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Childhood Cancer Survivors: Does chemotherapy alone increase second cancer risk?

GregoryAuneby Gregory Aune, MD, PhD, CKN Editor


Childhood Cancer Survivors have their own unique set of issues that often go unaddressed by health care professionals once treatment has ended and the child enters adulthood.  Although the last 20 years have seen growth in survivorship research, this research is rarely filtered down to the people who need it most – the survivors and their families.  Dr. Gregory Aune, Pediatric Oncologist, researcher, childhood cancer survivor and advocate, has taken on the position of CKN Editor, Knowledge Translation – Childhood Cancer Survivorship.  His goal is simple:  to help empower childhood cancer survivors to start a dialogue with their doctors by publishing short, easy-to-read research study summaries, like this one.


THE HEADLINE: Thinking about Subsequent Malignancy Risk Outside of the Radiation Paradigm


THE RESEARCH: Journal of Clinical Oncology: Long-Term Risk of Subsequent Malignant Neoplasms After Treatment of Childhood Cancer in the DCOG LATER Study Cohort: Role of Chemotherapy.  Researchers in the Netherlands identified second cancers in 5-year childhood cancer survivors in the Dutch Childhood Cancer Oncology Group Long-Term Effects After Childhood Cancer (DCOG LATER) cohort. Cumulative incidences of breast cancer, sarcoma, and all solid cancers were calculated for this cohort, with a particular focus on the risks associated with individual chemotherapeutic agents.


KEY FINDINGS:  291 secondary cancers were identified in a cohort of 6,165 5-year survivors of childhood cancer diagnosed between 1963 and 2001.  Median follow-up time from diagnosis in the cohort was 20.7 years, with a range of 5 to 49.8 years.  In this group, the cumulative incidence of a second malignancy at 25 years post diagnosis was 3.9%.  Importantly, an analysis of second malignancy risk with respect to era of diagnosis did not reveal a difference between survivors diagnosed in the 1990’s vs. those from earlier decades.  Analysis based on chemotherapy exposure indicated a dose-dependent relationship between doxorubicin and all solid cancers and breast cancer.  This dose-dependency was strongest among the cancers associated with Li-Fraumeni syndrome (leukemia, CNS, and non-Ewing sarcoma).  Finally, a dose-dependent relationship between cyclophosphamide and secondary sarcomas was found.



The evidence regarding second malignancies in childhood cancer has been rapidly accumulating as these patients are surviving in greater numbers than ever before and aging.  The link between therapeutic radiation exposure and second cancers has been extensively studied and there is sound evidence that documents the risks for second cancers, especially in the anatomic site of radiation delivery.  In contrast, the contribution of chemotherapy has been more difficult to tease out, notably because most survivors count both radiation and chemotherapy among their previous exposures.  Because many chemotherapy agents are clearly linked to DNA damage, common sense would suggest that these exposures contribute to second cancer risk independent of radiation exposure.  A recent study of survivors showed a clear relationship between chemotherapy and breast cancer in women treated with chemotherapy alone.  The study detailed here evaluates the risk of second malignancies associated with individual chemotherapy agents in a Dutch population of survivors.  Importantly, this study documents a clear dose-dependent relationship between second cancers and doxorubicin and cyclophosphamide.  Because these agents are among the most commonly used chemotherapies in childhood cancer treatment regimens, all survivors should be aware of this exposure and the lifetime cumulative dose they received.  In addition, survivors of cancers related to Li-Fraumeni syndrome (leukemia, CNS, non-Ewing Sarcoma) should be particularly vigilant in follow-up.  While secondary malignancies are a major concern for all survivors and their families, consistent follow-up and monitoring can facilitate early detection and increase hope for good long-term outcome in the event a second cancer is found.



Medical Disclaimer:  The information on this site is not intended or implied to be a substitute for professional medical advice, diagnosis or treatment. All content, including text, graphics, images and information, contained on or available through this web site is for general information purposes only.  If you feel the research summarized applies to you or someone you know, talk to your doctor about your concerns.



Videos with Dr. Aune

Presentation on YouTube (Jan 2015):  Eliminating Long-term Health Effects in Cancer Survivors – Gregory Aune, MD, PhD

Interview for the National Coalition for Cancer Survivorship (June 2015):  Hodgkin’s Lymphoma Survivor Dr. Greg Aune Discusses Issues in Long-Term Survivorship Care

Interview with the Washington Post Live Summit (Dec 2016): How cancer lives on in young adults after treatment ends



Dr. Gregory J. Aune is the Stephanie Edlund Distinguished Professor of Pediatric Cancer Research and a St. Baldrick’s Foundation Scholar.  His experience in pediatric cancer spans over 27 years and encompasses his own patient experiences, research in experimental therapeutics, clinical care of pediatric oncology patients, and childhood cancer advocacy.  His interest in pediatric oncology began at age 16, when he was diagnosed with Hodgkin’s lymphoma.  While fortunate to survive, the experiences he encountered as a patient initiated a path towards a research and clinical career aimed at developing less toxic chemotherapy regimens.  His experience as a long-term survivor included open-heart surgery at age 35 to replace his aortic valve and bypass three blocked coronary arteries that were damaged by his teenage cancer therapies.  This life-changing event initiated his research interest in cardiac disease.  His training to become a successful physician scientist and pediatric oncologist has included time spent at some of the most well-respected oncology institutions in the United States including, M.D. Anderson Cancer Center, the National Cancer Institute, and Johns Hopkins Hospital.

Dr. Aune is a national leader in childhood cancer advocacy efforts.  In San Antonio, he has been a leader in local fundraising and awareness efforts.   Since 2010, he has spearheaded efforts by the St. Baldrick’s Foundation and For the Kids Dance Marathon at the University of Texas San Antonio that have raised over $830,000 for childhood cancer patients and research efforts.  In September 2014, his appointment to the National Cancer Institute Council of Research Advocates (NCRA) was announced by NCI Director Dr. Harold Varmus at a White House briefing on childhood cancer.

In addition, Dr. Aune is a policy advisor for the National Coalition for Cancer Survivorship, serves on the Board of Directors of the American Childhood Cancer Organization, is a member of the St. Baldrick’s Foundation National Advocacy Committee, and serves on the scientific advisory board for the Canines-N-Kids foundation.

In May 2015, Dr. Aune addressed the 68th World Health Assembly in Geneva, Switzerland and called on the World Health Organization to make childhood cancer a top global health priority.



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