Profiling Metastatic Lesions, Cell-Free DNA Improves GEA Treatment Decisions

Submitted by admin5 on Tue, 11/21/2017 - 14:12

Investigating genetic variations within a primary tumor, the differences between the primary tumor and a metastatic branch of that tumor, and additional diversity found in tumor DNA in the bloodstream could help guide and improve treatment choices in patients with gastroesophageal adenocarcinoma (GEA), according to a recent study.

Precision medicine, which encompasses various current approaches to genome-guided therapy, has often provided imprecise results, especially in the case of GEA. Because of this, better approaches are needed to help guide treatment for GEA.

Daniel Catenacci, MD, University of Chicago, and colleagues evaluated four cohorts of patients with GEA across multiple institutions. In the first cohort (n = 11), researchers performed whole exome sequencing on samples from paired synchronous primary and metastatic tumors. In the second cohort (n = 26), multiple samples were taken from patients’ primary tumors, regional lymph nodes, and distant metastases.

In the third cohort (n = 11), the researchers examined patients’ cell-free DNA (cfDNA). In the fourth cohort (n = 28), which included patients from the ongoing Personalized ANtibodies for GastroEsophageal Adenocarcinoma (PANGEA) trial, the researchers conducted genetic analysis of biopsies of both patients’ primary tumors and metastatic tumors, as well as a cfDNA analysis using a Guardant Health commercial assay.

Results from the first cohort indicated that 5 (45%) patients had discrepant pathogenic alterations in the metastasis that were not present in the primary tumor, and that an average of 42% of mutations and 63% of gene amplifications differed between primary and metastatic tumors. In the second cohort, researchers observed “striking heterogeneity” within the primary tumors and significant differences between the primary and metastatic tumors.

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Findings from the third cohort showed that using cfDNA had uncovered the presence of several altered cancer-related genes that were not always concordant with genomic aberrations found in primary tumors. In the fourth cohort, results showed that allowing the metastatic lesions and the cfDNA findings to guide treatment decisions instead of the primary tumor findings had resulted in medication changes in nine (32%) patients. In addition, the researchers noted that the cfDNA results were 87.5% concordant those from the metastatic lesions.

"These provocative results challenge current guidelines and practice,” the researchers concluded. “[Current tissue sampling practices] do not effectively guide precision medicine in this disease. Routine profiling of metastatic lesions and/or cfDNA should be systematically evaluated."—Christina Vogt