Prospective detection of mutations in cerebrospinal fluid, pleural effusion, and ascites of advanced cancer patients to guide treatment decisions

Abstract

Many advanced cases of cancer show central nervous system, pleural, or peritoneal involvement. In this study, we prospectively analyzed if cerebrospinal fluid (CSF), pleural effusion (PE), and/or ascites (ASC) can be used to detect driver mutations and guide treatment decisions. We collected 42 CSF, PE, and ASC samples from advanced non‐small‐cell lung cancer and melanoma patients. Cell‐free DNA (cfDNA) was purified and driver mutations analyzed and quantified by PNA‐Q‐PCR or next‐generation sequencing. All 42 fluid samples were evaluable; clinically relevant mutations were detected in 41 (97.6%). Twenty‐three fluids had paired blood samples, 22 were mutation positive in fluid but only 14 in blood, and the abundance of the mutant alleles was significantly higher in fluids. Of the 34 fluids obtained at progression to different therapies, EGFR resistance mutations were detected in nine and ALK acquired mutations in two. The results of testing of CSF, PE, and ASC were used to guide treatment decisions, such as initiation of osimertinib treatment or selection of specific ALK tyrosine–kinase inhibitors. In conclusion, fluids close to metastatic sites are superior to blood for the detection of relevant mutations and can offer valuable clinical information, particularly in patients progressing to targeted therapies.

An Observational Study of Acquired EGFR T790M-Dependent Resistance to EGFR-TKI Treatment in Lung Adenocarcinoma Patients in Taiwan

“…The prior reports showed that there was discordance in EGFR mutation status between primary tumor and CSF (35). It may result from low cellularity or ctDNA in the small amount of CSF or the low concentrations of the first and second generation of EGFR TKIs in CSF inadequate to drive the occurrence of T790M (36).…”

Liquid Biopsy in Non-Small Cell Lung Cancer: Highlights and Challenges

“…In this regard, other body fluids have been evaluated as an alternative source of tumor derived DNA. In fact, cfDNA from fluids in sites adjacent to metastases such as cerebrospinal fluid, pleural effusion, and ascites was found at higher levels, resulting in a more effective method in for detecting relevant mutations [50].…”

Current and future trends in non–small cell lung cancer biomarker testing: The American experience

“…One of the alternate, more readily accessible liquid biopsy sources that has been exploited for molecular profiling is ctDNA obtained from serous body cavity effusion fluids. 30,46 A large percentage of patients with advanced stage NSCLC initially present with a malignant pleural effusion that may be the only tissue source for diagnosis and biomarker testing. Recent studies evaluating the cellfree component of these samples for tumor mutational profiling have highlighted the role of centrifuged supernatant fluids from these effusion samples in providing clinically relevant genomic information for primary driver mutations as well as those in a resistance setting.…”