PROJECT SUMMARY / ABSTRACT Children and adolescents diagnosed with cancer now have, on average, nearly 85% 5-year survival. However, premature cardiovascular (CV) disease has become the leading non-cancer cause of late mortality among childhood cancer survivors. There is a robust body of evidence from the general population, and increasingly, among cancer survivors (even those exposed to cardiotoxic cancer therapies), that greater physical activity (PA) and improved diet quality can reduce future CV-related morbidity. However, while many general population and cancer-specific intervention studies have focused on a single lifestyle factor (e.g., PA or diet alone), given the interplay between PA and dietary factors in influencing CV health, a multi-faceted approach may result in overall better long-term CV health profiles. Research on lifestyle interventions in cancer survivors also has been predominantly conducted in women with breast cancer, and the evidence for survivors of childhood cancer is limited. To accomplish our aims, we will use the largest prospectively followed childhood cancer survivor cohort in the world, the Childhood Cancer Survivor Study (CCSS; n>24,000), to recruit adult-aged participants at increased risk of early CV disease (n=403) for a remotely conducted 12-month randomized controlled trial testing a multi-faceted approach at improving PA and diet quality. Specifically, the study will use a sequential multiple assignment randomized trial (SMART) design, where participants with low PA or poor diet will first be randomized between intervention and control conditions. Intervention participants will be further randomized to receive either clinician-led telehealth sessions focused on risk factor self-management, or weekly mobile health (mHealth) supported individualized PA and dietary goal-setting with social media peer support. The adaptive SMART design will allow further tailoring of the intervention experience based on initial response, which may increase overall intervention efficacy. Participants not initially responsive to their assigned intervention will be further randomized to receive an alternate intervention. The study will use consumer-grade mHealth applications that track PA and diet, thereby increasing future dissemination capacity. The study’s primary analyses will determine the overall intervention efficacy and whether specific intervention strategies and sequence of strategies are associated with optimal outcomes. Secondary analyses will examine potential predictors, mediators, and moderating factors associated with PA and dietary changes over time, as well as changes in participants’ cardiometabolic profiles. In summary, lifestyle change represents one of the few available strategies to mitigate CV risk in childhood cancer survivors. Significant barriers (e.g., time, training, resources) limit the ability of healthcare systems to facilitate such change. To fill this void, remote-based, personalized, and easily disseminated multi-faceted mHealth-supported interventions may play a transformative role.

PROJECT NARRATIVE With improved treatments, the vast majority of children diagnosed with cancer are now cured. However, premature cardiovascular disease has become the leading non-cancer cause of death among childhood cancer survivors. Using an adaptive study design, the proposed trial seeks to determine if various innovative intervention strategies can help childhood cancer survivors improve their physical activity and dietary habits in order to reduce their long-term risk of early cardiovascular disease.