Prognostic genomic alterations in patients undergoing liver resection for hepatocellular carcinoma.

INTRODUCTION: Genetic mutations and amplifications found in hepatocellular carcinoma (HCC) have a potentially prognostic impact. The aim of this study was to investigate the prognostic value of mutations and amplifications in HCC from patients that were liver resected. METHODS: Patients liver resected for HCC at Copenhagen University Hospital Rigshospitalet between May 2014 and January 2018 were included. DNA from freshly frozen tumour tissue was investigated with TruSight Oncology 500. Mutations and amplifications were correlated with disease-free survival and overall survival using multivariate Cox regression to assess the effect on prognosis. RESULTS: Of the 51 patients included, 88% were male and the median age was 69 years. Most patients had a single tumour (84%) with no vascular invasion (67%) in a non-cirrhotic liver (76% with fibrosis, 24% with cirrhosis). The median follow-up was 37 months. Patients with a MYC amplification (8%) were significantly younger than the remaining patients. Furthermore, they had a significantly shorter overall survival (15 months (95% CI: 0.0-31.6) vs. 59 months (95% CI: 34.4-83.6), p = < 0.001) and disease-free survival (8 months (95% CI: 4.6-11.4) vs. 19 months (95% CI: 12.3-25.7), p = 0.03). However, only overall survival remained statistically significant in the adjusted analysis. Furthermore, all patients with an ARID1A mutation (6%) had microvascular invasion and significantly larger tumours than the patients without ARID1A mutation. CONCLUSION: MYC amplifications had a prognostic influence on survival, whereas ARID1A gene mutations were correlated with microvascular invasion. These may serve as prognostic biomarkers and should be validated in large, independent cohort.

Personalized circulating tumor DNA in patients with hepatocellular carcinoma: a pilot study.

BACKGROUND: Mutational analysis of circulating tumor DNA (ctDNA) can potentially be used for early detection of recurrence after resection for hepatocellular carcinoma (HCC). Mutations from tumor may be identified in plasma as an early sign of recurrence. We conducted a pilot study investigating if somatic mutations could be detected in plasma in patients undergoing liver resection for HCC and in patients with advanced non-resectable HCC. METHODS AND RESULTS: We prospectively included patients undergoing curative liver resection for HCC. Tumor tissue was investigated with whole exome sequencing and preoperative blood samples were evaluated for ctDNA using targeted next-generation sequencing (NGS) with TruSight Oncology 500 including 523 cancer-associated genes. Subsequently, the method was evaluated in patients with advanced HCC. We included eight patients curatively resected for HCC, where tumor tissue mutations were identified in seven patients. However, only in one patient tumor specific mutations were found in the preoperative blood sample. In all three patients with advanced HCC, tumor mutations were detected in the blood. CONCLUSIONS: In patients with resectable HCC, ctDNA could not be reliably detected using the applied targeted NGS method. In contrast, ctDNA was detected in all patients with advanced HCC. Small tumors, tumor heterogeneity and limited sequencing coverage may explain the lack of detectable ctDNA.