons for not receiving the appropriate randomized treatment were progressive disease, early death, parent or physician refusal, young age, or surgery. The toxicity assessment revealed more mucositis with HFRT (66%) than with CFRT (46%) (p = 0.03) for the parameningeal patients, and more skin reactions (16%) and nausea/vomiting (13%) with HFRT than with CFRT (7% and 5%, respectively) for patients with nonparameningeal primary tumors (p = 0.03 and p = 0.02, respectively). The analysis by treatment actually received revealed a 5-year FFS rate of 73% and OS rate of 77%, with no difference between CFRT and HFRT. As well, there was no difference in FFS or OS between CFRT and HFRT when analyzed by age, gender, tumor size, tumor invasiveness, modal status, histology, stage or site of primary. The 5-year estimated cumulative incidence of failure for the irradiated patients was local, 13%; regional, 3%; and distant, 13%; with no differences between HFRT and CFRT. The 5-year local failure rate by site was orbit, 5%; head and neck, 12%; parameningeal, 16%; bladder/prostate, 19%; extremity, 7%; and all others, 14%. The 5-year regional failure rate was parameningeal,1%; extremity, 20%; and all others, 5%. The 5-year distant failure rate was orbit, 2%; head and neck, 6%; parameningeal, 11%; bladder/prostate, 15%; extremity, 28%; and all others, 17%.HFRT, as given in this study, did not improve local/regional control, FFS, or OS compared with CFRT. The risk of local/regional failure was comparable to that of distant failure in children with Group III RMS. The standard of care for Group III RMS continues to be CFRT with chemotherapy.

    View details for Web of Science ID 000171892800020

    View details for PubMedID 11597814

  • Long-term results of irradiation for patients with progressive Graves' ophthalmopathy Marquez, S. D., Lum, B. L., McDougall, I. R., Katkuri, S., Levin, P. S., MacManus, M., Donaldson, S. S. ELSEVIER SCIENCE INC. 2001: 766-774

    Abstract

    To determine the long-term outcome of radiotherapy (RT) in patients with progressively symptomatic thyroid eye disease and to evaluate the potential long-term sequelae.Four hundred fifty-three patients provided written informed consent and received retrobulbar RT for Graves' ophthalmopathy at Stanford University Medical Center; 197 with 1 year of follow-up were retrospectively analyzed. Of the 197 patients, 189 received RT to the bilateral retrobulbar regions, and 4 received unilateral RT. The technical information was unavailable for 4 patients. Patients were assessed by chart review, telephone interview, questionnaire, and multidisciplinary physician examination. Eye impairment was scored using the SPECS system. The end point review included the before and after treatment SPECS score, surgical intervention, and patient satisfaction. Potential complications, including cataract development, retinopathy, and tumor formation, were investigated. Multivariate analyses were performed to assess the prognostic variables.Improvement or resolution was 89% for soft-tissue findings; 70% for proptosis; 85% for extraocular muscle dysfunction; 96% for corneal abnormalities; and 67% for sight loss. The response to RT may take >6 months to stabilize. Factors predictive of response varied in the individual SPECS categories but included the initial SPECS score, pretreatment thyroid status, female gender, a 20-Gy RT dose, and a history of hypertension. Nonpredictive factors included a history of tobacco use, diabetes mellitus, steroids, and prior cataracts. Only 16% required surgical intervention to preserve their vision or restore binocular vision. Twenty-two patients (12%) developed cataracts after irradiation (median 11 years). No patient developed a tumor within the RT field during the follow-up period (range 1-29 years). Ninety-eight percent of patients were pleased with their results, and 2% believed their symptoms progressed despite RT.Retrobulbar irradiation (20 Gy) is safe and effective treatment for progressive Graves' ophthalmopathy, with a 96% overall response rate, 98% patient satisfaction rate, and no irreparable long-term sequelae, with follow-up extending 29 years. The most common late effect observed was cataract development, which occurred more frequently in older patients and was reversible with extraction. Elective surgical intervention after RT should be withheld until patients have demonstrated a plateau in response.

    View details for Web of Science ID 000171892800026

    View details for PubMedID 11697323

  • Which patients with microscopic disease and rhabdomyosarcoma experience relapse after therapy? A report from the soft tissue sarcoma committee of the children's oncology group JOURNAL OF CLINICAL ONCOLOGY Smith, L. M., Anderson, J. R., Qualman, S. J., Crist, W. M., Paidas, C. N., Teot, L. A., Pappo, A. S., Link, M. P., Grier, H. E., Wiener, E. S., Breneman, J. C., Raney, R. B., Maurer, H. M., Donaldson, S. S. 2001; 19 (20): 4058-4064

    Abstract

    To identify which patients with rhabdomyosarcoma and microscopic residual disease (group II) are likely to not respond to therapy.Six hundred ninety-five patients with group II tumors received chemotherapy and 90% received radiation therapy on Intergroup Rhabdomyosarcoma Study (IRS)-I to IRS-IV (1972 to 1997). Tumors were subgrouped depending on the presence of microscopic residual disease only (subgroup IIa), resected positive regional lymph nodes, (subgroup IIb), or microscopic residual disease and resected positive regional lymph nodes (subgroup IIc).Overall, the 5-year failure-free survival rate (FFSR) was 73%, and patients with embryonal rhabdomyosarcoma treated on IRS-IV fared especially well (5-year FFSR, 93%; n = 90). Five-year FFSRs differed significantly by subgroup (IIa, 75% and n = 506; IIb, 74% and n = 101; IIc, 58% and n = 88; P = .0037) and treatment (IRS-I, 68%; IRS-II, 67%; IRS-III, 75%; IRS-IV, 87%; P < .001). Multivariate analysis revealed positive associations between primary site (favorable), histology (embryonal), subgroup IIa or IIb, treatment (IRS-III/IV), and better FFSRs. Patterns of treatment failure revealed local failure to be 8%, regional failure, 4%, and distant failure, 14%. The relapse pattern noted over the course of IRS-I to IRS-IV shows a decrease in the systemic relapse rates, particularly for patients with embryonal histology, suggesting that improvement in FFSRs is primarily a result of improved chemotherapy.Group II rhabdomyosarcoma has an excellent prognosis with contemporary therapy as used in IRS-III/IV, and those less likely to respond can be identified using prognostic factors: histology, subgroup, and primary site. Patients with embryonal rhabdomyosarcoma are generally cured, although patients with alveolar rhabdomyosarcoma or undifferentiated sarcoma, particularly subgroup IIc at unfavorable sites, continue to need better therapy.

    View details for Web of Science ID 000171634200009

    View details for PubMedID 11600608

  • Controversies in the management of paratesticular rhabdomyosarcoma: is staging retroperitoneal lymph node dissection necessary for adolescents with resected paratesticular rhabdomyosarcoma? Seminars in pediatric surgery Wiener, E. S., Anderson, J. R., Ojimba, J. I., Lobe, T. E., Paidas, C., Andrassy, R. J., Raney, R. B., Qualman, S. J., Donaldson, S. S., Maurer, H. M., Link, M. P., Crist, W. M., Grier, H. E. 2001; 10 (3): 146-152

    Abstract

    Use of retroperitoneal lymph node dissection (RPLND) in paratesticular rhabdomyosarcoma (PTRMS) is controversial and has changed over the past 2 decades. The Intergroup Rhabdomyosarcoma Study Group (IRSG) required ipsilateral RPLND (IRPLND) for all patients with PTRMS treated on IRS-III (1984-91), but changed to clinical evaluation of RPLNs using computerized tomography (CT) in IRS-IV (1991 through 1997). In IRS-IV, only those patients with identified lymph node involvement on CT required surgical evaluation of the RPLNs. Nodal radiation therapy was administered only to patients with RPLNs recognized as positive; such patients received more intensive chemotherapy as well. Thus, they compared the incidence of recognized RPLN involvement using these 2 different approaches. They then analyzed patient outcome to determine whether this change in management affected outcome.Eligible patients with group I or II PTRMS who were treated on IRS III (n = 100) or IRS IV (n = 134) were analyzed. Failure-free survival (FFS) and survival (S) rates were estimated using the Kaplan-Meier method and compared using the log-rank test.There was a significant change in the distribution of patients with group I versus II tumors from IRS-III to IRS-IV (group I, 68% in IRS-III versus 82% in IRS-IV). This was the result of decreased node recognition when CT was used to stage RPLNs in IRS-IV and was most notable for adolescents (>10 years of age). Overall, 3-year FFS was 92% for patients treated on IRS-III and 86% for those treated on IRS-IV (P =.10), whereas survival estimates were 96% and 92%, respectively (P =.30). Adolescents were at higher risk of RPLN relapse than were children (<10 years of age) and their FFS and survival were worse, regardless of IRS protocol. Furthermore, adolescents with recognized group II tumors experienced better 3-year FFS than those with group I tumors on IRS-IV (100% versus 68%, P =.06), most likely as a result of receiving radiotherapy and intensified chemotherapy.Use of only CT scan evaluation of RPLN in IRS-IV led to a decrease in identification of RPLN involvement in boys who present with localized PTRMS, and a higher rate of regional relapse as compared with IRS-III. Adolescents had much higher likelihood of RPLN disease, and they fared significantly worse than did younger children on both studies. Furthermore, adolescent boys with group I tumors experienced worse FFS than those with Group II tumors on IRS-IV, probably because some patients with group II tumors were not identified by CT imaging and thus received less effective therapy. These data suggest that adolescents should have ipsilateral RPLN dissection as part of their routine staging, and those with positive lymph nodes require intensified chemotherapy as well as nodal irradiation.

    View details for PubMedID 11481652

  • Intergroup rhabdomyosarcoma study-IV: Results for patients with nonmetastatic disease JOURNAL OF CLINICAL ONCOLOGY Crist, W. M., Anderson, J. R., Meza, J. L., Fryer, C., Raney, R. B., Ruymann, F. B., Breneman, J., Qualman, S. J., Wiener, E., Wharam, M., Lobe, T., Webber, B., Maurer, H. M., Donaldson, S. S. 2001; 19 (12): 3091-3102

    Abstract

    The study goal was to improve outcome in children with rhabdomyosarcoma by comparing risk-based regimens of surgery, radiotherapy (RT) and chemotherapy.Eight hundred eighty-three previously untreated eligible patients with nonmetastatic rhabdomyosarcoma entered the Intergroup Rhabdomyosarcoma Study-IV (IRS-IV) (1991 to 1997) after surgery and were randomized treatment by primary tumor site, group (1 to 3), and stage (I to III). Failure-free survival (FFS) rates and survival were the end points used in comparisons between randomized groups and between patient subgroups treated on IRS-III and IRS-IV. Most patients were randomized to receive vincristine and dactinomycin (VA) and cyclophosphamide (VAC, n = 235), or VA and ifosfamide (VAI, n = 222), or vincristine, ifosfamide, and etoposide (VIE, n = 236). Patients with group 3 tumors were randomized to receive conventional RT (C-RT) versus hyperfractionated RT (HF-RT).Overall 3-year FFS and survival were 77% and 86%, respectively. Three-year FFS rates with VAC, VAI, and VIE were 75%, 77%, and 77%, respectively (P =.42). No significant difference in outcome was noted with HF-RT versus C-RT (P =.85 and P =.90, respectively). Overall, patients with embryonal tumors benefited from intensive three-drug chemotherapy in IRS-IV (3-year FFS, 83%). The improvement was seen for patients with stage I or stage II/III, group 1/2 disease, many of whom received VA chemotherapy on IRS-III. Patients with stage 2/3, group 3 disease had similar outcomes on IRS-III and IRS-IV. Three-year FFS for the nonrandomized patient subsets was 75% with renal abnormalities; 81% for paratesticular, group 1 cases; and 91% for group 1/2 orbit or eyelid tumors. Patients with paratesticular primaries had poorer outcomes if they were more than 10 years old (3-year FFS, 63% v 90%). Myelosuppression occurred in most patients, but toxic deaths occurred in less than 1%.VAC and VAI or VIE with surgery (with or without RT), are equally effective for patients with local or regional rhabdomyosarcoma and are more effective for embryonal tumors than therapies used previously. Younger patients with group 1 paratesticular embryonal tumors and all patients with group 1/2 orbit or eyelid tumors can usually be cured with VA chemotherapy along with postoperative RT for group 2 disease.

    View details for Web of Science ID 000169303900015

    View details for PubMedID 11408506

  • What constitutes optimal therapy for patients with rhabdomyosarcoma of the female genital tract? Arndt, C. A., Donaldson, S. S., Anderson, J. R., Andrassy, R. J., Laurie, F., Link, M. P., Raney, R. B., Maurer, H. M., Crist, W. M. JOHN WILEY & SONS INC. 2001: 2454-2468

    Abstract

    Factors affecting outcome for rhabdomyosarcoma (RMS) of the female genital tract in patients treated on Intergroup Rhabdomyosarcoma Study Group (IRSG) protocols I-IV were evaluated to define optimal therapy.Records of 151 patients with tumors of the female genital tract who were treated on IRSG protocols I-IV were reviewed for details regarding chemotherapy, surgery, radiotherapy (RT), and outcome.The overall 5-year survival was 82%, (87% for patients with locoregional tumors). Chemotherapy was primarily vincristine, actinomycin-D, and cyclophosphamide (VAC) based. Local therapy was surgery alone in 42% of patients, surgery plus RT in 19% of patients, biopsy plus RT in 12% of patients, and biopsy without RT in 21% of patients. The rate of hysterectomy decreased from 48% in IRS-I/II to 22% in IRS-III/IV with an increase in the use of RT from 23% in IRS-II to 45% in IRS-IV and continued excellent survival. Many patients with vaginal primary tumors received delayed RT or had it omitted on later studies with excellent outcome. For patients with localized embryonal/botryoid tumors, there were no significant differences in 5-year survival among patients with tumors at different sites or among patients treated on IRS-I-IV. In patients with Group I-III tumors, 43% of deaths were from toxicity. Analysis of prognostic factors, with toxic deaths censored, revealed that an age of 1-9 years at the time of diagnosis, noninvasive tumors, and the use of IRS-II or IRS-IV treatments were associated significantly with better outcome. Patients ages 1-9 years fared best (5-year survival of 98%) and patients outside of this age range especially benefited from the intensified therapy used in IRS-III or IRS-IV (5-year survival of 67% on the IRS-I/II vs. 90% in IRS-III/IV).Localized female genital RMS usually is curable with combination chemotherapy, a conservative surgical approach, and the use of RT for selected patients.

    View details for Web of Science ID 000169348200032

    View details for PubMedID 11413538

  • Ifosfamide and etoposide are superior to vincristine and melphalan for pediatric metastatic rhabdomyosarcoma when administered with irradiation and combination chemotherapy: A report from the Intergroup Rhabdomyosarcoma Study Group JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Breitfeld, P. P., Lyden, E., Raney, R. B., Teot, L. A., Wharam, M., Lobe, T., Crist, W. M., Maurer, H. M., Donaldson, S. S., Ruymann, F. B. 2001; 23 (4): 225-233

    Abstract

    This study was designed to estimate the partial and complete response rates (CR and PR) of two novel drug pairs (vincristine and melphalan vs. ifosfamide and etoposide) and to improve overall survival of previously untreated patients with metastatic rhabdomyosarcoma.One hundred twenty-eight patients were randomly assigned to phase II window therapy consisting of vincristine and melphalan (VM-containing regimen) or ifosfamide and etoposide (IE-containing regimen). Brief window therapy (12 wks) was immediately followed-up by vincristine, dactinomycin, and cyclophosphamide (VAC), chemotherapy, surgery, and irradiation, with continuation of either VM or IE in patients with initial response. Major endpoints were initial CR and PR rates after the phase II window phase of therapy, failure-free survival (FFS), and survival.Patients who received the VM-containing regimen experienced significantly more anemia, neutropenia, thrombocytopenia, and had more cyclophosphamide dose reductions. The initial PR and CR rates were not significantly different for patients treated with either regimen (VM, 74%; IE, 79%; P = 0.428). However, FFS and overall survival (OS) at 3 years were significantly better with the IE-containing regimen (FFS: 33% vs. 19%; P = 0.043; OS: 55% vs. 27%; P = 0.012).Although the VM-containing regimen produced a high response rate, inclusion of melphalan appeared to limit the cyclophosphamide dose that could be administered, and ultimately, this regimen was associated with a significantly worse outcome than was the IE-containing regimen. Also, the IE-containing regimen was associated with a gratifyingly high survival rate at 3 years (55%), which is significantly higher than has been observed on any previous Intergroup Rhabdomyosarcoma Study Group regimen for similar patients. We believe that this promising outcome indicates that this drug pair merits further randomized testing in metastatic rhabdomyosarcoma.

    View details for Web of Science ID 000168710500009

    View details for PubMedID 11846301

  • Rhabdomyosarcoma and undifferentiated sarcoma in the first two decades of life: A selective review of Intergroup Rhabdomyosarcoma Study Group experience and rationale for intergroup rhabdomyosarcoma study V JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Raney, R. B., Anderson, J. R., Barr, F. G., Donaldson, S. S., Pappo, A. S., Qualman, S. J., Wiener, E. S., Maurer, H. M., Crist, W. M. 2001; 23 (4): 215-220

    Abstract

    To review the importance of prognostic factors in developing new protocols for children with rhabdomyosarcoma (RMS).Four studies conducted by the Intergroup Rhabdomyosarcoma Study (IRS) Group from 1972 through 1991.Favorable prognostic factors are: (1) undetectable distant metastases at diagnosis; (2) primary sites in the orbit and nonparameningeal head/neck and genitourinary nonbladder/prostate regions; (3) grossly complete surgical removal of localized tumor at the time of diagnosis; (4) embryonal/botryoid histology; (5) tumor size < or = 5 cm; and (6) age younger than 10 years at diagnosis. The IRS-V protocols are risk-based and refine therapy by reducing exposure to cyclophosphamide and radiation therapy (XRT) in patients at low risk while adding new, active agents such as topotecan or irinotecan to the standard therapy of vincristine, actinomycin D, and cyclophosphamide (VAC) plus XRT for patients with unfavorable histology or advanced disease. Collection of biologic specimens from patients with newly diagnosed disease continues to identify other factors that may distinguish patients with favorable features from those who need more intensive therapy. A new protocol that takes into account their previous treatment is needed for patients with recurrent disease. This program (being planned) does not include bone marrow/stem cell reconstitution because this strategy has thus far failed to improve survival rates of patients with metastases at diagnosis.Better understanding of biologic differences and new, active agents are needed to improve outcome of patients with unfavorable features at presentation.

    View details for Web of Science ID 000168710500007

    View details for PubMedID 11846299

  • Second malignant neoplasms in five-year survivors of childhood cancer: Childhood cancer survivor study JOURNAL OF THE NATIONAL CANCER INSTITUTE Neglia, J. P., Friedman, D. L., Yasui, Y., Mertens, A. C., Hammond, S., Stovall, M., Donaldson, S. S., Meadows, A. T., Robison, L. L. 2001; 93 (8): 618-629

    Abstract

    Because survival rates among childhood cancer patients are increasing, assessing the risk of second and subsequent malignant neoplasms (SMNs) is ever more important. Using the Childhood Cancer Survivor Study cohort, we identified the risk of SMNS:A retrospective cohort of 13 581 children diagnosed with common cancers before age 21 years and surviving at least 5 years was constructed with the use of data from patients treated at 25 U.S. and Canadian institutions. SMNs were ascertained through self-administered questionnaires and verified by pathology reports. Information on therapeutic exposures was abstracted from medical records. The risk of SMN was evaluated by standardized incidence ratios (SIRs) and excess absolute risk. Poisson multiple regression models were used to assess the impact of host and therapy factors on the risk of developing SMNS: All statistical tests were two-sided.In 298 individuals, 314 SMNs were identified (SIR = 6.38; 95% confidence interval [CI] = 5.69 to 7.13). The largest observed excess SMNs were bone and breast cancers (SIR = 19.14 [95% CI = 12.72 to 27.67] and SIR = 16.18 [95% CI = 12.35 to 20.83], respectively). A statistically significant excess of SMNs followed all childhood cancers. In multivariate regression models adjusted for therapeutic radiation exposure, SMNs of any type were independently associated with female sex (P<.001), childhood cancer at a younger age (P for trend <.001), childhood Hodgkin's disease or soft-tissue sarcoma (P<.001 and P =.01, respectively), and exposure to alkylating agents (P for trend =.02). Twenty years after the childhood cancer diagnosis, the cumulative estimated SMN incidence was 3.2%. However, only 1.88 excess malignancies occurred per 1000 years of patient follow-up.Success in treating children with cancer should not be overshadowed by the incidence of SMNS: However, patients and health-care providers must be aware of risk factors for SMNs so that surveillance is focused and early prevention strategies are implemented.

    View details for Web of Science ID 000168084800012

    View details for PubMedID 11309438

  • Childhood cancer: Patterns of protocol participation in a national survey CA-A CANCER JOURNAL FOR CLINICIANS Shochat, S. J., Fremgen, A. M., Murphy, S. B., Hutchison, C., Donaldson, S. S., Haase, G. M., Provisor, A. J., Clive-Bumpus, R. E., Winchester, D. P. 2001; 51 (2): 119-130

    Abstract

    Cancer is still the chief cause of death by disease in children, ages one to 14. As improved survival rates have been reported for pediatric cancer patients who are treated on controlled clinical trials, it is important to understand the national utilization of such protocols. In 1993, a survey of childhood cancer was conducted by the Commission on Cancer of the American College of Surgeons. Data regarding type of disease, protocol participation, age, sex, race, insurance, and geographical region were voluntarily submitted by more than 200 hospital cancer registries. Included in this study were 2,208 children and adolescents 21 years of age or younger who were diagnosed in 1987, and 2,293 who were diagnosed in 1992. Pediatric centers (i.e., members of the Pediatric Oncology Group or Children's Cancer Group) submitted 55.1% of the cases and other institutions, 44.9%. It was found that more patients treated at pediatric centers were on protocols (53.8%) than were those treated at other institutions (25.1%). In general, the younger the patient (five years of age or younger), the greater the chance of being on protocol (pediatric centers, 63.7%; others, 42.0%), with very poor adolescent protocol participation (pediatric centers, 34.8%; others, 12.1%). Nevertheless, overall protocol participation was still lower than expected, even in children younger than five years of age, and adolescent participation in controlled clinical trials was low and similar to adult figures. The percentage of childhood cancer cases seen at pediatric centers was smaller than in other series. It was concluded that pediatric cancer centers need to continue to encourage patient participation in controlled clinical trials, with special emphasis on adolescents.

    View details for Web of Science ID 000167949900003

    View details for PubMedID 11577480

  • The Intergroup Rhabdomyosarcoma Study Group (IRSG): Major Lessons from the IRS-I through IRS-IV Studies as Background for the Current IRS-V Treatment Protocol Sarcoma Sarcoma Raney, R., Maurer HM, Anderson JR, Andrassy RJ, Donaldson SS, Qualman SJ, Wharam MD, Wiener ES, Crist WM 2001; 5: 9-15
  • The Intergroup Rhabdomyosarcoma Study Group (IRSG): Major Lessons From the IRS-I Through IRS-IV Studies as Background for the Current IRS-V Treatment Protocols. Sarcoma Raney, R. B., Maurer, H. M., Anderson, J. R., Andrassy, R. J., Donaldson, S. S., Qualman, S. J., Wharam, M. D., Wiener, E. S., Crist, W. M. 2001; 5 (1): 9-15

    Abstract

    Purpose. To enumerate lessons from studying 4292 patients with rhabdomyosarcoma (RMS) in the Intergroup Rhabdomyosarcoma Study Group (IRSG, 1972-1997).Patients. Untreated patients < 21 years of age at diagnosis received systemic chemotherapy, with or without irradiation (XRT) and/or surgical removal of the tumor.Methods. Pathologic materials and treatment were reviewed to ascertain compliance and to confirm response and relapse status.Results. Survival at 5 years increased from 55 to 71% over the period. Important lessons include the fact that extent of disease at diagnosis affects prognosis. Re-excising an incompletely removed tumor is worthwhile if acceptable form and function can be preserved. The eye, vagina, and bladder can usually be saved. XRT is not necessary for children with localized, completely excised embryonal RMS. Hyperfractionated XRT has thus far not produced superior local control rates compared with conventional, once-daily XRT. Patients with non-metastatic cranial parameningeal sarcoma can usually be cured with localized XRT and systemic chemotherapy, without whole-brain XRT and intrathecal drugs. Adding doxorubicin, cisplatin, etoposide, and ifosfamide has not significantly improved survival of patients with gross residual or metastatic disease beyond that achieved with VAC (vincristine, actinomycin D, cyclophosphamide) and XRT. Most patients with alveolar RMS have a tumor-specific translocation. Mature rhabdomyoblasts after treatment of patients with bladder rhabdomyosarcoma are not necessarily malignant, provided that the tumor has shrunk and malignant cells have disappeared.Discussion. Current IRSG-V protocols, summarized herein, incorporate recommendations for risk-based management. Two new agents, topotecan and irinotecan, are under investigation for patients who have an intermediate or high risk of recurrence.

    View details for DOI 10.1080/13577140120048890

    View details for PubMedID 18521303

  • Results from the IRS IV Randomized Trial of Hyperfractionated Radiotherapy in Children with Rhabdomyosarcoma: A Report from the IRSG International Journal of Radiation Oncology, Biology, and Physics Donaldson SS, Meza J, Breneman JC, Crist WM, Laurie F, Qualman SJ, Wharam M 2001; 51: 718-728
  • Second Malignant Neoplasms in Five-Year Survivors of Childhood Cancer: Childhood Cancer Survivor Study Journal of the National Cancer Institute Neglia JP, Friedman DL, Yasui Y, Mertens AC, Hammond S, Stovall M, Donaldson SS, Meadows AT, Robison LL 2001; 93: 618-29
  • Long-term Results of Irradiation for Patients with Progressive Graves' Ophthalmopathy International Journal of Radiation Oncology, Biology, and Physics Marquez SD, Lum BL, McDougall IR, Katkuri S, Levin PS, MacManus M, Donaldson SS 2001; 51: 766-774
  • Intergroup Rhabdomyosarcoma Study IV: Results for Patients with Non-metastatic Disease Journal of Clinical Oncology Crist WM, Anderson JR, Meza JL, Fryer C, Raney RB, Ruymann FB, Breneman J, Qualmann SJ, Wiener E, Wharam M, Lobe T, Webber B, Maurer HM, Donaldson SS 2001; 19: 3091-3102
  • Soft-tissue sarcomas of the diaphragm: A report from the intergroup Rhabdomyosarcoma Study Group from 1972 to 1997 JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Raney, R. B., Anderson, J. R., Andrassy, R. J., Crist, W. M., Donaldson, S. S., Maurer, H. M. 2000; 22 (6): 510-514

    Abstract

    To describe clinical details and outcome of children and adolescents with primary sarcomas of the diaphragm treated on Intergroup Rhabdomyosarcoma Studies (IRS) I through IV.We reviewed the records of 15 patients with sarcoma of the diaphragm who were entered on IRS Group protocols between 1972 and 1997. Patient ages at diagnosis ranged from 0.5 to 20 years (median, 13 yrs), and 10 were girls. Patients had chest pain, dyspnea, and/or coughing, decreased breath sounds, and occasionally hepatomegaly.Localized, gross residual disease after initial surgery was present in 10 patients, and five had metastases at diagnosis (pleura, 3; pericardium, 1; lungs and bones, 1). Tumor subtypes were alveolar rhabdomyosarcoma (RMS) in five cases, embryonal RMS in three, undifferentiated sarcoma in three, extraosseous Ewing sarcoma in three, and unclassified sarcoma in one. Treatment consisted of radiation therapy to the primary tumor and metastases when feasible, and combination chemotherapy with vincristine, actinomycin D, and cyclophosphamide with or without doxorubicin, ifosfamide, cisplatin, and etoposide. Ten patients achieved complete remission (67%), four obtained a partial remission, and one was improved. Five patients (33%) are continuously failure-free and alive at a median of 8.8 years from diagnosis (range, 1.1-15 yrs). However, the other 10 patients experienced relapse at 0.3 to 2 years from start of therapy (median, 1 yr). Sites of relapse were local in five, distant in three, and combined in two. Death after relapse occurred at 0.39 to 2.6 years (median, 1.6 yrs) from diagnosis.Sarcomas of the diaphragm are generally deemed unresectable at diagnosis and/or are metastatic. Most of them are not embryonal rhabdomyosarcomas. Treatment with more effective primary chemotherapy to shrink the tumor, followed-up by surgical resection and radiation therapy, should improve the prognosis for patients with sarcomas arising in the diaphragm, especially for the majority who have localized tumors.

    View details for Web of Science ID 000165933100007

    View details for PubMedID 11132218

  • Soft-tissue Sarcomas of the Diaphragm: From the Intergroup Rhabdomyosarcoma Study Group from 1972-1977 Journal of Pediatric Hematology and Oncology Raney RB, Anderson JR, Andrassy RJ, Crist WM, Donaldson SS, Maurer HM 2000; 22: 510-514
  • Hodgkin's disease - Finding the balance between cure and late effects CANCER JOURNAL Donaldson, S. S., Hancock, S. L., Hoppe, R. T. 1999; 5 (6): 325-333
  • Indications for radiotherapy and chemotherapy after complete resection in rhabdomyosarcoma: A report from the intergroup rhabdomyosarcoma studies I to III JOURNAL OF CLINICAL ONCOLOGY Wolden, S. L., Anderson, J. R., Crist, W. M., Breneman, J. C., Wharam, M. D., Wiener, E. S., Qualman, S. J., Donaldson, S. S. 1999; 17 (11): 3468-3475

    Abstract

    To evaluate the outcome of patients with rhabdomyosarcoma (RMS) treated with complete surgical resection and multiagent chemotherapy, with or without local radiotherapy (RT).Four hundred thirty-nine patients with completely resected (ie, group I) RMS were further treated with chemotherapy (vincristine and actinomycin D +/- cyclophosphamide, doxorubicin, and cisplatin) on Intergroup Rhabdomyosarcoma Studies (IRS) I to III between 1972 and 1991. Eighty-three patients (19%) also received local RT as a component of initial treatment.Eighty-six patients relapsed (10-year failure-free survival [FFS] 79%, overall survival 89%). Six percent of failure sites were local, 6% were regional, and 7% were distant. Poor prognostic factors were tumor size greater than 5 cm, alveolar or undifferentiated histology, primary tumor sites other than genitourinary, and treatment on IRS-I or II. For patients with embryonal RMS who were treated with RT, there was a trend for improved FFS but no difference in overall survival. On IRS-I and II, patients with alveolar or undifferentiated sarcoma who received RT compared with those who did not receive RT had greater 10-year FFS rates (73% v 44%, respectively; P =.03) and overall survival rates (82% v 52%, respectively; (P =.02). Such patients who received RT on IRS III also benefited more than those who did not receive RT (10-year FFS, 95% v 69%; P =.01; overall survival, 95% v 86%; P =.23).Patients with group I embryonal RMS have an excellent prognosis when treated with adjuvant multiagent chemotherapy without RT. Patients with alveolar RMS or undifferentiated sarcoma fare worse; however, FFS and overall survival are substantially improved when RT is added to multiagent chemotherapy (IRS-I and II). The best outcome occurred in IRS-III, when RT was used in conjunction with intensified chemotherapy.

    View details for Web of Science ID 000083473700016

    View details for PubMedID 10550144

  • Late complications of therapy in 213 children with localized, nonorbital soft-tissue sarcoma of the head and neck: A descriptive report from the intergroup rhabdomyosarcoma studies (IRS)-II and -III MEDICAL AND PEDIATRIC ONCOLOGY Raney, R. B., Asmar, L., Vassilopoulou-Sellin, R., Klein, M. J., Donaldson, S. S., Green, J., Heyn, R., Wharam, M., Glicksman, A. S., Gehan, E. A., Anderson, J., Maurer, H. M. 1999; 33 (4): 362-371

    Abstract

    This review of children and adolescents with nonorbital soft-tissue sarcoma of the head and neck was undertaken to describe late sequelae of treatment, as manifested primarily by problems with statural growth, facial and nuchal symmetry, dentition, vision and hearing, and school performance.Four hundred sixty-nine patients entered the IRS-II and -III protocols with localized, nonorbital soft-tissue sarcomas of the head and neck from 1978 through 1987. Their overall survival rate was 53% (250/469) at 5 years. Two hundred thirteen patients were surviving relapse-free 5 or more years after diagnosis, for whom there were serial height measurements at 2 or more years after initiation of therapy. Their median age at diagnosis was 5 years; the median length of follow-up was 7 years. All received multiple-agent chemotherapy, and all but 3 received irradiation to the primary tumor volume. Sixty-eight percent of the tumors arose in cranial parameningeal sites, 22% in nonparameningeal sites, and 10% in the neck. We reviewed flow sheets submitted to the IRS Group Statistical Office to ascertain which late sequelae were recorded.One hundred sixty-four patients (77%) had one or more problems recorded. One hundred ninety of the two hundred thirteen patients (89%) were under 15 years of age at study entry, and at follow-up 92 (48%) had failed to maintain their initial height velocity, which had decreased by more than 25 percentile points from the original value. Thirty-six of the one hundred ninety patients (19%) were receiving growth hormone injections. Hypoplasia or asymmetry of tissues in the primary tumor site was reported in 74 patients, and 13 underwent reconstructive surgery. Poor dentition or malformed teeth were noted in 61 patients. Impaired vision developed in 37 patients, owing primarily to cataracts, corneal changes, and optic atrophy. Thirty-six patients had decreased hearing acuity, and 9 were fitted with hearing aids; 5 of these 9 had received cisplatin. Thirty-five patients were noted to have problems learning in school. Four patients developed a second malignancy (two sarcomas, one carcinoma, one leukemia).Late sequelae affected the majority of these patients treated for soft-tissue sarcoma of the head and neck on IRS-II and -III. The potential impact of certain sequelae could be reduced by specific measures, such as surgical reconstruction and hormonal therapy. Late sequelae must be taken into account in designing future curative treatments.

    View details for Web of Science ID 000082710400003

    View details for PubMedID 10491544

  • Treatment of pediatric Hodgkin's lymphoma SEMINARS IN HEMATOLOGY Hudson, M. M., Donaldson, S. S. 1999; 36 (3): 313-323

    Abstract

    Today the majority of children and adolescents diagnosed with Hodgkin's lymphoma will enjoy long-term disease-free survival. As a result, contemporary treatment strategies have focused on reducing therapy for patients with favorable disease presentations and reserved aggressive treatment modalities for patients with relapsed or refractory disease. The desire to avoid late treatment toxicity has prompted refinements in therapy designed to reduce growth impairment, second malignancy, and life-threatening organ dysfunction in long-term survivors. Treatment with radiation therapy alone is recommended only for older patients with localized disease who have achieved skeletal maturity, but requires surgical staging and places greater volumes of normal tissues at risk for late carcinogenesis. Treatment with chemotherapy alone avoids the long-term growth, organ dysfunction, and solid tumor induction associated with high-dose, extended-field radiation. However, these protocols prescribe higher cumulative doses of alkylating agent chemotherapy, which may increase the risk of treatment complications from myelosuppression, gonadal injury, and secondary leukemia. Combined modality therapy regimens have resulted in excellent treatment outcomes and reduced the incidence of treatment sequelae by utilizing lower doses and smaller volumes of radiation therapy and fewer cycles of less toxic chemotherapy in clinically staged children. Risk-adapted therapies using two to four cycles of multiagent chemotherapy and lower radiation doses and volumes have maintained excellent disease-free survival rates in clinically staged patients with localized favorable disease presentations. Novel approaches including compacted dose-intensive multiagent chemotherapy are currently under investigation with the objectives of improving outcome and reducing treatment sequelae in patients with advanced and unfavorable disease.

    View details for Web of Science ID 000081774400011

    View details for PubMedID 10462331

  • Does debulking improve survival rate in advanced-stage retroperitoneal embryonal rhabdomyosarcoma? JOURNAL OF PEDIATRIC SURGERY Blakely, M. L., Lobe, T. E., Anderson, J. R., Donaldson, S. S., Andrassy, R. J., Parham, D. M., Wharam, M. D., Qualman, S. J., Wiener, E. S., Grier, H. E., Crist, W. M. 1999; 34 (5): 736-741

    Abstract

    BACKGROUND, METHODS, AND PURPOSE: The authors examined demographic and clinical features, therapy, and outcome of patients with advanced (group III or IV) rhabdomyosarcoma (RMS) of the retroperitoneum and nongenitourinary pelvis treated in the Intergroup Rhabdomyosarcoma Study Group (IRSG) III (1984 to 1991, n = 41) or IV pilot (1987 to 1991, n = 53) studies to assess the role of initial debulking surgery.Ninety-four patients with retroperitoneal primary tumors and gross locoregional residual tumor (group III, n = 53) or metastatic disease (group IV tumors, n = 41) were treated with combination chemotherapy (ie, vincristine, dactinomycin, and cyclophosphamide with or without other agents plus radiation therapy, RT) after biopsy only or subtotal resection. These retroperitoneal tumors usually were invasive (T2, 76%). Most patients were younger than 10 years of age (n = 69, 73%), the male to female ratio was 1.4, and tumors usually were embryonal (n = 64, 68%). Overall 4-year failure-free survival (FFS) was 50%; survival was 60%. Survival rate was better for girls (4-year survival rate, 75% v49% for boys; P = .05) and was not significantly different for patients treated in IRS-III (66%) or IRS-IV pilot (52%). However, it was better for patients with embryonal versus alveolar or undifferentiated tumors (4-year survival rate, 70% v 42%; P = .002). In adolescents, RMS is different from that seen in children less than 10 years old; most cases are alveolar or undifferentiated (16 of 29, 55%). Surgery for most (21 of 24) patients with alveolar tumors comprised biopsy only. By contrast, of 64 patients with embryonal tumors, 39 (61%) underwent biopsy only, whereas 25 (39%) had debulking surgery. Patients whose tumors were debulked fared better than those whose tumors underwent biopsy only (4-year FFS rate, 72% v48%; P = 0.03). Patients with group IV embryonal tumors fared unexpectedly better than those with group IV alveolar or undifferentiated tumors (70% versus 42% 4-year survival rate, P < .05), and patients less than 10 years of age with group IV embryonal tumors had 4-year survival rate of 77%, indicating the importance of the biology of these tumors.Multimodal therapy, including multiagent chemotherapy plus RT, appears to improve survival rate in patients with advanced embryonal RMS arising in the retroperitoneum. These data suggest that debulking tumors of embryonal histology improves outcome further. This approach will be assessed in IRSG V.

    View details for Web of Science ID 000080447500033

    View details for PubMedID 10359174

  • Primary and metastatic rhabdomyosarcoma in the breast: Neoplasms of adolescent females, a report from the intergroup rhabdomyosarcoma study MEDICAL AND PEDIATRIC ONCOLOGY Hays, D. M., Donaldson, S. S., Shimada, H., Crist, W. M., Newton, W. A., Andrassy, R. J., Wiener, E., Green, J., Triche, T., Maurer, H. M. 1997; 29 (3): 181-189

    Abstract

    The occurrence of rhabdomyosarcoma (RMS) primary in or metastatic to breast has been regarded as an uncommon event, associated with an unfavorable outcome. Records of 26 patients with diagnoses of breast RMS, either primary or secondary, entered in the Intergroup Rhabdomyosarcoma Study (IRS) (1972-1992) were reviewed and compared with data regarding 47 similar patients in published reports. Of the 26 IRS cases, the histologic subtype was alveolar in 24, embryonal in 1, and not determined in 1. All were female with ages ranging from 11.5 to 20.2 years (median, 15.2 years; mode, 14-16 years). This compact age distribution of both primary (n = 7) and metastatic (n = 19) breast RMS was seen in previously reported series. Among the 19 cases of RMS with initial dissemination to breast, primary tumor sites, were extremity (n = 8), nasopharynx/paranasal sinuses (n = 7), and trunk (n = 4). IRS treatment was risk-based according to site and extent of disease. Four of 7 patients with primary RMS remain disease free 2.9 to 7 years post diagnosis. Among 19 patients with RMS initially metastatic to breast, including 7 in IRS clinical group IV at original diagnosis, three are disease free at 7.6, 15.7 and 17.0 years. Conclusions: primary or metastatic RMS in breast is almost confined to adolescent females having tumors with alveolar histology. Approximately one-half of the patients with primary breast disease and 15% of those with metastatic breast disease as an initial recurrence are long-term survivors.

    View details for Web of Science ID A1997XH25700004

    View details for PubMedID 9212842

  • Hodgkin's disease PEDIATRIC CLINICS OF NORTH AMERICA Hudson, M. M., Donaldson, S. S. 1997; 44 (4): 891-?

    Abstract

    Despite incomplete understanding of the etiology of Hodgkin's disease and its malignant cell of origin, the majority of children and adolescents diagnosed with Hodgkin's disease will be longterm survivors. Staging and treatment for pediatric Hodgkin's disease has evolved over the past 30 years in attempts to reduce late treatment sequelae. Today, most children are clinically staged and treated with multitreatment chemotherapy, either alone or in conjunction with low-dose, involved field radiation therapy. Initial results with "risk-adapted" combined modality regimens limiting chemotherapy cycles and radiation doses and volumes demonstrate maintenance of cure rates for early stage, favorable Hodgkin's disease. Challenges for the future include identification of prognostic factors in patients at risk for treatment failure who may benefit from intensification of therapy.

    View details for Web of Science ID A1997XT84000007

    View details for PubMedID 9286290

  • Venoocclusive disease of the liver after chemotherapy with vincristine, actinomycin D, and cyclophosphamide for the treatment of rhabdomyosarcoma - A report of the intergroup rhabdomyosarcoma study group CANCER Ortega, J. A., Donaldson, S. S., Ivy, S. P., Pappo, A., Maurer, H. M. 1997; 79 (12): 2435-2439

    Abstract

    Venoocclusive disease (VOD) of the liver is a common complication after allogenic and autologous bone marrow transplantation for malignant disease. The authors report the unusual and unexpected complication of VOD of the liver occurring in children with rhabdomyosarcoma who were receiving vincristine, actinomycin D, and cyclophosphamide (VAC) according to the chemotherapy regimens of the Intergroup Rhabdomyosarcoma Study (IRS) IV.The authors evaluated 821 patients with newly diagnosed rhabdomyosarcoma receiving treatment according to IRS IV who were considered at risk for VOD.Ten patients developed VOD of the liver for an overall incidence of 1.2%. VOD was found only after the administration of VAC chemotherapy. The highest incidence of VOD was observed among patients who had previously received vincristine and melphalan (Regimen 48). None of the patients receiving the chemotherapy regimen of vincristine and actinomycin D (Regimen 44) developed VOD.Patients receiving VAC-containing regimens on the IRS IV were found to be at risk for VOD. The VAC combination was used extensively in previous IRS studies (I, II, and III) and VOD was not reported during these studies, strongly suggesting that the escalation of the cyclophosphamide dose to 2.2 g/m2 (with the vincristine and actinomycin D doses and schedule remaining unchanged) triggered the development of VOD. The contributing role of previous therapy or events is unknown. At last follow-up, none of the nine surviving patients had developed recurrent VOD on continuation of chemotherapy.

    View details for Web of Science ID A1997XC74500021

    View details for PubMedID 9191535

  • The Internet Radiation Oncology Journal Club - A multi-institutional collaborative education project. Goldsmith, B. J., Donaldson, S. S., Mendenhall, W. M., Recht, A., Hoppe, R. T., Grigsby, P. W., Turrisi, A. T., Tepper, J. E., Roach, M., Larson, D. A., Withers, H. R., Purdy, J. A. ELSEVIER SCIENCE INC. 1997: 356-356
  • THE THIRD INTERGROUP RHABDOMYOSARCOMA STUDY JOURNAL OF CLINICAL ONCOLOGY Crist, W., Gehan, E. A., Ragab, A. H., Dickman, P. S., Donaldson, S. S., Fryer, C., Hammond, D., Hays, D. M., Herrmann, J., Heyn, R., Jones, P. M., LAWRENCE, W., Newton, W., Ortega, J., Raney, R. B., Ruymann, F. B., Tefft, M., Webber, B., Wiener, E., Wharam, M., Vietti, T. J., Maurer, H. M. 1995; 13 (3): 610-630

    Abstract

    The ultimate goal of the Third Intergroup Rhabdomyosarcoma Study (IRS-III, 1984 to 1991) was to improve treatment outcome in children with rhabdomyosarcoma through clinical trials comparing risk-based protocols of surgery and multiagent chemotherapy, with or without irradiation.One thousand sixty-two previously untreated, eligible patients who were entered onto the study after surgery were randomized or assigned to treatment by clinical group (I through IV), histology (unfavorable or favorable), and site of the primary tumor. Initial responses, progression-free survival (PFS), and survival (S) were the end points used in comparisons between randomized groups and between patients treated in IRS-III and IRS-II (1978 to 1984).The overall outcome of therapy in IRS-III was significantly better than in IRS-II (5-year PFS, 65% +/- 2% v 55% +/- 2%; P < .001 by stratified testing). Patients with group I favorable-histology tumors fared as well on a 1-year regimen of vincristine and dactinomycin (VA), as did a comparable group treated with VA plus cyclophosphamide (C) (5-year PFS, 83% +/- 3% v 76% +/- 4%; P = .18). Results for patients with group II favorable-histology tumors, excluding orbit, head, and paratesticular sites, were inconclusive regarding the benefit from addition of doxorubicin (ADR) to VA. Patients with group III tumors, excluding those in special pelvic, orbit, and other selected nonparameningeal head sites, fared much better on the more intensive regimens of IRS-III than on pulsed VAC or VAC-VADRC in IRS-II (5-year PFS estimates, 62% +/- 3% v 52% +/- 3%; P < .01); however, there were no significant differences in outcome among the groups treated in IRS-III. Patients with metastatic disease at diagnosis (clinical group IV) did not benefit significantly from the more complex therapies evaluated in IRS-III.Intensification of therapy for most patients in IRS-III, using a risk-based study design, significantly improved treatment outcome overall. The largest gain from this strategy was realized in patients with gross residual tumor after biopsy (clinical group III). It was also possible to decrease therapy for selected patient subsets without compromising survival.

    View details for Web of Science ID A1995QL03400012

    View details for PubMedID 7884423

  • PROGNOSTIC FEATURES OF EWINGS-SARCOMA ON RADIONUCLIDE BONE-SCAN AFTER INITIAL TREATMENT EUROPEAN JOURNAL OF RADIOLOGY Reinus, W. R., Gilula, L. A., Donaldson, S. S., Shuster, J., Vietti, T. 1994; 19 (1): 1-6

    Abstract

    To study short-term changes in the radiopharmaceutical bone scan (BS) appearance of Ewing's sarcoma for indicators of decreased survival or future disease progression.One-hundred and four patients with non-metastatic Ewing's sarcoma were evaluated at three time points: time of diagnosis (pre-biopsy), after induction chemotherapy (13 weeks) and after radiation therapy (20 weeks). Radiographs, computed tomograms (CTs) and BSs were obtained at each interval. Primary lesion activity and size on BS were evaluated and compared to radiographic and CT findings.No significant relationship was found at any time point between absolute radiopharmaceutical activity within the primary lesion and either disease progression or patient survival. Relative changes in BS activity between time points were also not significantly related to disease progression or survival despite a significant decrease in activity among the three time points. The size of the BS abnormality compared to the CT abnormality at the primary lesion site was related to both survival and disease progression at the post-induction chemotherapy time point (P = 0.025 and P = 0.014, respectively) with larger BS abnormalities indicating worse prognosis and survival. This relationship lost its significance at the post-radiation time point. No other significant relationship between the relative size of the BS abnormality and the size of the plain radiographic or CT abnormality was detected.Our data suggest that BS imaging of the primary lesion of Ewing's sarcoma provides little information in terms of predicting long-term survival or disease progression in patients with non-metastatic Ewing's sarcoma.

    View details for Web of Science ID A1994PY19200001

    View details for PubMedID 7859751

  • RETROPERITONEAL NODE BIOPSY IN PARATESTICULAR RHABDOMYOSARCOMA JOURNAL OF PEDIATRIC SURGERY Wiener, E. S., LAWRENCE, W., Hays, D., Lobe, T. E., Andrassy, R., Donaldson, S., Crist, W., Newton, W., Johnson, J., Gehan, E., Rodary, C. 1994; 29 (2): 171-178

    Abstract

    Retroperitoneal lymph node dissection (RPLND) was used in 121 Intergroup Rhabdomyosarcoma Study (IRS) III patients with nonmetastatic paratesticular (PT) rhabdomyosarcoma (RMS) to assess retroperitoneal lymph node (RPLN) involvement so as to determine the need for x-ray therapy (XRT). Clinical node evaluation (CNE) was accomplished by a computed tomography (CT) scan in 105 and a sonogram in six. Pathological node evaluation (PNE) was performed in 113: lymphadenectomy (9 bilateral, 85 unilateral) and biopsy in 19. Vincristine and actinomycin D were used for 1 year postoperatively in 89%; all patients who had positive PNE received RPLN XRT. This study compares CNE with PNE and evaluates predictors of relapse and survival.There were clinically negative nodes (cN0) in 81% of the 121 patients. Among cN0 patients, 14% had positive nodes (pN1). Of the clinically positive (cN1) patients, 94% had pN1. RPLN relapse occurred in only two of the 121 patients. Initially both had cN0 and one had PNE that was negative. For all 121 patients, the 5-year survival was 91%. For cN0 patients, the 5-year survival was 96% compared with 69% for cN1 patients (P < .001). Among the children in whom treatment failed, nodes were cN1 in 5 of 11 (45%) compared with 15 of 107 (14%) in those whose treatment did not fail (P < .008).(1) Results of RPLN imaging studies were negative in 81% of patients with PT RMS (specificity 99%, sensitivity 57%). (2) RPLN recurrence is uncommon (even when RPLN are initially involved) if regional XRT and appropriate chemotherapy are used.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1994MX66700008

    View details for PubMedID 8176587

  • ACUTE MYELOID-LEUKEMIA IN PATIENTS TREATED FOR RHABDOMYOSARCOMA WITH CYCLOPHOSPHAMIDE AND LOW-DOSE ETOPOSIDE ON INTERGROUP RHABDOMYOSARCOMA STUDY .3. AN INTERIM-REPORT MEDICAL AND PEDIATRIC ONCOLOGY Heyn, R., Khan, F., Ensign, L. G., Donaldson, S. S., Ruymann, F., Smith, M. A., Vietti, T., Maurer, H. M. 1994; 23 (2): 99-106

    Abstract

    The early occurrence of five cases of acute myeloid leukemia (AML) in children treated for primary rhabdomyosarcoma on the Intergroup Rhabdomyosarcoma Study III (IRS III) has prompted this report. These patients received cyclophosphamide and four received etoposide in addition to other agents. There were 1,062 eligible patients entered on IRS III between 1984 and 1991. Following surgery, treatment consisted of multiagent chemotherapy and radiotherapy in select clinical groups. Median follow-up time is 3.7 years (range 0-7.4 years). Incidence densities and odds ratios for AML were calculated for various treatment groups. Five cases of secondary AML have been reported through August 1992. A single case of osteogenic sarcoma was reported in the same period and a patient with myelodysplastic syndrome has occurred since that time. Median time to development of AML was 39 months. Incidence density of AML for patients receiving neither cyclophosphamide nor etoposide was 0, for those receiving cyclophosphamide but no etoposide it was 7.6, and when both agents were given, it was 51.6. The odds ratios of AML for the latter two groups indicated a risk of AML which was seven times higher in the patients who received both agents. A history of breast cancer was present in all five families of patients with AML and several other cancers had occurred in three families. Preliminary analysis suggests a possible causal role for low-dose etoposide in addition to that assumed for cyclophosphamide in the early development of AML among pediatric patients treated for rhabdomyosarcoma.

    View details for Web of Science ID A1994NT35700005

    View details for PubMedID 8202048

  • PROGNOSTIC FEATURES OF EWING SARCOMA ON PLAIN RADIOGRAPH AND COMPUTED-TOMOGRAPHY SCAN AFTER INITIAL TREATMENT - A PEDIATRIC-ONCOLOGY-GROUP STUDY (8346) CANCER Reinus, W. R., Gilula, L. A., Donaldson, S., Shuster, J., GLICKSMAN, A., Vietti, T. J. 1993; 72 (8): 2503-2510

    Abstract

    The authors studied the short-term changes in the plain radiographic and computed tomography (CT) appearance of Ewing sarcoma for indicators of decreased survival or future disease progression.The authors evaluated CT scans and plain radiographs of the primary tumor site from 105 patients with Ewing sarcoma at diagnosis (prebiopsy), after induction chemotherapy (13 weeks), and after radiation therapy (20 weeks).Data suggest an association between postinduction CT findings of medullary involvement, cortical destruction, lysis, permeation, and unhealed pathologic fracture and decreased survival. On the postradiation scans, only medullary involvement was associated with worsened survival. No plain radiographic features were significant at any time. Absolute greatest tumor dimension was not significantly related to survival or tumor progression. The Cox model suggested that fractional change in greatest tumor dimension on CT at the time points studied relative to the prebiopsy CT was correlated to survival. Log-rank testing did not corroborate this finding. All significant associations appeared to result from adverse outcomes in small subgroups.Our data suggest that CT obtained immediately after induction chemotherapy and radiation may have some limited use in predicting the long-term prognosis of patients with Ewing sarcoma.

    View details for Web of Science ID A1993MA71300031

    View details for PubMedID 8402468

  • ACUTE HYPERSENSITIVITY REACTIONS TO ETOPOSIDE IN A VEPA REGIMEN FOR HODGKINS-DISEASE JOURNAL OF CLINICAL ONCOLOGY Hudson, M. M., Weinstein, H. J., Donaldson, S. S., Greenwald, C., Kun, L., Tarbell, N. J., HUMPHREY, W. A., Rupp, C., Marina, N. M., Wilimas, J., Link, M. P. 1993; 11 (6): 1080-1084

    Abstract

    We report an unexpectedly high incidence of hypersensitivity to etoposide among 45 patients with newly diagnosed Hodgkin's disease treated with vinblastine, etoposide, prednisone, and doxorubicin (VEPA) plus radiation.Twenty-three of 45 patients (51%) had one or more acute hypersensitivity reactions to etoposide administration. The 23 patients were 8 to 18 years of age (median, 15 years); 12 were males. Four patients had experienced prior allergic reactions to antibiotics or intravenous contrast media.Hypersensitivity reactions followed the first or second dose of VEPA in most cases. The reactions occurred at a median time of 5 minutes (range, 3 to 120) from the start of the etoposide infusion. Fifteen patients reacted early (within 10 minutes), four midway through the infusion, and four after completion of the infusion. Signs and symptoms included flushing, respiratory problems, changes in blood pressure, and abdominal pain with or without nausea and vomiting. Respiratory problems included dyspnea, chest pain/tightness, bronchospasm, and cyanosis. Symptoms were alleviated by discontinuing the etoposide infusions and administering diphenhydramine and/or hydrocortisone; epinephrine was required to reverse bronchospasm in three cases. All 23 patients recovered without adverse sequelae and were rechallenged with etoposide. Fifteen patients tolerated subsequent etoposide infused at a slower rate, with antihistamine and/or corticosteroid premedication; five had recurrent hypersensitivity despite these measures. Three of these five developed similar symptoms when teniposide was substituted for etoposide. Three patients who had isolated episodes of hypotension on completion of the etoposide infusion successfully received subsequent infusions without premedication or change in infusion rate or concentration.Despite this unexpectedly high incidence of hypersensitivity among Hodgkin's disease patients treated with etoposide, rechallenge with the drug was successful in 78% of cases.

    View details for Web of Science ID A1993LF31000011

    View details for PubMedID 8501494

  • THE INTERGROUP RHABDOMYOSARCOMA STUDY-II CANCER Maurer, H. M., Gehan, E. A., BELTANGADY, M., Crist, W., Dickman, P. S., Donaldson, S. S., Fryer, C., Hammond, D., Hays, D. M., Herrmann, J., Heyn, R., Jones, P. M., LAWRENCE, W., Newton, W., Ortega, J., Ragab, A. H., Raney, R. B., Ruymann, F. B., Soule, E., Tefft, M., Webber, B., Wiener, E., Wharam, M., Vietti, T. J. 1993; 71 (5): 1904-1922

    Abstract

    Intergroup Rhabdomyosarcoma Study (IRS)-II, (1978-1984) had the general goals of improving the survival and treatment of children with rhabdomyosarcoma (RMS).Nine hundred ninety-nine previously untreated eligible patients entered the study after surgery and were randomized or assigned to therapy by IRS Clinical Group (I-IV), tumor site, and histologic type. Outcomes were compared between treatments and with results of IRS-I (1972-1978).Patients in Group I, excluding extremity alveolar (EA) RMS, were randomized to standard vincristine (V), dactinomycin (A), and cyclophosphamide (C) or standard VA. At 5 years, disease-free survival (DFS) and survival (S) rates were similar between VAC and VA (DFS: 80%, 70%, P = 0.47; S: 85%, 84%, P = 0.73). Patients in Group II, excluding EA RMS, received radiation and were randomized to intensive VA or repetitive-pulse VAC. Outcomes were similar for rates of DFS (69%, 74%, P = 0.83) and S (88%, 79%, P = 0.17). Patients in Group III, excluding certain pelvic tumors, received radiation and were randomized to repetitive-pulse VAC or repetitive-pulse VAdrC-VAC (Adr, Adriamycin [doxorubicin]). Complete remission (CR) rates were close at 74%, 78%, respectively (P = 0.32), as were percentages in CR (73%) and S (66%) rates; the latter outcomes were significantly better than IRS-I (CR: 56%, P < 0.001; S: 50%, P < 0.001). Central nervous system prophylaxis for Group III patients with cranial parameningeal sarcoma increased S rate to 67% from 45% in IRS-I (P < 0.001). Patients in Group IV received the same regimens as Group III; the CR rate was 53%, 38% remained in CR and S rate was 27% with and 26% without Adr (P = 0.90). At 5 years, S rate for IRS-II, including EA and all pelvic tumors, was 63%: an 8% increase over IRS-I (P < 0.001). Outcomes by primary site were as good as, or better than, the IRS-I experience.Combining all Groups and treatments in IRS-II, the major improvement in S rate at 5 years between studies was in nonmetastatic patients (71% for IRS-II versus 63% for IRS-I, P = 0.01).

    View details for Web of Science ID A1993KP99000029

    View details for PubMedID 8448756

  • PEDIATRIC RADIATION ONCOLOGY - SUBSPECIALTY TRAINING INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Constine, L. S., Donaldson, S. S. 1992; 24 (5): 881-884

    View details for Web of Science ID A1992KA57000020

    View details for PubMedID 1447024

  • TREATMENT OF CHILDHOOD HODGKINS-DISEASE - REPLY JOURNAL OF CLINICAL ONCOLOGY Donaldson, S. S., Link, M. P., Plowman, P. N., Malpas, J. S. 1991; 9 (3): 528-529
  • DIFFUSE SMALL NONCLEAVED CELL LYMPHOMA IN CHILDREN, BURKITT VERSUS NON-BURKITT TYPES - RESULTS FROM THE PEDIATRIC ONCOLOGY GROUP AND ST-JUDE-CHILDRENS-RESEARCH-HOSPITAL CANCER Hutchison, R. E., Murphy, S. B., Fairclough, D. L., Shuster, J. J., Sullivan, M. P., Link, M. P., Donaldson, S. S., Berard, C. W. 1989; 64 (1): 23-27

    Abstract

    The clinical relevance of a morphologic distinction between Burkitt's (B) and non-Burkitt's (NB) types of small non-cleaved cell (SNC) non-Hodgkin's lymphoma (NHL) has been controversial. Numerous attempts to discern an important clinical difference between the subtypes have failed to provide a convincing reason to maintain this distinction for other than descriptive purposes. Because of conflicting reports in the literature, the authors have analyzed 183 cases of SNC NHL in children from the Pediatric Oncology Group and 129 from St. Jude Children's Research Hospital (Memphis, TN). The results from both series, which consist of approximately the same proportions of B and NB subtypes, (i.e., approximately 54%-58% B, 36% NB, and 6%-10% not otherwise specified) show no significant differences in age at presentation, extent of disease, primary site of involvement, or survival. The authors conclude that the morphologic distinction between B and NB types of SNC NHL in children lacks demonstrable clinical importance.

    View details for Web of Science ID A1989AB56100004

    View details for PubMedID 2731117

  • HYPERCALCEMIA AND VITAMIN-D METABOLISM IN HODGKINS-DISEASE - IS THERE AN UNDERLYING IMMUNOREGULATORY RELATIONSHIP CANCER Rieke, J. W., Donaldson, S. S., Horning, S. J. 1989; 63 (9): 1700-1707

    Abstract

    Hypercalcemia is not common in Hodgkin's disease, but in reported cases is often unassociated with bone involvement. A case is presented demonstrating a mechanism involving elevated levels of 1,25-dihydroxy vitamin D3 (calcitriol). Similar cases in the literature are reviewed. Data implicating calcitriol as a hematolymphoid regulatory hormone are discussed as they may relate to lymphomas, leukemias, and paraneoplastic lymphocyte and monocyte/macrophage activity.

    View details for Web of Science ID A1989U165800009

    View details for PubMedID 2649225

  • SUPERVOLTAGE ORBITAL RADIOTHERAPY FOR PROGRESSIVE GRAVES OPHTHALMOPATHY - RESULTS OF A 20-YEAR EXPERIENCE ACTA ENDOCRINOLOGICA KRISS, J. P., Petersen, I. A., Donaldson, S. S., McDougall, I. R. 1989; 121: 154-159
  • LANGERHANS CELL HISTIOCYTOSIS OF THE HEAD AND NECK LARYNGOSCOPE ANONSEN, C. K., Donaldson, S. S. 1987; 97 (5): 537-542

    Abstract

    Langerhans' cell histiocytosis has been accepted by many to replace the term Histiocytosis X, describing a poorly defined continuum of diseases involving neoplastic proliferation of histiocytes. Twenty-four cases of histologically confirmed Langerhans' cell histiocytosis with head and neck involvement were seen between the years 1970 to 1986, and charts were reviewed retrospectively. Control of local osseous disease was successful using radiation therapy in 100% of those cases with follow-up. Surgical curettage of bone lesions was successful in a small number of cases. Chemotherapy alone or in combination with radiation appeared to enhance survival in patients with recurrent disease or multisystem involvement. Sixteen of the 24 patients (67%) are disease free with a mean follow-up of 6 years. Prompt diagnosis and careful follow-up are important to improve survival and prevent complications.

    View details for Web of Science ID A1987H246800002

    View details for PubMedID 3494895

  • COMBINED MODALITY TREATMENT WITH LOW-DOSE RADIATION AND MOPP CHEMOTHERAPY FOR CHILDREN WITH HODGKINS-DISEASE JOURNAL OF CLINICAL ONCOLOGY Donaldson, S. S., Link, M. P. 1987; 5 (5): 742-749

    Abstract

    High doses of radiation administered to children with Hodgkin's disease may be associated with long-term alterations in soft tissue and bone growth. In an attempt to minimize this complication, we initiated a protocol using low doses of radiation in conjunction with six cycles of MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) chemotherapy in newly diagnosed, pathologically staged children with Hodgkin's disease. Of 55 children treated in this fashion, the actuarial survival and freedom from relapse rates are 89% and 90%, respectively, with median follow-up of 7 1/2 years and maximum follow-up of 15 1/2 years. The local control rate is 97%. The previously encountered growth alteration did not occur when lower doses of radiation were used. However, three children developed acute leukemia. This study demonstrates that the vast majority of children with Hodgkin's disease can be cured with combined modality therapy. This experience provides long-term follow-up and thus serves as the basis for new ongoing protocols using low-dose involved field radiation with new drug combinations.

    View details for Web of Science ID A1987H206400011

    View details for PubMedID 3572464

  • RHABDOMYOSARCOMA - THE STANFORD EXPERIENCE USING A TNM STAGING SYSTEM JOURNAL OF CLINICAL ONCOLOGY PEDRICK, T. J., Donaldson, S. S., Cox, R. S. 1986; 4 (3): 370-378

    Abstract

    Seventy-four patients with rhabdomyosarcoma were initially staged according to the Intergroup Rhabdomyosarcoma Study (IRS) grouping classification and then retrospectively using a TNM staging system based on the initial clinical extent of disease. The TNM system includes T1, tumor confined to site or organ of origin; T2, regional extension beyond the site of origin; N0, normal lymph nodes; N1, lymph nodes containing tumor; M0, no evidence of metastases; and M1, distant metastases. All patients received combination chemotherapy, and more than 90% received radiation therapy as part of their initial treatment program with curative intent. Fifty-three of 74 patients (72%) were group III according to the IRS system, indicating unresectable or gross residual tumor. A more uniform distribution was achieved using the TNM system. Freedom from relapse (FFR) was 43% and the actuarial survival rate was 47% for the entire study group at 10 years. All but one relapse occurred within 3 years of initial diagnosis, and only three of 38 relapsed patients were salvaged. All TNM stage I patients are surviving disease free. Among patients having stages II, III, and IV disease by the TNM system, FFR was 53%, 26%, and 11%, and the survival rates were 47%, 36%, and 33%, respectively. Thirty-two of 74 patients (43%) had evidence of lymph node involvement at presentation, and 28 (88%) of these had primary lesions that extended beyond the site of origin (T2 primary). Histologic subtype and primary site had little impact on outcome in a multivariate analysis, and T stage was identified as the single most significant covariate correlated with survival; a model composed of both T stage and M stage was the best one for predicting relapse. The presented data support a study using a prospectively assigned TNM staging system based on the initial clinical extent of disease for use in future therapeutic trials.

    View details for Web of Science ID A1986A378100013

    View details for PubMedID 3950676

  • TOPOGRAPHY OF CHILDHOOD TUMORS - PEDIATRIC CODING SYSTEM PEDIATRIC HEMATOLOGY AND ONCOLOGY Donaldson, S. S., Draper, G. J., Flamant, F., GERARDMARCHANT, R., Mouriesse, H., Newton, W. A., Lemerle, J. 1986; 3 (3): 249-258

    Abstract

    The importance of a uniform coding system for cancer research, tumor registry, and exchange of information is recognized. However, tumors arising in children differ from those in adults, resulting in lack of precision when one coding system is used for both. Because the topographic code of the International Classification of Disease for Oncology for adult tumors does not lend itself well to pediatric tumors, the International Society of Paediatric Oncology (SIOP) developed a four-digit topographic coding system particularly adapted to childhood tumors. The four digits correspond to anatomic site, general and specific localization, and tissue of origin. An SIOP pilot study demonstrated the usefulness of this code.

    View details for Web of Science ID A1986F094100007

    View details for PubMedID 3153237

  • NEUROOCULAR DAMAGE IN PEDIATRIC ONCOLOGY PATIENTS - PREDICTOR OF LONG-TERM VISUAL DISABILITY OR TOOL FOR LIMITING TOXICITY MEDICAL AND PEDIATRIC ONCOLOGY Newman, N. M., Donaldson, S., Dewit, S., King, O., Wilbur, J. R. 1986; 14 (5): 262-270

    Abstract

    We present a group of eight pediatric cancer patients with a spectrum of visual afferent pathway abnormalities. Changes include decreased visual acuity, visual field alterations, abnormal visual evoked potentials, changes in the optic disc and nerve fiber layer of the retina, radiation retinopathy, and CNS injury. These changes occur in long term survivors of pediatric malignancy (especially those with prolonged, multimodal, and multicourse therapy), but they may be minimally symptomatic. The changes appear to be analogous to the CNS changes (leukoencephalopathy) described in patients with leukemia and attributed to multimodal therapy. By taking advantage of opportunities to detect adverse effects earlier in the treatment course, the present excellent cure rate may be improved by refinements in therapy that also improve the quality of survival.

    View details for Web of Science ID A1986F211000004

    View details for PubMedID 3784980

  • VONWILLEBRAND-FACTOR LEVELS DO NOT PREDICT OR DIAGNOSE RADIATION PNEUMONITIS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Fajardo, L. F., Donaldson, S. S., KELLY, N. I. 1986; 12 (1): 107-110

    Abstract

    In search for an index of endothelial injury that would provide an early diagnosis of radiation pneumonitis, we investigated the plasma levels of von Willebrand Factor (Factor VIII Related Antigen, FVIII:RAg) in 14 patients undergoing pulmonary irradiation. This study was based on observations indicating that damage to the endothelium-rich pulmonary parenchyma may produce alterations in the synthesis, storage or release of FVIII:RAg, detectable in plasma. There was no correlation between FVIII:RAg levels and radiation pneumonitis, radiation dose, volume of irradiated lung, tumor burden, or time-interval between exposure and sampling. The heterogeneity of the neoplasms and the inconstant effects of radiation in the tumor vasculature are among several variables that may explain this lack of correlation. The plasma levels of FVIII:RAg cannot be used to diagnose or predict radiation pneumonitis.

    View details for Web of Science ID A1986AYV1700017

    View details for PubMedID 3484736

  • RADIOTHERAPY OF LYMPHOID DISEASES OF THE ORBIT INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS AUSTINSEYMOUR, M. M., Donaldson, S. S., Egbert, P. R., McDougall, I. R., KRISS, J. P. 1985; 11 (2): 371-379

    Abstract

    Thirty-two patients with orbital pseudotumor (18), reactive lymphoid hyperplasia (2), atypical lymphoid infiltrate (4) or malignant lymphoma (8) were treated in the Division of Radiation Therapy at Stanford University between January 1973 and May 1983. Of the 20 patients with pseudotumor or reactive lymphoid hyperplasia, 10 had unilateral lesions and 10 had bilateral lesions. Biopsy samples were obtained in 15 patients; in five patients with bilateral disease the diagnosis was made on the basis of computed tomography (CT) and clinical findings. The majority of patients were referred because of disease refractory to treatment with corticosteroids. The patients were given a mean dose of 2360 rad using complex, individualized megavoltage techniques including lens shielding. Radiotherapy was well tolerated with no significant acute or late complications. Fifteen patients had complete resolution of symptoms after treatment; five had continued symptoms. Of the 12 patients with malignant lymphoma or atypical lymphoid infiltrate, four had systemic lymphoma with orbital involvement and eight had orbital involvement only. The diagnosis was made by biopsy in all patients and immunophenotyping was done in six cases, of which 5 were monoclonal. Patients were evaluated with a chest radiograph, lymphogram or abdominal CT, bone marrow biopsy and orbital CT. A mean dose of 3625 rad was delivered to the orbit only. Most of the patients received complex megavoltage treatment using bolus. All patients in this group had a complete response and local control. There were no relapses in those with localized disease. Two patients developed cataracts. Carefully planned orbital radiotherapy provides local control without symptomatic sequelae for orbital masses ranging from pseudotumor to malignant lymphoma.

    View details for Web of Science ID A1985ACJ5900020

    View details for PubMedID 3918966

  • NEURO-BLASTOMA IN INFANTS - WHEN IS THERAPY NECESSARY Amylon, M. D., Link, M. P., Perrine, S. P., Shochat, S. J., Donaldson, S. S., Glader, B. E. INT PEDIATRIC RESEARCH FOUNDATION, INC. 1985: A257-A257
  • LATE RELAPSE AMONG PATIENTS TREATED FOR HODGKINS-DISEASE ANNALS OF INTERNAL MEDICINE Herman, T. S., Hoppe, R. T., Donaldson, S. S., Cox, R. S., Rosenberg, S. A., KAPLAN, H. S. 1985; 102 (3): 292-297

    Abstract

    Of 1360 consecutive patients with Hodgkin's disease treated at Stanford University, 1312 patients (96%) had complete remission, but 424 patients had a relapse. Fifty-five patients had relapses 36 months or more after completion of therapy. The actuarial risk of relapse in patients disease-free 3 years after therapy was 12.9%. The occurrence of late relapse was significantly related to stage I disease and nodular sclerosis histologic subtype. Late relapse was detected in 88% of patients by history, physical findings, or chest radiographs. Most patients with stage III and IV disease had late relapses in previously irradiated nodes or extranodally, but patients with stage I and II disease had late relapses primarily in unirradiated nodes. Disease-free survival after salvage therapy for late relapse was similar to that seen after treatment of earlier relapse. Prolonged surveillance of patients for late relapse is necessary after treatment of patients with Hodgkin's disease.

    View details for Web of Science ID A1985ACZ2400002

    View details for PubMedID 3970468

  • INTRA-ARTERIAL INFUSION OF RADIOSENSITIZER (BUDR) COMBINED WITH HYPOFRACTIONATED IRRADIATION AND CHEMOTHERAPY FOR PRIMARY-TREATMENT OF OSTEOGENIC-SARCOMA INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Martinez, A., Goffinet, D. R., Donaldson, S. S., Bagshaw, M. A., KAPLAN, H. S. 1985; 11 (1): 123-128

    Abstract

    Combined modality treatment was given in nine patients of osteogenic sarcoma wherein the tumor was unresectable because of location or amputation was refused. This alternative to massive surgery comprised hypofractionated irradiation, intra-arterial infusion of the radiosensitizer 5'-bromodeoxyuridine (BUdR) and adjuvant systemic chemotherapy. Local control was achieved in seven of the nine patients. Four survived, all without evidence of disease at 6, 7.1, 8.8, and 10.5 years after completion of irradiation. Pulmonary metastases developed in six patients--of whom one survives, following high-dose pulmonary irradiation and additional chemotherapy. Significant soft-tissue injury occurred in five patients. On the basis of our experience, we believe that new approaches using modifications of external beam irradiation with different fractionation schedules or better radiosensitizing compounds may hold promise for patients with non-resectable osteosarcoma.

    View details for Web of Science ID A1985ABW5500015

    View details for PubMedID 3855408

  • ACUTE NONLYMPHOCYTIC LEUKEMIA DEVELOPING DURING THE COURSE OF EWINGS-SARCOMA MEDICAL AND PEDIATRIC ONCOLOGY Link, M. P., Donaldson, S. S., Kempson, R. L., Wilbur, J. R., Glader, B. E. 1984; 12 (3): 194-200

    Abstract

    Two children with Ewing's sarcoma developed acute nonlymphocytic leukemia (ANLL) during the course of their illness. One patient developed ANLL after apparently successful treatment of his primary malignancy with radiation therapy and multiagent chemotherapy. In the second patient, acute leukemia developed before the administration of radiotherapy or systemic chemotherapy. The development of secondary ANLL after Ewing's sarcoma has been reported only twice previously, most likely representing a therapy-induced complication. The occurrence of ANLL in Patient 2 prior to therapy suggests that these two disorders may have a more than treatment-related association. Close follow-up of long-term survivors of Ewing's sarcoma with surveillance for secondary acute leukemia is advised.

    View details for Web of Science ID A1984SW62300009

    View details for PubMedID 6727775

  • CHILDHOOD HODGKINS-DISEASE - PATTERNS OF RELAPSE JOURNAL OF CLINICAL ONCOLOGY Russell, K. J., Donaldson, S. S., Cox, R. S., KAPLAN, H. S. 1984; 2 (2): 80-87

    Abstract

    One hundred seventy-nine consecutive children with Hodgkin's disease seen at Stanford University Medical Center between the years 1961-1980 have been analyzed for survival and freedom-from-relapse as a function of clinical versus laparotomy staging as well as primary treatment modalities. Of laparotomy-staged patients, 86% are alive at 10 years after primary radiation with chemotherapy reserved for relapse, as compared with 90% managed by planned combined modality therapy (p = 0.62). Patients who were clinically staged and managed with primary radiation have only a 69% survival (p = 0.05). A favorable subgroup of patients with lymphocyte-predominant Hodgkin's disease experienced a low relapse rate regardless of primary treatment modality. Patterns of relapse in clinically staged patients reflect understaging, with most relapses in distant, nonirradiated sites, whereas the less frequent relapses in laparotomy-staged patients usually reflect regional recurrence. It is concluded that laparotomy staging is highly desirable to allow greatest flexibility in optimizing individual therapy. Routine combined modality treatment for all patients would overtreat certain favorable subgroups, who can be managed more conservatively as long as the information derived from surgical staging is available. For young children, in whom bone growth issues are paramount, combined modality treatment using low-dose radiation is recommended. For older children and adolescents, where concerns over chemotherapy-related leukemogenesis and infertility are more important than height considerations, radiation alone may be used for stages I-IIIA with equal overall success.

    View details for Web of Science ID A1984SC82600003

    View details for PubMedID 6699666

  • PROTECTION FROM RADIATION NEPHROPATHY BY WR-2721 RADIATION RESEARCH Donaldson, S. S., MOSKOWITZ, P. S., Evans, J. W., Fajardo, L. F. 1984; 97 (2): 414-423

    Abstract

    The efficacy of WR-2721 pretreatment against radiation injury to the growing kidney was evaluated in the weanling mouse. Immediately following unilateral nephrectomy, animals received intraperitoneal injections of saline or WR-2721 (220 mg/kg). Thirty minutes later both nonprotected (saline-treated) control animals and protected (WR-2721-treated) animals received 1000-rad single-fraction radiation to the remaining kidney. Other animals received WR-2721 immediately following unilateral nephrectomy but no radiation. Animals were sacrificed at 3 and 24 weeks. Nonirradiated animals treated with WR-2721 only showed normal compensatory renal growth, body growth, and renal function at 24 weeks. The nonprotected, irradiated animals exhibited renal growth inhibition without body growth inhibition, and renal functional abnormalities including elevation of serum BUN and reduction of glomerular filtration rate. Pretreatment with WR-2721 prior to 1000 rad prevented the renal growth inhibition and functional abnormalities seen in the nonprotected irradiated animals. Within the observation period there were no differences in renal morphology by light and electron microscopy between protected and nonprotected groups; only mild glomerular and tubular abnormalities compatible with radiation injury were seen. WR-2721 can modulate renal radiation injury; however, the growth and functional protection is not well correlated with specific histologic change. The dose reduction factor for WR-2721 renal growth protection is between 1.16 and 1.2. WR-2721 may have future clinical utility by increasing radiation tolerance of the kidney.

    View details for Web of Science ID A1984SD80900019

    View details for PubMedID 6320252

  • NUTRITIONAL SUPPORT AS AN ADJUNCT TO RADIATION-THERAPY JOURNAL OF PARENTERAL AND ENTERAL NUTRITION Donaldson, S. S. 1984; 8 (3): 302-310

    Abstract

    Patients with malignancies which are treated with therapeutic radiation are at risk for nutritional problems, both from their underlying malignancy as well as from their treatment. These effects may be acute or chronic and relate to the site of the tumor and regions irradiated. There is a large experience with nutritional intervention in irradiated patients, including oral feedings and enteral and parenteral nutritional support. The indications for the specific administration of nutritional support during radiotherapy depend on the nutritional status of the patient and the area irradiated, as well as the individual prognosis. Patients who are malnourished at the time of treatment are most likely to profit from nutritional intervention. To date, prospective randomized trials of nutritional support in patients undergoing radiotherapy fail to show a benefit of routine adjuvant nutritional intervention in terms of improved response and tolerance to treatment, improved local control or survival rates, or reduction of complications from therapy.

    View details for Web of Science ID A1984SS25400016

    View details for PubMedID 6429369

  • THYROID-DYSFUNCTION AFTER RADIOTHERAPY IN CHILDREN WITH HODGKINS-DISEASE CANCER Constine, L. S., Donaldson, S. S., McDougall, I. R., Cox, R. S., Link, M. P., KAPLAN, H. S. 1984; 53 (4): 878-883

    Abstract

    Thyroid function was measured in 119 children, 16 years of age or less, after radiotherapy (XRT) for Hodgkin's disease. Thyroid abnormalities developed in 4 of 24 children (17%) who received 2600 rad or less, and in 74 of 95 children (78%) who received greater than 2600 rad to the cervical area, including the thyroid. The abnormality in all but three (one with hyperthyroidism and two with thyroid nodules) included the development of elevated levels of thyroid stimulating hormone (TSH). Age, sex, and administration of chemotherapy were not significant factors in the development of thyroid dysfunction. All children had lymphangiograms (LAG) and no time relationship was noted between thyroid dysfunction and LAG-XRT interval. The mean interval from radiotherapy to documented thyroid dysfunction was 18 months in the low-dose group and 31 months in the high-dose group, with most patients becoming abnormal within 3 to 5 years. Of interest was a spontaneous return of TSH to within normal limits in 20 children and substantial improvement in another 7. This study confirms the occurrence of dose-related occult hypothyroidism in children following external irradiation of the neck.

    View details for Web of Science ID A1984SB64800010

    View details for PubMedID 6692289

  • CRANIAL NERVE INVOLVEMENT IN CHILDREN WITH LEUKEMIA AND LYMPHOMA JOURNAL OF CLINICAL ONCOLOGY PARYANI, S. B., Donaldson, S. S., Amylon, M. D., Link, M. P. 1983; 1 (9): 542-545

    Abstract

    Between 1965 and 1982, 52 children with acute lymphoblastic leukemia or non-Hodgkin's lymphoma were found to have central nervous system involvement of their disease. Of this group, 20 developed clinically apparent cranial nerve paresis or palsy. The cranial nerve most frequently affected was No. VII. With therapy, 16 of the patients had objective control of their central nervous system disease. Among these 16 patients, cranial nerve palsies resolved completely in 14, and only two children were left with residual cranial nerve dysfunction. Seven patients received intrathecal chemotherapy before radiation therapy was instituted in an attempt to control their cranial nerve palsies. Cranial nerve palsy resolved in only two of these seven patients. However, the addition of whole-brain irradiation in the remaining five patients reversed cranial nerve dysfunction in four of them. The combination of intrathecal chemotherapy and central nervous system irradiation was successful in reversing cranial nerve dysfunction in 11 of 13 patients in whom central nervous system disease was ultimately controlled. As cranial nerve dysfunction is associated with distressing signs and symptoms, the combination of central nervous system irradiation and intrathecal chemotherapy is important palliative therapy to initiate promptly. Intrathecal therapy alone appears to be inadequate therapy for prompt and durable reversal of symptoms in this group of patients.

    View details for Web of Science ID A1983RK55800005

    View details for PubMedID 6583324

  • PREGNANCY AND HODGKINS-DISEASE ANNALS OF INTERNAL MEDICINE Jacobs, C., Donaldson, S. S., Rosenberg, S. A., KAPLAN, H. S. 1982; 96 (4): 532-532
  • HODGKINS-DISEASE AND THE PREGNANT PATIENT - RESPONSE ANNALS OF INTERNAL MEDICINE Jacobs, C., Donaldson, S. S., Rosenberg, S. A., KAPLAN, H. S. 1982; 96 (5): 682-682
  • HODGKINS-DISEASE - TREATMENT WITH LOW-DOSE RADIATION AND CHEMOTHERAPY FRONTIERS OF RADIATION THERAPY AND ONCOLOGY Donaldson, S. S. 1982; 16: 122-133
  • EFFECTS OF THERAPY ON NUTRITIONAL-STATUS OF THE PEDIATRIC CANCER-PATIENT CANCER RESEARCH Donaldson, S. S. 1982; 42 (2): S729-S736
  • COMPLICATIONS OF TREATMENT OF HODGKINS-DISEASE IN CHILDREN CANCER TREATMENT REPORTS Donaldson, S. S., KAPLAN, H. S. 1982; 66 (4): 977-989

    Abstract

    An analysis of complications of therapy requires long-term and frequent followup. Reported here is a review of 179 consecutive children with Hodgkin's disease from Stanford University Medical Center who were seen, treated, and followed over a 20-year period. Complications of treatment are related to the extent of disease and the aggressiveness of therapy. Severe complications from radiotherapy are associated with high-dose, extended-field treatment in preadolescent children. Severe chemotherapy-associated complications include immunosuppression, sterility, and secondary oncogenesis. As cure rates are increasingly optimistic among children with Hodgkin's disease, successful treatment with minimal morbidity remains our greatest challenge. Therapy programs require continual refinement utilizing assessment of short- and long-term side effects of treatment.

    View details for Web of Science ID A1982NQ55100042

    View details for PubMedID 7074658

  • EFFECT OF NUTRITIONAL-STATUS ON RESPONSE TO THERAPY CANCER RESEARCH Donaldson, S. S. 1982; 42 (2): S754-S755
  • THE CLINICAL SPECTRUM OF RADIATION-CHEMOTHERAPY NEPHROPATHY IN CHILDREN WITH WILMS TUMOR MOSKOWITZ, P. S., Donaldson, S. S. SPRINGER VERLAG. 1981: 171-171
  • PROTECTION AGAINST RADIATION NEPHROPATHY BY WR-2721 IN THE GROWING-MOUSE KIDNEY MOSKOWITZ, P. S., Donaldson, S. S., Fajardo, L. F. SLACK INC. 1981: A137-A137
  • MANAGEMENT OF THE PREGNANT PATIENT WITH HODGKINS-DISEASE ANNALS OF INTERNAL MEDICINE Jacobs, C., Donaldson, S. S., Rosenberg, S. A., KAPLAN, H. S. 1981; 95 (6): 669-675

    Abstract

    Fifteen pregnant women with Hodgkin's disease were followed. Five patients had irradiation, 1000 to 3000 rad to the neck, mediastinum, or both, during the second or third trimester with normal outcome of pregnancy. One patient had a spontaneous abortion in the first trimester after radiotherapy of 4400 rad to the breast, an estimated fetal dose of 9 rad. One patient who received chlorambucil throughout pregnancy delivered a normal infant. Six patients had therapeutic abortions; one had early induction of labor. In one patient previously treated for supradiaphragmatic Hodgkin's disease, detection of a supradiaphragmatic relapse was delayed because of pregnancy. We recommend abortion for patients who develop Hodgkin's disease early in pregnancy or who have received chemotherapy or irradiation during the first trimester. During the latter half of pregnancy, asymptomatic disease may be closely followed but early delivery is recommended. Supradiaphragmatic, symptomatic disease can be treated with modified irradiation. For subdiaphragmatic, symptomatic, or extranodal disease, single-agent chemotherapy may be preferable. Treatment requires individualization to insure that the patient will be cured and the fetus protected.

    View details for Web of Science ID A1981MT14300001

    View details for PubMedID 7305142

  • RADIATION NEPHROPATHY- -PROTECTION BY WR-2721 IN THE GROWING-MOUSE KIDNEY Donaldson, S. S., MOSKOWITZ, P. S., Fajardo, L. F. PERGAMON-ELSEVIER SCIENCE LTD. 1981: 1271-1272
  • RESPONSE TO PNEUMOCOCCAL VACCINE AMONG CHILDREN WITH HODGKINS-DISEASE REVIEWS OF INFECTIOUS DISEASES Donaldson, S. S., Vosti, K. L., Berberich, F. R., Cox, R. S., KAPLAN, H. S., SCHIFFMAN, G. 1981; 3: S133-S143

    Abstract

    Nineteen children with Hodgkin's disease were immuized with dodecavalent pneumococcal vaccine; the efficacy of vaccination, the duration of response, and the significance of the time of immunization in relation to splenectomy and subsequent irradiation and chemotherapy were investigated. Eight children were immunized before splenectomy, and 11 were immunized after splenectomy, irradiation, and chemotherapy. All children were irradiated, and all but two received chemotherapy with MOPP (nitrogen mustard, vincristine sulfate, procarbazine, and prednisone). Sera were assayed for antibodies to the 12 polysaccharide types in the vaccine. The group of children immunized before splenectomy had a significant antibody response to 67% of the antigens tested, whereas the group immunized after splenectomy responded to 40% of the antigens (P less than 0.0001). The duration of response was variable. Pneumococcal vaccine was more likely to provoke an immunologic response if administered before splenectomy than if administered after splenectomy, irradiation, and chemotherapy; however, the response was not uniform. A response to one antigen did not necessarily imply a response to other antigens. In the absence of a readily available assay to determine a protective antibody response, one cannot rely on the vaccine as the sole means of preventing pneumococcal infections in asplenic children with Hodgkin's disease.

    View details for Web of Science ID A1981MA01000014

    View details for PubMedID 6895119

  • THE CLINICAL SPECTRUM OF RADIATION-CHEMOTHERAPY NEPHROPATHY IN CHILDREN WITH WILMS TUMOR MOSKOWITZ, P. S., Donaldson, S. S. AMER ROENTGEN RAY SOC. 1981: 445-445
  • RADIATION-DOSE MODIFICATION BY CHEMOTHERAPY IN THE GROWING-MOUSE KIDNEY MOSKOWITZ, P. S., Donaldson, S. S., Fajardo, L. F. AMER ASSOC CANCER RESEARCH. 1981: 63-63
  • John Caffey Award: chemotherapy-induced inhibition of compensatory renal growth in the immature mouse. AJR. American journal of roentgenology MOSKOWITZ, P. S., Donaldson, S. S., CANTY, E. 1980; 134 (3): 491-496

    Abstract

    Minimal-lethal-doses (LD1/21) of Actinomycin-D (AMD), Vincristine (VCR), or Adriamycin (ADR) inhibited compensatory renal growth in unilaterally nephrectomized weanling mice. AMD transiently inhibited compensatory renal and body growth. VCR transiently inhibited kidney growth only, while ADR produced persistent kidney and body growth inhibition. 3H thymidine uptake was decreased at 5 days from controls with AMD and ADR, and increased at 14 days from controls with ADM, VCR, and ADR. Kidney DNA concentration was increased from controls at 3 days with AMD and at 8 and 14 days with ADR, but decreased from controls of 8 days with AMD and VCR. AMD and ADR inhibit compensatory renal growth and body growth in the immature mouse. VCR selectively inhibits renal growth. Renal growth inhibition with AMD, VCR, and ADR is related, in part, to a delay in the renal mitotic response to contralateral nephrectomy, and with AMD and ADR to generalized body growth supression. Chemotherapy injury to the growing mammalian kidney may be manifest as growth inhibition.

    View details for PubMedID 6766611

  • CHEMOTHERAPY-INDUCED INHIBITION OF COMPENSATORY RENAL GROWTH IN THE IMMATURE MOUSE AMERICAN JOURNAL OF ROENTGENOLOGY MOSKOWITZ, P. S., Donaldson, S. S., CANTY, E. 1980; 134 (3): 491-496
  • POSTERIOR OCULAR ABNORMALITIES AFTER IRRADIATION FOR RETINOBLASTOMA - A HISTOPATHOLOGICAL STUDY BRITISH JOURNAL OF OPHTHALMOLOGY Egbert, P. R., Fajardo, L. F., Donaldson, S. S., MOAZED, K. 1980; 64 (9): 660-665

    Abstract

    Radiation-induced ocular lesions in the posterior eye and orbit were investigated in 33 surgical specimens of patients with retinoblastoma. The eyes were obtained from children 7 months to 6 years of age. Seventeen eyes were irradiated; 16 eyes had not received irradiation and served as controls. The majority of the irradiated eyes were treated with 6000 rads of external beam radiation. They were removed at a mean of 23 months after radiotherapy. All specimens were examined simultaneously by 2 observers without knowledge of treatment and analysed for the presence or absence of 15 lesions. The most consistent lesions in the irradiated eyes were abnormalities of the retinal vessels (11 of 17 eyes) and striking changes in the ciliary arteries (13 of 17 eyes). The retinal vessels showed thickening of the wall, often caused by deposition of fibrillary material, sometimes with fibrin deposits. The most consistent lesion was myointimal proliferation with narrowing of the ciliary arteries. Lesions of the central retinal artery were less common but occurred only in irradiated patients.

    View details for Web of Science ID A1980KL85500004

    View details for PubMedID 7426587

  • COMBINATION RADIATION-ADRIAMYCIN THERAPY - RENOPRIVAL GROWTH, FUNCTIONAL AND STRUCTURAL EFFECTS IN THE IMMATURE MOUSE INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Donaldson, S. S., MOSKOWITZ, P. S., CANTY, E. L., Fajardo, L. F. 1980; 6 (7): 851-859

    View details for Web of Science ID A1980KA92600010

    View details for PubMedID 7204121

  • GROWTH, FUNCTIONAL AND STRUCTURAL EFFECTS OF ACTINOMYCIN-D, VINCRISTINE, ADRIAMYCIN AND RADIATION IN THE IMMATURE MOUSE KIDNEY MOSKOWITZ, P. S., Donaldson, S. S., Fajardo, L. F. LIPPINCOTT-RAVEN PUBL. 1980: 420-420
  • COMBINED RADIATION-CHEMOTHERAPY EFFECTS IN THE IMMATURE MOUSE KIDNEY Donaldson, S. S., MOSKOWITZ, P. S., Fajardo, L. F. RADIATION RESEARCH SOC. 1980: 421-421
  • CHEMOTHERAPY-INDUCED INHIBITION OF COMPENSATORY RENAL GROWTH IN THE IMMATURE MOUSE MOSKOWITZ, P. S., Donaldson, S. S. AMER ROENTGEN RAY SOC. 1979: 306-306
  • APPEARANCE OF GRAVES-DISEASE ON ORBITAL COMPUTED-TOMOGRAPHY JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY Enzmann, D. R., Donaldson, S. S., KRISS, J. P. 1979; 3 (6): 815-819

    Abstract

    Extraocular muscle enlargement was symmetrical in 70% and asymmetrical in 30% of patients with Graves' ophthalmopathy. True unilateral muscle involvement occurred in 6%. Computed tomography (CT) showed bilateral orbital involvement in 50% of patients presenting clinically with unilateral eye signs. In patients without a clinically apparent ophthalmopathy, CT demonstrated muscle enlargement in 40%. The medial and inferior rectus muscles were the most frequently and most severely involved. Orbital radiation therapy can result in a decrease in size of involved muscles.

    View details for Web of Science ID A1979HT47600018

    View details for PubMedID 583152

  • CURRENT CONCEPTS IN CANCER - EFFECTS OF CANCER AND CANCER-TREATMENT ON THE NUTRITION OF THE HOST NEW ENGLAND JOURNAL OF MEDICINE Costa, G., Donaldson, S. S. 1979; 300 (26): 1471-1474

    View details for Web of Science ID A1979HA22300006

    View details for PubMedID 377071

  • CHEMOTHERAPY-INDUCED INHIBITION OF COMPENSATORY RENAL GROWTH IN IMMATURE MOUSE MOSKOWITZ, P. S., Donaldson, S. S. LIPPINCOTT-RAVEN PUBL. 1978: 384-384
  • BACTERIAL-INFECTIONS IN PEDIATRIC HODGKIN DISEASE - RELATIONSHIP TO RADIOTHERAPY, CHEMOTHERAPY AND SPLENECTOMY CANCER Donaldson, S. S., Glatstein, E., Vosti, K. L. 1978; 41 (5): 1949-1958

    Abstract

    The occurrence of bacterial infections (B.I.) among 181 children with Hodgkin's disease (121 with splenectomy, 60 without splenectomy) was analyzed. Twenty-seven B.I. occurred among 22 children and included 15 episodes of bacteremia-meningitis in 14 children. B.I. occurred in all age groups, but bacteremia-meningitis occurred most commonly in splenectomized children 10 years of age or less. The frequency of B.I. in splenectomized children receiving radiotherapy was 1.4%, compared to 18.3% among those receiving chemotherapy (p less than 0.05); the frequency of B.I. among non-splenectomized children receiving radiotherapy was 2.8%, compared to 23.1% among those receiving chemotherapy (p less than 0.05). There was no difference in the probability of B.I. as a function of splenectomy for the corresponding groups, although all cases of Streptococcus pneumoniae and Hemophilus influenzae bacteremia-meningitis in splenectomized children. Overwhelming postsplenectomy bacteremia infection not related to active disease or treatment occurred in 3/121 (2.5%) children, accounting for only one fatality (0.8%).

    View details for Web of Science ID A1978EY41000039

    View details for PubMedID 306282

  • HERPES-ZOSTER AND VARICELLA INFECTIONS IN CHILDREN WITH HODGKINS-DISEASE - ANALYSIS OF CONTRIBUTING FACTORS CANCER Reboul, F., Donaldson, S. S., KAPLAN, H. S. 1978; 41 (1): 95-99

    Abstract

    181 children with Hodgkin's disease were analyzed with respect to the occurrence of herpes zoster and varicella (HZ-V) infections, possible contributing factors, and prognostic significance. The overall frequency of HZ-V was 34.8%. The occurrence in stage I was significantly lower than in other stages. Previous splenectomy was not found to increase significantly the risk of infection. High-risk patients were those receiving extensive radiotherapy plus combination chemotherapy; 56% developed HZ-V infections in this group. The frequency with extensive field radiotherapy alone was 23.8%. 80% of infections occurred during the first year after completion of treatment. Their occurrence was not a poor prognostic sign in terms of relapse or fatality, even when occurring late. The high frequency of disseminated infection (27%) with its subsequent morbidity should lead toward a better understanding of the immunologic deficiencies in these patients and the possible role of prophylactic measures, in patients undergoing extensive radiotherapy in combination with multiagent chemotherapy.

    View details for Web of Science ID A1978EK24400014

    View details for PubMedID 626945

  • VISUAL RESULTS AND OCULAR COMPLICATIONS FOLLOWING RADIOTHERAPY FOR RETINOBLASTOMA ARCHIVES OF OPHTHALMOLOGY Egbert, P. R., Donaldson, S. S., MOAZED, K., Rosenthal, A. R. 1978; 96 (10): 1826-1830

    Abstract

    Between 1956 and 1974, 28 children with retinoblastoma have been irradiated with the linear accelerator at the Stanford University Medical Center. Twenty-seven children (96%) have been cured of their tumor, with follow-up ranging from 2 1/2 to 21 years. In these survivors, 50 eyes were affected. Twelve were treated by primary enucleation and 38 were irradiated. Sixteen of the 38 irradiated eyes (42%) were ultimately enucleated for recurrent tumor, neovascular glaucoma, or inability to observe the tumor through opaque media. Thus, 22 (58%) irradiated eyes were saved. Of these, five eyes had visual acuity of 20/40 or better, five had 20/50 to 20/100, nine had 20/200 to hand motion, and three had light perception or no light perception. Radiation therapy can sterilize the tumor and maintain useful vision in many children with retinoblastoma.

    View details for Web of Science ID A1978FS98000008

    View details for PubMedID 697618

  • ENDODERMAL SINUS TUMOR - STANFORD EXPERIENCE AND 1ST REPORTED CASE ARISING IN VULVA CANCER Ungerleider, R. S., Donaldson, S. S., Warnke, R. A., Wilbur, J. R. 1978; 41 (4): 1627-1634

    Abstract

    A review of the histology, clinical findings and results of therapy in 9 females with endodermal sinus tumor (EST) is presented. Five patients had histologically pure EST; 4 had EST mixed with other germ cell components. The site of primary tumor was the ovary in 8 of the 9 females; the remaining patient with an extraovarian primary represents the first reported case of EST arising in the vulva. The addition of combination chemotherapy has prolonged survival over historical controls treated with surgery or surgery plus irradiation. Adjuvant chemotherapy appears warranted as treatment for occult metastatic disease; postoperative radiation therapy appears useful in providing local control of primary disease. There is a suggestion of increased sensitivity of EST to combination chemotherapy as compared to other germ cell histologies with which it is commonly admixed.

    View details for Web of Science ID A1978EV58400054

    View details for PubMedID 639017

  • ADRIAMYCIN-INDUCED INHIBITION OF COMPENSATORY RENAL GROWTH IN IMMATURE MOUSE KIDNEY MOSKOWITZ, P. S., Donaldson, S. S. AMER ASSOC CANCER RESEARCH. 1978: 210-210
  • MALIGNANT ASTROCYTOMA FOLLOWING RADIOTHERAPY OF A CRANIOPHARYNGIOMA - CASE-REPORT JOURNAL OF NEUROSURGERY SOGG, R. L., Donaldson, S. S., YORKE, C. H. 1978; 48 (4): 622-627

    Abstract

    A 9-year-old schoolgirl received 6007 rads to the suprasellar region for craniopharyngioma. Five years later, a malignant astrocytoma developed in the right temporal lobe. We cite clinical and experimental evidence to support our suspicion that the glioma may have been induced by radiation.

    View details for Web of Science ID A1978ES78300015

    View details for PubMedID 632887

  • EPITHELIOID GRANULOMAS ASSOCIATED WITH HODGKINS-DISEASE - CLINICAL CORRELATIONS IN 55 PREVIOUSLY UNTREATED PATIENTS CANCER SACKS, E. L., Donaldson, S. S., Gordon, J., Dorfman, R. F. 1978; 41 (2): 562-567

    Abstract

    Non-caseating sarcoid-like epithelioid granulomas associated with Hodgkin's disease have been found in 55 patients initially staged and treated at the Stanford University School of Medicine. These patients are compared to 553 concurrent patients not having granulomas associated with their Hodgkin's disease. Pre-treatment parameters of the two groups are presented and found not to be different. Patterns of relapse in granuloma patients are presented and no relationship between location of granulomas and subsequent relapse is found. Survival and relapse-free survival curves are significantly different in favor of the granuloma group (p = 0.005 and p = 0.03, respectively). Correlation with skin test data has been attempted using a matched control analysis and no difference is found in reaction to intradermal antigens between the two groups.

    View details for Web of Science ID A1978EQ15900024

    View details for PubMedID 630538

  • RADIATION-INDUCED INHIBITION OF COMPENSATORY RENAL GROWTH IN WEANLING MOUSE KIDNEY RADIOLOGY Donaldson, S. S., MOSKOWITZ, P. S., CANTY, E. L., Efron, B. 1978; 128 (2): 491-495

    Abstract

    Weanling mice were given 500, 1,000, 1,500, or 2,000 rads single-fraction renal irradiation immediately following unilateral nephrectomy and sacrificed 3 days or 3, 6, 12, or 24 weeks later. Inhibition of compensatory renal growth was related to both radiation dose and time following treatment; it was transient following 500 and 1,000 rads but persisted following 1,500 and 2,000 rads. Renal growth was inhibited more than body growth. These studies indicate that the weanling mouse kidney is more sensitive to radiation-induced inhibition of compensatory renal growth than adult mice or other rodents.

    View details for Web of Science ID A1978FH28200041

    View details for PubMedID 663265

  • SPECIAL SET-UP AND TREATMENT TECHNIQUES FOR RADIOTHERAPY OF PEDIATRIC MALIGNANCIES INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Martinez, A., Donaldson, S. S., Bagshaw, M. A. 1977; 2 (9-10): 1007-1016

    View details for Web of Science ID A1977EJ73300023

    View details for PubMedID 271145

  • COMBINED MODALITY THERAPY IN MALIGNANT-LYMPHOMAS CANCER TREATMENT REPORTS Glatstein, E., Donaldson, S. S., Rosenberg, S. A., KAPLAN, H. S. 1977; 61 (6): 1199-1207

    Abstract

    The treatment of patients with non-Hodgkin's lymphomas remains controversial. The Rappaport classification system has established its clinical value in distinguishing relatively favorable disease (ie, nodular or follicular lymphoma) from relatively unfavorable disease (ie, diffuse lymphoma). Despite the problems of multiple histologies in a given patient posed by the existence of composite lymphomas and by a spectrum of nodularity in a given node, no newer classification has yet proved superior to the Rappaport system. The relative roles of radiotherapy and chemotherapy are reviewed. The primary role of radiation appears to be the control of detectable disease, when adequate doses and volumes are employed. The primary role of chemotherapy appears to be the eradication of microfoci of tumor. Randomized studies of combined modality approaches have produced no definitive evidence of benefit from adjuvant chemotherapy in stage I and II disease of unfavorable histology. The addition of adjuvant radiotherapy in stage III and IV disease of unfavorable histologic types appears to produce some improvement. Aggressive treatment regimes have yet to show any significant advantage over more conservative treatment in patients with favorable histologic types of stage IV extent. This paper emphasizes the need for expert hematopathologic interpretation in every study of non-Hodgkin's lymphoma.

    View details for Web of Science ID A1977DX62400032

    View details for PubMedID 332354

  • NUTRITIONAL CONSEQUENCES OF RADIOTHERAPY CANCER RESEARCH Donaldson, S. S. 1977; 37 (7): 2407-2413

    Abstract

    Curative doses of radiotherapy, when directed to any portion of the gastrointestinal tract, may result in serious nutritional consequences from the effects of radiation on the altered function of normal tissues. Symptoms from radiotherapy resulting in nutritional alterations are usually dependent upon dose, time, and fractionation of radiation administered, and the volume included in the treatment field. These effects directly related to radiation may be enhanced by other associated cancer therapy, e.g., surgery or chemotherapy. Careful observation and prompt attention to supportive therapy are mandatory to minimize the nutritional consequences of radiation injury. Well-designed clinical trials are necessary to demonstrate any possible increased tolerance to radiation therapy and the preventative benefits of nutritional support.

    View details for Web of Science ID A1977DL37000015

    View details for PubMedID 861954

  • COMPUTED TOMOGRAPHY IN ORBITAL PSEUDOTUMOR (IDIOPATHIC ORBITAL INFLAMMATION) RADIOLOGY ENZMANN, D., Donaldson, S. S., Marshall, W. H., KRISS, J. P. 1976; 120 (3): 597-601

    Abstract

    CT scans of 9 patients with orbital pseudotumor (bilateral in 6 and unilateral in 3) showed findings distinct from those observed in Graves' ophthalmopathy. In bilateral involvement, they ranged from localized mass lesions to complete obiliteration of normal orbital CT anatomical landmarks; diffuse or multifocal lesions involving the posterior globe and muscle insertions were most typical of the diagnosis. However, findings in unilateral psedotumor may be indistinguishable from orbital mass lesions other than Graves' ophthalmopathy. Serial CT scans were used to show progression of disease and response to treatment.

    View details for Web of Science ID A1976CC61100018

    View details for PubMedID 988925

  • PEDIATRIC HODGKINS-DISEASE .2. RESULTS OF THERAPY CANCER Donaldson, S. S., Glatstein, E., Rosenberg, S. A., KAPLAN, H. S. 1976; 37 (5): 2436-2447

    Abstract

    Between 1962 and 1972, 79 previously untreated children, aged 15 years and under, with biopsy-proven Hodgkin's disease were seen, evaluated, and treated at Standford University Medical Center. The 5-year actuarial survival for all patients was 89%; relapse-free survival was 66%. No relapse was seen following aggressive treatment with irradiation and MOPP chemotherapy. In patients who were pathologically staged, no relapse was seen beyond 2 years. Patients with mixed cellularity subtype fared surprisingly well as compared to those with the nodular sclerosing subtype. An analysis of the types of treatment administered and complications of therapy suggests that the major difference between children and adults with Hodgkin's disease is the potential for long-term sequelae resulting from aggressive treatment. In an attempt to maximize the quality of survival, a proposal is made for low-dose radiation and planned MOPP chemotherapy.

    View details for Web of Science ID A1976BS20300036

    View details for PubMedID 1260726

  • SERIOUS BACTERIAL-INFECTIONS IN PEDIATRIC HODGKINS-DISEASE - RELATIVE RISKS OF RADIOTHERAPY, CHEMOTHERAPY AND SPLENECTOMY Donaldson, S. S., Glatstein, E., Vosti, K. L., Wilbur, J. R., Rosenberg, S. A., KAPLAN, H. S. AMER ASSOC CANCER RESEARCH. 1976: 252-252
  • RADIOGRAPHIC EVALUATION OF 105 CONSECUTIVE CHILDREN WITH HODGKINS-DISEASE ANALES ESPANOLES DE PEDIATRIA Parker, B. R., Castellino, R. A., Donaldson, S. S., KAPLAN, H. S. 1976; 9: 68-68

    View details for Web of Science ID A1976CY68300012

    View details for PubMedID 1015693

  • PREGNANCY FOLLOWING OOPHOROPEXY AND TOTAL NODAL IRRADIATION IN WOMEN WITH HODGKINS-DISEASE CANCER Lefloch, O., Donaldson, S. S., KAPLAN, H. S. 1976; 38 (6): 2263-2268

    Abstract

    During the past decade at Stanford University Medical Center, in an attempt to protect ovarian function in young female patients irradiated for Hodgkin's disease, oophoropexy has been performed at the time of surgical staging. When pelvic irradiation is administered, a 10-cm thick lead block is used to shield the ovaries in the midline. With this technique, two-thirds of women have retained ovarian function, and nine women who underwent oophoropexy prior to high-dose pelvic irradiation have become pregnant. Six patients have given birth to eight babies. An additional two patients have had therapeutic abortions and one, a spontaneous abortion. The minimum radiation dose to the ovaries was 350 to 400 rads in 39 to 46 days. No abnormalities have been observed in the children; no ectopic pregnancies have occurred.

    View details for Web of Science ID A1976CQ60600011

    View details for PubMedID 826312

  • Letter: Orbital radiotherapy for the ophthalmopathy of Graves's disease. New England journal of medicine Donaldson, S. S., Bagshaw, M. A., KRISS, J. P. 1974; 290 (14): 805-?

    View details for PubMedID 4406001