Department of Medicine, Division of Pulmonary and Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Department of Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Republic of Korea.
PLoS One. 2024 Sep 19;19(9):e0310079. doi: 10.1371/journal.pone.0310079. eCollection 2024.
This study was performed to investigate the detection rate of EGFR T790M mutation by repeated rebiopsy, to identify the clinical factors related to repeated rebiopsy, and to assess survival outcomes according to the methods and numbers of repeated rebiopsies in patients with lung adenocarcinoma who received sequential osimertinib after failure of previous 1st or 2nd generation EGFR-tyrosine kinase inhibitors.
This retrospective study included patients with advanced-stage lung adenocarcinoma who were confirmed to have EGFR T790M mutation and to have received osimertinib from January 2020 to February 2021 at Samsung Medical Center. The presence of T790M mutation was assessed based on either plasma circulating tumor DNA (ctDNA) or tissue specimens. Results A total of 443 patients underwent rebiopsy, with 186 (42.0%) testing positive for the T790M mutation by the sixth rebiopsy. The final analysis included 143 eligible patients. Progression-free survival was not significantly different in terms of the methods (tissue: 13.3 months, 95% confidence interval [CI]: [9.4, 23.5] vs plasma: 11.1 months, 95% CI: [8.1, 19.4], p = 0.33) and numbers (one: 13.4 months, 95% CI: [9.4, 23.5] vs two or more: 11.0 months, 95% CI: [8.1, 14.8], p = 0.51) of repeated rebiopsies. Longer overall survival (OS) was found in patients in whom T790M was detected by tissue specimens rather than by plasma ctDNA (2-year OS rate: 81.7% for tissue vs 63.9% for plasma, p = 0.0038). Factors related to the lower numbers of rebiopsies included age and bone metastasis. Factor associated with T790M detection in tissue rather than in plasma was pleural metastasis, while advanced tumor stage was related to T790M confirmation in plasma rather than in tissue.
Repeated rebiopsy for T790M detection in patients with NSCLC can increase the detection rate of the mutation. Detection of T790M by plasma ctDNA might be related to poor survival outcomes.
本研究旨在探讨重复活检检测 EGFR T790M 突变的检出率，确定与重复活检相关的临床因素，并根据接受序贯奥希替尼治疗的肺腺癌患者重复活检的方法和次数评估生存结局。
本回顾性研究纳入了 2020 年 1 月至 2021 年 2 月在三星医疗中心接受奥希替尼治疗的晚期肺腺癌患者，这些患者的 EGFR T790M 突变已通过血浆循环肿瘤 DNA（ctDNA）或组织标本得到确认。T790M 突变的存在基于血浆 ctDNA 或组织标本进行评估。
共 443 例患者接受了重复活检，第 6 次重复活检时 186 例（42.0%）T790M 突变阳性。最终分析纳入了 143 例符合条件的患者。无进展生存期在方法（组织：13.3 个月，95%置信区间[CI]：[9.4，23.5] vs 血浆：11.1 个月，95% CI：[8.1，19.4]，p=0.33）和重复活检次数（一次：13.4 个月，95% CI：[9.4，23.5] vs 两次或更多次：11.0 个月，95% CI：[8.1，14.8]，p=0.51）方面无显著差异。与血浆 ctDNA 相比，组织标本检测到 T790M 的患者的总生存期（OS）更长（组织：2 年 OS 率为 81.7% vs 血浆：63.9%，p=0.0038）。与重复活检次数较少相关的因素包括年龄和骨转移。与组织而非血浆中 T790M 检测相关的因素是胸膜转移，而晚期肿瘤分期与血浆而非组织中的 T790M 确认相关。
对非小细胞肺癌患者进行重复活检以检测 T790M 可提高突变的检出率。通过血浆 ctDNA 检测到 T790M 可能与较差的生存结局相关。
