Overweight in the Dutch National Cohort of Long-Term Survivors of Childhood Cancer
Authors: Pluimakers Vincent G. , Van Atteveld Jenneke E. , de Winter Demi T.C. , Fiocco Marta , Nievelstein Rutger A.J. , Bresters Dorine , Van der Heiden-Van der Loo Margriet , de Vries Andrica , Janssens Geert O , Louwerens Marloes , Van der Pal Helena J. , Ronckers Cecile M. , Van Santen Hanneke M. , Versluys Birgitta , Kremer Leontien , Loonen Jacqueline J. , Tissing Wim J.E. , Van Dulmen-Den Broeder Eline , van den Heuvel-Eibrink Marry M. , Neggers Sebastian J.C.M.M. 
Published: November 2021

Abstract
BACKGROUND
Overweight is a common problem in the general population, but occurs more frequently among childhood cancer survivors (CCS) and is regarded as a late adverse effect. However, risk factors are not fully elucidated and it is often disguised in CCS because they can have normal weight but high fat percentage (fat%) on dual-energy X-ray absorptiometry (DXA, gold standard). We aimed to assess overweight prevalence in a nationwide survivor cohort, to clarify risk factors and to identify which measurement method captures overweight best.
METHODS
The prevalence of overweight and obesity (body mass index (BMI) ≥25 and ≥30 kg/m 2) was assessed in the Dutch nationwide cohort of adult CCS treated between 1963 and 2002. Risk factors for overweight were analyzed using multivariable logistic regression models. In addition, overweight prevalence was calculated according to fat%, waist circumference (WC), waist/hip ratio (WHR) and waist/height ratio (WHtR). The validity of BMI, WC, WHR and WHtR for characterizing obesity, compared to fat% (expressed as false-negative percentage and in logistic regression models to identify treatment-related risk factors for disguised overweight) was studied.
RESULTS
A total of 2,338 (51.2% male) survivors (54.7% hematologic malignancies) participated, with mean age 35.5 (±9.3) years and 28.3 (±8.4) years follow-up. In men and women respectively, overweight prevalence was 45.9% and 43.8%, for obesity this was 11.2% and 15.5%.
Risk factors for overweight included overweight at cancer diagnosis (adjusted odds ratio (aOR) 3.43, p&lt;0.001), cranial radiotherapy (CRT, aOR 3.27, p&lt;0.001) and growth hormone deficiency (GHD) (unadjusted OR 2.28, p&lt;0.001, after adjustment the effect partially disappeared, aOR 1.60, p=0.072). Previous treatment with corticosteroids was not associated with overweight.
Using BMI, WC, WHR and WHtR, similar overweight prevalence was observed. However, this was 58.4% in men and even 83.7% in women when measured with DXA. Disguised overweight was more frequent after treatment with abdominal radiotherapy, high dose anthracyclines and stem cell transplantation (SCT) (aOR up to 3.37).
CONCLUSIONS
Overweight occurs in almost half of all long-term CCS, and risk factors include overweight at cancer diagnosis, CRT and potentially GHD. DXA identified overweight in an additional 25% of survivors. In CCS treated with abdominal irradiation, anthracyclines and SCT, overweight is more often missed with conventional methods. Hence, in these risk groups DXA needs serious consideration in surveillance, to enable early intervention and prevent complications of overweight including diabetes and atherosclerotic disease.

Disclosures
No relevant conflicts of interest to declare.