3523 - Proton Beam Therapy vs. Intensity-Modulated Radiation Therapy in Oropharyngeal Cancer: A Systematic Review and Individual Patient Data Meta-Analysis
Presenter(s)
C. C. Lee1, W. Sittiwong2, and U. Parvathaneni3; 1Department of Radiation Oncology, National University Cancer Institute, Singapore, Singapore, Singapore, 2Division of Radiation Oncology, Department of Radiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, 3University of Washington, Department of Radiation Oncology, Seattle, WA
Purpose/Objective(s): Whether proton beam therapy (PBT) improves survival compared with intensity-modulated radiation therapy (IMRT) for locally advanced oropharyngeal carcinoma (OPC) remains uncertain. This study aims to compare survival outcomes and adverse events between PBT and IMRT.
Materials/Methods: A systematic search of PubMed, Embase, Cochrane, and conference proceedings was conducted for comparative studies of PBT vs IMRT in the definitive treatment of OPC. Primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS) and adverse events. Risk of bias was assessed using the Cochrane RoB-2 for randomized trials and Newcastle-Ottawa Scale for non-randomized studies. Individual patient data (IPD) from published Kaplan-Meier curves were reconstructed using a graphical reconstruction algorithm and pooled as a one-stage meta-analysis. A sensitivity analysis was performed using a two-stage meta-analysis random-effect model. Between-study heterogeneity was evaluated using I2 statistics. Subgroup analysis was performed based on study design (prospective vs retrospective), HPV status, smoking, and T/N-stage. Odd ratios (ORs) for adverse events were calculated. Evidence certainty was evaluated for primary outcome using GRADE framework. The study was registered with PROSPERO (CRD420261304104).
Results: Four studies (including 2 randomized trials) with 1,087 patients were identified. Three studies demonstrated a low risk of bias; one had some concerns. PBT significantly improved OS compared with IMRT (HR, 0.63; 95% CI, 0.40-0.98; P= 0.04; moderate certainty). Sensitivity analysis yielded a consistent result for OS (HR, 0.60; 95% CI, 0.38-0.96; P= 0.03; I2= 0%). OS rates for PBT vs IMRT at 2, 3 and 5 years were 94%, 93%, and 92%, vs 93%, 91%, and 83%, respectively. No significant effect modifications were observed across the predefined subgroups (interaction P > 0.05). PBT did not significantly improve PFS compared with IMRT (HR, 0.82; 95% CI, 0.49-1.37; P= 0.45; I2= 26%). PBT was associated with significantly lower rates of gastrostomy tube dependence within 3 months (OR, 0.53; 95% CI, 0.35-0.80; P < 0.01) and acute grade =3 weight loss (OR, 0.64; 95% CI, 0.43-0.97; P= 0.03), xerostomia (OR, 0.60; 95% CI, 0.37-0.95; P= 0.03), and dysphagia (OR, 0.52; 95% CI, 0.34-0.81; P < 0.01). No significant differences were found in long-term gastrostomy tube dependence (OR, 0.35; 95% CI, 0.10-1.22; P= 0.10) and osteoradionecrosis (OR, 0.40; 95% CI, 0.08-1.95; P= 0.26).
Conclusion: This IPD meta-analysis provides high-level evidence that PBT significantly improves OS compared with IMRT in oropharyngeal cancer, characterized by a 9% absolute survival benefit at 5 years. PBT significantly reduces acute high-grade adverse events and early tube dependence. These findings suggest that PBT optimizes the therapeutic ratio and should be considered a preferred treatment modality. Further research is needed to define late normal tissue effects and cost-effectiveness.