2015 American Society of Clinical Oncology Annual Meeting:

Cell-Free DNA Sequencing: A Clinically Practicable Alternative to Biopsy-Based Sequencing in Advanced Pancreatobiliary Carcinomas

Eric Andrew Collisson, MD, Assistant Professor in Residence, University of California, San Francisco, presented a paper describing his team’s experience using cell-free DNA sequencing as genetic testing and monitoring for patients with advanced pancreatobiliary carcinoma. Dr. Collisson presented the research at the 2015 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, from May 29–June 2.

Pancreatobiliary Carcinoma Carries a Poor Prognosis
Pancreatobiliary carcinomas carry a poor prognosis, but patients with this cancer have not yet benefited from the revolution in precision oncology, partly because biopsy tissue is often inadequate for molecular characterization.

Gene Sequencing May Offer an Answer
Cell-free DNA sequencing may provide access to genetic testing and monitoring for patients with advanced pancreatobiliary carcinoma.

Prospective Trial of Cell-Free DNA Next-Generation Sequencing
Twenty-five patients with advanced pancreatobiliary cancer were enrolled prospectively in a trial to assess the feasibility, accuracy, and clinical utility of cell-free DNA next-generation sequencing of 54 cancer genes.

Cell-free DNA mutations were compared to those detected by biopsy-based next-generation sequencing, and the concordance of the two was determined. Cell-free DNA sequencing from disease monitoring was compared to changes observed in secreted tumor markers in a subset of patients.

Cancer Mutations Were Detected in 84% of Patients with Advanced Pancreatobiliary Carcinoma
The next generation sequencing-based cell-free DNA test detected cancer mutations in 21 of 25 (84%) of patients with advanced pancreatobiliary carcinoma and provided actionable findings for four patients.

Over 90% of Mutations Were Detected in Patients Who Underwent Blood- and Biopsy-Based Methods
Multigene sequencing data was available from both blood- and biopsy-based methods for 17 patients. Over 90% of mutations detected by the biopsy-based genetic tests were detected in the cell-free DNA of these 17 evaluable patients. Four additional mutations were detected by cell-free DNA sequencing that were not detected in tumor tissue.

32% of Next-Generation  Sequenced Biopsies Failed
Tumor biopsy next-generation sequencing failed in eight patients, equating to a considerably higher failure rate (32%) than the overall failure rate reported by commercial vendors.

An Activating Exon Deletion Led to Successful Erlotinib Treatment
Three cell-free DNA mutations in patients in whom next generation sequenced biopsies failed suggested a new therapeutic option. An activating epithelial growth factor receptor exon 19 deletion was observed in the cell-free DNA of one patient, which was later confirmed by biopsy and empowered successful treatment with erlotinib (Tarceva®, OSI Pharmaceuticals, LLC).

Cell-Free DNA Sequencing Conferred 97% Diagnostic Accuracy
The average diagnostic accuracy of cell-free DNA sequencing was 97%, with 92% average sensitivity and 100% specificity across the cohort. Changes in cell-free DNA mutation frequencies correlated with changes in tumor marker measurements (Pearson’s r = 0.7).

Conclusion
Cell-free DNA sequencing is a clinically practicable alternative to biopsy-based tumor DNA sequencing in pancreatobiliary carcinoma. Cell-free DNA from most pancreatobiliary carcinomas showed high mutational concordance with tissue biopsy, and high tumor-burden concordance with tumor markers. Cell-free DNA sequencing should be considered for prospective therapeutic trials in pancreatobiliary malignancies.

June 30, 2015

Next Summary:
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