Open AccessProspective detection of mutations in cerebrospinal fluid, pleural effusion, and ascites of advanced cancer patients to guide treatment decisions
Author(s) -
Villatoro Sergio,
MayodelasCasas Clara,
JordanaAriza Núria,
ViteriRamírez Santiago,
GarzónIbañez Mónica,
MoyaHorno Irene,
GarcíaPeláez Beatriz,
GonzálezCao María,
Malapelle Umberto,
BaladaBel Ariadna,
MartínezBueno Alejandro,
Campos Raquel,
Reguart Noemí,
Majem Margarita,
Blanco Remei,
Blasco Ana,
Catalán María J.,
González Xavier,
Troncone Giancarlo,
Karachaliou Niki,
Rosell Rafael,
MolinaVila Miguel A.
Publication year - 2019
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12574
Subject(s) - ascites , cerebrospinal fluid , pleural effusion , medicine , lung cancer , mutation , pathology , cancer , circulating tumor cell , effusion , cancer research , oncology , biology , metastasis , gene , surgery , biochemistry
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.