ORIGINAL RESEARCH article
Front. Oncol.
Sec. Radiation Oncology
Effect, Safety, Timing and Dose of Thoracic Radiotherapy Plus Third-Generation EGFR-TKIs as First-Line Treatment in Patients with EGFR-Mutated Oligo-Organ Metastatic NSCLC
Provisionally accepted
- Shandong Cancer Hospital, Shandong University, Jinan, China
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Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-based combination therapy modalities for patients with EGFR-mutated stage IV non-small cell lung cancer (NSCLC) are being investigated. We evaluated the value and safety of third-generation EGFR-TKIs combined with thoracic radiotherapy (TRT) in patients with oligo-organ metastatic, along with the optimal TRT timing and dose. Methods: We retrospectively enrolled patients with EGFR-mutated oligo-organ metastatic NSCLC who received first-line third-generation EGFR-TKIs from 2018 to 2023. Patients were divided into TKI-alone and TKI+TRT groups according to whether TRT was added. Propensity score matching (PSM) was implemented to decrease bias.The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and safety. Results: A total of 236 patients were included, the median follow-up was 28.4 months . After PSM, baseline characteristics were balanced between the TKI+TRT (n=69) and TKI-alone (n=108) groups. Compared with the TKI-alone group, the TKI+TRT group presented significantly better PFS (28.6 vs. 19.8 months, hazard ratio [HR]=0.48, P=0.00024) and OS (42.2 vs. 35.1 months, HR=0.54, P=0.039). In patients who received TRT, the tumor shrinkage group demonstrated significantly improved PFS (HR=0.36, P=0.0035) and OS (HR=0.13, P=0.0012) compared to the tumor enlargement/Stabilizationg group. The high-dose group showed superior PFS (HR=0.43, P=0.011) and OS (HR=0.36, P=0.023) compared to the low-dose group. Only 5.8% of patients in the TKI+TRT group developed grade ≥3 pneumonitis. Conclusion: Incorporating TRT provided significant survival benefits in patients with oligo-organ metastatic NSCLC who received first-line third-generation EGFR TKIs, with acceptable side effects. The administration of higher radiation doses during a phase of tumor shrinkage may be associated with optimal outcomes.
Keywords: Non-small cell lung cancer, Radiotherapy, epidermal growth factor receptor, tyrosine kinase inhibitor, Radiation Dosage
Received: 18 Sep 2025; Accepted: 12 Nov 2025.
Copyright: © 2025 Gu, Geng, Sun, Cao, Yi and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Baosheng Li, bsli@sdfmu.edu.cn
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