PROJECT ABSTRACT Cancer-related fatigue (CRF) is one of the most common and functionally limiting symptoms reported by cancer survivors. While no standard of care exists for CRF management, clinically supervised exercise is one of the best-known interventions for CRF. Exercise prescription (ExRx) for survivors, however, is currently guideline- driven, lacking personalization and limiting overall efficacy. Rural cancer survivors experience poor health outcomes, including increased risk of CRF, have limited access to clinical exercise programs, and stand to benefit from improved ExRx personalization. The long-term goal of this investigation is to develop an effective telehealth exercise program for rural cancer survivors with CRF. While many investigations of interventions for rural survivors focus on the implementation of established services, this proposal utilizes innovative accessible methodology to integrate assessments of exercise-associated mechanisms of CRF remediation into a clinical efficacy trial. The purpose of these assessments is to provide the foundation for future innovations in improved ExRx personalization, optimizing individual survivor outcomes, and to do so first in an underserved population that stands to benefit from the outcomes. This investigation will be accomplished by pursuing three specific aims. Aim 1 investigates the efficacy of a novel telehealth exercise program for rural cancer survivors with CRF (the BfitBwell Telehealth Program [BfitBwell-TP]) in a randomized control trial. Rural breast and prostate cancer survivors within five years of completing curative treatment and experiencing CRF (N=134) will be recruited into the intervention or wait-list control group. A pilot investigation of BfitBwell-TP demonstrated feasibility, acceptability, and similar reductions in CRF compared to the clinically supervised program upon which it is based. BfitBwell-TP utilizes existing telehealth methodologies to deliver a combination of synchronous and asynchronous exercise sessions paired with CRF monitoring and symptom-triggered ExRx personalization to support CRF improvement. Aim 2 examines the effects of impaired objective physical function and fatty acid oxidation on reduced CRF response to exercise during the intervention with integrated within-program (every two weeks) remote assessments. Both have been associated with fatigue and both can be specifically targeted by ExRx personalization. Recent advances have allowed the remote assessment of objective physical function and the use of remotely collected, stable dried blood spot (DBS) samples in metabolomic analyses of impaired fatty acid oxidation. Finally, Aim 3 explores additional biomarkers of exercise-associated CRF remediation through the investigation of dynamic exercise metabolic profiles established during controlled, laboratory-based exercise sessions. This Aim performs necessary work to provide the foundation for the development of remotely assessed dynamic exercise metabolic profiles. This proposal is significant because it utilizes an accessible intervention to reduce CRF in underserved rural cancer survivors and integrates innovative methodology to drive continued improvement in this intervention, ultimately reducing the burden of cancer for rural survivors.

PROJECT NARRATIVE The proposed investigation is relevant to public health because it focuses on establishing the efficacy of an accessible telehealth exercise intervention specifically for rural cancer survivors experiencing cancer-related fatigue. Novel methods of remotely assessing objective physical function and performing state-of-the-art metabolomic analyses are utilized to investigate exercise-associated mechanisms of cancer-related fatigue remediation first in an underserved population that stands to benefit from subsequent innovations in exercise prescription due to existing health disparities. Thus, the proposed research is relevant to the interest of the NCI Division of Cancer Control and Population Sciences in reducing the burden of cancer through improved survivorship.