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Background:Body composition parameters have been reported to be prognostic factors in patients with oncologic diseases. However, the available data on patients with HCC are conflicting. The aim of this study was to assess the impact of body composition on survival in patients with HCC treated with sorafenib or selective internal radioembolization (SIRT) and sorafenib. Methods:This is an exploratory subanalysis of the prospective, randomized controlled SORAMIC trial. Within the palliative arm of the study, patients were selected if a baseline abdominal CT was available. A broad set of skeletal muscle and adipose tissue parameters were measured at the L3 level. Low skeletal muscle mass (LSMM) and density parameters were defined using published cutoffs. The parameters were correlated with overall survival. Results:Of 424 patients in the palliative study arm, 369 patients were included in the analysis. There were 192 patients in the combined sorafenib/SIRT and 177 patients in the sorafenib group. Median overall survival was 9.9 months for the entire cohort and 10.8 and 9.2 months for the SIRT/sorafenib and sorafenib groups, respectively. There was no relevant association of either body composition parameter with overall survival in either the overall cohort or in the SIRT/sorafenib or sorafenib subgroups. Conclusions:This subanalysis of the prospective SORAMIC trial does not suggest a relevant influence of body composition parameters of survival in patients with advanced HCC. Body composition parameters therefore do not serve in patient allocation in this palliative treatment cohort.

Objectives To identify clinical and imaging parameters associated with progression of non-hypervascular hepatobiliary phase hypointense lesions during follow-up in patients who received treatment for hepatocellular carcinoma. Methods A total of 67 patients with 106 lesions were identified after screening 538 patients who underwent gadoxetic acid-enhanced MRI within the SORAMIC trial. All patients were allocated to the trial treatment according to the trial scheme, and 61 of 67 patients received systemic treatment with sorafenib (either alone or combined with locoregional therapies) during the trial period. Follow-up images after treatment according to trial scheme were reviewed for subsequent hypervascularization or > 1 cm size increase. The correlation between progression and several imaging and clinical parameters was assessed using univariable and multivariable analyses. Results On a median 178 (range, 48-1072) days follow-up period, progression was encountered in 18 (16.9%) lesions in 12 (17.9%) patients. In univariable analysis size > 12.6 mm (p = 0.070), ECOG-PS (p = 0.025), hypointensity at T1-weighted imaging (p = 0.028), hyperintensity at T2-weighted imaging (p < 0.001), hyperintensity at DWI images (p = 0.007), and cirrhosis (p = 0.065) were correlated with progression during follow-up. Hyperintensity at T2 images (p = 0.011) was an independent risk factor for progression in multivariable analysis, as well as cirrhosis (p = 0.033) and ECOG-PS (p = 0.030). Conclusions Non-hypervascular hepatobiliary phase hypointense lesions are associated with subsequent progression after treatment in patients with HCC. T2 hyperintensity, diffusion restriction, cirrhosis, and higher ECOG-PS could identify lesions with increased risk. These factors should be considered for further diagnostic evaluation or treatment of such lesions.

The combination of the anti-PD-L1 antibody atezolizumab and the anti-VEGF bevacizumab is the first approved immunotherapeutic regimen for first-line therapy in patients with unresectable hepatocellular carcinoma (HCC), currently approved in more than 80 countries. The efficacy and tolerability of this regimen suggest that the use of atezolizumab bevacizumab could be extended to the treatment of patients with intermediate-stage HCC in combination with transarterial chemoembolization (TACE). The authors describe the rationale and design of the DEMAND study. This investigator-initiated, multicenter, randomized phase 2 study is the first trial to evaluate the safety and efficacy of atezolizumab bevacizumab prior to or in combination with TACE in patients with intermediate-stage HCC. The primary end point is the 24-month survival rate; secondary end points include objective response rate, progression-free survival, safety and quality of life.

Background: To investigate whole-body contrast-enhanced CT and hepatobiliary contrast liver MRI for the detection of extrahepatic disease (EHD) in hepatocellular carcinoma (HCC) and to quantify the impact of EHD on therapy decision. Methods: In this post-hoc analysis of the prospective phase II open-label, multicenter, randomized controlled SORAMIC trial, two blinded readers independently analyzed the whole-body contrast-enhanced CT and gadoxetic acid-enhanced liver MRI data sets of 538 HCC patients. EHD (defined as tumor manifestation outside the liver) detection rates of the two imaging modalities were compared using multiparametric statistical tests. In addition, the most appropriate treatment recommendation was determined by a truth panel. Results: EHD was detected significantly more frequently in patients with portal vein infiltration (21% vs. 10%, p < 0.001), macrovascular infiltration (22% vs. 9%, p < 0.001), and bilobar liver involvement (18% vs. 9%, p = 0.006). Further on, the maximum lesion diameter in patients with EHD was significantly higher (8.2 cm vs. 5.8 cm, p = 0.002). CT detected EHD in significantly more patients compared to MRI in both reader groups (p < 0.001). Higher detection rates of EHD in CT led to a change in management only in one patient since EHD was predominantly present in patients with locally advanced HCC, in whom palliative treatment is the standard of care. Conclusions: Whole-body contrast-enhanced CT shows significantly higher EHD detection rates compared to hepatobiliary contrast liver MRI. However, the higher detection rate did not yield a significant impact on patient management in advanced HCC.

Objectives To evaluate the correlation between liver enhancement on hepatobiliary phase and liver function parameters in a multicenter, multivendor study. Methods A total of 359 patients who underwent gadoxetic acid-enhanced MRI using a standardized protocol with various scanners within a prospective multicenter phase II trial (SORAMIC) were evaluated. The correlation between liver enhancement on hepatobiliary phase normalized to the spleen (liver-to-spleen ratio, LSR) and biochemical laboratory parameters, clinical findings related to liver functions, liver function grading systems (Child-Pugh and Albumin-Bilirubin [ALBI]), and scanner characteristics were analyzed using uni- and multivariate analyses. Results There was a significant positive correlation between LSR and albumin (rho = 0.193; p < 0.001), platelet counts (rho = 0.148; p = 0.004), and sodium (rho = 0.161; p = 0.002); and a negative correlation between LSR and total bilirubin (rho = -0.215; p < 0.001) and AST (rho = -0.191; p < 0.001). Multivariate analysis confirmed independent significance for each of albumin (p = 0.022), total bilirubin (p = 0.045), AST (p = 0.031), platelet counts (p = 0.012), and sodium (p = 0.006). The presence of ascites (1.47 vs. 1.69, p < 0.001) and varices (1.55 vs. 1.69, p = 0.006) was related to significantly lower LSR. Similarly, patients with ALBI grade 1 had significantly higher LSR than patients with grade 2 (1.74 +/- 0.447 vs. 1.56 +/- 0.408, p < 0.001); and Child-Pugh A patients had a significantly higher LSR than Child-Pugh B (1.67 +/- 0.44 vs. 1.49 +/- 0.33, p = 0.021). Also, LSR was negatively correlated with MELD-Na scores (rho = -0.137; p = 0.013). However, one scanner brand was significantly associated with lower LSR (p < 0.001). Conclusions The liver enhancement on the hepatobiliary phase of gadoxetic acid-enhanced MRI is correlated with biomarkers of liver functions in a multicenter cohort. However, this correlation shows variations between s

Purpose: To compare the treatment response and progression-free survival (PFS) in advanced hepatocellular carcinoma (HCC) patients who received sorafenib treatment either alone or combined with radioembolization (RE). Methods: Follow-up images of the patients treated within a multicenter phase II trial (SORAMIC) were assessed by mRECIST. A total of 177 patients (73 combination arm [RE + sorafenib] and 104 sorafenib arm) were included in this post-hoc analysis. Response and progression characteristics were compared between treatment arms. Survival analyses were done to compare PFS and post-progression survival between treatment arms. Multivariate Cox regression analysis was used to compare survival with factors known to influence PFS in patients with HCC. Results: The combination arm had significantly higher objective response rate (61.6% vs. 29.8%, p < 0.001), complete response rate (13.7% vs. 3.8%, p = 0.022), and a trend for higher disease control rate (79.2% vs. 72.1%, p = 0.075). Progression was encountered in 116 (65.5%) patients and was more common in the sorafenib arm (75% vs. 52.0%, p = 0.001). PFS (median 8.9 vs. 5.4 months, p = 0.022) and hepatic PFS were significantly better in the combination arm (9.0 vs. 5.7 months, p = 0.014). Multivariate analysis confirmed the treatment arm as an independent predictor of PFS. Conclusion: In advanced HCC patients receiving sorafenib, combination with RE has an additive anticancer effect on sorafenib treatment resulting in a higher and longer tumor response. However, the enhanced response did not translate into prolonged survival. Better patient selection and superselective treatment could improve outcomes after combination therapy.

Purpose: Gadoxetic acid uptake on hepatobiliary phase MRI has been shown to correlate with ß-catenin mutation in patients with HCC, which is associated with resistance to certain therapies. This study aimed to evaluate the prognostic value of gadoxetic acid uptake on hepatobiliary phase MRI in patients with advanced HCC receiving sorafenib. Methods: 312 patients with available baseline hepatobiliary phase MRI images received sorafenib alone or following selective internal radiation therapy (SIRT) within SORAMIC trial. The signal intensity of index tumor and normal liver parenchyma were measured on the native and hepatobiliary phase MRI images, and relative tumor enhancement higher than relative liver enhancement were accepted as high gadoxetic acid uptake, and its prognostic value was assessed using univariate and multivariate Cox proportional hazard models. Results: The median OS of the study population was 13.4 (11.8-14.5) months. High gadoxetic acid uptake was seen in 51 (16.3%) patients, and none of the baseline characteristics was associated with high uptake. In univariate analysis, high gadoxetic acid uptake was significantly associated with shorter overall survival (10.7 vs. 14.0 months, p = 0.005). Multivariate analysis confirmed independent prognostic value of high gadoxetic acid uptake (HR, 1.7 [1.21-2.3], p = 0.002), as well as Child-Pugh class (p = 0.033), tumor diameter (p = 0.002), and ALBI grade (p = 0.015). Conclusion: In advanced HCC patients receiving sorafenib (alone or combined with SIRT), high gadoxetic acid uptake of the tumor on pretreatment MRI, a surrogate of ß-catenin mutation, correlates with shorter survival. Gadoxetic acid uptake status might serve in treatment decision-making process.