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

the Dutch LATER Study group, Jenneke E van Atteveld*, Demi T C de Winter, Vincent G Pluimakers, Marta Fiocco, Rutger A J Nievelstein, Monique G G Hobbelink, Leontien C M Kremer, Martha A Grootenhuis, Heleen Maurice-Stam, Wim J E Tissing, Andrica C H de Vries, Jacqueline J Loonen, Eline van Dulmen-den Broeder, Helena J H van der Pal, Saskia M F Pluijm, Margriet van der Heiden-van der Loo, A Birgitta Versluijs, Marloes Louwerens, Dorine BrestersHanneke M van Santen, Imo Hoefer, Sjoerd A A van den Berg, Jaap den Hartogh, Jan H J Hoeijmakers, Sebastian J C M M Neggers, Marry M van den Heuvel-Eibrink

*Corresponding author for this work

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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.

Original languageEnglish
Pages (from-to)e155-e165
JournalThe Lancet Healthy Longevity
Issue number4
Publication statusPublished - Apr 2023

Bibliographical note

Funding Information:
This study was supported by the Children Cancer-free Foundation (KiKa grant numbers 171 and 276), KiKaRoW (private funding, granted to the Princess Máxima Center Foundation [MMvdH-E]), Dutch Cancer Society, and the ODAS Foundation. We thank all physicians, research nurses, data managers, and participating survivors for their contribution. Additionally, the authors wish to acknowledge services of the Lifelines Cohort Study, the contributing research centres delivering data to Lifelines, and all the study participants.

Publisher Copyright:
© 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license


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