Chemotherapy-induced cognitive impairment: A novel prospective study of the cognitive effects of platinum/taxane-based chemotherapy in ovarian cancer patients

Background: Chemotherapy-induced cognitive impairment (CICI) is a spectrum of neurocognitive deficits experienced with cheomtherapy for cancer. The incidence of CICI is significant, affecting 25 to 75% of survivors. Hypothosis: Ovarian cancer patients receiving platinum-taxane chemotherapy experience quantifiable declines in cognitive function when measured pre- and post-chemotherapy. Mechanistic markers of cognitive impairment hypothesized to change with chemotherapy include serum markers of ixidative stress and alterations in brain function measured through neuroimaging. Specific Aims: In a group of ovarian cancer patients undergoing platinum/taxane cheomtherapy, we aim to: 1) Identify and quantify cognitive changes; 2) Measure changes in serum levels of tumor necrosis factor alpha, protein carbonyls and 4-hydorxynonenal protein adducts and correlate these findings with neurocognitive outcomes; 3) Gain an understanding of structural and functional changes in the brain, and correlate these findings with neurocognitive outcomes and serum markers of oxidative stress. Study Design: This prospective, phase II study evaluates cognitive changes in ovarian cancer patients undergoing platinum/taxane chemotherapy with correlative studies evaluating markers of oxidative stress and neuroimaging. "Cognitive changes" is defined by a significant relaibel change index (|RCI| > Z0.975) between pre- and post-chemotherapy neurocognitive measurements for the Montreal Cognitive Assessment total score. Cancer Relevance: This novel study addresses the incidence and cause for CICI, while gaining an understanding of the structural and functional effects of chemotherapy on the brain. Outcomes will impact cancer research by enhancing the approach to patients with CICI, while providing a comprehensive understanding of the etiology to direct future therapeutic interventions.