Circulating Cell-Free DNA in Advanced Colorectal Cancer Provides Clinical Utility

08/30/17

Sequencing cell-free DNA may be able to provide baseline information on actionable mutations and improve the quality of care in colorectal cancer, according to recent research published in PLOS One (online August 29, 2017; doi:10.1371/journal.pone.0183949).

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Prior research has shown that circulating cell-free DNA that is isolated from the plasma of patients with cancer may reflect the genomic mutation profiles of their tumors. Biomarker-related decisions based on sequencing tissue samples have been critical in the management of metastatic colorectal cancer. However, the fullest extent of clinical utility of these assays in patients with metastatic colorectal cancer has yet to be determined.

Van Morris, MD, department of gastrointestinal medical oncology, University of Texas MD Anderson Cancer Center, and colleagues conducted a study to determine the clinical utility of circulating cell-free DNA in colorectal cancer by comparing the use of such DNA and formalin-fixed paraffin-embedded (FFPE) tissue collections for practicality and convenience in assessing mutation profiles. A total of 128 patients were recruited from 2014 to 2015 and were prospectively consented to a genomic matching protocol (Assessment of Targeted Therapies Against Colorectal Cancer). Patients had blood samples taken for cell-free DNA extraction and sequencing of a 54-gene panel.

FFPE from prior resections or biopsies underwent 50-gene sequencing. Results from both assays were provided to the treating physicians for patient care and clinical trial selection. Further follow-up surveys of these physicians and chart reviews assessed clinical utility.

Results were returned after a median of 13 and 26 days for cell-free DNA and FFPE sequencing returns, respectively.

Results of the sequencing showed that 78% (n = 100) of samples in the cell-free DNA cohort had a detectable somatic genomic alteration, 50% of samples in the cell-free DNA cohort had potentially actionable alterations, and 60% of these could be genomically matched to at least one clinical trial at the researcher’s cancer center. Fifty percent of these patients were subsequently enrolled into an identified matched trial.

Additionally, physicians reported that the cell-free DNA testing improved the quality of care they could provide in 73% of cases. Furthermore, 83% of patients reported higher satisfaction with the efforts to personalize experimental therapeutic agents.

Authors of the study concluded that cell-free DNA sequencing in metastatic colorectal cancer can provide timely information of potentially actionable mutations, which could help facilitate clinical trial enrollment and improve the quality of care for patients.—Zachary Bessette