• Ben-Yuan Jiang, Yang-Si Li, Wei-Bang Guo, Xu-Chao Zhang, Zhi-Hong Chen, Jian Su, Wen-Zhao Zhong, Xue-Ning Yang, Jin-Ji Yang, Yang Shao, Biao Huang, Yan-Hui Liu, Qing Zhou, Hai-Yan Tu, Hua-Jun Chen, Zhen Wang, Chong-Rui Xu, Bin-Chao Wang, Shu-Yu Wu, Cun-Yi Gao, Xian Zhang, and Yi-Long Wu.
• Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.
• Clin Cancer Res. 2017 Sep 15; 23 (18): 5480-5488.

AbstractPurpose: Leptomeningeal metastases are more common in non-small cell lung cancer (NSCLC) with EGFR mutations. The diagnosis is difficult by traditional imaging only, and leads to poor understanding of resistance mechanisms of leptomeningeal metastases.Experimental Design: We compared the CellSearch Assay, the Thinprep cytologic test (TCT), and brain magnetic resonance imaging (MRI) in 21 NSCLC patients with suspected leptomeningeal metastases. Next-generation sequencing that included 416 cancer-associated genes was also performed on cerebrospinal fluid circulating tumor cells (CSFCTC) of 19 patients.Results: Twenty-one patients were diagnosed with leptomeningeal metastases, and CSFCTCs were captured by CellSearch in 20 patients (median, 969 CSFCTCs/7.5 mL; range, 27-14,888). CellSearch had a sensitivity of 95.2% for leptomeningeal metastases diagnosis, which was higher than that of TCT (12/21, 57.1%), MRI (10/21, 47.6%), and MRI plus TCT (19/21, 90.5%), respectively. CTCs were found only in 5 of 14 patients (median, 2 CTCs/7.5 mL; range, 2-4), which was a much lower ratio than CSFCTCs. Genetic profiles of CSFCTCs were highly concordant with molecular mutations identified in the primary tumor (17/19, 89.5%). The resistance gene EGFR T790M was detected in 7 of 9 patients with extracranial lesions, but was detected in only 1 of 14 CSFCTC samples. Other potential resistant mutations, such as MET amplification and ERBB2 mutation, were also identified in CSFCTCs.Conclusions: CSFCTCs captured by CellSearch may be a more sensitive and effective way to diagnose leptomeningeal metastases, and may serve as a liquid biopsy medium for gene profiles in NSCLC patients with leptomeningeal metastases. Clin Cancer Res; 23(18); 5480-8. ©2017 AACR.©2017 American Association for Cancer Research.

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