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Background: We aim to identify the multifaceted risk factors that can affect the development of severe radiation pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC) treated with curative high-dose radiotherapy with or without concurrent chemotherapy. Methods: We retrospectively reviewed the medical records of 175 patients with stage-I-III NSCLC treated with curative thoracic X-ray radiotherapy at the Korea University Guro Hospital between June 2019 and June 2022. Treatment-related complications were evaluated using the Common Terminology Criteria for Adverse Events (version 4.03). Results: The median follow-up duration was 15 months (range: 3–47 months). Idiopathic pulmonary fibrosis (IPF) as an underlying lung disease (P < 0.001) and clinical stage, regarded as the concurrent use of chemotherapy (P = 0.009), were associated with a high rate of severe RP. In multivariate analyses adjusting confounding variables, the presence of IPF as an underlying disease was significantly associated with severe RP (odds ratio [95% confidence interval] = 48.4 [9.09–347]; P < 0.001). In a subgroup analysis of stage-I-II NSCLC, the incidence of severe RP in the control, chronic obstructive pulmonary disease (COPD), and IPF groups was 3.2%, 4.3%, and 42.9%, respectively (P < 0.001). The incidence of severe RP was 15.2%, 10.7%, and 75.0% in the control, COPD, and IPF groups, respectively (P < 0.001) in the stage-III NSCLC group. Conclusions: This study revealed that IPF as an underlying lung disease and the concurrent use of chemotherapy are associated with a high rate of severe RP. In contrast, COPD did not increase the risk of pulmonary toxicity after receiving curative high-dose radiotherapy. [ABSTRACT FROM AUTHOR]

Introduction: The PACIFIC study demonstrated that durvalumab consolidation therapy significantly improved progression‐free survival (PFS) and overall survival (OS) in patients with unresectable stage III non‐small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CCRT). However, there was no clinical benefit in both PFS and OS in epidermal growth factor receptor (EGFR) mutation‐positive patient groups in a post hoc exploratory analysis. Moreover, the clinical effects of immune checkpoint inhibitors (ICIs) in EGFR mutation‐positive stage IV NSCLC were demonstrated to be poor. Personalized treatment according to the mutation status is also required in stage III NSCLC. Lazertinib, a third‐generation EGFR tyrosine kinase inhibitor (TKI), is newly developed and approved for use in Korea. Methods: This prospective, open, single‐arm, multicenter, phase II clinical trial aims to evaluate the efficacy and safety of lazertinib as a consolidative therapy after CCRT treatment in unresectable, EGFR mutation‐positive NSCLC stage III patients. The primary endpoint of this study is PFS, and the secondary endpoints are OS, objective response rate (ORR), duration of response (DoR), time to death or distant metastasis (TTDM), and safety profiles. Discussion: Our study may extend the indications for third‐generation EGFR‐TKIs to treat patients with stage III NSCLC. Moreover, using this drug to treat stage III NSCLC would emphasize the value of mutation analysis and personalized medicine. [ABSTRACT FROM AUTHOR]