Jin Shidai, Zhou Chengzhi, Hou Xue, Fan Zaiwen, Zhao Jun, Ai Xinghao, Chu Yuxing, Chen Rongrong, Guo Renhua, Chen Likun
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
State Key Laboratory of Respiratory Disease, National Clinical Research Center of Respiratory Disease, Guangzhou Institute of the Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Transl Lung Cancer Res. 2020 Aug;9(4):1507-1515. doi: 10.21037/tlcr-20-882.
Pleural effusion (PE) is commonly observed in advanced lung cancer. Research has suggested that molecular profiling of PE could be used to detect tumor driver mutations, thus informing clinical decision-making. However, the performance of PE samples in a real-world setting has yet to be examined.
A total of 678 metastatic lung cancer patients with pleural effusion were enrolled in this study. Cohort 1 included 22 patients whose PE and matched plasma samples were simultaneously collected as a pilot study. Cohort 2 comprised 656 patients, from whom 734 samples were collected in a real world setting. These samples were subjected to targeted next-generation sequencing (NGS) of 1,021 cancer-related genes.
PE supernatant was the preferred choice for genetic profiling. While the maximal somatic allele frequency (MSAF) of plasma in patients with M1a stage was significantly lower than that in patients with M1b/c stages (4.4%±9.6% . 9.0%±14.1%, P<0.01), the MSAF of PE supernatant was similar between M1a and M1b/c stages. PE supernatant demonstrated higher sensitivity than plasma in detecting actionable mutations in cohort 1 (81.8% . 45.5%, P=0.01) as well as in M1a disease (84.7% . 42.1%, P<0.01), but not in M1b/c disease, in cohort 2. Known resistant mutations were identified in 72 of the 117 patients who were resistant to first- or second-generation EGFR-TKIs, 22 of the 42 patients who were resistant to osimertinib, and 9 of the 13 patients who were resistant to crizotinib. Remarkably, PE supernatant outperformed plasma in identifying mutations that confer resistance to first- and second-generation EGFR-TKIs (75.4% . 29.8%, P<0.001).
This real-world large cohort study verified that PE supernatant had higher sensitivity than plasma for identifying actionable mutations, including resistance mutations. PE supernatant would be preferred by physicians for assessing tumor genomics in advanced lung cancer when tumor tissue is not available.
胸腔积液（PE）在晚期肺癌中较为常见。研究表明，对胸腔积液进行分子分析可用于检测肿瘤驱动基因突变，从而为临床决策提供依据。然而，在实际临床环境中胸腔积液样本的性能尚未得到检验。
本研究共纳入678例伴有胸腔积液的转移性肺癌患者。队列1包括22例患者，作为初步研究同时采集了他们的胸腔积液和配对血浆样本。队列2包含656例患者，在实际临床环境中从他们身上采集了734份样本。这些样本接受了1021个癌症相关基因的靶向二代测序（NGS）。
胸腔积液上清液是基因分析的首选样本。M1a期患者血浆中的最大体细胞等位基因频率（MSAF）显著低于M1b/c期患者（4.4%±9.6%对9.0%±14.1%，P<0.01），而M1a期和M1b/c期胸腔积液上清液的MSAF相似。在队列1中（81.8%对45.5%，P=0.01）以及在队列2的M1a疾病患者中（84.7%对42.1%，P<0.01），胸腔积液上清液在检测可操作突变方面表现出比血浆更高的灵敏度，但在M1b/c疾病患者中并非如此。在117例对第一代或第二代EGFR-TKI耐药的患者中，72例检测到已知的耐药突变；在42例对奥希替尼耐药的患者中，22例检测到已知的耐药突变；在13例对克唑替尼耐药的患者中，9例检测到已知的耐药突变。值得注意的是，在识别对第一代和第二代EGFR-TKI耐药的突变方面，胸腔积液上清液的表现优于血浆（75.4%对29.8%，P<0.001）。
这项实际临床环境中的大型队列研究证实，胸腔积液上清液在识别可操作突变（包括耐药突变）方面比血浆具有更高的灵敏度。当无法获取肿瘤组织时，胸腔积液上清液将是医生评估晚期肺癌肿瘤基因组学的首选样本。
