Prevalence and Predictors of Frailty in Childhood Cancer Survivors and Siblings: A Report From the Childhood Cancer Survivor Study

Abstract

Purpose: To estimate the prevalence of frailty among childhood cancer survivors and to determine the direct and indirect effects of treatment exposures, lifestyle factors, and severe, disabling, and life-threatening chronic condition on frailty.

Methods: Childhood cancer survivors (≥ 5 years since diagnosis), treated between 1970 and 1999 when < 21 years old (n = 10,899; mean age, 37.6 ± 9.4 years; 48% male, 86% white) and siblings were included (n = 2,097; mean age, 42.9 ± 9.4 years). Frailty was defined as ≥ 3 of the following: low lean mass, exhaustion, low energy expenditure, walking limitations, and weakness. Generalized linear models were used to evaluate direct and indirect associations between frailty and treatment exposures, sociodemographic characteristics, lifestyle factors, and chronic condition.

Results: The overall prevalence of frailty among survivors was 3 times higher compared with siblings (6.4%; 95% CI, 4.1% to 8.7%; v 2.2%; 95% CI, 1.2% to 3.2%). Survivors of CNS tumors (9.5%; 95% CI, 5.2% to 13.8%) and bone tumors (8.1%; 95% CI, 5.1% to 11.1%) had the highest prevalence of frailty. Survivors exposed to cranial radiation, pelvic radiation ≥ 34 Gy, abdominal radiation > 40 Gy, cisplatin ≥ 600 mg/m², amputation, or lung surgery had increased risk for frailty. These associations were partially but not completely attenuated when sociodemographic characteristics, lifestyle factors, and chronic conditions were added to multivariable models. Cranial radiation (prevalence ratio [PR], 1.47; 95% CI, 1.20 to 1.76), pelvic radiation ≥ 34 Gy (PR, 1.46; 95% CI, 1.01 to 2.11), and lung surgery (PR, 1.75; 95% CI, 1.28 to 2.38) remained significant after sociodemographic, lifestyle, and chronic conditions were accounted for.

Conclusion: Childhood cancer survivors reported a higher prevalence of frailty compared with siblings. Radiation and lung surgery exposures were associated with increased risk for frailty. Interventions to prevent, delay onset, or remediate chronic disease and/or promote healthy lifestyle are needed to decrease the prevalence of frailty and preserve function in this at-risk population.

FIG 1.

(A) Associations between treatment exposures and frailty (model A), adjusted for grade 3-4 chronic health conditions (model B), and lifestyle (model C). Models adjusted for sex, race/ethnicity, age at diagnosis, and age at assessment. Model A includes treatment exposures. Model B includes treatment exposures (significant in model A) and cardiac, neurologic, respiratory, musculoskeletal, endocrine, and all other chronic conditions. Model C includes treatment exposures, chronic conditions from model B, and smoking, obesity, and sedentary behavior. Appendix Table A6 (online only) includes data on model fit. (B) Associations between treatment exposures and prefrailty (Model A), adjusted for grade 3-4 chronic health conditions (Model B), and lifestyle (Model C). Models adjusted for sex, race/ethnicity, age at diagnosis, and age at assessment. Model A includes treatment exposures. Model B includes treatment exposures (significant in model A) and cardiac, neurologic, respiratory, musculoskeletal, endocrine, and all other chronic conditions. Model C includes treatment exposures, chronic conditions from model B, and smoking, obesity, and sedentary behavior. Appendix Table A7 (online only) includes data on model fit. (*) The difference between the model and model A (with treatment exposures only) was significant; P value < .05.

Fig A1.

Hypothesized model.

Fig A2.

Selection of study participants from Childhood Cancer Survivors Study: survivors.

Fig A3.

Selection of study participants from Childhood Cancer Survivors Study: siblings.

Fig A4.

Age-adjusted prevalence of frailty by sex. Weighted percentages and 95% CIs are presented. Frailty ≥ 3 components.

Fig A5.

Contribution of frailty components to the frailty and prefrailty phenotypes. Weighted percentages and 95% CIs are presented. Frailty ≥ 3 components; prefrailty ≥ 2 components.

Fig A6.

Age-adjusted prevalence of frailty and prefrailty among childhood cancer survivors by primary diagnosis. Weighted percentages and 95% CIs are presented. Frailty ≥ 3 components; prefrailty ≥ 2 components.