Monica Messori

Background: Cancer-Related Fatigue (CRF) significantly impairs physical performance and quality of life (QoL) in patients with non-small-cell lung cancer (NSCLC). The OVER-CRF study evaluated the feasibility, safety, and preliminary efficacy of a personalized pulmonary rehabilitation (PR) program combining supervised exercise and education during active treatment. Methods: Patients with stage II–III NSCLC were randomized to Early-PR (initiated at the start of anticancer therapy) or Delayed-PR (initiated three months later). The 3-month intervention included two educational sessions and eight supervised exercise sessions. The primary outcome was adherence; secondary outcomes included safety, CRF (FACIT-FS), QoL (EORTC-QLQ-C30), and physical performance (6MWT). Results: Thirty-one patients were randomized (mean age 67.4 years). Adherence was excellent (Early: 86.7%; Delayed: 91.7%), exceeding feasibility thresholds. No exercise-related adverse events occurred. At 12 months, 50% of participants showed clinically meaningful CRF improvements. While both groups improved 6MWT performance during the intervention, the Delayed-PR group demonstrated more sustained QoL improvements from T1 through T3 compared to the Early-PR group. The dropout rate (25.8%) was consistent with the existing literature. Conclusions: Personalized PR is feasible and safe for NSCLC patients undergoing multimodal therapy. While early intervention provides immediate benefits, initiation timing may influence long-term QoL trajectories. These findings support integrating exercise and education into standard oncological care pathways.