3672 - Proton vs. Photon Radiotherapy Combined with EGFR-TKI in EGFR-Mutant Non-Small Cell Lung Cancer: A Real-World Comparative Effectiveness Study
Presenter(s)
Y. Xu1, X. Zhang2, H. Li3, B. Li4, J. Yu5, and L. Wang6; 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, 2Shandong First Medical University, Jinan, China, 3Shandong University Cancer Center, Jinan, China, 4Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China, 5Department of Radiation Oncology and Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, 6Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, Jinan, Shandong, China
Purpose/Objective(s):
Intensity-modulated proton therapy (IMPT) may better preserve normal tissues and mitigate overlapping toxicities compared with intensity-modulated photon radiotherapy (IMRT) due to its favorable dosimetric profile, making it a potentially superior modality when combined with EGFR tyrosine kinase inhibitors (TKIs). This study aimed to evaluate the clinical benefits of IMPT versus IMRT in patients with EGFR-mutant non-small cell lung cancer receiving EGFR-TKI therapy.Materials/Methods:
Patients with EGFR-mutant non-small cell lung cancer who received EGFR-TKIs combined with thoracic radiotherapy between January 2023 and December 2025 were retrospectively enrolled. Patients were divided into IMPT group and IMRT group. Propensity score matching was applied to balance baseline covariates including age, sex, BMI, KPS, disease stage, irradiation site, and treatment sequence. Progression-free survival was estimated using the Kaplan-Meier method and compared by log-rank test. Toxicity profiles, particularly radiation-induced lung injury and TKI-related adverse effects, were systematically recorded and compared between groups. Subgroup analyses based on clinically relevant variables were conducted to identify populations most likely to benefit from IMPT.Results:
A total of 143 patients were included, with 53 in the IMPT group and 90 in the IMRT group. After propensity score matching, baseline characteristics were well balanced between the two groups. The median PFS was 10.03 months in the IMPT group and 9.33 months in the IMRT group (HR = 0.91, 95% CI: 0.48-1.70, p = 0.761). Regarding safety, the incidence of grade =2 myelosuppression was 25.6% in both groups; the incidence of esophagitis was 16.28% and 25.58%, respectively; the incidence of all-grade pneumonitis was 18.6% and 34.88%, respectively; and the incidence of grade =2 pneumonitis was 4.65% and 13.95%, respectively. Subgroup analysis showed that the PFS benefit of IMPT was consistent across most subgroups. A nomogram for PFS prediction constructed in the IMPT group revealed that M1 stage and WBC count within one week after radiotherapy were independent risk factors for PFS, with a C-index of 0.771 (0.712-0.831).Conclusion:
For patients with EGFR-mutant non-small cell lung cancer receiving EGFR-TKIs combined with thoracic radiotherapy, IMPT did not significantly prolong PFS compared with IMRT, but significantly reduced the incidence of pneumonitis (both all-grade and grade =2) and showed a trend toward lower esophagitis. The nomogram based on M1 stage and post-radiotherapy WBC count demonstrated good predictive performance for PFS in patients receiving IMPT combined with TKIs. This study provides safety evidence supporting the application of IMPT in combination with EGFR-TKIs.