Many advanced cases of cancer show central nervous system, pleural, or peritoneal involvement. In this study, we prospectively analyzed if cerebrospinal fluid (CSF), pleural effusion (PE), and/or ascites (ASC) can be used to detect driver mutations and guide treatment decisions. We collected 42 CSF, PE, and ASC samples from advanced non-small-cell lung cancer and melanoma patients. Cell-free DNA (cfDNA) was purified and driver mutations analyzed and quantified by PNA-Q-PCR or next-generation sequencing. All 42 fluid samples were evaluable; clinically relevant mutations were detected in 41 (97.6%). Twenty-three fluids had paired blood samples, 22 were mutation positive in fluid but only 14 in blood, and the abundance of the mutant alleles was significantly higher in fluids. Of the 34 fluids obtained at progression to different therapies, EGFR resistance mutations were detected in nine and ALK acquired mutations in two. The results of testing of CSF, PE, and ASC were used to guide treatment decisions, such as initiation of osimertinib treatment or selection of specific ALK tyrosine-kinase inhibitors. In conclusion, fluids close to metastatic sites are superior to blood for the detection of relevant mutations and can offer valuable clinical information, particularly in patients progressing to targeted therapies.

中文翻译：

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对晚期癌症患者的脑脊液，胸腔积液和腹水中的突变进行前瞻性检测，以指导治疗决策。

许多晚期癌症病例显示中枢神经系统，胸膜或腹膜受累。在这项研究中，我们前瞻性地分析了脑脊液（CSF），胸腔积液（PE）和/或腹水（ASC）是否可用于检测驾驶员突变并指导治疗决策。我们从晚期非小细胞肺癌和黑色素瘤患者中收集了42份CSF，PE和ASC样本。纯化无细胞DNA（cfDNA），并通过PNA-Q-PCR或下一代测序对驱动程序突变进行分析和定量。所有42个流体样品都是可评估的；临床相关突变的检出率为41（97.6％）。23份体液中有成对的血液样本，其中22例体液中突变阳性，而血液中只有14例，并且突变体等位基因的丰度在体液中明显更高。在发展为不同疗法的过程中获得的34种液体中，在9个检测到EGFR抗性突变，在2个检测到ALK获得性突变。CSF，PE和ASC的测试结果可用于指导治疗决策，例如启动奥西替尼治疗或选择特定的ALK酪氨酸激酶抑制剂。总之，对于相关突变的检测，靠近转移部位的液体要优于血液，并且可以提供有价值的临床信息，尤其是在进行靶向治疗的患者中。