Pain and frailty progression in adult survivors of childhood cancer: a report from the St Jude Lifetime Cohort study

Lancet Healthy Longev. 2026 May 28:100851. doi: 10.1016/j.lanhl.2026.100851. Online ahead of print.

ABSTRACT

BACKGROUND: Ageing survivors of childhood cancer experience pain that substantially affects daily activities and health. We investigated the contribution of pain to frailty development or progression in survivors.

METHODS: In this analysis of the St Jude Lifetime Cohort (SJLIFE), adult survivors of childhood cancer treated at a single institution in the USA completed a a baseline assessment including a frailty assessment at cohort entry and a follow-up frailty assessment 4-6 years later. Eligible participants were between ages 18 years and 45 years and were at least 10 years from their childhood cancer diagnosis at cohort entry. Women who were pregnant and participants currently receiving treatment for cancer were not eligible. Criteria for frailty were low lean muscle mass, muscle weakness, poor endurance, slow walking speed, and exhaustion; pre-frailty was defined as meeting two of the criteria, and frailty was defined as meeting three or more. Survivors self-reported pain (bodily pain and headache or migraine pain), pain interference, and health behaviours (including smoking status, alcohol consumption, and sedentary behaviour). Outcomes were analysed in participants who completed clinical assessments at both baseline and follow-up. Multinomial logistic regression examined associations between pain and frailty (odds ratios [ORs] and 95% CIs reported).

FINDINGS: 1261 adult survivors of childhood cancer recruited for SJLIFE between Jan 1, 2008, and June 30, 2013 completed clinical assessments at baseline (mean age 30·7 years [SD 7·0]; mean time since diagnosis 22·7 years [7·4]) and follow-up (mean time from baseline 5·2 years [0·7]). At baseline, 471 (37·4%) participants reported pain, with 194 (15·4%) also reporting pain interference; 294 (23·3%) participants were pre-frail or frail. From baseline to follow-up, 262 (20·8%) survivors had persistent pain, 211 (16·7%) had increasing pain, and 370 (29·3%) had persistent or progressive frailty. After adjusting for age, sex, race and ethnicity, time since diagnosis, BMI, anxiety, depression, and chronic health conditions, pain with interference was associated with pre-frailty (OR 1·85, 95% CI 1·19-2·88) and frailty (5·66, 2·75-11·68) at baseline and with persistent (3·44, 1·88-6·31) and progressed frailty (2·09, 1·25-3·49). Persistent (1·70, 1·11-2·61) and increasing pain (1·69, 1·09-2·61) from baseline to follow-up were associated with progressed frailty. Physical activity and sedentary behaviour were associated with frailty across models.

INTERPRETATION: Pain that interferes with daily functioning is associated with frailty and frailty progression in survivors of childhood cancer, underscoring the need for interventions targeting pain and lifestyle factors to mitigate frailty risk and improve long-term health outcomes.

FUNDING: US National Institutes of Health and American Lebanese Syrian Associated Charities.

PMID:42208952 | DOI:10.1016/j.lanhl.2026.100851