Accelerated Aging in Survivors of Childhood Cancer—Early Onset and Excess Risk of Chronic Conditions

Importance The lifetime risk of aging-related diseases among survivors of childhood cancer, accelerated by cancer treatment exposures, is unknown. Understanding this risk can provide a more comprehensive assessment of long-term health across the lifespan of survivors and guide adult care. Objective To estimate the lifetime risks of 8 treatment-related cancers and cardiovascular conditions among childhood cancer survivors and compare them with the general population. Design, Setting, Participants Using data from the Childhood Cancer Survivor Study and national databases, this simulation modeling study projected long-term outcomes for 5-year survivors diagnosed between 1970 and 1999 based on treatment exposures and age-related risks. The general population comparator was simulated using age-, sex-, and calendar year–matched individuals who faced only age-related risks. Exposures Treatment era (1970s, 1980s, 1990s), original cancer diagnosis, radiation treatment for primary diagnosis (any, none). Main Outcomes and Measures Estimated lifetime risks of 8 health conditions (breast cancer, colorectal cancer, glial tumors, sarcomas, heart failure, coronary heart disease/myocardial infarction, stroke, and valvular disease). Risks were projected and compared with the general population, stratified by radiation exposure. Results In the general population, 20% developed at least 1 health condition by age 65.0 years; in 5-year survivors this threshold was reached at age 47.3 years, representing a 17.7-year (95% uncertainty interval [UI], 14.0-21.0) acceleration in disease onset. By age 65 years, 55% of survivors were projected to develop at least 1 condition, indicating a 2.7-fold (95% UI, 2.2-3.5) higher relative risk and 34.2% (95% UI, 28.3-42.5) absolute excess risk compared with the general population. Risks were higher among those treated with radiation therapy for childhood cancer (22.0 years earlier onset [95% UI, 18.0-25.0]; 37.3% excess risk [95% UI, 31.6%-44.7%]) but still elevated for those without radiation exposure (13.5 years earlier onset [95% UI, 10.0-16.0]; 31.0% excess risk [95% UI, 23.9%-40.3%]). Reaching middle age was still associated with increased health risks. Compared with the general population, survivors who reached age 40 years had a 6.2-fold higher risk (95% UI, 4.8-9.4) of developing a new condition within 10 years. Conclusions and Relevance This study found that survivors of childhood cancer experience accelerated onset of aging-related diseases, regardless of prior radiation exposure. These findings underscore the importance of prioritizing cancer and cardiovascular disease prevention among survivors decades earlier than for the general population.