Modeling long-term mortality and morbidity in pediatric Hodgkin lymphoma survivors after reduced radiotherapy exposure.

Abstract

Long-term survivors of pediatric Hodgkin lymphoma are at risk of late treatment-related mortality, cancer, and heart disease. While modified treatments have reduced radiation exposure, long-term risks in late adulthood are unknown. Using a simulation model based on data from the Childhood Cancer Survivor Study and national databases, we projected overall survival and cumulative incidence of breast cancer and heart failure for 5-year survivors treated with extended-field RT, chest RT ≥ 35 Gy, chest RT < 35 Gy, or chemotherapy only. Estimates were compared with general population individuals who faced only age-related risks. We report the mean and 95% uncertainty intervals (UIs) among 1000 iterations. At age 65, projected overall survival ranged from 24.7% (95% UI, 17.7 to 32.5) after extended-field RT to 71.8% (44.9 to 81.8) after chemotherapy only, compared with 86.4% (83.8 to 88.8) in the general population. Cumulative breast cancer incidence among female survivors was 61.1% for extended-field RT, 59.7% for chest RT ≥ 35 Gy, 49.8% for chest RT < 35 Gy, and 17.9% for chemotherapy only, respectively, versus 6.1% in the general population. Heart failure risks among all survivors were 34.8%, 33.4%, 28.4%, and 16.0, respectively, versus 4.3%. Across all subgroups, breast cancer and heart failure were projected to occur 16.1-31.7 and 21.0-25.9 years earlier, respectively, relative to general population risks at age 65. Although historical reductions in RT dose and field have substantially improved long-term survival, survivors treated with lower-dose or chemotherapy alone remain at markedly elevated risk for early-onset breast cancer and heart failure.