Diet and Exercise Interventions in Pediatric Cancer Survivors and Effects on Cardiometabolic Disease Risk and Inflammaging Biomarkers: A Systematic Review

The population of pediatric cancer survivors (PCS) in the United States has been steadily increasing over the last decade. However, due to cancer related treatment and subsequent lifestyle behaviors related to diet and physical activity, PCS are burdened by accelerated biological aging leading to early onset of chronic diseases. The accelerated aging process may be due to “inflammaging,” a phenomenon associated with cardiometabolic diseases risk factors including chronic inflammation and changes in gut microbiome structure and function. This systematic review was conducted to explore the literature as it relates to the impact of diet and/or exercise interventions in survivors of a pediatric cancer on markers of inflammaging and cardiometabolic risk markers. PubMed, CINAHL and clinicaltrials.gov were searched for relevant interventional trials. Studies were included if they contained 1) an intervention arm that included survivors of a pediatric cancer, 2) an intervention that contained a dietary and/or exercise intervention 3) had outcomes related to cardiometabolic disease risk or inflammaging. Bias was assessed using the Cochrane “Risk of Bias Tool” or “Risk Of Bias In Non-randomized Studies - of Interventions” and extracted data was qualitatively reported. Of the sixteen studies identified, two studies employed a diet intervention, six studies employed an exercise intervention and the remaining eight implemented a combined diet and exercise intervention. Exercise was associated with an improvement in glucose homeostasis, yet results were inconsistent across studies. Decreases in body mass index and increases in lean body mass were reported in some diet and exercise interventions. Cautionary interpretation of the outcomes is warranted as the studies had a high risk of bias. Future studies in this area should include trials with a rigorous design, larger sample sizes and increased accessibility of the intervention to address the chronic disease burden among this group of cancer survivors. The study and protocol were registered in PROSPERO (CRD42024511586). Early onset chronic disease driven by accelerated biological aging (inflammaging) and cardiometabolic risk factors in survivors of a pediatric cancer may pose a significant burden on the healthcare system as well negatively impacting the quality of life and increasing early mortality rates in this population. Lifestyle behavior recommendations related to diet and exercise may have a beneficial impact on inflammaging and cardiometabolic risk for pediatric cancer survivors, providing a low cost and salient intervention to mitigate chronic disease burden in this population.