Smith Clayton P, Xiang Michael, Yoon Stephanie M, Lee Alan, Ruan Dan, Goldman Jonathan W, Cummings Amy L, Lisberg Aaron, Garon Edward B, Moghanaki Drew
Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
JTO Clin Res Rep. 2023 Feb 2;4(3):100468. doi: 10.1016/j.jtocrr.2023.100468. eCollection 2023 Mar.
Osimertinib is an effective treatment for metastatic NSCLC. Occasionally, thoracic radiation therapy (TRT) is delivered to patients receiving osimertinib to treat residual or progressing pulmonary tumors. Anecdotal reports suggest that the delivery of TRT in combination with osimertinib may be associated with a high risk of severe pneumonitis.
A retrospective study was performed at a single academic medical center in the United States to investigate the incidence of severe pneumonitis among patients treated with combined TRT and osimertinib between June 2016 and December 2021. Baseline patient characteristics, tumor size and location, and dosimetric parameters were evaluated. The highest grade of radiation pneumonitis that developed within 6 months of treatment was scored in accordance with the Common Terminology Criteria for Adverse Events version 5.0.
A total of 16 patients were identified who were treated with combined TRT and osimertinib. All had a diagnosis of metastatic NSCLC. Treatment-related grade greater than or equal to 2 pneumonitis developed in 56%, grade greater than or equal to 3 in 37.5%, and grade 4 in 6.3%; no patient developed grade 5 pneumonitis. Median time to any-grade pneumonitis was 29 days (1-84 d); all patients had symptom resolution with expectant management or oral steroid therapies. All patients discovered to have grade greater than or equal to 3 pneumonitis (n = 6) received TRT to tumors located within 2 cm of the proximal bronchial tree, including tumors abutting the proximal bronchial tree (n = 2) and within the mediastinum (n = 1).
The combination of TRT with osimertinib was associated with a high rate of severe pneumonitis that required oral steroid medications. Larger studies are needed to validate these findings and to understand the clinical and treatment factors that influence this risk and how they can be mitigated.
奥希替尼是治疗转移性非小细胞肺癌（NSCLC）的有效药物。偶尔，会对接受奥希替尼治疗的患者进行胸部放射治疗（TRT），以治疗残留或进展性肺部肿瘤。轶事报道表明，TRT联合奥希替尼治疗可能与严重肺炎的高风险相关。
在美国一家学术医疗中心进行了一项回顾性研究，以调查2016年6月至2021年12月期间接受TRT联合奥希替尼治疗的患者中严重肺炎的发生率。评估了患者的基线特征、肿瘤大小和位置以及剂量学参数。根据不良事件通用术语标准第5.0版对治疗后6个月内发生的放射性肺炎的最高等级进行评分。
共确定16例接受TRT联合奥希替尼治疗的患者。所有患者均诊断为转移性NSCLC。56%的患者发生与治疗相关的2级及以上肺炎，37.5%的患者发生3级及以上肺炎，6.3%的患者发生4级肺炎；无患者发生5级肺炎。任何等级肺炎的中位发生时间为29天（1 - 84天）；所有患者通过观察管理或口服类固醇疗法症状均得到缓解。所有被发现患有3级及以上肺炎的患者（n = 6）接受TRT治疗的肿瘤位于距近端支气管树2 cm以内，包括紧邻近端支气管树的肿瘤（n = 2）和位于纵隔内的肿瘤（n = 1）。
TRT联合奥希替尼与需要口服类固醇药物治疗的严重肺炎的高发生率相关。需要更大规模的研究来验证这些发现，并了解影响这种风险的临床和治疗因素以及如何减轻这些因素。
