Ma Chunhua, Zhang Juncheng, Tang Dongjiang, Ye Xin, Li Jing, Mu Ning, Li Zhi, Liu Renzhong, Xiang Liang, Huang Chuoji, Jiang Rong
Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Disease, Department of Intervention, Tianjin HuanHu Hospital, Tianjin, China.
Zhuhai SanMed Biotech Ltd., Zhuhai, China.
Front Oncol. 2020 Mar 5;10:224. doi: 10.3389/fonc.2020.00224. eCollection 2020.
The significance of uncommon () mutations in patients with non-small cell lung cancer (NSCLC) and brain metastasis (BM) remains unclear. Cerebrospinal fluid (CSF) liquid biopsy is a novel tool for assessing mutations in BM. This study aimed to evaluate the mutations in patients with NSCLC and newly diagnosed BM and to examine the effect of EGFR tyrosine kinase inhibitors (TKI) on BM harboring CSF-tested uncommon mutations. This was a prospective study of 21 patients with NSCLC and BM diagnosed between 04/2018 and 01/2019. CSF was obtained to detect the BM mutations by next-generation sequencing. BM characteristics at magnetic resonance imaging (MRI) and EGFR-TKI response were examined. Of 21 patients with NSCLC, 10 (47.6%) had leptomeningeal metastasis (LM), while 11 (52.4%) had brain parenchymal metastasis (BPM); 13 (61.9%) had confirmed mutation-positive primary tumors. The uncommon mutation rate in CSF ctDNA was 33.3% (7/21). Among those with mutation-positive primary tumors, the rate of uncommon mutations in CSF was 53.8% (7/13). Uncommon mutations were more common in patients with LM than in patients with PBM (6/11, 54.5% vs. 1/10, 10%), and included G719A, L861Q, L703P, and G575R. TKI was effective for four patients with BMs harboring uncommon mutations. In patients with NSCLC and LM, the rate of uncommon mutation was high. The BMs with uncommon mutations seem to respond to EGFR-TKI treatment. CSF liquid biopsy could reveal the genetic profile of the BM and help guide treatment using small-molecule TKI.
非小细胞肺癌（NSCLC）合并脑转移（BM）患者中罕见的（）突变的意义仍不明确。脑脊液（CSF）液体活检是评估BM中（）突变的一种新型工具。本研究旨在评估NSCLC合并新诊断BM患者中的（）突变，并研究表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）对携带经CSF检测为罕见（）突变的BM的影响。这是一项对2018年4月至2019年1月期间诊断的21例NSCLC合并BM患者的前瞻性研究。通过下一代测序获取CSF以检测BM中的（）突变。检查了磁共振成像（MRI）时的BM特征和EGFR-TKI反应。在21例NSCLC患者中，10例（47.6%）有软脑膜转移（LM），而11例（52.4%）有脑实质转移（BPM）；13例（61.9%）原发性肿瘤经确认（）突变阳性。CSF循环肿瘤DNA（ctDNA）中的罕见突变率为33.3%（7/21）。在原发性肿瘤（）突变阳性的患者中，CSF中罕见（）突变的发生率为53.8%（7/13）。罕见（）突变在LM患者中比在PBM患者中更常见（6/11，54.5%对1/10，10%），包括G719A、L861Q、L703P和G575R。TKI对4例携带罕见（）突变的BM患者有效。在NSCLC合并LM的患者中，罕见（）突变率较高。具有罕见（）突变的BM似乎对EGFR-TKI治疗有反应。CSF液体活检可以揭示BM的（）基因特征，并有助于指导小分子TKI的治疗。
