Impact of Radiation Therapy on Survivors of Pediatric Abdominal and Pelvic Tumors

A study published in Cancer Epidemiology, Biomarkers & Prevention suggested that among survivors of childhood abdominal or pelvic tumors, abdominal or pelvic radiotherapy is associated with body composition changes that can adversely influence metabolic outcomes and performance status.¹

The impacts of radiation therapy on metabolic health have previously been reported for survivors of pediatric leukemia, brain tumors, and hematopoietic stem cell transplants, according to Carmen Wilson, PhD, assistant member in the Epidemiology and Cancer Control department at St. Jude Children’s Research Hospital, though the impacts on survivors of pediatric abdominal and pelvic tumors were unclear.²

“Body composition abnormalities and cardiometabolic impairments are of concern among survivors given that in the general population, these conditions increase the risk of developing life-threatening diseases including cardiovascular disease and type 2 diabetes,” Wilson said in a press release.

In total, the study cohort included 431 survivors of abdominal or pelvic tumors. Relative lean mass and fat mass were assessed in participants using dual X-ray absorptiometry and metabolic outcomes, including insulin resistance, high-density lipoprotein, low-density lipoprotein, and triglycerides, were based on laboratory values and medication usage.

Lean mass was found to be lower than values from the National Health and Nutrition Examination Survey (NHANES) in both males (Z-score = -0.67 ± 1.27; P < .001) and females (Z-score = -0.72 ± 1.28; P < .001). Higher cumulative abdominal and pelvic radiation doses were also associated with lower lean mass among males (abdominal: b = -0.22 [SE] ± 0.07; P = .002 and pelvic: b = -0.23 ± 0.07; P = .002) and females (abdominal: b = -0.30 ± 0.09; P = .001 and pelvic: b = -0.16 ± 0.08; P = .037).

“Collectively, ours and others data suggest that survivors may be at risk of developing diabetes through multiple pathways, either from direct damage to the pancreas following radiotherapy, and following [insulin resistance] as a result of alterations in function and secretions of adipocytes and from increased adiposity,” the authors explained.

Moreover, the prevalence of insulin resistance (40.6% vs. 33.8%; P = .006), low HDL (28.9% vs. 33.5%; P = .046), and high triglycerides (18.4% vs. 10.0%; P < .001) was increased among survivors relative to NHANES. Compared with survivors with normal to high lean mass and normal to low fat mass, those with normal to high lean mass and high fat mass had an increased risk of insulin resistance (P < .001), low HDL (P < .001), reduced quadriceps strength at 60° per second (P < .001) and 300° per second (P < .001), and reduced distance covered in a 6-minute walk (P < .01).

“High adiposity and associated reductions in strength, mobility, and flexibility among survivors are of concern because these measures are markers of physical fitness; higher levels of fitness are associated with decreased risk of cardiovascular disease, hypertension, and noninsulin-dependent diabetes mellitus in the general population,” the authors noted.

Notably, given that the researchers used data from NHANES for comparisons of prevalence, differences in the measurement of cardiometabolic outcomes among the survivor cohort and NHANES may have adversely influenced comparisons of prevalence. Even further, though the investigators were unable to examine the influence of abdominal or pelvic surgeries on functional performance among survivors, survivors with serious, severe, or disabling chronic musculoskeletal and neurologic conditions were excluded from analyses.

Moving forward, though it may not be possible to avoid radiotherapy as a key treatment for many solid tumors, the researchers suggested that further research is required to evaluate whether interventions in both child- and adulthood could meliorate abnormalities in body composition and cardiometabolic impairments. In addition, Wilson suggested she is interested in exploring how interventions directed at lifestyle behaviors could improve lean mass and decrease fat mass among survivors of pediatric cancers.

“While it may not be possible to avoid radiation therapy as a key treatment for many solid tumors, early research suggests that resistance training interventions in survivors increase lean mass,” said Wilson. “Further work is needed to see if training would also impact cardiometabolic impairments in this population.”

References:

1. Wilson CL, Liu W, Chemaitilly W, et al. Body Composition, Metabolic Health, and Functional Impairment among Adults Treated for Abdominal and Pelvic Tumors during Childhood. Cancer Epidemiology, Biomarkers & Prevention 2020. doi: 10.1158/1055-9965.EPI-19-1321.

2. Radiation Therapy for the Treatment of Pediatric Cancers May Have Long-term Impacts on Cardiovascular and Metabolic Health [news release]. Published August 13, 2020. Accessed August 17, 2020.