Mitochondrial Bioenergetics in Resilience of Older Adults with Gynecologic Cancer: Design and Rationale of a Pilot Study.

Resilience, the ability to recover and maintain function following stresses, is a critical factor influencing treatment tolerance and recovery in older adults with cancer. Despite the high incidence of gynecologic cancers in postmenopausal individuals, resilience in this population remains underexplored, even though patients commonly face compounded stress from both chemotherapy and surgery. The goal of our research is 1) to test the feasibility of cognitive and physical function assessments in older women with gynecologic cancers and 2) to discover reliable predictors that enhance clinical decision-making and guide personalized treatment strategies. Current clinical assessments focus on isolated physiological systems. As such, there is a need for a reliable predictor that captures systemic resilience more comprehensively. A reliable predictor of resilience following cancer treatment could improve clinical decision-making and identify potential targets for therapeutic intervention. Both mitochondrial bioenergetics and oxidative stress are presumably mechanistically linked to resilience of patients with gynecologic cancers because of widely known effects of chemotherapy and tumor burden on mitochondrial bioenergetics. Mitochondria generate more than 95% of cellular ATP through oxidative phosphorylation, a process essential for recovery following physiological stress. Oxidative stress disrupts excitation-contraction coupling and reduces metabolic efficiency in skeletal muscle, contributing to weakness and fatigue. In the brain, oxidative modifications have been associated with impaired neurotransmission and cognitive dysfunction. This protocol paper describes a longitudinal study design aimed at evaluating the feasibility of resilience assessment and testing mitochondria and oxidative stress as predictors of resilience in older adults diagnosed with advanced endometrial or ovarian cancer.