Article Abstract

Feasibility of circulating tumor DNA testing in hepatocellular carcinoma

Authors: Kabir Mody, Pashtoon Murtaza Kasi, Ju Dong Yang, Phani Keerthi Surapaneni, Ashton Ritter, Ali Roberts, Rebecca Nagy, Mitesh J. Borad

Abstract

Background: Advancement of technologies enabling clinical assessment of circulating tumor DNA (ctDNA) are allowing for assessment of tumor specific genetic alterations in patients. This holds incredible promise for early detection of disease, serial monitoring of tumor heterogeneity, elucidation of therapeutic targets, and evaluation of treatment response and mechanisms of resistance. Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is often diagnosed late, recurs commonly, and is often diagnosed based upon imaging features alone. A comprehensive evaluation of real-time evaluation of ctDNA in patients with HCC has thus far not been undertaken.
Methods: From January 2015 to February 2018, 35 patients with biliary tract cancer (BTC) at the Mayo Clinic Comprehensive Cancer Center underwent ctDNA testing using a clinically available assay. The majority of samples were tested utilizing the 73-gene panel which includes somatic genomic targets, including complete or critical exon coverage in 30 and 40 genes, respectively; and in some, amplifications, fusions, and indels.
Results: A total of 44 samples were collected on these 35 patients, with >70% having stage 3 or 4 disease. Among all samples the median number of alterations per sample, excluding variants of undetermined significance (VUS), was 3.5, with a median allele frequency of 0.65%. A total of 122 unique genetic alterations, excluding VUS or synonymous alterations, were seen. The overall landscape of alterations is described. The top 10 genes altered in this cohort of patients, excluding VUS or synonymous alterations, were TP53 (18%), TERT (14%), CTNNB1 (13%), ARID1A (9%), MYC (5%), BRAF (4%), CCND1 (4%), CDK6 (4%), and MET (4%), and EGFR (3%).
Conclusions: Herein, we describe feasibility of ctDNA testing and results from such testing in HCC patients undergoing ctDNA testing in a real-time clinical context. Patients with these cancers stand to benefit immensely from the use of ctDNA technologies, and concerted efforts at further investigation of such are critically needed.

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