Risk factors associated with secondary sarcomas in childhood cancer survivors: A report from the childhood cancer survivor study

Tara O. Henderson, Preetha Rajaraman, Marilyn Stovall, Louis S. Constine, Aliza Olive, Susan A. Smith, Ann Mertens, Anna Meadows, Joseph P. Neglia, Sue Hammond, John Whitton, Peter D. Inskip, Leslie L. Robison, Lisa Diller

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113 Scopus citations


Purpose: Childhood cancer survivors have an increased risk of secondary sarcomas. To better identify those at risk, the relationship between therapeutic dose of chemotherapy and radiation and secondary sarcoma should be quantified. Methods and Materials: We conducted a nested case-control study of secondary sarcomas (105 cases, 422 matched controls) in a cohort of 14,372 childhood cancer survivors. Radiation dose at the second malignant neoplasm (SMN) site and use of chemotherapy were estimated from detailed review of medical records. Odds ratios (ORs) and 95% confidence intervals were estimated by conditional logistic regression. Excess odds ratio (EOR) was modeled as a function of radiation dose, chemotherapy, and host factors. Results: Sarcomas occurred a median of 11.8 years (range, 5.3-31.3 years) from original diagnosis. Any exposure to radiation was associated with increased risk of secondary sarcoma (OR = 4.1, 95% CI = 1.8-9.5). A dose-response relation was observed, with elevated risks at doses between 10 and 29.9 Gy (OR = 15.6, 95% CI = 4.5-53.9), 30-49.9 Gy (OR = 16.0, 95% CI 3.8-67.8) and >50 Gy (OR = 114.1, 95% CI 13.5-964.8). Anthracycline exposure was associated with sarcoma risk (OR = 3.5, 95% CI = 1.6-7.7) adjusting for radiation dose, other chemotherapy, and primary cancer. Adjusting for treatment, survivors with a first diagnosis of Hodgkin lymphoma (OR = 10.7, 95% CI = 3.1-37.4) or primary sarcoma (OR = 8.4, 95% CI = 3.2-22.3) were more likely to develop a sarcoma. Conclusions: Of the risk factors evaluated, radiation exposure was the most important for secondary sarcoma development in childhood cancer survivors; anthracycline chemotherapy exposure was also associated with increased risk.

Original languageEnglish (US)
Pages (from-to)224-230
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number1
StatePublished - Sep 1 2012

Bibliographical note

Funding Information:
The Childhood Cancer Survivor Study is a collaborative, multi-institutional study funded by the National Cancer Institute (NCI, grant # U24 CA55727 ; L.L. Robison, Principal Investigator). Additional support was provided by the Intramural Research Program of the NIH and NCI, and the American Lebanese-Syrian Associated Charities. The primary investigator, Dr. Henderson, received support from the NCI (grant # K07CA134935 , Health Beliefs and Behaviors: Cohort Studies in Childhood Cancer Survivors).


  • Childhood cancer survivors
  • Radiation late effects
  • Secondary sarcomas


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