Accumulation of Chronic Disease Among Survivors of Childhood Cancer Predicts Early Mortality

Cancer survivors develop cancer and treatment-related morbidities at younger than normal ages and are at risk for early mortality, suggestive of an aging phenotype. The Cumulative Illness Rating Scale for Geriatrics (CIRS-G) is specifically designed to describe the accumulation of comorbidities over time with estimates of severity such as total score (TS) which is a sum of possible conditions weighted by severity. These severity scores can then be used to predict future mortality. CIRS-G scores were calculated in cancer survivors and their siblings from Childhood Cancer Survivor Study cohort members from two time points 19 years apart and members of the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004. CIRS-G metrics were analyzed using Cox proportional hazards regression to determine subsequent mortality risk. In total, 14,355 survivors with a median age of 24 (IQR, 18-30) years and 4,022 siblings with a median age of 26 (IQR, 19-33) years provided baseline data; 6,138 survivors and 1,801 siblings provided follow-up data. Cancer survivors had higher median baseline TS than siblings at baseline (5.75 3.44) and follow-up (7.76 4.79), all < .01. The mean increase in TS from baseline to follow-up was significantly steeper in cancer survivors (2.89 males and 3.18 females) vs. siblings (1.79 males and 1.69 females) and NHANES population (2.0 males and 1.94 females), all < .01. Every point increase in baseline TS increased hazard for death by 9% (95% CI, 8 to 10) among survivors. Application of a geriatric rating scale to characterize disease supports the hypothesis that morbidity accumulation is accelerated in young adult survivors of childhood cancer when compared with siblings and the general population.