Frailty and sarcopenia within the earliest national Dutch childhood cancer survivor cohort (DCCSS-LATER):a cross-sectional study

Background: Childhood cancer survivors appear to be at increased risk of frailty and sarcopenia, but evidence on the occurrence of and high-risk groups for these aging phenotypes is scarce, especially in European survivors. The aim of this cross-sectional study was to assess the prevalence of and explore risk factors for pre-frailty, frailty, and sarcopenia in a national cohort of Dutch childhood cancer survivors diagnosed between 1963 and 2001. Methods: Eligible individuals (alive at the time of study, living in the Netherlands, age 18–45 years, and had not previously declined to participate in a late-effects study) from the Dutch Childhood Cancer Survivor Study (DCCSS-LATER) cohort were invited to take part in this cross-sectional study. We defined pre-frailty and frailty according to modified Fried criteria, and sarcopenia according to the European Working Group on Sarcopenia in Older People 2 definition. Associations between these conditions and demographic and treatment-related as well as endocrine and lifestyle-related factors were estimated with two separate multivariable logistic regression models in survivors with any frailty measurement or complete sarcopenia measurements. Findings: 3996 adult survivors of the DCCSS-LATER cohort were invited to participate in this cross-sectional study. 1993 non-participants were excluded due to lack of response or a decline to participate and 2003 (50·1%) childhood cancer survivors aged 18–45 years were included. 1114 (55·6%) participants had complete frailty measurements and 1472 (73·5%) participants had complete sarcopenia measurements. Mean age at participation was 33·1 years (SD 7·2). 1037 (51·8%) participants were male, 966 (48·2%) were female, and none were transgender. In survivors with complete frailty measurements or complete sarcopenia measurements, the percentage of pre-frailty was 20·3% (95% CI 18·0–22·7), frailty was 7·4% (6·0–9·0), and sarcopenia was 4·4% (3·5–5·6). In the models for pre-frailty, underweight (odds ratio [OR] 3·38 [95% CI 1·92–5·95]) and obesity (OR 1·67 [1·14–2·43]), cranial irradiation (OR 2·07 [1·47–2·93]), total body irradiation (OR 3·17 [1·77–5·70]), cisplatin dose of at least 600 mg/m2 (OR 3·75 [1·82–7·74]), growth hormone deficiency (OR 2·25 [1·23–4·09]), hyperthyroidism (OR 3·72 [1·63–8·47]), bone mineral density (Z score ≤–1 and >–2, OR 1·80 [95% CI 1·31–2·47]; Z score ≤–2, OR 3·37 [2·20–5·15]), and folic acid deficiency (OR 1·87 [1·31–2·68]) were considered significant. For frailty, associated factors included age at diagnosis between 10–18 years (OR 1·94 [95% CI 1·19–3·16]), underweight (OR 3·09 [1·42–6·69]), cranial irradiation (OR 2·65 [1·59–4·34]), total body irradiation (OR 3·28 [1·48–7·28]), cisplatin dose of at least 600 mg/m2 (OR 3·93 [1·45–10·67]), higher carboplatin doses (per g/m2; OR 1·15 [1·02–1·31]), cyclophosphamide equivalent dose of at least 20 g/m2 (OR 3·90 [1·65–9·24]), hyperthyroidism (OR 2·87 [1·06–7·76]), bone mineral density Z score ≤–2 (OR 2·85 [1·54–5·29]), and folic acid deficiency (OR 2·04 [1·20–3·46]). Male sex (OR 4·56 [95%CI 2·26–9·17]), lower BMI (continuous, OR 0·52 [0·45–0·60]), cranial irradiation (OR 3·87 [1·80–8·31]), total body irradiation (OR 4·52 [1·67–12·20]), hypogonadism (OR 3·96 [1·40–11·18]), growth hormone deficiency (OR 4·66 [1·44–15·15]), and vitamin B12 deficiency (OR 6·26 [2·17–1·81]) were significantly associated with sarcopenia. Interpretation: Our findings show that frailty and sarcopenia occur already at a mean age of 33 years in childhood cancer survivors. Early recognition and interventions for endocrine disorders and dietary deficiencies could be important in minimising the risk of pre-frailty, frailty, and sarcopenia in this population. Funding: Children Cancer-free Foundation, KiKaRoW, Dutch Cancer Society, ODAS Foundation.