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Selective internal radiation therapy (SIRT) has emerged as a viable endovascular treatment strategy for hepatocellular carcinoma (HCC). According to the Barcelona Clinic Liver Cancer (BCLC) classification, SIRT is currently recommended for early- and intermediate-stage HCC that is unsuitable for alternative locoregional therapies. Additionally, SIRT remains a recommended treatment for patients with advanced-stage HCC and portal vein thrombosis (PVT) without extrahepatic metastasis. Several studies have shown that SIRT is a versatile and promising treatment with a wide range of applications. Consequently, given its favourable characteristics in various scenarios, SIRT could be an encouraging treatment option for patients with HCC across different BCLC stages. Over the past decade, an increasing number of studies have focused on better understanding the prognostic factors associated with SIRT to identify patients who derive the most benefit from this treatment or to refine the optimal technical procedures of SIRT. Several variables can influence treatment decisions, with a growing emphasis on a personalised approach. This review, based on the literature, will focus on the prognostic factors associated with the effectiveness of radioembolization and related complications. By comprehensively analysing these factors, we aimed to provide a clearer understanding of how to optimise the use of SIRT in managing HCC patients, thereby enhancing outcomes across various clinical scenarios.

Background & Aims: We aimed to explore patient expectations regarding their treatments and prognosis in comparison to physicians' assessments in patients with advanced hepatocellular carcinoma (HCC) receiving systemic treatments. Methods: We prospectively enrolled 205 patients in France and Belgium with Barcelona Clinic Liver Cancer (BCLC) stage B/C HCC receiving systemic treatment (NCT04823754). Patients completed a 28-question survey and the hospital anxiety and depression scale (HADS), while physicians filled a 17-question survey after the initial consultation. Univariate and multivariate models were used to assess factors associated with concordant patient-physician responses, HADS, as well as predicted (by physicians) and observed overall survival. Results: Patients had a median age of 68 years with 75% having BCLC C HCC; 86.3% received atezolizumab/bevacizumab. 60% of patients did not discuss life expectancy with the physician. 63% of the patients believed they had a life expectancy >5 years. Among shared questions between patients and physicians, 36.4% concordance was observed; major differences centered on life expectancy with patients more optimistic than physicians. A lower patient-physician concordance was seen with shorter-consultations (p = 0.003), female physicians (p = 0.02), BCLC C (p = 0.03) and >100 HCC patients/year per physician (p = 0.008). Compared to France, patients from Belgium were more likely to be satisfied with the consultation (p

Background & Aims: Despite its growing incidence, hepatocellular carcinoma (HCC) related to metabolic dysfunction-associated steatotic liver disease (MASLD) in non-cirrhotic livers remains poorly characterized. We compared the characteristics, management, survival, and trends of MASLD-related HCC in patients with or without underlying cirrhosis in a large multicenter cohort. Methods: A total of 354 cases of MASLD-related HCC presented at the liver tumor meetings of four French university hospitals between 2007 and 2018 were included in the study. Data were extracted from the meetings’ databases and from the French Birth and Death Registry. Results: Of HCC cases, 35% occurred in the absence of cirrhosis. HCC was diagnosed through screening in 60% of patients with cirrhosis, and incidentally in 72% of patients without it. Patients without cirrhosis were older, had a greater tumor burden, but also better liver function than patients with cirrhosis. Patients without cirrhosis showed better overall survival than those with cirrhosis (p = 0.043). However, cirrhosis was not independently associated with overall survival, the independent predictors were age, liver function, tumor burden and BCLC classification. Patients without cirrhosis underwent surgery more frequently than patients with cirrhosis (41% vs. 11%, p

Abstract Primary liver cancer arises either from hepatocytic or biliary lineage cells, giving rise to hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICCA). Combined hepatocellular- cholangiocarcinomas (cHCC-CCA) exhibit equivocal or mixed features of both, causing diagnostic uncertainty and difficulty in determining proper management. Here, we perform a comprehensive deep learning-based phenotyping of multiple cohorts of patients. We show that deep learning can reproduce the diagnosis of HCC vs. CCA with a high performance. We analyze a series of 405 cHCC-CCA patients and demonstrate that the model can reclassify the tumors as HCC or ICCA, and that the predictions are consistent with clinical outcomes, genetic alterations and in situ spatial gene expression profiling. This type of approach could improve treatment decisions and ultimately clinical outcome for patients with rare and biphenotypic cancers such as cHCC-CCA.

Abstract Background Several cancer immunotherapies that target the PD-L1/PD-1 pathway show promising clinical activity in patients with hepatocellular carcinoma (HCC). However, the standard of care in first-line treatment with atezolizumab (anti-PD-L1 therapy) in combination with bevacizumab is associated with a limited objective response rate. Telomerase reverse transcriptase (TERT) activation meets the criteria of oncogenic addiction in HCC and could be actionable therapeutic target and a relevant tumor antigen. Therefore we hypothesized that combining anti-PD-1/PD-L1 therapy with an anti-telomerase vaccine might be an attractive therapy in HCC. UCPVax is a therapeutic cancer vaccine composed of two separate peptides derived from telomerase (human TERT). UCPVax has been evaluated in a multicenter phase I/II study in non–small cell lung cancers and has demonstrated to be safe and immunogenic, and is under evaluation in combination with atezolizumab in a phase II clinical trial in tumors where telomerase reactivation contributes to an oncogene addiction (HPV+ cancers). The aim of the TERTIO study is to determine the clinical interest and immunological efficacy of a treatment combining the CD4 helper T-inducer cancer anti-telomerase vaccine (UCPVax) with atezolizumab and bevacizumab in unresectable HCC in a multicenter randomized phase II study. Methods Patients with locally advanced, metastatic or unresectable HCC who have not previously received systemic anti-cancer treatment are eligible. The primary end point is the objective response rate at 6 months. Patients will be allocated to a treatment arm with a randomization 2:1. In both arms, patients will receive atezolizumab at fixed dose of 1200 mg IV infusion and bevacizumab at fixed dose of 15 mg/kg IV infusion, every 3 weeks, according to the standard of care. In the experimental arm, these treatments will be combined with the UCPVax vaccine at 0.5 mg subcutaneously. Discussion Combining anti-PD-1/PD-L1 therapy with an anti-telomerase vaccine gains serious consideration in HCC, in order to extend the clinical efficacy of anti-PD-1/PD-L1. Indeed, anti-cancer vaccines can induce tumor-specific T cell expansion and activation and therefore restore the cancer-immunity cycle in patients lacking pre-existing anti-tumor responses. Thus, there is a strong rational to combine immune checkpoint blockade therapy and anticancer vaccine (UCPVax) in order to activate antitumor T cell immunity and bypass the immunosuppression in the tumor microenvironment in HCC. This pivotal proof of concept study will evaluate the efficacy and safety of the combination of a CD4 Th1-inducer cancer vaccine derived from telomerase (UCPVax) and atezolizumab plus bevacizumab in unresectable HCC, as well as confirming their synergic mechanism, and settling the basis for a new combination for future clinical trials. Trial registration NCT05528952.

Introduction and Objectives: The lockdown policy introduced in 2020 to minimize the spread of the COVID-19 pandemic, significantly affected the management and care of patients affected by hepatocellular carcinoma (HCC). The aim of this follow-up study was to determine the 12 months impact of the COVID-19 pandemic on the cohort of patients affected by HCC during the lockdown, within six French academic referral centers in the metropolitan area of Paris. Materials and Methods: We performed a 12 months follow-up of the cross-sectional study cohort included in 2020 on the management of patients affected by HCC during the first six weeks of the COVID-19 pandemic (exposed), compared to the same period in 2019 (unexposed). Overall survival were compared between the groups. Predictors of mortality were analysed with Cox regression. Results: From the initial cohort, 575 patients were included (n = 263 Exposed_COVID, n = 312 Unexposed_COVID). Overall and disease free survival at 12 months were 59.9 ± 3.2% vs. 74.3 ± 2.5% (p

Background & Aims: Transcatheter arterial chemoembolisation (TACE) is recommended for patients with hepatocellular carcinoma devoid of macrovascular invasion or extrahepatic spread but not eligible for curative therapies. We compared the efficacy and safety of the combination of a single TACE and external conformal radiotherapy (CRT) vs. classical TACE. Methods: TACERTE was an open-labelled, randomised controlled trial with a 1:1 allocation rate to two or three TACE (arm A) or one TACE + CRT (arm B). Participants had a mean age of 70 years, and 86% were male. The aetiology was alcohol in 85%. The primary endpoint was liver progression-free survival (PFS) in the intention-to-treat population. The typical CRT schedule was 54 Gy in 18 sessions of 3 Gy. Results: Of the 120 participants randomised, 64 were in arm A and 56 in arm B; 100 participants underwent the planned schedule and defined the ‘per-protocol’ group. In intention-to-treat participants, the liver PFS at 12 and 18 months were 59% and 19% in arm A and 61% and 36% in arm B (hazard ratio [HR] 0.69; 95% CI 0.40–1.18; p = 0.17), respectively. In the per-protocol population, treated liver PFS tended to be better in arm B (HR 0.61; 95% CI 0.34–1.06; p = 0.081) than in arm A. Liver-related grade III–IV adverse events were more frequent in arm B than in arm A. Median overall survival reached 30 months (95% CI 23–35) in arm A and 22 months (95% CI 15.7–26.2) in arm B. Conclusions: Although TACE + CRT tended to improve local control, this first Western randomised controlled trial showed that the combined strategy failed to increase PFS or overall survival and led more frequently to liver-related adverse effects. Impact and implications: Hepatocellular carcinoma is frequently treated by arterial embolisation of the tumour and more recently by external radiotherapy. We tried to determine whether combination of the two treatments (irradiation after embolisation) might produce interesting results. Our results in this prospective randomised study were not able to demonstrate a beneficial effect of combining embolisation and irradiation in these patients. On the contrary, we observed more adverse effects with the combined treatment. Clinical Trials Registration: NCT01300143.

Introduction and objectives: Liver resection is the only curative therapeutic option for large hepatocellular carcinoma (> 5 cm), but survival is worse than in smaller tumours, mostly due to the high recurrence rate. There is currently no proper tool for stratifying relapse risk. Herein, we investigated prognostic factors before hepatectomy in patients with a single large hepatocellular carcinoma (HCC). Material and methods: We retrospectively identified 119 patients who underwent liver resection for a single large HCC in 2 tertiary academic French centres and collected pre- and post-operative clinical, biological and radiological features. The primary outcome was overall survival at five years. Secondary outcomes were recurrence-free survival at five years and prognostic factors for recurrence. Results: A total of 84% of the patients were male, and the median age was 66 years old (IQR 58–74). Thirty-nine (33%) had Child–Pugh A cirrhosis, and the mean Model for End-Stage Liver Disease (MELD) score was 6 (6–6). The aetiology of liver disease was predominantly alcohol-related (48%), followed by nonalcoholic steatohepatitis (22%), hepatitis B (18%) and hepatitis C (10%). The mean tumour size was 70 mm (55–110). The median overall survival was 72.5 months (IC 95%: 56.2-88.7), and the five-year overall survival was 55.1 ± 5.5%. The median recurrence-free survival was 26.6 months (95% CI: 16.0-37.1), and the five-year recurrence-free survival rate was 37.8 ± 5%. In multivariate analysis, preoperative prognostic factors for recurrence were baseline alpha-fetoprotein (AFP) > 7 ng/mL (p

Backgrounds and aims: Even if no systemic treatment is currently validated for unresectable hepato-cholangiocarcinoma (cHCC-CCA), tyrosine kinase inhibitors (TKI), and platinum-based chemotherapy are frequently used in clinical practice. Our study aims to describe the effectiveness of first-line systemic treatments in patients with cHCC-CCA. Patients and Methods: Patients with histological diagnosis of unresectable or metastatic cHCC-CCA confirmed by a centralized review (WHO classification 2019) and who received systemic treatment from 2009 to 2020 were included retrospectively in 11 centers. The outcomes of patients with cHCC-CCA were compared with patients with hepatocellular carcinoma (HCC) treated by sorafenib (n=117) and with intrahepatic cholangiocarcinoma (iCCA, n=94) treated mainly by platinum-based chemotherapy using a frailty Cox model. The efficacy of tyrosine kinase inhibitors and platinum-based chemotherapies in patients with cHCC-CCA was assessed using a doubly robust estimator. Results: A total of 83 patients with cHCC-CCA were included and were predominantly male (72%) with underlying cirrhosis (55%). 67% of patients had extrahepatic metastases and 31% macrovascular tumor invasion. cHCC-CCAs were more often developed on cirrhosis (55.4%) than iCCA (26.6%) but less frequently than HCC (80.2%)(p

Background & Aims: Patients affected by hepatocellular carcinoma (HCC) represent a vulnerable population during the COVID-19 pandemic and may suffer from altered allocation of healthcare resources. The aim of this study was to determine the impact of the COVID-19 pandemic on the management of patients with HCC within 6 referral centres in the metropolitan area of Paris, France. Methods: We performed a multicentre, retrospective, cross-sectional study on the management of patients with HCC during the first 6 weeks of the COVID-19 pandemic (exposed group), compared with the same period in 2019 (unexposed group). We included all patients discussed in multidisciplinary tumour board (MTB) meetings and/or patients undergoing a radiological or surgical programmed procedure during the study period, with curative or palliative intent. Endpoints were the number of patients with a modification in the treatment strategy, or a delay in decision-to-treat. Results: After screening, n = 670 patients were included (n = 293 exposed to COVID, n = 377 unexposed to COVID). Fewer patients with HCC presented to the MTB in 2020 (p = 0.034) and fewer had a first diagnosis of HCC (n = 104 exposed to COVID, n = 143 unexposed to COVID, p = 0.083). Treatment strategy was modified in 13.1% of patients, with no differences between the 2 periods. Nevertheless, 21.5% vs. 9.5% of patients experienced a treatment delay longer than 1 month in 2020 compared with 2019 (p