Risk factors for radiation pneumonitis in NSCLC patients treated with third-generation EGFR TKIs and chest radiotherapy

Radiat Oncol. 2025 May 9;20(1):72. doi: 10.1186/s13014-025-02649-0.

Abstract

Background: Non-small cell lung cancer (NSCLC) patients receiving third-generation EGFR TKIs with thoracic radiotherapy (TRT) significantly prolong survival and also increase the incidence of radiation pneumonitis (RP). The aim of our study was to investigate the incidence and risk factors of RP in NSCLC patients receiving third-generation EGFR TKIs and TRT.

Patients and methods: We retrospectively evaluated NSCLC patients who received both third-generation EGFR TKIs and TRT at the General Hospital of Ningxia Medical University from January 2023 to September 2024. RP was diagnosed by clinical symptoms on computed tomography (CT) scans and graded according to the Common Terminology Criteria for Adverse Events 5.0. Risk factors for RP were determined by univariate and multivariate logistic regression analysis.

Results: Of the 42 patients included, 26 (61.9%) developed RP and 14 (33.3%) developed grade ≥ 2 RP. Grade ≥ 2 RP all occurred within 6 months of receiving TRT, and the median time from TRT to RP was 3.69 months (2-10 months). GTV ≥ 39 ml and total lung V20 ≥ 14.95% were found to be independent risk factors for RP development.

Conclusion: The strategy of combining a third-generation TKI with TRT significantly increases the incidence of RP, and the risk of RP in these patients can be reduced by adjusting lung radiation dosimetry parameters. In NSCLC patients taking triple-generation TKIs with primary tumour progression, the timing and dose of TRT addition must be strictly controlled to optimise the therapeutic strategy and reduce the incidence of RP.

Clinical trial number: Not applicable.

Keywords: Chest radiotherapy; Non-small cell lung cancer; Radiation pneumonitis; Risk factors; Third-generation EGFR TKIs.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Carcinoma, Non-Small-Cell Lung* / radiotherapy
  • Carcinoma, Non-Small-Cell Lung* / therapy
  • ErbB Receptors / antagonists & inhibitors
  • Female
  • Humans
  • Incidence
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / pathology
  • Lung Neoplasms* / radiotherapy
  • Lung Neoplasms* / therapy
  • Male
  • Middle Aged
  • Prognosis
  • Protein Kinase Inhibitors* / adverse effects
  • Protein Kinase Inhibitors* / therapeutic use
  • Radiation Pneumonitis* / epidemiology
  • Radiation Pneumonitis* / etiology
  • Retrospective Studies
  • Risk Factors

Substances

  • ErbB Receptors
  • Protein Kinase Inhibitors
  • EGFR protein, human