Author information
1 GI Medical Oncology, University of Texas MD Anderson Cancer Center akaseb@mdanderson.org.
2 Genomic Medicine, The University of Texas MD Anderson Cancer Center.
3 Cancer Medicine, University of Texas MD Anderson Cancer Center.
4 Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco.
5 Internal Medicine, Washington University in St. Louis School of Medicine.
6 Gastrointestinal Oncology, Helen Diller Family Comprehensive Cancer Center-University of California San Francisco.
7 Department of Medicine, Washington University in St. Louis School of Medicine.
8 GI Medical Oncology, University of Texas MD Anderson Cancer Center.
9 Cancer Medicine, The University of Texas MD Anderson Cancer Center.
10 Biostatistics, University of Texas MD Anderson Cancer Center.
11 Hematopathology, University of Texas MD Anderson Cancer Center.
12 Pathology, University of Texas MD Anderson Cancer Center.
13 Medical Affairs, Guardant Health, Inc.
14 Department of Medical Affairs, Guardant Health, Inc.
15 President, Guardant Health, Inc.
16 Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center.
17 Hematopathology, The University of Texas MD Anderson Cancer Center.
18 Department of Hematopathology, University of Texas MD Anderson Cancer Center.
19 Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center.
20 Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center.
21 GI Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
22 Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center.
23 Center for Personalized Cancer Therapy, UC San Diego Moores Cancer Center.
24 Center for Personalized Cancer Therapy, Division of Blood and Marrow Transplantation, University of California San Diego Moores Cancer Center.
Abstract
PURPOSE:
Molecular profiling has been used to select patients for targeted therapy and determine prognosis. Noninvasive strategies are critical to hepatocellular carcinoma (HCC) given the challenge of obtaining liver tissue biopsies.
EXPERIMENTAL DESIGN:
We analyzed blood samples from 206 HCC patients using comprehensive genomic testing (Guardant Health, CA) of circulating tumor DNA (ctDNA).
RESULTS:
153/206 (74.3%) were men; median age, 62 years (range, 18-91 years). 181/206 patients had 1 alteration. The total number of alterations was 680 (non-unique); median number of alterations/patient was 3 (range, 1-13); median mutant allele frequency (% cfDNA), 0.49% (range 0.06 - 55.03%). TP53 was the common altered gene (>120 alterations (non-unique)) followed by EGFR, MET, ARID1A, MYC, NF1, BRAF, and ERBB2 (20-38 alterations (non-unique)/gene). Of the patients with alterations, 56.9% (103/181) had 1 actionable alterations, most commonly in MYC, EGFR, ERBB2, BRAF, CCNE1, MET, PIK3CA, ARID1A, CDK6, and KRAS. In these genes, amplifications occurred more frequently than mutations. Hepatitis B (HBV)-positive patients, were more likely to have ERBB2 alterations, 35.7% (5/14) versus 8.8% HBV- negative (p=0.04).
CONCLUSIONS:
This study represents the first large-scale analysis of blood-derived ctDNA in HCC in USA. The genomic distinction based on HCC risk factors and the high percentage of potentially actionable genomic alterations suggests potential clinical utility for this technology.