نبذة مختصرة : Simple Summary: Non-small cell lung cancer (NSCLC) is a major cause of cancer-related mortality. While radiotherapy is a standard treatment, traditional photon (X-ray) radiation can inadvertently expose healthy organs, such as the heart and lungs, to excess dose. Proton beam therapy (PBT) allows for more precise radiation delivery, potentially reducing the risk of side effects. In this systematic review and meta-analysis of seven studies involving over 240,000 patients, we compared the clinical outcomes of PBT versus photon radiotherapy. Our analysis indicated that while long-term survival rates appeared similar between the two modalities, PBT was associated with improved odds of survival during the first year following treatment. These findings are hypothesis-generating and suggest that PBT might be a valuable option for patients who are frail or at high risk of toxicity, potentially helping to mitigate early treatment-related mortality. Purpose: Proton beam therapy (PBT) offers superior dosimetric sparing of organs at risk compared to photon radiotherapy for non-small cell lung cancer (NSCLC); however, comparative clinical evidence regarding survival benefits remains conflicting. This systematic review and meta-analysis aimed to evaluate the clinical outcomes and toxicity profiles of PBT versus photon radiotherapy, with a specific focus on time-dependent survival patterns. Methods: We searched PubMed, EMBASE, and Cochrane CENTRAL databases for comparative studies published up to 10 October 2025. Primary outcomes were overall survival (OS), progression-free survival (PFS), and local progression-free survival (LPFS). Individual patient data (IPD) were reconstructed from Kaplan–Meier curves when hazard ratios (HRs) were not reported. Odds ratios (ORs) were calculated for survival at fixed time points (1, 3, and 5 years) and for toxicity endpoints. Results: Seven studies comprising 244,604 patients were included, encompassing retrospective cohorts, multi-institutional datasets, and one randomized trial. In the overall pooled analysis, PBT showed no statistically significant superiority over photon radiotherapy for OS (HR = 0.91, 95% CI: 0.69–1.19, p = 0.483), PFS (HR = 1.09, 95% CI: 0.81–1.47, p = 0.572), or LPFS (HR = 0.89, 95% CI: 0.47–1.69, p = 0.732). Sensitivity and subgroup analyses restricted to Stage I and Stage I–II NSCLC similarly failed to demonstrate significant differences in survival outcomes. However, exploratory time point analysis utilizing ORs revealed a distinct temporal pattern: PBT was associated with improved odds of all-cause mortality at 1 year (OR = 0.60, 95% CI: 0.49–0.73, p < 0.001). This survival advantage dissipated over time, with no significant differences observed at 3 years or 5 years. Regarding safety, PBT did not significantly reduce the odds of grade ≥ 2 radiation pneumonitis (OR = 0.98, 95% CI: 0.41–2.33, p = 0.967) or grade ≥ 3 events (OR = 1.40, p = 0.540) compared to photons. Conclusions: While long-term oncologic control appears comparable between proton and photon radiotherapy, exploratory analyses suggest that PBT is associated with improved odds of 1-year overall survival. This potential early benefit, observed in retrospective cohorts, likely reflects the mitigation of acute treatment-related mortality. These findings are hypothesis-generating and support the use of PBT for patients at high risk of toxicity and advocate for a model-based approach to patient selection. [ABSTRACT FROM AUTHOR]
Processing Request
No Comments.