3622 - Safety and Efficacy of Proton Beam Therapy vs. IMRT for Postoperative Radiotherapy in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis
Presenter(s)
K. Shin1, M. El-Jammal1, Simran2,3, L. Martinka3,4, K. Olabode3,4, J. Baldonado5, J. Fontaine5, S. T. Freyaldenhoven5, L. A. Robinson5, E. M. Toloza5, J. Gray6, S. Puri6, A. N. Saltos6, T. Tanvetyanon6, S. A. Rosenberg3, T. J. Dilling3, S. K. Jabbour7, P. A. S. Johnstone3, and J. Kim8,9; 1Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2Department of Radiation Oncology, All India Institute of Medical Sciences (AIIMS), New Delhi, India, 3Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 4Morsani College of Medicine, University of South Florida, Tampa, FL, 5Department of Thoracic Surgery, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 6Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 7Department of Radiation Oncology, Rutgers Cancer Institute, New Brunswick, NJ, 8Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 9Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL
Purpose/Objective(s):
Intensity-modulated radiation therapy (IMRT) enables conformal postoperative radiotherapy (PORT) delivery in non-small cell lung cancer (NSCLC), but normal tissue exposure remains unavoidable. Proton beam therapy (PBT) may further reduce dose to organs at risk due to its distinct physical properties. We performed a systematic review and meta-analysis to compare toxicity, dosimetry, and overall survival between PBT and IMRT for PORT in NSCLC.Materials/Methods:
We systematically searched PubMed, Embase, and the Cochrane Library through February 4, 2026 for comparative studies of PBT versus IMRT in patients who underwent lung resection followed by PORT for NSCLC. The primary endpoints were grade 2+ and grade 3 esophagitis and pneumonitis, captured using the Common Terminology Criteria for Adverse Events. Secondary endpoints included dosimetric parameters and overall survival (OS). Adverse events were summarized as relative risks (RRs), and survival outcomes as hazard ratios (HRs); when HRs were not reported, they were estimated from Kaplan–Meier curves. Random-effects models were used, and heterogeneity was assessed with I².Results:
Three retrospective comparative studies including 295 patients (PBT 139, IMRT 156) were identified. Median age was 63–67 years, and 70–87% of patients had pathologic stage III disease in studies reporting stage distribution. PORT was administered for high-risk features, primarily pN2 nodal involvement and/or positive or concerning surgical margins. PBT was associated with a significantly lower risk of grade 2 or higher esophagitis compared with IMRT (RR 0.56, 95% CI 0.33–0.95; I² = 56%). No statistically significant differences were observed for grade 3 esophagitis (RR 0.52, 95% CI 0.13–2.04), grade 2 or higher pneumonitis (RR 0.58, 95% CI 0.15–2.29), or grade 3 pneumonitis (RR 1.12, 95% CI 0.23–5.32). PBT demonstrated lower mean lung dose (12.15 vs 14.80 Gy), lung V20 (20.27% vs 26.38%), and mean heart dose (5.13 vs 11.79 Gy). With median follow up of 33.8 (Range 26.5-40.3) months, no significant difference in overall survival was observed between modalities (HR 0.92, 95% CI 0.67–1.26).Conclusion:
In this pooled analysis of retrospective studies, PBT was associated with significantly lower rates of grade =2 esophagitis and improved cardiopulmonary dosimetric parameters compared with IMRT in the PORT of NSCLC. However, these advantages did not translate into a demonstrable OS benefit. Given the limited sample size and retrospective design, prospective studies are warranted to determine whether these dosimetric advantages translate into improved long-term clinical outcomes.