Brain networks involved in cancer treatment response: insights from ¹⁸F-FDG PET scans

Objective. To determine whether pre-treatment brain metabolic network patterns measured with 18 F-FDG PET are associated with treatment response and survival in cancer patients. Approach. Exploratory retrospective study of two independent cohorts: stage III breast cancer patients treated with neoadjuvant chemotherapy and stage IV melanoma patients treated with anti-PD-1 immunotherapy. Metabolic brain network scores were derived from pre-treatment 18 F-FDG PET scans and evaluated for their ability to stratify good versus poor responders using ROC analysis (AUC). Longitudinal changes in network scores were assessed across follow-up, and progression-free survival (PFS) and overall survival (OS) analyses were performed in the melanoma cohort. Main results. Specific brain networks were associated with treatment outcome; the cognition/language network was the strongest predictor (AUC > 0.84 for distinguishing good vs. poor responders in both cohorts). Good responders showed lower cognition/language scores than poor responders and healthy controls. Longitudinally, cognition/language scores remained stable in good responders, while poor responders exhibited a gradual convergence toward the scores observed in good responders. In the melanoma cohort, lower cognition/language scores were significantly associated with longer PFS and OS. Significance. These findings indicate that metabolic brain network patterns, particularly the cognition/language network, may serve as noninvasive biomarkers linked to treatment efficacy and survival in oncology. The results support a possible complex interaction between brain metabolism, immune response, and clinical outcomes. Key limitations include the retrospective design and lack of direct immune-function and psychometric measures; prospective, multimodal studies are needed to validate these observations and elucidate underlying mechanisms.