Treatment Of Advanced Hepatocellular Carcinoma Research Articles

A novel approach for the treatment of advanced hepatocellular carcinoma (HCC).

35 Background: No established treatments for patients with advanced HCC and moderate hepatic dysfunction (Child-Pugh B; CPB) are available. Namodenoson is an A3 adenosine-receptor agonist currently under clinical development as a treatment for advanced HCC with CPB. Methods: Wereport the results of a prospective placebo-controlled randomized (2:1) phase 2 trial investigating namodenoson (25 mg BID) as a second-line therapy in HCC with CPB and focus on a case of a long-term complete response (CR). Results: The study included 78 patients (50 namodenoson-treated, 28 placebo-treated). Namodenoson was well-tolerated and no treatment-related deaths were reported. Median overall survival (OS, the primary endpoint) was not statistically significantly different between the namodenoson and placebo arms (4.1 and 4.3 months, respectively, hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.49‒1.38; p=.46). The difference in 12-month OS was statistically significant (44% vs 18%, respectively, p=.028). Pre-planned analysis of patients with CPB7 (34 namodenoson-treated, 22 placebo-treated) showed nonsignificant improvements in OS and progression-free survival (PFS). OS: 6.9 vs 4.3 months; HR, 0.81; 95% CI: 0.45‒1.43; p=.46. PFS: 3.5 vs 1.9 months; HR, 0.89; 95% CI: 0.51‒1.55; p=.67. Of the patients with ≥1 assessment post-baseline, partial response (PR) was reported in 3 of 34 (8.8%) namodenoson-treated patients and none of the 21 placebo-treated patients. One of 3 the patients who achieved a PR (a 61-year old woman with CPB7, Barcelona Clinic Liver Cancer stage C, and Eastern Cooperative Oncology Group performance status 2) continued treatment with namodenoson under an open-label extension program (treatment is ongoing for >6 years). The patient achieved a CR (determined via CT scans) 4 years after treatment initiation. Furthermore, the patient's baseline ALT and AST levels which were elevated at baseline (68 U/L and 44 U/L, respectively) normalized after 4 weeks, and her serum α-fetoprotein level, which was 47 ng/ml at baseline, declined to normal levels after 20 weeks of treatment and reached 1.3 ng/mL at time of CR. The patient experienced no treatment-related adverse events. At present (6 years from treatment initiation), the response is ongoing as shown by liver function evaluation and imaging studies. Conclusions: Treatment with namodenoson can result in a complete and long-term response. The findings support the clinical development of namodenoson as a treatment for HCC with CPB7. Clinical trial information: NCT02128958 .

Role of radiotherapy and its contribution to immunotherapy in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a major contributor to cancer-related deaths, with the incidence of HCC increasing in regions of the world with a high incidence of hepatitis B and C. The therapeutic landscape for HCC management has substantially transformed over recent years, shifting towards a multimodal treatment paradigm. This approach provides a range of medical and surgical interventions aimed at managing the disease effectively. Radiotherapy (RT) has surfaced as a critical player in the preoperative management of inoperable HCC, demonstrating potential in downstaging the disease and achieving disease stability. This advantage may potentially be attributed to the abscopal effect, where localized radiation leads to the regression of metastatic cancer outside of the irradiated site through upregulation of the immune system. The advent of recent technological breakthroughs has paved the way for innovative approaches, notably the integration of immunotherapy and RT. This strategy is emerging as a promising avenue for managing HCC. Preliminary findings from the fusion of RT and immunotherapy are encouraging, with ongoing trials keenly evaluating the optimal parameters for therapy administration, such as timing, dosage, and sequence. The development of combined treatments involving immune checkpoint inhibitors (ICIs) has opened new avenues for advanced HCC treatment. Several immunotherapeutic agents with RT are concurrently being explored for their potential contributions to HCC management.

FGD5-AS1/miR-5590-3p/PINK1 induces Lenvatinib resistance in hepatocellular carcinoma

BackgroundLenvatinib is a common systemic treatment for advanced hepatocellular carcinoma (HCC), the resistance to which presents a great challenge. However, the mechanism of lenvatinib resistance in HCC remains unclear. Therefore, elucidating the underlying and key regulatory molecular mechanisms of lenvatinib resistance is urgently needed. MethodsBioinformatic enrichment analysis was used to investigate the gene associated with lenvatinib resistance. RT-PCR, Western blot, immunohistochemistry, and luciferase assays were used to explore the mechanisms of lenvatinib resistance. The effects of the FGD5-AS1/miR-5590-3p/PINK1 axis on lenvatinib resistance were evaluated by colony formation assay, cell viability, apoptosis, mitochondrial homeostasis, and morphology analyses. ResultsHigher expression of PINK1 was observed in lenvatinib-resistant cells and tissues. PINK1 could be activated by increased FGD5-AS1 expression, thereby maintaining the mitochondrial structure and function and promoting the antioxidative stress response. FGD5-AS1/miR-5590-3p showed competitive regulation of PINK1, which affected lenvatinib sensitivity through regulation of mitochondrial structure and antioxidative stress. ConclusionsPINK1 was identified as a key gene leading to lenvatinib resistance by maintaining the mitochondrial structure and function. The FGD5-AS1/miR-5590-3p/PINK1 axis may be a promising strategy to overcome lenvatinib resistance in treatment-negative patients.

A contrast-enhanced ultrasound-based nomogram for the prediction of therapeutic efficiency of anti-PD-1 plus anti-VEGF agents in advanced hepatocellular carcinoma patients.

There is no study focusing on noninvasive predictors for the efficacy of sintilimab (anti-PD-1) plus IBI305 (a bevacizumab biosimilar) treatment in advanced hepatocellular carcinoma (HCC). A total of 33 patients with advanced HCC were prospectively enrolled and received sintilimab plus IBI305 treatment from November 2018 to October 2019. Baseline characteristics including clinical data, laboratory data, and tumor features based on pretreatment CT/MR were collected. Meanwhile, pretreatment contrast-enhanced ultrasound (CEUS) for target tumor was performed and quantitative parameters were derived from time-intensity curves (TICs). A nomogram was developed based on the variables identified by the univariable and multivariable logistic regression analysis. The discrimination, calibration, and clinical utility of the nomogram were evaluated. Tumor embolus and grad ratio were significant variables related to the efficacy of sintilimab plus IBI305 strategy. The nomogram based on these two variables achieved an excellent predictive performance with an area under curve (AUC) of 0.909 (95% CI, 0.813-1). A bootstrapping for 500 repetitions was performed to validate this model and the AUC of the bootstrap model was 0.91 (95% CI, 0.8-0.98). The calibration curve and decision curve analysis (DCA) showed that the nomogram had a good consistency and clinical utility. This study has established and validated a nomogram by incorporating the quantitative parameters of pretreatment CEUS and baseline clinical characteristics to predict the anti-PD-1 plus anti-VEGF treatment efficacy in advanced HCC patients.

Complications of Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma: A Case Report of Bronchobiliary Fistula Development in a 68-Year-Old Man.

BACKGROUND Bronchobiliary fistulas (BBFs) are abnormal communications between the biliary tract and bronchial tree. Transcatheter arterial chemoembolization (TACE) is a widely employed treatment for advanced hepatocellular carcinoma (HCC). While TACE is generally considered safe, there have been reports of severe complications. This case report is about a 68-year-old man who developed a BBF 6 months after undergoing TACE for HCC. CASE REPORT A 68-year-old man was diagnosed with HCC and underwent TACE at a local medical department. Two months after TACE, he presented with a liver abscess, which was drained and catheterized. Subsequently, the patient was transferred to our hospital. Initial MRI revealed abscesses in the right hepatic lobe extending into the lung cavity. Intrahepatic catheter replacement was performed. Six months after TACE, the patient developed cough and yellow sputum. Subsequent MRI confirmed smaller lung and liver abscesses, along with a BBF. Endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous catheter replacement were conducted, closing the BBF with a covered stent. Despite drainage, antibiotics, and nutritional support, the patient's condition deteriorated. Transition to hospice care was initiated, and the patient died due to sepsis and multiple organ failure. CONCLUSIONS This case highlights the importance of obtaining a comprehensive patient history when a patient has bile in the sputum, and discusses the rare but previously reported BBF as a complication of TACE for HCC. The presence of bile collections in the lungs and liver can result in tissue necrosis, potentially leading to chronic infection, emphasizing the need for early diagnosis and management.

Balancing Efficacy and Tolerability of First-Line Systemic Therapies for Advanced Hepatocellular Carcinoma: A Network Meta-Analysis

Background: Atezolizumab + bevacizumab represent the current standard of care for first-line treatment of advanced hepatocellular carcinoma (HCC). However, direct comparison with other combination treatments including immune checkpoint inhibitors (ICI) + tyrosine kinase inhibitors (TKIs) are lacking. Objectives: This network meta-analysis (NMA) aims to indirectly compare the efficacy and the safety of first-line systemic therapies for unresectable advanced HCC. Method: A literature search of MEDLINE, Embase, and SCOPUS databases was conducted up to October 31, 2022. Phase 3 randomized controlled trials (RCTs) testing TKIs, including sorafenib and lenvatinib, or ICIs reporting overall survival (OS) and progression-free survival (PFS) were included. Individual survival data were extracted from OS and PFS curves to calculate restricted mean survival time. A Bayesian NMA was performed to compare treatments in terms of efficacy (15- and 30-month OS, 6-month PFS) and safety, represented by grade ≥3 (severe) adverse events (SAEs). The incremental safety-effectiveness ratio as measure of net health benefit was calculated as the difference in SAE probability divided by survival difference between the 2 most effective treatments. Results: Nine RCTs enrolling 6,600 patients were included. Atezolizumab plus bevacizumab showed the highest probability (88%) of achieving the 30-month OS landmark. Lenvatinib showed a probability of 86% of achieving best PFS outcomes. ICI monotherapies ranked as most tolerable. Atezolizumab plus bevacizumab showed the best net health benefit for OS, compared to durvalumab plus tremelimumab. When evaluating the net health benefit for PFS, at a willingness-to-risk threshold of 10% of SAEs for life-month gained, atezolizumab plus bevacizumab was favoured in 78% of cases, while at threshold of 30% of SAEs for life-month gained, lenvatinib was favoured in 76% of cases. Conclusions: Atezolizumab plus bevacizumab is the best treatment in terms of net benefit and therefore it should be recommended as standard of care. Compared to atezolizumab plus bevacizumab, lenvatinib monotherapy had the best net benefit for PFS when physicians and patients are available to accept a higher risk of toxicity.

Combined radiotherapy and immune checkpoint inhibition for the treatment of advanced hepatocellular carcinoma.

Hepatocellular Carcinoma (HCC) is one of the most common cancers and a leading cause of cancer related death worldwide. Until recently, systemic therapy for advanced HCC, defined as Barcelona Clinic Liver Cancer (BCLC) stage B or C, was limited and ineffective in terms of long-term survival. However, over the past decade, immune check point inhibitors (ICI) combinations have emerged as a potential therapeutic option for patients with nonresectable disease. ICI modulate the tumor microenvironment to prevent progression of the tumor. Radiotherapy is a crucial tool in treating unresectable HCC and may enhance the efficacy of ICI by manipulating the tumor microenvironment and decreasing tumor resistance to certain therapies. We herein review developments in the field of ICI combined with radiotherapy for the treatment of HCC, as well as look at challenges associated with these treatment modalities, and review future directions of combination therapy.

Safety, efficacy, and survival of drug-eluting beads-transarterial chemoembolization vs. conventional-transarterial chemoembolization in advanced HCC patients with main portal vein tumor thrombus

ObjectivesTo compare the efficacy, overall survival (OS) and safety of drug-eluting beads-TACE (DEB-TACE) and C-TACE as initial treatment in advanced hepatocellular carcinoma (HCC) patients with main portal vein tumor thrombus (mPVTT).MethodsThe medical records of consecutive advanced HCC patients with mPVTT who underwent initial DEB-TACE or C-TACE from September 2015 to October 2021 were retrospectively evaluated. Treatment crossover was allowed in this retrospective research. The adverse events, disease control rate (DCR), time to tumor progression (TTP) and OS of patients who underwent DEB-TACE were compared with those of patients who underwent C-TACE.ResultsEighty-three patients were included: 42 patients in DEB-TACE group and 41 patients in C-TACE group. DEB-TACE could be safely performed in HCC patients with mPVTT, and they gained a better DCR than those submitted to the C-TACE (76.2% vs. 53.7%, P = 0.031), which might have resulted in longer TTP (median TTP: 9.0 months vs. 3.0 months, P < 0.001). Furthermore, DEB-TACE showed significant OS benefits compared with C-TACE (median OS: 12.0 months vs. 5.0 months, P < 0.001). DEB-TACE, absence of arterioportal shunts (APS), leisons with capsular non-infiltration were found to be independent prognostic factors for better OS. Furthermore, subgroup analysis proved that patients with good DCR gained longer OS in DEB-TACE group.ConclusionsDEB-TACE could be safely performed and improve the DCR of HCC patients with mPVTT, which resulting in longer TTP and OS, compared with C-TACE.

Immunotherapy for Advanced Hepatocellular Carcinoma-a Large Tertiary Center Experience

IntroductionCombination of immune-checkpoint inhibitor (ICI) and vascular endothelial growth factor (VEGF) antagonist has become the first line systemic treatment for advanced hepatocellular carcinoma (HCC). However, two-thirds of patients do not respond to ICI-based treatments and biomarkers for response remain elusive. MethodsPatients with advanced HCC who received Atezolizumab/Bevacizumab combination or Nivolumab during 2016-2022 were identified in our Liver Cancer Database. Retrospective review of their clinical data was performed to investigate parameters that could be predictive of immunotherapy response. Results96 patients received Atezolizumab/Bevacizumab (n=60) or Nivolumab (n=36). Median age at diagnosis was 67.1 years. 70 patients had received treatment and 26 patients were treatment naïve before starting immunotherapy. Mean pre-treatment AFP was 9780.7 (±32035) ng/mL. Confirmed objective response (complete or partial) was seen in 29% of the population (n=27). Disease remained stable in 12% (n=11) and progressed in 60% (n=56). On univariate analysis, pre-treatment AFP>400 ng/mL was associated with objective response (OR=4.5, 95% CI:1.7-11.9, p=0.0015), while white race (OR=0.35, 95% CI:0.13-0.92, p=0.030) and prior radiotherapy (OR=0.14, 95% CI:0.01-1.1, p=0.033) or systemic therapy with TKIs (OR=0.25, 95% CI:0.08-0.81, p=0.017) were associated with poor response. On multivariate analysis only AFP>400 ng/mL remained associated with response (OR=3.7, 95% CI:1.3-10.5, p=0.014). Overall survival (OS) at one and three years was 86% and 43% in responders, and 45% and 29% in non-responders, respectively. ConclusionIn our institutional experience, treatment naivety and pre-treatment AFP>400 ng/mL were associated with objective response. Prospective studies aimed at identifying factors associated with response to immunotherapy will aide patient selection.

Analysis and prediction of the efficacy and influencing factors of camrelizumab combined with TACE and sorafenib in the treatment of advanced hepatocellular carcinoma.

TACE combined with targeted therapy is a method for the treatment of hepatocellular carcinoma. After adding camrelizumab, some patients had gained benefits, but some patients have produced serious adverse reactions. Therefore, more studies are needed to prove the efficacy and adverse reactions, and prediction models are needed to help with decision-making. With ethics committee approval, a bi-center retrospective study was finished. A total of 235 patients were enrolled and divided into the treatment group of camrelizumab combined with TACE and sorafenib and the treatment group of TACE and sorafenib. The survival rate, short-term efficacy and adverse reactions were compared, and the efficacy prediction model was established. The 2-year survival time and objective response rate of the treatment group of camrelizumab combined with TACE plus sorafenib were higher than those of TACE plus sorafenib. Camrelizumab increased the proportion of reactive capillary proliferation, but had no effect on other adverse reactions. The established nomogram can accurately predict the response to the treatment. Camrelizumab combined with TACE and sorafenib can improve the survival rate of patients with hepatocellular carcinoma, and it is an effective treatment. The nomogram model can predict the efficacy, which is beneficial for patients.

Microfluidic controllable preparation of iodine-131-labeled microspheres for radioembolization therapy of liver tumors.

Transcatheter arterial radioembolization (TARE) is of great significance for the treatment of advanced hepatocellular carcinoma (HCC). However, the existing radioembolic microspheres still have problems such as non-degradability, non-uniform size, and inability to directly monitor in vivo, which hinders the development of TARE. In this paper, a novel radioembolic agent, 131 I-labeled methacrylated gelatin microspheres (131 I-GMs), is prepared for the treatment of HCC. Water-in-oil (W/O) emulsion templates are prepared by a simple one-step microfluidic method to obtain methacrylated gelatin microspheres (GMs) after UV irradiation. A series of GMs with uniform and controllable size are obtained by adjusting the flow rate of each fluid. Both air-dried and freeze-dried GMs can quickly restore their original shape and size, and still have good monodispersity, elasticity and biocompatibility. The radiolabeling experiments show that 131 I can efficiently bind to GMs by chloramine-T method, and the obtained 131 I-GMs have good radioactive stability in vitro. The results of in vivo TARE treatment in rats show that 131 I-GMs can be well retained in the hepatic artery and have a good inhibitory effect on the progression of liver cancer, showing the potential for the treatment of HCC. This article is protected by copyright. All rights reserved.

Identification of immune-related target and prognostic biomarkers in PBMC of hepatocellular carcinoma

Background Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, and is characterized by insidious onset, rapid progression, and poor prognosis. Immunotherapy is a first-line treatment for advanced HCC. The identification of immune-related prognostic markers may be an effective strategy to predict and improve clinical response rate of immunotherapy.Methods The DESeq2, edgeR, and limma R packages were used to compare the transcriptomes of HCC with different prognoses. Cancer-related databases such as UALCAN, TNMplot, GEPIA, muttarget and Human Protein Atlas (HPA), and the Kaplan–Meier Plotter platform were used to analyze the relationship between CLDN18 and the clinical characteristics, as well as prognosis of HCC. The co-expressed genes of CLDN18 were obtained from LinkedOmics platform, and GO functional enrichment and KEGG pathway analysis were performed. The CIBERSORT, TIMER, Timer 2.0 and TISIDB algorithms were used to analyze immune infiltration.Results CLDN18 was differentially expressed in HCC patients with different prognoses, and its expression level in PBMC was positively correlated with the stage of BCLC. In addition, CLDN18 was significantly overexpressed in HCC tumor tissues compared to adjacent non-tumor tissues, which was consistent with PBMC sequencing results and immunohistochemical data from human protein profiles. CLDN18 was also positively correlated with HCC staging and grading, and high expression levels of CLDN18 predicted shorter overall survival. Functional annotation of CLDN18 in HCC revealed enrichment of the cellular senescence and protein activation cascade, along with biological processes such as cell cycle, inflammatory response, and cellular ketone metabolism. In addition, CLDN18 was also associated with tumor infiltrating immune cells, suppressive immune cell markers, T lymphocyte depletion and activation of HCC, and low expression of CLDN18 was associated with higher CD8 + T cell infiltration and better survival rates.ConclusionsCLDN18 is a potential prognostic marker and immunotherapeutic target for HCC.

Application and Resistance Mechanisms of Lenvatinib in Patients with Advanced Hepatocellular Carcinoma.

Lenvatinib, a multitargeted tyrosine kinase inhibitor (TKI), is one of the preferred targeted drugs for the treatment of advanced hepatocellular carcinoma (aHCC). Since the REFLECT study showed that lenvatinib was noninferior to sorafenib in overall survival (OS), lenvatinib monotherapy has been widely used for aHCC. Moreover, lenvatinib combination therapy, especially lenvatinib combined with immune checkpoint inhibitors (ICIs), has shown more encouraging clinical results. However, drug development and comprehensive treatment have not significantly improved the prognosis, and lenvatinib resistance is often encountered in treatment. The underlying molecular mechanism of lenvatinib resistance is still unclear, and studies to solve drug resistance are ongoing. The molecular mechanisms of lenvatinib resistance in patients with aHCC include the regulation of signaling pathways, the regulation of noncoding RNAs, the impact of the immune microenvironment, tumor stem cell activation and other mechanisms. This review aims to (1) summarize the progress of lenvatinib in treating aHCC, (2) delineate the known lenvatinib resistance mechanisms of current therapy, and (3) describe the development of therapeutic methods intended to overcome these resistance mechanisms.

Noninvasive imaging-based machine learning algorithm to identify progressive disease in advanced hepatocellular carcinoma receiving second-line systemic therapy

The aim of this study was to predict tyrosine kinase inhibitors (TKI) plus anti-PD-1 antibodies (TKI-PD-1) efficacy as second-line treatment in advanced hepatocellular carcinoma (HCC) using radiomics analysis. From November 2018 to November 2019, a total of 55 patients were included. Radiomic features were obtained from the CT images before treatment and filtered using intraclass correlation coefficients (ICCs) and least absolute shrinkage and selection operator (LASSO) methods. Subsequently, ten prediction algorithms were developed and validated based on radiomic characteristics. The accuracy of the constructed model was measured through area under the receiver operating characteristic curve (AUC) analysis; survival analysis was performed via Kaplan–Meier and Cox regression analyses. Overall, 18 (32.7%) out of 55 patients had progressive disease. Through ICCs and LASSO, ten radiomic features were entered into the algorithm construction and validation. Ten machine learning algorithms showed different accuracies, with the support vector machine (SVM) model having the highest AUC value of 0.933 in the training cohort and 0.792 in the testing cohort. The radiomic features were associated with overall survival. In conclsion, the SVM algorithm is a useful method to predict TKI-PD-1 efficacy in patients with advanced HCC using images taken prior to treatment.

Atezolizumab and Bevacizumab in Therapy for Patients with Hepatocellular Carcinoma in Real Clinical Practice

Randomized clinical trials and actual clinical practice differsignificantly. Evidence-based medicine develops new agents referring to, primarily, pharmaceutical findings, preclinical studies and, most importantly, randomized clinical trials. Hepatocellular carcinoma is the most common primary malignancy of the liver, and one of the main causes of fatal outcomes among cancer patients worldwide, including in the Asia-Pacific region, with an estimated 800,000 deaths annually. For more than 10 years, sorafenib, a tyrosine kinase inhibitor, was the only authorized treatment for advanced hepatocellular carcinoma. The next stage in the development of drug therapy for hepatocellular carcinoma involved immune checkpoint inhibitors. The combination of atezolizumab with bevacizumab in the phase III trial (IMbrave150) improved outcomes of advanced hepatocellular carcinoma, such as overall survival and progression-free survival (6.8 versus 4.3). The paper presents the trials of atezolizumab and bevacizumab combination, demonstrates comparable data on the treatment of patients with HCC in real clinical practice and data on the phase III IMbrave150. To further analyze the efficacy of the combination of atezolizumab and bevacizumab, prospective clinical trials should include heterogeneous patient groups.

Cisplatin in Liver Cancer Therapy.

Hepatocellular carcinoma (HCC) is the most common primary liver tumor and is often diagnosed at an unresectable advanced stage. Systemic chemotherapy as well as transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) are used to treat advanced HCC. TACE and HAIC have long been the standard of care for patients with unresectable HCC but are limited to the treatment of intrahepatic lesions. Systemic chemotherapy with doxorubicin or chemohormonal therapy with tamoxifen have also been considered, but neither has demonstrated survival benefits. In the treatment of unresectable advanced HCC, cisplatin is administered transhepatic arterially for local treatment. Subsequently, for cisplatin-refractory cases due to drug resistance, a shift to systemic therapy with a different mechanism of action is expected to produce new antitumor effects. Cisplatin is also used for the treatment of liver tumors other than HCC. This review summarizes the action and resistance mechanism of cisplatin and describes the treatment of the major hepatobiliary cancers for which cisplatin is used as an anticancer agent, with a focus on HCC.

Safety and Efficacy of TACE + Lenvatinib in Treating Advanced Hepatocellular Carcinoma: A Systematic Review and Meta- analysis.

To compare the efficacy and safety of transarterial chemoembolization (TACE) + lenvatinib (TACE+L) versus lenvatinib (L) monotherapy in the treatment of advanced hepatocellular carcinoma by a meta-analysis. PubMed, Embase, the Cochrane Library, CNKI, VIP e-Journals Database, and Wanfang Data were systematically searched to collate literature comparing TACE+L with L alone for the treatment of advanced liver cancer. The literature search, quality assessment, and data extraction were performed independently by two reviewers. The Stata 16 software package was used to process and analyze the data. We assessed heterogeneity using both I2 and the p-value, performed a publication bias assessment, and conducted a sensitivity analysis. Five studies were finally included, including one randomized controlled study and four retrospective studies; these involved a total of 1,167 patients, including 523 patients in the TACE+L combination group and 644 patients in the L monotherapy group. In this meta-analysis, the TACE+L group showed a significantly better objective response rate (ORR) (OR=2.54, 95%CI: 1.34 - 4.80) and disease control rate (DCR) compared to the L monotherapy group (OR=2.68, 95%CI: 1.75 - 4.08). The combined group had significantly improved progression-free survival (PFS) (HR=0.47, 95%CI: 0.40 - 0.56) and overall survival (OS) (HR=0.48, 95%CI: 0.39-0.59). In addition, there was no significant difference found in the overall adverse events of any grade between the two groups (OR=1.13, 95%CI: 0.99 - 1.29). Compared to L alone, TACE+L treatment resulted in better tumor response, better long-term survival, and was accompanied by controllable adverse events.

Clinical efficacy and safety of atezolizumab plus bevacizumab versus lenvatinib in the treatment of advanced hepatocellular carcinoma: A systematic review and meta-analysis.

Assess the effectiveness and safety of treatment options atezolizumab plus bevacizumab (Atez/Bev) or lenvatinib in clinical practice for patients with advanced hepatocellular carcinoma (HCC) patients. To compare the effectiveness of Atez/Bev and lenvatinib in treating advanced HCC, we systematically searched the PubMed, EMBASE, and Web of Science databases. We utilized Review Manager 5.3 to extract and analyze the data. The present systematic review included 8 nonrandomized studies comprising a total of 6628 cases. There was no significant difference in 0.5-, 1-, 1.5-year OS rates and 0.5-, 1-year PFS rates between the 2 groups. However, patients with HCC caused by viral hepatitis would benefit more from the Atez/Bev therapy (hazard ratio = 0.75, 95% confidence interval: 0.63-0.89) but patients with a Child-Pugh class B liver function would benefit more from lenvatinib (hazard ratio = 1.70, 95% confidence interval: 1.07-2.70). At the same time, there are no major differences in safety between the 2 treatment options. Our study did not find any significant difference in effectiveness and safety between Atez/Bev and lenvatinib. However, Additional verification is required to determine whether these 2 therapeutic approaches have varying effects on distinct populations.

A Comparative Efficacy of Atezolizumab plus Bevacizumab Versus Sorafenib in Advanced Hepatocellular Carcinoma: A Review

&lt;p&gt;Hepatocellular carcinoma (HCC) ranks sixth as the most common cancer and fourth as the most common cause of cancer-related death globally. The standard treatment for advanced HCC is by prescribing sorafenib, a tyrosine kinase inhibitor. Despite its moderate efficacy and concerning side effects, there is no better alternative to sorafenib to treat HCC. However, a new combination of atezolizumab (an inhibitor of PD-L1) and bevacizumab (an inhibitor of vascular endothelial growth factor), has shown a potential to surpass the efficacy of sorafenib. This review was written to provide an insight into pharmacodynamics of sorafenib and atezolizumab plus bevacizumab, effectiveness of sorafenib and the one of atezolizumab plus bevacizumab, utilization of atezolizumab plus bevacizumab in the clinical practice, as well as to argue that this combination can replace sorafenib as the standard palliative treatment for HCC.&lt;/p&gt;

Transarterial chemoembolization for advanced hepatocellular carcinoma without macrovascular invasion or extrahepatic metastasis: analysis of factors prognostic of clinical outcomes.

To evaluate the safety and efficacy of TACE and factors predicting survival in patients with advanced hepatocellular carcinoma (HCC) without macrovascular invasion (MVI) or extrahepatic spread (EHS). This single-center retrospective study included 236 treatment-naïve patients who underwent TACE as first-line treatment for advanced HCC without MVI or EHS between January 2007 and December 2021. Following TACE, the median overall survival (OS) was 24 months. Multivariate Cox regression analyses revealed that tumor number ≥4 (risk point: 3), maximal tumor size >10cm (risk point: 2), Child-Pugh class B (risk point: 2), alpha-fetoprotein (AFP) concentration ≥400 ng/mL (risk point: 2), and presence of HCC rupture (risk point: 2) were risk factors significantly associated with OS. The expected median OS among patients with <2, 2-4, and 5-9 risk points were 72, 29, and 12 months respectively. The major complication rates were significantly lower in patients with maximal tumor size ≤10 cm than in those with maximal tumor size >10cm (4% [5/138] vs 21% [21/98], p = 0.001). TACE may be safe and effective in selected patients with advanced HCC without MVI or EHS, with a median OS of 24 months. Patients with limited tumor burden, compensated liver function, absence of HCC rupture, and favorable biologic markers may benefit the most from TACE. TACE is not recommended for patients with huge HCCs (>10cm) because of its high rate of major complications (21%).