Abstract 2217: More somatic mutations can be detected in cerebrospinal fluid ctDNA of NSCLC patients with brain metastases

Abstract

Abstract Background: Brain metastasis is a common and serious clinical condition in NSCLC, and it is also one of the common reasons for the failure of lung cancer treatment. About 30% of patients with non-small cell lung cancer develop brain metastases during the progression of the disease. Targeted therapy is an important method in treatment of brain metastases from lung cancer, and ctDNA in cerebrospinal fluid can better detect somatic mutations of brain metastases. This study will analyze and compare somatic mutations detected in plasma ctDNA and cerebrospinal fluid ctDNA in order to evaluate whether plasma can be used as an alternative sample for cerebrospinal fluid. Design: A total of 58 NSCLC patients with brain metastases were enrolled and the paired blood and cerebrospinal fluid samples were collected on the same day. Then multi-gene panel was used to detect somatic mutations in ctDNA from plasma and cerebrospinal fluid samples respectively. Results: On the whole, the detection rate of somatic mutations in ctDNA of cerebrospinal fluid was significantly higher than that in plasma ctDNA, whether it was SNV (81% vs. 67.2%), CNV (19% vs. 3.4%) or gene fusion (15.5% vs. 8.6%). What's more, the mutation pattern of EGFR, BRAF, NTRK1 and TP53 in the two groups were significantly different according to the Fisher‘s test (Pvalue <0.05). In both cerebrospinal fluid and plasma ctDNA, the top three frequently mutated genes were EGFR (67.2% vs. 41.4%), TP53 (48.3% vs. 27.6%) and LRP1B (19.0% vs. 8.6%). For EGFR sensitive mutations, L858R and Del19 were detected in 19 cases (32.8%) and 14 cases (24.1%) of cerebrospinal fluid ctDNA, which were significantly higher than 11 cases (19.0%) and 7 cases (12.1%) of plasma ctDNA. For the EGFR resistant mutation, T790M was detected in 0 cases (0%), and 5 cases (8.6%) in cerebrospinal fluid and plasma ctDNA respectively which was adverse to EGFR sensitive mutations and might reflect poor ability of first/second-generation EGFR-TKI to break blood-brain barrier. As to CNV detection, CNVs detected in ctDNA of cerebrospinal fluid included CDK4 (4, 6.9%), EGFR (4, 6.9%), MYC (2, 3.4%), RICTOR (1, 1.7%), ERBB2 (1, 1.7%) amplification, while only EGFR amplification (2, 3.4%) and PIK3CA amplification (1, 1.7%) were detected in plasma ctDNA. In addition, the common fusions detected in ctDNA of cerebrospinal fluid involved BRAF (3, 5.2%), PDGFRA (2, 3.4%), ROS1 (2, 3.4%), ALK (2, 3.4%) and EGFR (2, 3.4%), while in plasma ctDNA fusions involving RET (3, 5.2%), BCR (2, 3.4%), and EGFR (1, 1.7%) were detected. Conclusion: Compared with plasma ctDNA, cerebrospinal fluid ctDNA can detect more somatic mutations in NSCLC patients with brain metastases, which can provide more comprehensive guidance for targeted therapy of brain metastases. Citation Format: Qingsheng Xu, Jie Liu, Wei Li, Xiaoyan Zhang, Chunyang Wang, Tonghui Ma. More somatic mutations can be detected in cerebrospinal fluid ctDNA of NSCLC patients with brain metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2217.