Prevalence, risk factors, and optimal way to determine overweight, obesity, and morbid obesity in the first Dutch cohort of 2338 long-term survivors of childhood cancer: a DCCSS-LATER study.

BACKGROUND: Overweight and obesity are common challenges among childhood cancer survivors. Overweight may be disguised, as survivors can have normal weight but high fat percentage (fat%) on dual-energy X-ray absorptiometry (DXA). We aimed to assess prevalence, identify determinants and biomarkers, and assess which method captures overweight best, in a nationwide cohort. METHODS: The prevalence of overweight and obesity, primarily defined by body mass index (BMI), was assessed in the DCCSS-LATER cohort of adult survivors treated from 1963-2002, with the LifeLines cohort as reference. The associations between risk factors and overweight metrics were investigated using logistic regression. Additional overweight metrics included DXA fat%, waist circumference (WC), waist/hip ratio (WHR), waist/height ratio (WHtR), and high-molecular-weight (HMW) adiponectin. RESULTS: A total of 2338 (mean age 35.5 years, follow-up 28.3 years) survivors participated. The overweight prevalence was 46.3% in men and 44.3% in women (obesity 11.2% and 15.9%, morbid obesity 2.4% and 5.4%), with highest rates among brain tumor survivors. Compared to controls, there was no overall increased overweight rate, but this was higher in women > 50 years, morbid obesity in men > 50 years. Overweight at cancer diagnosis (adjusted odds ratio [aOR] = 3.83, 95% CI 2.19-6.69), cranial radiotherapy (aOR = 3.21, 95% CI 1.99-5.18), and growth hormone deficiency (separate model, aOR = 1.61, 95% CI 1.00-2.59) were associated with overweight. Using BMI, WC, WHR, and WHtR, overweight prevalence was similar. Low HMW adiponectin, present in only 4.5% of survivors, was an insensitive overweight marker. Dual-energy X-ray absorptiometry-based classification identified overweight in an additional 30%, particularly after abdominal radiotherapy, total body irradiation, anthracyclines, and platinum. CONCLUSIONS: Overweight occurs in almost half of long-term survivors. There was no overall increased incidence of overweight compared to controls. We identified factors associated with overweight, as well as subgroups of survivors in whom DXA can more reliably assess overweight.

Acute and early-onset cardiotoxicity in children and adolescents with cancer: a systematic review.

BACKGROUND: Cardiotoxicity is among the most important adverse effects of childhood cancer treatment. Anthracyclines, mitoxantrone and radiotherapy involving the heart are its main causes. Subclinical cardiac dysfunction may over time progress to clinical heart failure. The majority of previous studies have focused on late-onset cardiotoxicity. In this systematic review, we discuss the prevalence and risk factors for acute and early-onset cardiotoxicity in children and adolescents with cancer treated with anthracyclines, mitoxantrone or radiotherapy involving the heart. METHODS: A literature search was performed within PubMed and reference lists of relevant studies. Studies were eligible if they reported on cardiotoxicity measured by clinical, echocardiographic and biochemical parameters routinely used in clinical practice during or within one year after the start of cancer treatment in ≥ 25 children and adolescents with cancer. Information about study population, treatment, outcomes of diagnostic tests used for cardiotoxicity assessment and risk factors was extracted and risk of bias was assessed. RESULTS: Our PubMed search yielded 3649 unique publications, 44 of which fulfilled the inclusion criteria. One additional study was identified by scanning the reference lists of relevant studies. In these 45 studies, acute and early-onset cardiotoxicity was studied in 7797 children and adolescents. Definitions of acute and early-onset cardiotoxicity prove to be highly heterogeneous. Prevalence rates varied for different cardiotoxicity definitions: systolic dysfunction (0.0-56.4%), diastolic dysfunction (30.0-100%), combinations of echocardiography and/or clinical parameters (0.0-38.1%), clinical symptoms (0.0-25.5%) and biomarker levels (0.0-37.5%). Shortening fraction and ejection fraction significantly decreased during treatment. Cumulative anthracycline dose proves to be an important risk factor. CONCLUSIONS: Various definitions have been used to describe acute and early-onset cardiotoxicity due to childhood cancer treatment, complicating the establishment of its exact prevalence. Our findings underscore the importance of uniform international guidelines for the monitoring of cardiac function during and shortly after childhood cancer treatment.

Long-term safety of growth hormone replacement therapy in survivors of cancer and tumors of the pituitary region.

Growth hormone deficiency (GHD) is a common complication in survivors of cancer and patients with tumors of the pituitary region. Growth hormone replacement therapy (GHT) has proven beneficial effects, including increased growth velocity, positive effects on body composition and skeletal integrity, and increased quality of life. However, due to known pro-proliferative, angiogenic, and anti-apoptotic properties of growth hormone, there are still some concerns about the safety of GHT in survivors. This narrative review aims to provide an overview of the long-term sequelae, and subsequently long-term safety, of GHT in survivors of (childhood) cancer and patients with tumors of the pituitary region. We identified predominantly reassuring results regarding the safety of survivors with GHT, although we must take into account the shortcomings of some studies and limited information on adult cancer survivors. Besides the already increased risk for second neoplasms, recurrences, or mortality in survivors due to host-, disease-, and treatment-related factors, we could not identify an increased risk due to GHT in particular. Therefore, we support the consensus that GHT can be considered in survivors after careful individual risk/benefit analysis and in open discussion with the patients and their families, taking into account the known morbidity of untreated GHD in cancer survivors and the positive effects of GHT.