Detection of Leptomeningeal Disease Using Cell-Free DNA From Cerebrospinal Fluid

作者：Michael White, Robert H. Klein, Brian Shaw, Albert Kim, Megha Subramanian, Joana L. Mora, Anita Giobbie‐Hurder, Deepika Nagabhushan, Aarushi Jain, Mohini Singh, Benjamin M. Kuter, Naema Nayyar, Mia Bertalan, Jackson H. Stocking, Samuel C. Markson, Matthew Lastrapes, Christopher Alvarez‐Breckenridge, Daniel P. Cahill, Gregory Gydush, Justin Rhoades, Denisse Rotem, Viktor A. Adalsteinsson, Maura Mahar, Alexander Kaplan, Kevin Oh, Ryan J. Sullivan, Elizabeth R. Gerstner, Scott L. Carter, Priscilla K. Brastianos · 发表于：JAMA Network Open · 年份：2021 · DOI：10.1001/jamanetworkopen.2021.20040 · 被引用次数：84 · 研究领域：Brain Metastases and Treatment、Cancer Genomics and Diagnostics、Lung Cancer Research Studies

Importance: Leptomeningeal disease (LMD) is a devastating complication of cancer that is frequently underdiagnosed owing to the low sensitivity of cerebrospinal fluid (CSF) cytologic assessment, the current benchmark diagnostic method. Improving diagnostic sensitivity may lead to improved treatment decisions. Objective: To assess whether cell-free DNA (cfDNA) analysis of CSF may be used to diagnose LMD more accurately than cytologic analysis. Design, Setting, and Participants: This diagnostic study conducted in a neuro-oncology clinic at 2 large, tertiary medical centers assessed the use of genomic sequencing of CSF samples obtained from 30 patients with suspected or confirmed LMD from 2015 through 2018 to identify tumor-derived cfDNA. From the same CSF samples, cytologic analyses were conducted, and the results of the 2 tests were compared. This study consisted of 2 patient populations: 22 patients with cytologically confirmed LMD without parenchymal tumors abutting their CSF and 8 patients with parenchymal brain metastases with no evidence of LMD. Patients were considered positive for the presence of LMD if previous CSF cytologic analysis was positive for malignant cells. The analysis was conducted from 2015 to 2018. Main Outcomes and Measures: The primary outcome was the diagnostic accuracy of cfDNA analysis, defined as the number of tests that resulted in correct diagnoses out of the total number of tests assayed. Hypotheses were formed before data collection. Results: In...