Serum GFAP as a Potential Biomarker for Chemotherapy-Associated Cognitive Impairment in Elderly Patients with Gastrointestinal Cancers: An Exploratory Study.

Abstract

Introduction: Chemotherapy-associated cognitive impairment (CACI) is a common yet underdiagnosed condition among elderly cancer patients. Glial fibrillary acidic protein (GFAP), a marker of astrocytic activation, has emerged as a potential indicator of neuroinflammation.

Materials and methods: This observational case-control study included 41 elderly patients with stage II-III colon, gastric, or pancreatic cancer who received 12 cycles of adjuvant chemotherapy, and 30 age- and sex-matched healthy controls. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) at baseline, mid-treatment, and 3 months post-treatment. Quality of life was evaluated using the Functional Assessment of Cancer Therapy-General (FACT-G). Serum GFAP and C-reactive protein (CRP) levels were measured at baseline and follow-up.

Results: Post-treatment MMSE scores significantly declined in the patient group (mean = 24.87 ± 2.14 vs. baseline = 26.92 ± 0.99, p < 0.001), with 51% of patients showing cognitive impairment. GFAP levels increased significantly in cognitively impaired patients (from 374.64 ± 142.14 to 464.79 ± 181.94 ng/ml, p < 0.001), while ROC analysis identified a GFAP cut-off of 337 ng/ml with 94.74% sensitivity and 92.48% specificity for predicting CACI. Logistic regression showed that both elevated follow-up GFAP levels were independent predictors of CACI.

Discussion: Elevated serum follow-up GFAP levels are significantly associated with cognitive impairment following chemotherapy in elderly patients with gastrointestinal cancers, suggesting a role for astrocytic activation in CACI pathogenesis. GFAP may serve as a promising biomarker for risk stratification and early intervention.