Circulating cell-free tumor DNA chromosomal instability and circulating tumor cells as tools to predict microvascular invasion of hepatocellular carcinoma.

person Jin Wang Department of Hepatobiliary and Pancreatic Surgical Oncology, Chinese PLA General Hospital and Chinese PLA Medical School, Beijing, China info_outline Jin Wang, Yanzhe Liu, Kuang Chen, Qu Liu, Qian Ziliang, Minggen HU

Authors person Jin Wang Department of Hepatobiliary and Pancreatic Surgical Oncology, Chinese PLA General Hospital and Chinese PLA Medical School, Beijing, China info_outline Jin Wang, Yanzhe Liu, Kuang Chen, Qu Liu, Qian Ziliang, Minggen HU Organizations Department of Hepatobiliary and Pancreatic Surgical Oncology, Chinese PLA General Hospital and Chinese PLA Medical School, Beijing, China, Prophet Genomics Inc, SAN Jose, CA Abstract Disclosures Research Funding Other Foundation Background: Extended hepatic surgical margins, especially anatomical resections, were suggested for hepatocellular carcinoma (HCC) patients with pathological microvascular invasion (MVI) to improve patient survival. Here we investigated plasma cell-free tumor DNA (ctDNA) and circulating tumor cells as a tool to evaluate MVI before surgery. Methods: 47 treatment-naïve patients with liver lesions were recruited since June 2018, Peripheral blood samples were collected before surgery for all the individuals. Plasma cfDNA was sent to low-coverage genome-wide sequencing, followed by chromosomal instability analyses by a customized workflow UCAD. Circulating tumor cells (CTC) were analyzed by CELLSEARCH @ System. MVI was reported by pathological examination after surgery. Results: Of the 47 patients recruited, there are 32 hepatocellular carcinoma (HCC), 8 intrahepatic cholangiocarcinoma (ICC), 4 benign lesions, 1 solitary fibrous tumor, 1 neuroendocrine tumor and 1 hepatic epithelioid cell tumor by pathological examinations. MVI was also reported for HCCs. Nineteen of 32 HCC patients (59.4%) was found with elevated chromosomal instability (CIN). The most frequent changed chromosomes include 1q, 6p and 8q. Nine of 19 (47.4%) elevated CIN patients were MVI positive by pathological examinations. Among them, 4 was confirmed as MVI = 2. The other 5 was MVI = 1. 11 of 13 (84.6%) patients with low CIN were MVI negative (MVI = 0) as reported by pathological examinations. The rest 2 were reported as MVI = 1. Two of 32 HCC patients (6.25%) was found with positive CTC (tumor cell count > 0). The patient with CTC = 2 was reported as MVI = 1. The other one with CTC = 1 was MVI = 0. Taking together, 20 patients (62.5%) were found either elevated ctDNA or positive CTC. 9 were confirmed as MVI negative. The overall positive predictive value is 45.0%. 12 patients (38.7%) were both ctDNA CIN low and CTC negative. 10 were confirmed as MVI negative. The negative predictive value (NPV) is 83.3%. Conclusions: Elevated circulating tumor DNA chromosomal instability has good PPV and NPV in the predicting of MVI. In such patients, anatomical hepatic resections might be recommended to improve survival.