Aging and risk of severe, disabling, life-threatening, and fatal events in the childhood cancer survivor study

Abstract

Purpose: The first generation of childhood cancer survivors is now aging into their fourth and fifth decades of life, yet health risks across the aging spectrum are not well established.

Methods: Analyses included 14,359 5-year survivors from the Childhood Cancer Survivor Study, who were first diagnosed when they were younger than 21 years old and who received follow-up for a median of 24.5 years after diagnosis (range, 5.0 to 39.3 years) along with 4,301 of their siblings. Among the survivors, 5,604 were at least 35 years old (range, 35 to 62 years) at last follow-up. Severe, disabling, life-threatening, and fatal health conditions more than 5 years from diagnosis were classified using the Common Terminology Criteria for Adverse Events, grades 3 to 5 (National Cancer Institute).

Results: The cumulative incidence of a severe, disabling, life-threatening, or fatal health condition was greater among survivors than siblings (53.6%; 95% CI, 51.5 to 55.6; v 19.8%; 95% CI, 17.0 to 22.7) by age 50 years. When comparing survivors with siblings, hazard ratios (HR) were significantly increased within the age group of 5 to 19 years (HR, 6.8; 95% CI, 5.5 to 8.3), age group of 20 to 34 years (HR, 3.8; 95% CI, 3.2 to 4.5), and the ≥ 35 years group (HR, 5.0; 95% CI, 4.1 to 6.1), with the HR significantly higher among those ≥ 35 years versus those 20 to 34 years old (P = .03). Among survivors who reached age 35 years without a previous grade 3 or 4 condition, 25.9% experienced a subsequent grade 3 to 5 condition within 10 years, compared with 6.0% of siblings (P < .001).

Conclusion: Elevated risk for morbidity and mortality among survivors increases further beyond the fourth decade of life, which affects the future clinical demands of this population relative to ongoing surveillance and interventions.

Fig 1.

Cumulative incidence of chronic health conditions for (A) grades 3 to 5 chronic health conditions, (B) multiple grade 3 to 5 conditions in survivors, (C) multiple grade 3 to 5 conditions in siblings, (D) conditioned based on no previous grade 3 to 5 conditions among survivors by ages 25, 35, or 45, and (E) conditioned based on no previous grade 3 to 5 conditions among siblings by ages 25, 35, or 45.

Fig 2.

Cumulative incidence of selected grade 3 to 5 conditions by organ system. (A) New malignancy, (B) cardiac, (C) hearing, (D) vision, (E) respiratory, and (F) renal.

Fig 3.

Hazard ratios and 95% CIs of survivors versus siblings for specific chronic conditions that first occurred at or after age 35 years, adjusted for age, race, and sex. CHF, congestive heart failure.

Fig A1.

(A) Study population: survivor recruitment and longitudinal participation among those ages 35 years or older as of last follow-up in 2007.(B) Study population: sibling recruitment and longitudinal participation among those ages 35 years or older as of last follow-up in 2007. (C) Study population: survivor recruitment and longitudinal participation among those ages 35 years or older as of last follow-up in 2007. (*) For 228 participants, age at baseline ≥ 35 years and baseline was the last follow-up. Median follow-up time since age 35 years was 3 years, with a maximum of 18 years. (†) For 322 participants, age at follow-up in 2000 was ≥ 35 years and follow-up 2000 was the last follow-up; median follow-up time since age 35 years was 3 years, with a maximum of 15 years. (‡) For 596 participants, age at follow-up in 2003 was ≥ 35 years and follow-up in 2003 was the last follow-up; median follow-up time since age 35 years was 5 years, with a maximum of 20 years. (§) For 4,458 participants, age at follow-up in 2007 was ≥ 35 years and follow-up in 2007 was the last follow-up; median follow-up time since age 35 years was 6 years, with a maximum of 23 years. Overall, for the 5,604 participants in the subcohort, median follow-up time since age 35 years was 5 years.

Fig A1.

(A) Study population: survivor recruitment and longitudinal participation among those ages 35 years or older as of last follow-up in 2007.(B) Study population: sibling recruitment and longitudinal participation among those ages 35 years or older as of last follow-up in 2007. (C) Study population: survivor recruitment and longitudinal participation among those ages 35 years or older as of last follow-up in 2007. (*) For 228 participants, age at baseline ≥ 35 years and baseline was the last follow-up. Median follow-up time since age 35 years was 3 years, with a maximum of 18 years. (†) For 322 participants, age at follow-up in 2000 was ≥ 35 years and follow-up 2000 was the last follow-up; median follow-up time since age 35 years was 3 years, with a maximum of 15 years. (‡) For 596 participants, age at follow-up in 2003 was ≥ 35 years and follow-up in 2003 was the last follow-up; median follow-up time since age 35 years was 5 years, with a maximum of 20 years. (§) For 4,458 participants, age at follow-up in 2007 was ≥ 35 years and follow-up in 2007 was the last follow-up; median follow-up time since age 35 years was 6 years, with a maximum of 23 years. Overall, for the 5,604 participants in the subcohort, median follow-up time since age 35 years was 5 years.

Fig A1.

(A) Study population: survivor recruitment and longitudinal participation among those ages 35 years or older as of last follow-up in 2007.(B) Study population: sibling recruitment and longitudinal participation among those ages 35 years or older as of last follow-up in 2007. (C) Study population: survivor recruitment and longitudinal participation among those ages 35 years or older as of last follow-up in 2007. (*) For 228 participants, age at baseline ≥ 35 years and baseline was the last follow-up. Median follow-up time since age 35 years was 3 years, with a maximum of 18 years. (†) For 322 participants, age at follow-up in 2000 was ≥ 35 years and follow-up 2000 was the last follow-up; median follow-up time since age 35 years was 3 years, with a maximum of 15 years. (‡) For 596 participants, age at follow-up in 2003 was ≥ 35 years and follow-up in 2003 was the last follow-up; median follow-up time since age 35 years was 5 years, with a maximum of 20 years. (§) For 4,458 participants, age at follow-up in 2007 was ≥ 35 years and follow-up in 2007 was the last follow-up; median follow-up time since age 35 years was 6 years, with a maximum of 23 years. Overall, for the 5,604 participants in the subcohort, median follow-up time since age 35 years was 5 years.

Fig A2.

Cumulative incidence of chronic health conditions for severe, disabling, life-threatening, or fatal health conditions, by primary childhood cancer diagnosis. (A) leukemia, (B) CNS tumors, (C) Hodgkin lymphoma, (D) non-Hodgkin lymphoma, (E) kidney tumors, (F) neuroblastoma, (G) soft-tissue sarcoma, and (H) bone tumors.

Fig A3.

Cumulative incidence of selected grade 3 to 5 conditions by organ system, based on having no previous grade 3 to 5 events among survivors and siblings. (A) New malignancy, (B) vision, (C) hearing, (D) respiratory, (E) cardiac, and (F) renal.

Fig A4.

Hazard ratios and 95% CIs for specific chronic conditions that first occurred on or after age 35 years, adjusted for age and sex for survivors of (A) leukemia, (B) CNS tumors, (C) Hodgkin lymphoma, (D) non-Hodgkin lymphoma, (E) soft-tissue sarcomas, and (F) bone tumors. CHF, congestive heart failure. (*) No events.