Comparison of the Incidence Rate of Radiation Pneumonitis Observed in Patients with Advanced Lung Adenocarcinoma Treated with Simultaneous Thoracic Radiotherapy and 1G/2G/3G EGFR-TKIs

Abstract

Abstract Background: The present study aimed to evaluate the incidence rate of radiation pneumonitis (RP) in patients with stage III-IV lung adenocarcinoma treated with first-generation (1G), second-generation (2G), or third-generation (3G) epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with thoracic radiotherapy (TRT). Methods: Patients with stage III-IV lung adenocarcinoma simultaneously treated with 1G, 2G, or 3G EGFR-TKIs and TRT between January 2015 to December 2021 at Shandong Cancer Hospital and Institute were screened in this retrospective study. The clinical and imaging grades of RP were evaluated using the Common Terminology Criteria for Adverse Events (version 5.0) grading system for pneumonitis and pulmonary fibrosis, respectively. Results: A total of 200 patients treated with EGFR-TKIs were enrolled in this study, including 100 patients who were treated with 1G EGFR-TKIs, 50 patients who were treated with 2G EGFR-TKIs, and 50 patients who were treated with 3G EGFR-TKIs (patients matched in a 2:1:1 ratio for tumor characteristics). Patients in the three groups were simultaneously treated with TRT. The overall incidence of clinical RP in the 1G, 2G, and 3G EGFR-TKI groups was 29%, 48%, and 28% (p=0.043), respectively, and that of imaging RP was 33%, 58%, and 36% (p=0.010), respectively. The incidence of RP with a clinical grade ≥3 in the three groups was 14%, 28%, and 12% (p=0.055), respectively, and that with an imaging grade ≥3 in the three groups was 11%, 32%, and 10% (p=0.002), respectively. In the 58 patients with both clinical and imaging assessments of RP, the median time from TRT to imaging assessment of RP was 62 d, and the median time of RP according to the clinical symptoms was 84 d (p=0.0397). Conclusion: Compared with 2G EGFR-TKIs combined with TRT, 1G or 3G EGFR-TKIs combined with TRT achieved a lower incidence of RP. The imaging manifestation of RP occurs earlier than the clinical symptoms, suggesting that imaging findings can provide an early warning of clinical symptoms.