ESPEYB20 7. Oncology and Chronic Disease Long-Term Surveillance for Endocrine Complications in Childhood Cancer Survivors (3 abstracts)
7.15. Frailty and sarcopenia within the earliest national Dutch childhood cancer survivor cohort (DCCSS-LATER): a cross-sectional study
van Atteveld JE , de Winter DTC , Pluimakers VG , Fiocco M , Nievelstein RAJ , Hobbelink MGG , Kremer LCM , Grootenhuis MA , Maurice-Stam H , Tissing WJE , de Vries ACH , Loonen JJ , van Dulmen-den Broeder E , van der Pal HJH , Pluijm SMF , van der Heiden-van der Loo M , Versluijs AB , Louwerens M , Bresters D , van Santen HM , Hoefer I , van den Berg SAA , den Hartogh J , Hoeijmakers JHJ , Neggers SJCMM , van den Heuvel-Eibrink MM & Dutch LATER study group
J.E.vanAtteveld@prinsesmaximacentrum.nl Lancet Healthy Longev. 2023 Apr;4(4): e155–e165.
Brief summary: This cross-sectional study explored the risk factors for pre-frailty, frailty, and sarcopenia in a cohort of Dutch childhood cancer survivors diagnosed between 1963 and 2001.
Frailty was defined as the presence of at least two (pre-frailty) or three (frailty) of the following criteria: low appendicular lean mass (low percentage of lean tissue in the limbs assessed by dual-energy X-ray absorptiometry, DXA), low muscle strength (measured with a hand-held dynamometer), exhaustion, slowness, or low physical activity measured by a specific scale already validated in patients with chronic diseases. Sarcopenia was defined as the presence of both low appendicular lean mass and low muscle strength (according to the definition of the European Working Group on Sarcopenia in Older People). Associations between these conditions and demographic, treatment-related, endocrine and lifestyle factors were analyzed.
In survivors with complete assessment, the prevalence of pre-frailty was 20.3%, frailty was 7.4%, and sarcopenia was 4.4%. Pre-frailty were associated with: underweight and obesity, cranial irradiation, total body irradiation, cisplatin dose ≥600 mg/m2, growth hormone deficiency, hyperthyroidism, low bone mineral density, and folic acid deficiency. Frailty was associated with: age at diagnosis between 10–18 years, underweight, cranial irradiation, total body irradiation, cisplatin ≥600 mg/m2, higher carboplatin doses, cyclophosphamide equivalent dose ≥20 g/m2, hyperthyroidism, low bone mineral density and folic acid deficiency. Sarcopenia was associated with: male sex, underweight, cranial irradiation, total body irradiation, hypogonadism, growth hormone deficiency, and vitamin B12 deficiency.
This study identifies childhood cancer survivors as individuals at high-risk of pre-frailty, frailty, and sarcopenia, and provide insights into opportunities to decrease the detrimental impact of these conditions on adult life. As expected, cranial and total body irradiation have the greatest adverse impact on body composition and muscle strength. This impact is likely to be even more severe when irradiation occurs during the rapid pubertal growth spurt. Interestingly, body weight seems to be related to body strength in different ways. Obese individuals have a greater risk of disability and impaired physical performance, and obesity is associated with a chronic inflammatory state, which might contribute to frailty. Conversely, underweight and body composition changes characterized by reduced lean mass (sarcopenia) and increased fat mass may be the result of premature systemic ageing.
Most antineoplastic treatments are genotoxic and their association with pre-frailty/frailty is consistent with the increasing evidence that DNA damage is at the basis of the process of ageing and multimorbidity (1). Genome instability, epigenetic changes, impaired mitochondrial function, proteostatic stress, and telomere dysfunction are the biological changes already identified as implicated in the ageing process (2). Early identification of modifiable risk factors as vitamin deficiencies and adequate replacement of hormonal deficiencies, may represent relatively simple interventions to decrease the risk of frailty and sarcopenia. Future studies are needed to evaluate the clinical effectiveness of these measures.
References: 1. Schumacher B, Pothof J, Vijg J, Hoeijmakers JHJ. The central role of DNA damage in the ageing process. Nature. 2021; 592: 695–703. 2. Qin N, Li Z, Song N, et al. Epigenetic age acceleration and chronic health conditions among adult survivors of childhood cancer. J Natl Cancer Inst. 2021;113:597–605.
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ESPE Yearbook of Paediatric Endocrinology
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