Identifying Sociodemographic, Behavioral, and Genetic Modifiers of a Behavioral Intervention for the Prevention of Overweight/Obesity in Children with ALL

Childhood acute lymphoblastic leukemia (ALL) is the most common childhood cancer, with a survival rate exceeding 90% for children classified with low-risk ALL. The success of treatment for childhood ALL has resulted in a growing population of survivors; however, this is not without short- and long-term side effects related to undergoing treatment for ALL. An underappreciated side effect of the treatment for ALL is the development of overweight/obesity (OW/OB). Up to 70% of children, adolescents, and young adults (C-AYA) with ALL become OW/OB by the end of the 2-year treatment. There are several groups of patients at especially high risk for its development, including females and Hispanic C-AYA. The implications of developing OW/OB have a profound effect on quality of life in survivorship. OW/OB on its own is associated with increased depression, limited social networks, as well as a number of medical conditions. For survivors of ALL, the risk is further compounded, as they are already at elevated risk for cardiac disorders and metabolic disease. The presence of OW/OB escalates the likelihood that a nutrition-related chronic disease will develop and persist throughout adulthood. Identifying variables that render C-AYA highly susceptible to the onset of OW/OB are pressing so that resources can be diverted to those C-AYA who may benefit the most.

It is well established that maintaining a healthy weight is harder for some C-AYA. Individual characteristics such as socioeconomic status, ethnicity, genetics, and lifestyle (e.g., increased intake of fast food and processed foods, low levels of physical activity) all contribute to an individual's risk of becoming OW/OB. Understanding how these variables impact C-AYA receptivity to participate in behavioral modification interventions, and if they have an effect on the efficacy of behavioral modification interventions targeting lifestyle variables is critical for the long-term success and sustainability in the clinical setting. The proposed study will examine well established variables that have been associated with healthy weight maintenance in the C-AYA population but have yet to be comprehensively investigated within the context of childhood ALL.

The proposed study is a companion study to a clinical trial being conducted by Children's Oncology Group (COG), the largest research group located in North America and funded by the National Cancer Institute (NCI), and National Institutes of Health. The PEdiatric Diet intervention for children, adolescents, and young adults with ALL (PEDALL) is a 6-month, bilingual (English/Spanish), telemedicine-based intervention aimed at preventing OW/OB in C-AYA with ALL. PEDALL will recruit 708 Hispanic and Non-Hispanic C-AYA to a 6-month lifestyle behavioral counseling program aimed at improving dietary behaviors during treatment for ALL, while also promoting healthy lifestyles. The conduct of PEDALL will be funded by NCI. The proposed study here requests support only for the ancillary studies so that we can examine individual characteristics that may contribute to the success of PEDALL.

We propose to examine personal characteristics to first determine if they promote or hinder the efficacy of PEDALL. We will then synthesize this information to develop a risk prediction model to identify C-AYA at high risk for the development of OW/OB and who may benefit the greatest from the intervention.

The study aims are: Aim 1: To examine the modifying effect of genetic predisposition to OW/OB, defined by a trans-ethnic genome-wide polygenic score (GPS) for obesity, on the efficacy of PEDALL for the prevention of OW/OB in C-AYA undergoing treatment for ALL; Aim 2: To identify if baseline lifestyle factors (dietary intake and physical activity) modify the efficacy of PEDALL for the prevention of OW/OB in C-AYA undergoing treatment for ALL; Aim 3: To examine the modifying effect of sociodemographic factors (e.g., self-reported race and ethnicity, foreign-born status, food security, and home food environments) on the efficacy of PEDALL for the prevention of OW/OB in C-AYA undergoing treatment for ALL; Aim 4: To develop a multifactorial risk prediction model comprised of genetic predisposition, baseline lifestyle variables, and sociodemographic factors to predict OW/OB.

The clinical impact of this study will improve our understanding of individual characteristics that may be predictive of the efficacy of intervention to prevent unhealthy weight gain among C-AYA patients treated for ALL. Our findings may lead to the allocation of limited clinical resources to individuals most susceptible to OW/OB. The long-term goal is to enhance the likelihood of success of weight maintenance during therapy, thereby mitigating excess toxicities during treatment and reducing nutrition-related late-effects associated with OW/OB among survivors of childhood ALL.