Circulating Tumor DNA Profiling of Advanced Biliary Tract Cancers

Author:

Mody Kabir1,Kasi Pashtoon M.1,Yang JuDong2,Surapaneni Phani Keerthi1,Bekaii-Saab Tanios3,Ahn Daniel H.3,Mahipal Amit2,Sonbol Mohamad B.3,Starr Jason S.1,Roberts Ali4,Nagy Rebecca4,Lanman Richard4,Borad Mitesh J.3

Affiliation:

1. Mayo Clinic, Jacksonville, FL

2. Mayo Clinic, Rochester, MN

3. Mayo Clinic, Scottsdale, AZ

4. Guardant Health, Redwood City CA

Abstract

PURPOSE Recent advances in molecular diagnostic technologies have allowed for the evaluation of solid tumor malignancies via noninvasive blood sampling, including circulating tumor DNA (ctDNA) profiling. We sought to characterize the ctDNA genomic alteration landscape in patients with biliary tract cancers (BTCs). PATIENTS AND METHODS From January 2015 to February 2018, 124 patients with BTC at the Mayo Clinic Comprehensive Cancer Center underwent ctDNA testing using a clinically available assay. The majority of samples (n = 122) were tested using the 73-gene panel that 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 138 samples were included, with approximately 70% of patients having intrahepatic BTC. All patients had locally advanced or metastatic BTC. Samples with one or more alterations, when variants of unknown significance were excluded, numbered 105 (76%). Each sample contained, on average, three alterations with a median allelic fraction of 0.52%. The overall landscape of alterations is summarized in Figures 1 and 2. After excluding variants of unknown significance, therapeutically relevant alterations were observed in 76 patients (55%), including BRAF mutations, ERBB2 amplifications, FGFR2 fusions, FGFR2 mutations, and IDH1 mutations seen in 21% of patients. A different spectrum of alterations was observed in patients with early-onset BTC (younger than age 50 years) compared with older patients (older than age 50 years). CONCLUSION Data on ctDNA in BTC is currently limited. Our study, the largest cohort reported to date to our knowledge, demonstrates the feasibility of ctDNA testing in this disease. We provide a foundation upon which the field can continue to grow.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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