Prospective detection of mutations in cerebrospinal fluid, pleural effusion and ascites of advanced cancer patients to guide treatment decisions.
Journal: 2019/September - Molecular Oncology
ISSN: 1878-0261
Abstract:
Many advanced cases of cancer show central nervous system (CNS), pleural or peritoneal involvement. In this study, we prospectively analyzed if cerebrospinal fluid (CSF), pleural effusion (PE) and/or ascites can be used to detect driver mutations and guide treatment decisions. We collected 42 CSF, PE and ascites samples from advanced NSCLC and melanoma patients. Cell free DNA (cfDNA) was purified and driver mutations analyzed and quantified by PNA-Q- PCR or NGS. 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 ascites 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.
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