Assessment of chemotherapy-induced cognitive impairment: A prospective study of the biochemical and metabolic effects of platinum/taxane-based chemotherapy in gynecologic cancer patients.

Abstract

e24051 Background: Chemotherapy-induced cognitive impairment (CICI) is a common side effect of cancer therapy, affecting up to 75% of cancer patients. Oxidative stress is thought to play a key role in CICI and patients who have been treated with chemotherapy have demonstrated biochemical brain changes on magnetic resonance spectroscopy (MRS). Methods: Following institutional review board approval, chemotherapy-naïve gynecologic cancer patients scheduled to receive intravenous platinum/taxane-based chemotherapy were identified. The primary objective of this study was identification of chemotherapy-induced cognitive function changes using the Montreal Cognitive Assessment (MoCA) tool. This exploratory analysis evaluates correlations between changes in MoCA scores, oxidative analytes TNF-a, protein carbonyls (PC), and 4-hydroxynonenal (HNE) protein adducts, and MRS metabolic signals. Testing was performed at baseline and three weeks post-treatment. Simple linear regression was performed to evaluate the correlation between changes in MoCA scores and oxidative metabolites. Results: Fourteen patients were enrolled. Six patients had complete pre/post oxidative stress data, and four patients had complete pre/post MRS data. Five of six had decreased PC values (mean net change -15.17%, SD 0.15), half had increased HNE levels (mean net change +16.38%, SD 0.38), and four of six had decreased TNF-a values (mean net change -15.10%, SD 0.27) (Table). MoCA scores were positively correlated with serum PC levels ( r = 0.86, p = 0.03) and not significantly correlated with TNF-a or HNE levels. Of those with complete pre/post MRS data, all patients had a decrease in glycerophosphocholine + phosphocholine/creatinine ratio signals. MoCA raw score prior to and after completion of chemotherapy. A higher score indicates improved test performance. Positive percentage of oxidative stress markers (PC, HNE, TNF-a) indicates increased post-therapy levels compared to pre-therapy. Conclusions: In this study, we evaluated candidate oxidative stress serum markers and changes in MRS metabolite signals for CICI. Serum PC levels correlate with cognitive screening scores. For patients undergoing brain imaging, MRS evaluation for individual choline components, glycerophosphocholine and phosphocholine, may serve as an additional marker of oxidative damage. This pilot study highlights the potential value of serum PC levels and dedicated brain imaging for signs of oxidative stress, including MRS, to guide future CICI identification studies. Clinical trial information: NCT03324945. [Table: see text]