Clinical data set of 143 study subjects.

Objectives
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.
Methods
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.
Conclusions
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.

### 研究目的
本研究旨在探究重复再次活检对表皮生长因子受体T790M（EGFR T790M）突变的检出率，明确与重复再次活检相关的临床因素，并评估在既往接受第一代或第二代表皮生长因子受体-酪氨酸激酶抑制剂（EGFR-tyrosine kinase inhibitors, EGFR-TKIs）治疗失败后接受序贯奥希替尼（osimertinib）治疗的肺腺癌患者中，不同重复再次活检方式与活检次数对患者生存结局的影响。

### 研究方法
本回顾性研究纳入2020年1月至2021年2月于三星医疗中心（Samsung Medical Center）确诊携带EGFR T790M突变且接受奥希替尼治疗的晚期肺腺癌患者。T790M突变的检测依托血浆循环肿瘤DNA（plasma circulating tumor DNA, ctDNA）或组织标本完成。

### 研究结果
共计443例患者接受了再次活检，至第六次活检时，T790M突变阳性检出率达42.0%（186例）。最终符合分析标准的病例共143例。在无进展生存期（progression-free survival, PFS）方面，不同活检方式（组织活检：13.3个月，95%置信区间[CI]：9.4~23.5；血浆ctDNA检测：11.1个月，95%CI：8.1~19.4，p=0.33）与活检次数（单次活检：13.4个月，95%CI：9.4~23.5；两次及以上活检：11.0个月，95%CI：8.1~14.8，p=0.51）的组间差异均无统计学意义。采用组织标本检出T790M的患者总生存期（overall survival, OS）更长：组织检测组2年总生存率为81.7%，血浆ctDNA检测组为63.9%（p=0.0038）。与活检次数较少相关的因素为年龄与骨转移；相较于血浆ctDNA检测，通过组织标本检出T790M的相关因素为胸膜转移，而晚期肿瘤分期则与通过血浆ctDNA而非组织标本确认T790M突变显著相关。

### 研究结论
针对非小细胞肺癌（non-small cell lung cancer, NSCLC）患者开展重复再次活检以检测T790M突变，可提升该突变的检出率。通过血浆ctDNA检测T790M或与不良生存结局相关。