Detection of Driver and Resistance Mutations in Leptomeningeal Metastases of NSCLC by Next-Generation Sequencing of Cerebrospinal Fluid Circulating Tumor Cells

Purpose: <p>Leptomeningeal metastases (LM) 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 LM.</p> <br />Experimental Design: <p>We compared the CellSearch Assay™, the Thinprep cytologic test (TCT), and brain magnetic resonance imaging (MRI) in 21 NSCLC patients with suspected LM. Next-Generation sequencing that included 416 cancer-associated genes was also performed on cerebrospinal fluid circulating tumor cells (CSFCTCs) of 19 patients.</p> <br />Results: <p>Twenty-one patients were diagnosed with LM, 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 LM 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 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 only detected in 1 of 14 CSFCTC samples. Other potential resistant mutations such as MET amplification and ERBB2 mutation were also identified in CSFCTCs.</p> <br />Conclusions: <p>CSFCTCs captured by CellSearch may be a more sensitive and effective way to diagnose LM, and may serve as a liquid biopsy medium for gene profiles in NSCLC patients with LM.

from Cancer via ola Kala on Inoreader http://ift.tt/2sW7hEE
via IFTTT