The pooled #HOPE4LIVER trials demonstrated the safety and technical success of the HistoSonics System for the destruction of liver tumors using histotripsy, a non-thermal, mechanical process of focused US.

Background: To date, there are inconsistent data about relationships between diffusion-weighted imaging (DWI) and tumor grading/microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Our purpose was to systematize the reported results regarding the role of DWI in prediction of tumor grading/MVI in HCC. Method: MEDLINE library, Scopus, and Embase data bases were screened up to December 2019. Overall, 29 studies with 2,715 tumors were included into the analysis. There were 20 studies regarding DWI and tumor grading, 8 studies about DWI and MVI, and 1 study investigated DWI, tumor grading, and MVI in HCC. Results: In 21 studies (1,799 tumors), mean apparent diffusion coefficient (ADC) values (ADCmean) were used for distinguishing HCCs. ADCmean of G1–3 lesions overlapped significantly. In 4 studies (461 lesions), minimum ADC (ADCmin) was used. ADCmin values in G1/2 lesions were over 0.80 × 10−3 mm2/s and in G3 tumors below 0.80 × 10−3 mm2/s. In 4 studies (241 tumors), true diffusion (D) was reported. A significant overlapping of D values between G1, G2, and G3 groups was found. ADCmean and MVI were analyzed in 9 studies (1,059 HCCs). ADCmean values of MIV+/MVI− lesions overlapped significantly. ADCmin was used in 4 studies (672 lesions). ADCmin values of MVI+ tumors were in the area under 1.00 × 10−3 mm2/s. In 3 studies (227 tumors), D was used. Also, D values of MVI+ lesions were predominantly in the area under 1.00 × 10−3 mm2/s. Conclusion: ADCmin reflects tumor grading, and ADCmin and D predict MVI in HCC. Therefore, these DWI parameters should be estimated for every HCC lesion for pretreatment tumor stratification. ADCmean cannot predict tumor grading/MVI in HCC.

Background: Liquid biopsy based on cell-free DNA circulating in plasma has shown solid results as a non-invasive biomarker. In the present study we evaluated the utility of circulating free DNA (cfDNA) and the sub-type tumor DNA (ctDNA) in hepatocellular cancer (HCC) patients to assess therapy response and clinical outcome.Methods: A cohort of 13 patients recruited in the context of the SORAMIC trial with unresectable, advanced HCC and different etiological and clinicopathological characteristics was included in this exploratory study. Plasma samples were collected between liver micro-intervention and beginning of sorafenib-based systemic therapy and then in correspondence of three additional follow-ups. DNA was isolated from plasma and next generation sequencing (NGS) was performed on a panel of 597 selected cancer-relevant genes.Results: cfDNA levels showed a significant correlation with the presence of metastases and survival. In addition cfDNA kinetic over time revealed a trend with the clinical history of the patients, supporting its use as a biomarker to monitor therapy. NGS-based analysis on ctDNA identified 28 variants, detectable in different combinations at the different time points. Among the variants, HNF1A, BAX and CYP2B6 genes showed the highest mutation frequency and a significant association with the patients’ clinicopathological characteristics, suggesting a possible role as driver genes in this specific clinical setting.Conclusions: Taken together, the results support the prognostic value of cfDNA/ctDNA in advanced HCC patients with the potential to predict therapy response. These findings support the clinical utility of liquid biopsy in advanced HCC improving individualized therapy and possible earlier identification of treatment responders.