Necrotizing fasciitis following targeted therapy in a patient with unresectable hepatocellular carcinoma: A case report

Surgical resection for recurrent hepatocellular carcinoma: Prognosis and analysis of risk factors

Ultrasound-guided percutaneous cryotherapy of hepatocellular carcinoma

Quality Improvement Guidelines for Transhepatic Arterial Chemoembolization, Embolization, and Chemotherapeutic Infusion for Hepatic Malignancy

How should patients with hepatocellular carcinoma recurrence after liver transplantation be treated?

Camrelizumab plus rivoceranib (camr-rivo) has been shown to significantly improve overall survival (OS) in patients with unresectable or advanced hepatocellular carcinoma (HCC) in the CARES-310 trial. However, the cost-utility of this treatment remains unclear. Therefore, this study evaluated the cost-utility of camr-rivo versus sorafenib as a first-line systemic therapy for patients with unresectable or advanced HCC from the perspectives of the Chinese healthcare system and the United States (US) payers. Based on the CARES-310 trial, a partitioned survival model was constructed to estimate economic costs and health outcomes over a 10-year lifetime horizon. Drug costs were obtained from the public database, Red Book, and relevant literature. Health utility values were derived from the literature. One-way and probabilistic sensitivity analyses were performed. The willingness-to-pay (WTP) threshold was $36,627.25/QALY in China and $150,000.00/QALY in the United States. Camr-rivo yielded an additional 0.34 quality-adjusted life years (QALY) compared to sorafenib for patients with unresectable or advanced HCC. The incremental costs in China and the United States were $4,762.10 and $92,700.49, respectively, and the incremental cost-utility ratios (ICURs) were $14,174.40/QALY and $272,852.59/QALY, respectively. Sensitivity analyses indicated that the cost of rivoceranib and camrelizumab had the greatest impact on the ICUR in China and the United States. Scenario analyses showed that a price reduction of approximately 30% for camrelizumab and rivoceranib could make camr-rivo a cost-utility option in the United States. At the set WTP threshold, camr-rivo is a cost-utility treatment strategy compared to sorafenib as a first-line therapy for patients with unresectable or advanced HCC in China but not in the United States.

Hepatocellular carcinoma (HCC) is not only common, but often presents at a stage when potentially curative therapies are not feasible. Although hepatic artery chemoembolization likely confers survival benefit in unresectable HCC, the associated toxicities are substantial and warrant investigation of more efficacious and safe therapies. Many patients who present with unresectable HCC are not chemoembolization candidates, either because of extensive disease or severely impaired hepatic function. We reviewed 44 randomized trials investigating non-embolization-based therapies in unresectable HCC. Hepatic artery infusion of [I]lipiodol appears safe; initial studies suggest a survival benefit and efficacy comparable to more toxic embolization-based therapies. Some cytotoxic chemotherapy may confer a modest survival benefit in advanced HCC (including oral fluoropyrimidines, and hepatic arterial or i.v. cisplatin and doxorubicin). Tamoxifen does not confer survival benefit, either in advanced or limited HCC. Other therapies warranting further study include interferon (in optimally cytoreduced HCC), megestrol in patients with variant estrogen receptors, octreotide and pravastatin. More adequately powered, rigorously conducted studies will hopefully identify useful chemo-, radio-, immuno-, embolization-based and biologically targeted therapies during the next decade.

Background The prognosis of unresectable large hepatocellular carcinomas is poor. This study evaluated the efficacy and safety of sorafenib combined with transcatheter arterial chemoembolization and radiofrequency ablation in the treatment of hepatocellular carcinomas larger than 5 cm. Methods The treatment of 22 patients with large, unresectable hepatocellular carcinomas (5.0-16.5 cm) treated with sorafenib after transcatheter arterial chemoembolization combined with radiofrequency ablation between 2007 and 2011 was reviewed. The local effects, survival rates, toxicity, and prognostic factors were analyzed. Results During a follow-up of 9-49 months, 19 patients died and three survived. The median overall survival was 32 months. The overall cumulative 12, 24, and 36-month survival rates were 85.9%, 66.8%, and 23.5% respectively. Technical effectiveness was achieved in 12 out of 28 lesions (42.85%) at the first CT check. The median time to tumor progression was 21 months. The progression-free survival rates at 6, 12, and 24 months were 90.9%, 72.0%, and 38.4%, respectively. Combined therapy was generally well tolerated. There was only one major procedure-related complication, biloma (4.5%). Sorafenib-related adverse events exceeding grade 3 were hand-foot skin reaction (2/22, 9.1%), gastrointestinal hemorrhage (1/22, 4.5%), and diarrhea (2/22, 9.1%). The absence of vascular invasion before treatment was found to be the best prognostic factor in the univariate analysis. Conclusions Sorafenib combined with transcatheter arterial chemoembolization and radiofrequency ablation is a promising approach to the treatment of large, unresectable hepatocellular carcinomas. However, large-scale randomized clinical trials are needed to determine the future role of this treatment.

Sorafenib is the only standard treatment for unresectable hepatocellular carcinoma (HCC), but it provides modest survival benefits over placebo, necessitating predictive biomarkers of the response to sorafenib. Serum samples were obtained from 115 consecutive patients with HCC before sorafenib treatment and analyzed by multiple reaction monitoring-mass spectrometry (MRM-MS) and ELISA to quantify candidate biomarkers. We verified a triple-marker panel to be predictive of the response to sorafenib by MRM-MS, comprising CD5 antigen-like (CD5L), immunoglobulin J (IGJ), and galectin-3-binding protein (LGALS3BP), in HCC patients. This panel was a significant predictor (AUROC > 0.950) of the response to sorafenib treatment, having the best cut-off value (0.4) by multivariate analysis. In the training set, patients who exceeded this cut-off value had significantly better overall survival (median, 21.4 months) than those with lower values (median, 8.6 months; p = 0.001). Further, a value that was lower than this cutoff was an independent predictor of poor overall survival [hazard ratio (HR), 2.728; 95% confidence interval (CI), 1.312-5.672; p = 0.007] and remained an independent predictive factor of rapid progression (HR, 2.631; 95% CI, 1.448-4.780; p = 0.002). When applied to the independent validation set, levels of the cut-off value for triple-marker panel maintained their prognostic value for poor clinical outcomes. On the contrast, the triple-marker panel was not a prognostic factor for patients who were treated with transarterial chemoembolization (TACE). The discriminatory signature of a triple-marker panel provides new insights into targeted proteomic biomarkers for individualized sorafenib therapy.

Objective: To evaluate the efficacy and safety of first-line treatment with atezolizumab plus bevacizumab compared to lenvatinib in patients with unresectable hepatocellular carcinoma (HCC) associated with hepatitis B virus (HBV) infection. Methods: This retrospective study included patients with unresectable HBV-related HCC from October 2020 to December 2024 at General Hospital of Tianjin Medical University. Baseline clinical characteristics, treatment response, and adverse events were collected. According to the different first-line treatment, patients were divided into the observation group (receiving atezolizumab combined with bevacizumab) and the control group (receiving oral lenvatinib monotherapy). Kaplan-Meier analysis was used for making survival curve. The overall survival (OS) and progression-free survival (PFS) were compared between two groups. And log-rank test was used to compare the survival differences between the two groups. Tumor response was evaluated per modified response evaluation criteria in solid tumors (mRECIST). The objective response rate (ORR), disease control rate (DCR) and safety were compared between the two groups. Results: A total of 110 patients were included, of whom 56 were in the observation group, with an age of [M(Q1, Q3)] 61 (39, 77) years, and 44 males; 54 were in the control group, with an age of 62 (38, 75) years, and 41 males. Overall, patients were predominantly classified as Child-Pugh class A for liver function, with a median follow-up time of 15.9 months. The median OS was significantly longer in the observation group compared to the control group (20.4 months vs 14.5 months), with 2-year OS rates of 33.7% vs 20.2%, respectively (P=0.018). Median PFS was also longer in the observation group (7.5 months vs 5.6 months) with 1-year PFS rates of 37.2% vs 14.8% (P=0.006). The ORR in the observation group and the control group was 32.1% and 20.4%, respectively, while the DCR was 75.0% and 72.2%, respectively. Grade≥3 treatment-related adverse events occurred in 46.4% (26/56) of patients in the atezolizumab plus bevacizumab group and 38.9% (21/54) in the lenvatinib group, with no statistically significant difference (P=0.424). The most common adverse events differed between groups: in the observation group, fatigue (73.2%, 41/56), gastrointestinal reactions (62.5%, 35/56), hypertension (28.6%, 16/56), proteinuria (21.4%, 12/56) and liver toxicity (17.9%, 10/56) were more frequent; in the control group, fatigue (61.1%, 33/54), hypertension (48.1%, 26/54) and hand-foot skin reaction (24.1%, 13/54) were more common. No severe liver failure or treatment-related deaths were observed. Conclusion: In patients with unresectable HBV-related HCC, atezolizumab plus bevacizumab demonstrated a longer OS and higher ORR compared to lenvatinib with a manageable safety profile.

Tiragolumab in combination with atezolizumab and bevacizumab in patients with unresectable, locally advanced or metastatic hepatocellular carcinoma (MORPHEUS-Liver): a randomised, open-label, phase 1b-2, study.

A Phase 2 Trial of Apatinib Combined With Intensity Modulated Radiation Therapy for Patients With Unresectable Hepatocellular Carcinoma

Hepatocellular carcinoma is a malignancy with an increasing incidence worldwide and is one of the most serious cancers in adults. We encountered a case of initially unresectable massive hepatocellular carcinoma in which conversion to curative resection and pathological complete response were achieved after atezolizumab plus bevacizumab therapy. Atezolizumab plus bevacizumab combination chemotherapy may be one of the most promising options for unresectable hepatocellular carcinoma.

The poor prognosis of hepatocellular carcinoma (HCC) was partly a result of the majority of unresectable HCCs in clinical patients. Fortunately, with the progress of regional cancer therapies and multimodality treatment, some of the localized unresectable HCCs were converted to resectable ones. During the period 1960-1994, 72 of the 663 patients with surgically verified unresectable HCCs have been converted to resectable. Successful cytoreduction with median diameter reduced from 10 cm to 5 cm was mainly a result of the triple or double combination treatment with hepatic artery ligation, hepatic artery cannulation with infusion, radioimmunotherapy, and fractionated regional radiotherapy. The interval between the first operation and the sequential resection was 5 months. The operative mortality was 1.4% for sequential resection, and the 5-year survival was 62.1%. Analysis of factor influencing sequential resection rate revealed HCCs that were single nodule, well encapsulated, situated at right lobe or hepatic hilum, associated with micronodular cirrhosis, and treated with triple or double combination modalities had higher sequential resection rate as compared to their counterparts. Analysis of factors influencing survival after sequential resection revealed that HCCs with a solitary tumor confined in one lobe, without tumor embolus, and without residual cancer in specimen of sequential resection, had longer survival. It is suggested that localized unresectable, solitary, well encapsulated, right lobe or hilar HCC, associated with micronodular cirrhosis, will be good candidates for cytoreduction and sequential resection; and HCCs with unilateral involvement, without tumor embolus, and with complete necrosis of tumor after multimodality treatment favored better prognosis.

The median survival time for patients with unresectable hepatocellular carcinoma (HCC) is <6 months, and no effective standard systemic chemotherapy is available. Both epirubicin (Ellence); Pfizer Pharmaceuticals, New York, NY, http://www.pfizer.com) and thalidomide (Thalomid); Celgene Corporation, Warren, NJ, http://www.celgene.com) have reported activity for HCC as single agents, and they have different mechanisms of action and nonoverlapping toxicities. Therefore, we performed a phase II study using the combination of epirubicin and thalidomide in patients with unresectable and metastatic HCC. Nineteen patients with measurable, unresectable, or metastatic HCC were enrolled. All patients were required to have adequate major organ function and performance status. The treatment consisted of weekly epirubicin at a dose of 20 mg/m(2) administered i.v. and daily thalidomide at a dose of 200 mg orally given as a 3-weeks-on/1-week-off schedule. Intrapatient dose escalation of thalidomide was allowed every 2 weeks up to 800 mg daily as long as tolerated. Physical examinations, toxicity assessments, and serum chemistry analyses were performed weekly, and tumor measurements were conducted every 8 weeks. All 19 patients enrolled into the study were evaluable for toxicity assessment and 17 patients were evaluable for response assessment. A total of 71 cycles of chemotherapy was administered, with a median of two cycles administered to each patient (range 1-14). No complete or partial responses were observed. Seven patients (41%) had stable disease, with a median duration of 6 months (range 5-14). The median survival time for all 19 patients was 196 days (95% confidence interval 93-302). The treatment was generally well tolerated. Treatment-related toxicities included constipation (grade 3, 5%; grade 2, 37%; grade 1, 21%), fatigue (grade 3, 5%; grade 2, 42%), and sensory neuropathy (grade 2, 5%; grade 1, 32%). Four patients required dose reductions of thalidomide due to treatment-related toxicities, and the median tolerated dose of thalidomide was 200 mg daily. The combination of epirubicin and thalidomide was well tolerated when administered in the schedule used in this study. This regimen has limited activity in HCC, with some patients achieving stable disease and clinical benefit. There is a need for defining more effective systemic therapies for HCC.

TPS4178 Background: Despite advances in treatment for unresectable hepatocellular carcinoma (HCC), long-term survival rates remain poor. The combination of bevacizumab (Bev) and atezolizumab (Atezo) is the preferred frontline therapy for advanced HCC, but a minority of patients (pts) respond, and secondary resistance usually occurs within months. HCC has an immune-suppressed tumor microenvironment, mediated by activated immune checkpoint signaling and angiogenesis pathways, which may contribute to therapeutic resistance. RP3 is a genetically modified herpes simplex virus type 1 (HSV-1) that expresses the fusogenic gibbon ape leukemia virus glycoprotein with the R sequence deleted (GALV-GP-R–), an anti–CTLA-4 antibody-like molecule, CD40 ligand, and 4-1BB ligand. The direct oncolytic effect coupled with immune stimulation by RP3 in the tumor microenvironment is intended to provide systemic antitumor activity and enhance therapeutic response to anti–PD-1/PD-L1 agents, such as Atezo. Preclinical data have demonstrated improved distribution of oncolytic HSV within tumors in combination with Bev, supporting the clinical combination of RP3 with Bev. This study will evaluate the safety and efficacy of RP3 combined with Atezo and Bev as first- (1L) and second-line (2L) systemic therapies for unresectable and advanced HCC. Methods: The 1L and 2L cohorts will each enroll up to 30 pts. Pts in the 1L cohort may not have received prior systemic treatment; pts in the 2L cohort must have progressed on or following one prior line of systemic therapy, which must have included a PD-1/PD-L1−directed agent. Key inclusion criteria include advanced, unresectable HCC with ≥1 measurable tumor of ≥1 cm in longest diameter, Child-Pugh Class A, and Eastern Cooperative Oncology Group performance status of 0−1. Key exclusion criteria include untreated esophageal and/or gastric varices with bleeding or at high risk for bleeding and macroscopic invasion of tumor into any major blood vessel(s) and/or main bile ducts. Pts with a history of medically refractory hepatic encephalopathy and/or hepato-renal syndrome are also excluded. Pts in the 1L cohort will receive 1200 mg Atezo and 15 mg/kg Bev every 3 weeks (Q3W) together with RP3 intratumorally Q3W for a total of up to 8 doses. Pts in the 2L cohort will receive RP3 every 2 weeks for 4 doses with Bev Q3W starting on cycle (C) 1 day (D) 1, then RP3 and Bev Q3W for up to 4 more doses with Atezo Q3W being added on C4D1. The primary endpoint is overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints are safety, ORR using HCC modified RECIST, duration of response, complete response rate, and progression-free survival. Clinical trial information: NCT05733598 .