Each year in the United States, nearly 16,000 children and adolescents between the ages of birth and 19 are diagnosed with cancer.1 And although survival rates have greatly improved for many types of childhood cancers, with more than 8 in 10 children and adolescents surviving at least 5 years after diagnosis,2 survival may include enduring health consequences from the toxicities associated with treatments.
According to the results from the 2017 St. Jude Lifetime Cohort study, by age 50, the average pediatric cancer survivor has had 17.1 chronic health conditions. They include nearly 5% that were considered severe/disabling, life-threatening, or fatal, vs 9.2% chronic health conditions in the general population.3
The findings from a recent Cancer Outcomes Microsimulation: Pediatric and Adolescent SurvivorShip (COMPASS) simulation modeling study of survivors of childhood cancers showed even greater health challenges for these individuals as they age. The study, conducted by Lisa R. Diller, MD, Vice Chair, Department of Pediatric Oncology; founder of the David B. Perini Jr. Quality of Life Clinic at Dana-Farber Cancer Institute; and Professor of Pediatrics at Harvard Medical School, and Jennifer M. Yeh, PhD, and their colleagues, investigated the estimated lifetime risks of eight treatment-related cancers and cardiovascular conditions compared with their peers in the general population. They included breast cancer, colorectal cancer, glial tumors, sarcomas, heart failure, coronary heart disease/myocardial infarction, stroke, and valvular disease.
Lisa R. Diller, MD
The study results showed that by age 65, 20% of those in the general population had developed at least one of these conditions, but in 5-year cancer survivors, that threshold was reached at age 47.3, a 17.7-year acceleration in disease onset. In addition, by age 65, 55% of cancer survivors were projected to develop at least one health condition, indicating a 2.7-fold higher relative risk and a 34.2% absolute excess risk compared with the general population. Although risks were higher among those cancer survivors who had been treated with radiation therapy (37.3% excess risk), those cancer survivors who had not been exposed to radiation therapy also faced an elevated health risk (31% excess risk).4
Establishing Survivorship Care Guidelines for Childhood and Adolescent Cancers
In 2023, the Children’s Oncology Group (COG) updated its Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers (www.survivorshipguidelines.org) as a resource for health-care professionals who provide ongoing care to survivors of pediatric and adolescent malignancies, including screening recommendations for asymptomatic cancer survivors presenting for routine exposure-based medical follow-up. More recently, St. Jude Children’s Research Hospital established the Adapted Resource and Implementation Application (ARIA) Guide (https://global.stjude.org/en-us/tools/sj-cares-tools/aria-guide.html), a free online global clinical resource for guidance on the treatment of childhood and adolescent cancers in both lower- and higher-resource settings. And, Texas Children’s Hospital, in partnership with COG, has launched Passport for Care (https://cancersurvivor.passportforcare.org/en/), a free tailored care plan for survivors of childhood, adolescent, and young adult cancers to access their treatment summary and long-term follow-up care recommendations.
“These survivorship care guidelines include breast cancer screening recommendations for women who have had chest radiation during childhood, colorectal cancer screening guidelines for survivors who have had radiation therapy to the abdomen, as well as recommendations for functional and echocardiographic testing for survivors at risk for cardiovascular disease,” said Dr. Diller. “For these survivors, the risks for the diseases of aging, such as cancer and heart disease, begin early in adulthood and remain high, despite the very distant exposure to childhood cancer therapies.”
In a recent interview with The ASCO Post, Dr. Diller discussed the results of her study and how treatment protocols are changing to reduce the long-term health risk for survivors of childhood cancers.
Eliminating Radiation Therapy May Still Pose Long-Term Risks
In your study, you found that although the risks of developing a treatment-related cancer or cardiovascular disease among childhood cancer survivors as they aged were higher among those cancer survivors treated with chemotherapy and radiation (including an onset of disease 22 years earlier and a 37.3% excess risk), risk was still elevated for those who had not been treated with radiation (who had an onset of disease 13.5 years earlier and a 31% excess risk of developing early-onset disease). Were you surprised by this finding?
Yes, that was a little bit of a surprise. Our model found that even if you remove radiation therapy in pediatric or adolescent patients with leukemia, for example, those survivors were still at increased risk for second cancers and heart disease later in life. We had hoped to see that without radiation therapy, a childhood cancer survivor’s health would return to that of the general population, but the model still predicted excess risk among these cancer survivors.
Developing Protective Measures for Childhood Cancer Survivors
Your study results are based on the long-term outcomes for 5-year cancer survivors diagnosed between 1970 and 1999. Please talk about how radiation and chemotherapy treatment protocols have changed over the past 3 decades to minimize accelerated aging in childhood cancer survivors from treatment toxicities.
Early on, we were seeing a wide range of severe late toxicities, including a high risk of breast cancer in women who had had chest radiation for a childhood cancer, cognitive late effects from cranial radiation among those treated for childhood leukemia, and heart disease in cancer survivors treated with high doses of anthracycline chemotherapies. Over the past couple of decades, pediatric oncology has not only been focused on increasing survival rates for children, adolescents, and young adults with primary tumors, but also on improving the health profile of these individuals as they age.
We are hoping that in the future, we will have better protective measures for young cancer survivors Unfortunately, our model suggests that their risk for accelerated aging does not appear to go away.— LISA R. DILLER, MD
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Many research studies since the 1990s have investigated how to protect young cancer survivors from the late effects of cancer and its treatment. Protective steps include reducing the radiation dose or limiting the field of radiation as well as limiting anthracycline exposure or using cardioprotective therapies such as dexrazoxane.
We are hoping that in the future, we will have better protective measures for young cancer survivors. Much of our understanding of the late effects of childhood cancers is based on our experiences caring for young cancer survivors in their 20s and 30s, who are concerned about their future health risks as a result of their childhood cancer treatment. Unfortunately, our model suggests that their risk for accelerated aging does not appear to go away.
One piece of positive news is that the risk of death from a late cancer relapse has definitely gone way down. So, many young patients today cured of their cancer are unlikely to relapse. However, the long-term effects on early mortality and early morbidity in the last third of life are concerning.
Tracking the Health of Childhood Cancer Survivors Over Time
The results from a study in 2016 by you and your colleagues showed that young adult survivors of childhood cancers (between the ages of 18 and 29) reported health-related quality of life that resembled that of older adults (between the ages of 40 and 49) in the general population.5 Please talk about any progress in the health-related quality of life of adolescent and young adult cancer survivors over the past decade.
What the data from that earlier study showed was that cancer survivors’ quality of life and sense of well-being were affected by the presence or absence of chronic health conditions more commonly seen in people aged 20 or older, including higher risks of heart disease, infertility, lung disease, second cancers, and other chronic conditions related to their prior chemotherapy, radiation therapy, and surgery.
Guest Editor
Brandon Hayes-Lattin, MD, FACP
Dr. Hayes-Lattin is Professor of Medicine and Deputy Division Head of the Adolescent and Young Adult Oncology Program at the Knight Cancer Institute at Oregon Health and Science University, Portland.
Over the past decade, there has been increased awareness about the cancer- and treatment-related long-term health risks childhood cancer survivors face as they age, and that has led to some improvements in caring for these individuals. For example, the availability of electronic medical records has made it easier for providers from multiple institutions to share notes on a cancer survivor’s health as well as document, for the future, the treatments the person received. In the past, childhood cancer treatment exposures “disappeared” as the child moved to other institutions or moved from pediatric to adult-based care.
We have also seen the advent of new upfront therapies, including targeted or immunotherapy, for some childhood cancers. For example, in 2022, the U.S. Food and Drug Administration approved the use of brentuximab vedotin, an effective anti-CD30 antibody-drug conjugate, in combination with chemotherapy for high-risk pediatric classical Hodgkin lymphoma.6 Although this advance has been radiation-sparing, with fewer patients requiring radiation for curative therapy, we don’t have 30- or 40-year follow-up on these newer immune-based therapies to know whether there are any long-term health risks associated with them.
In the future, we hope to have a much better profile of pediatric, adolescent, and young adult patients to better understand the long-term health-related risks associated with having had cancer as a young person and how to reduce or avoid them as these cancer survivors age.
DISCLOSURE: Dr. Diller reported no conflicts of interest.
REFERENCES
- American Childhood Cancer Organization: US Childhood Cancer Statistics. Available at www.acco.org/us-childhood-cancer-statistics/. Accessed July 24, 2025.
- Sansbury BM, Blackman E: Unprecedented advances and persistent challenges: Key insights from AACR’s 2024 Cancer Progress Reports. December 23, 2024. Available at www.aacr.org/blog/2024/12/23/unprecedented-advances-and-persistent-challenges-key-insights-from-aacrs-2024-cancer-progress-reports/. Accessed July 24, 2025.
- Bhakta N, Liu Q, Ness KK, et al: The cumulative burden of surviving childhood cancer: An initial report from the St. Jude Lifetime Cohort Study (SJLIFE). Lancet 390:2569-2582, 2017.
- Yeh JM, Ward ZJ, Stratton KL, et al: Accelerated aging in survivors of childhood cancer—Early onset and excess risk of chronic conditions. JAMA Oncol 11:535-543, 2025.
- Yeh JM, Hanmer J, Ward ZJ, et al: Chronic conditions and utility-based health-related quality of life in adult childhood cancer survivors. J Natl Cancer Inst 108:djw046, 2016.
- U.S. Food and Drug Administration: FDA approves brentuximab vedotin in combination with chemotherapy for pediatric patients with classical Hodgkin lymphoma. Available at www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-brentuximab-vedotin-combination-chemotherapy-pediatric-patients-classical-hodgkin#:~:text=On%20November%2010%2C%202022%2C%20the,classical%20Hodgkin%20lymphoma%20(cHL). Accessed July 24, 2025.
