IMPACT OF LATE-EFFECTS ON THE LIFE EXPECTANCY OF CHILDHOOD CANCER SURVIVORS

Background:  Although advancements in treatment have dramatically increased childhood cancer survival rates, survivors continue to face elevated risks for late-effects, including secondary cancers. As the potentially harmful effects of treatment are becoming more widely recognized, we sought to estimate the impact of disease and treatment-related mortality risks on the life expectancy of childhood cancer survivors.

 Methods: We developed a state-transition model to simulate the lifetime clinical course of a cohort of five-year childhood cancer survivors. Each month, individuals faced competing mortality risks which we categorized as (1) the risk of dying from the original cancer diagnosis (i.e., late recurrences), (2) excess mortality from other late-effects (i.e., subsequent cancers, cardiac, pulmonary and other complications) and (3) background mortality. Late recurrence risks were based on large-scale population- and hospital-based cohort studies. We used absolute excess risk estimates from published studies to reflect the additional mortality risks faced by survivors compared to the general population for specific late-effects. Background mortality rates were based on U.S. life tables. Outcomes included lifetime cause-specific mortality, life expectancy, and life years lost.

 Results: For a 15-year old cohort, the average lifetime risk of cause-specific mortality was 5.8% for late recurrence, 5.8% for excess risk of subsequent cancers, cardiac and pulmonary complications, and 38.4% for excess risk of other complications. Life expectancy for the cohort was 46.9 years, a loss of 10.6 years, or 18.5%, compared to the general population. The reduction in life expectancy varied by diagnosis, ranging from 5.9 years (10.5%) for Non-Hodgkin’s lymphoma to 14.6 years (24.5%) for central nervous system tumors. Compared to the general population, the relative risk of 10-year survival also varied by diagnosis, ranging from 0.93-0.97 for 40-year olds, 0.86-0.95 for 50-year olds and 0.71-0.90 for 60-year olds. The estimated reduction in life expectancy was sensitive to the excess relative risk of other causes mortality and the duration of late recurrence risk.

 Conclusions: Despite surviving their initial cancer, childhood cancer survivors continue to face considerable mortality throughout their lifetimes, with disease and treatment-related late effects reducing life expectancy by as much as 25%. These results highlight the need to monitor the health of current childhood cancer survivors who were treated in previous decades and minimize toxicity for newly diagnosed patients.