Advanced Hepatocellular Carcinoma Research Articles

Expert consensus on sequential surgery following conversion therapy based on combination of immune checkpoint inhibitors and antiangiogenic targeted drugs for advanced hepatocellular carcinoma(2024 edition)

Up to half of hepatocellular carcinoma(HCC) cases are diagnosed at an advanced stage,for which effective treatment options are lacking,resulting in a poor prognosis. In recent years,the combination of immune checkpoint inhibitors and anti-angiogenic targeted therapy has demonstrated high efficacy in treating advanced HCC,significantly extending patients' survival,and providing a potential for sequential curative surgery. After sequential curative hepatectomy or liver transplantation following conversion therapy,patients can obtain long-term survival benefits. In order to improve the long-term survival rate of the overall population with liver cancer and achieve the goal of a 15% increase in the overall 5-year survival rate outlined in the "Healthy China 2030" blueprint,the Professional Committee for Prevention and Control of Hepatobiliary and Pancreatic Diseases of Chinese Preventive Medicine Association,Chinese Society of Liver Cancer,and the Liver Study Group of Surgery Committee of Beijing Medical Association organized in-depth discussions among relevant domestic experts in the field. These discussions focus on the latest progress since the release of Chinese expert consensus on conversion therapy of immune checkpoint inhibitors combined antiangiogenic targeted drugs for advanced hepatocellular carcinoma(2021 Edition) and have reached new consensus on the modifications and supplements to related key points. This consensus aims to further guide clinical practice,standardize medical behavior,and promote the development of the discipline.

Long noncoding RNA DDX11-AS1 represses sorafenib-induced ferroptosis in hepatocellular carcinoma cells via Nrf2-Keap1 pathway

Sorafenib, a first-line therapeutic option for advanced hepatocellular carcinoma (HCC), faces a formidable challenge in the form of emerging resistance. Recently, the oncogene DDX11 antisense RNA 1 (DDX11-AS1) has been implicated in various cancers, including HCC. However, its role in sorafenib resistance remains unknown. Our findings reveal that DDX11-AS1 is upregulated in sorafenib-resistant HCC cells, contributing to their resistance by suppressing ferroptosis. Further investigation elucidated the mechanism by which DDX11-AS1 activates the antioxidant Nrf2-Keap1 pathway. By interacting with Nrf2 and hindering its association with Keap1, DDX11-AS1 enhances the stability and nuclear translocation of Nrf2. In summary, our study unveils the potent role of DDX11-AS1 as an enhancer of sorafenib resistance, inhibiting sorafenib-induced ferroptosis through the activation of the Nrf2-Keap1 pathway in HCC. These findings offer a promising therapeutic strategy to overcome resistance and effectively treat HCC.

Clinical evaluation of oxaliplatin-loaded drug-eluting callispheres beads transarterial chemoembolization for unresectable or recurrent esophageal carcinoma

BackgroundA majority of esophageal carcinoma patients are diagnosed at an advanced stage and are no longer suitable for surgical resection. Drug-eluting beads transarterial chemoembolization (DEB-TACE) with oxaliplatin-loaded CalliSpheres beads (CB) have been used for advanced hepatocellular carcinoma and lung cancer, but they have not been reported for the treatment of unresectable or recurrent esophageal carcinoma.MethodsDEB-TACE was performed on 22 patients with unresectable or recurrent esophageal carcinoma between March 2019 and May 2022. The clinical outcomes, complications, and efficacy were retrospectively recorded and analyzed.ResultsA total of 39 sessions of DEB-TACE were performed in 22 patients, with a technical success rate of 92.3% and clinical success rate of 65.0%. No severe complications such as procedure-related death, esophageal rupture or paraplegia were observed. Complete response, partial response, and stable disease were observed in 14.3% (2/14), 42.9% (6/14), and 21.4% (3/14) of patients 6 months after DEB-TACE, respectively. The objective response rates were 62.5%, 42.9% and 57.1% respectively at 1-, 3-, and 6-month after DEB-TACE. Subsequent interventional treatments were administered to 12 patients, including DEB-TACE for hepatic metastasis in 3 (13.6%), esophageal stenting in 5 (22.7%), and airway stent placement in 5 (22.7%). Two patients were lost to follow up. A total of 9 patients died due to tumor progression (n = 5), pneumatic infection (n = 1), and tumor-related massive esophageal hemorrhage (n = 3). The median overall survivals were 13.9 months and 26.5 months from the first session of DEB-TACE and the diagnosis of esophageal carcinoma, respectively.ConclusionsDEB-TACE with oxaliplatin-loaded CB is suggested as a safe and effective treatment of unresectable or recurrent esophageal carcinoma, and more studies are required to confirm its efficacy and safety.

Evaluating the impact of treatment sequencing on outcomes in hepatocellular carcinoma: a comparative analysis of TACE and systemic therapies

This study aimed to evaluate how the timing of transarterial chemoembolization (TACE) relative to systemic therapy (tyrosine-kinase inhibitors [TKIs] and immune checkpoint inhibitors [ICIs]) influences oncological outcomes in patients with hepatocellular carcinoma (HCC). A retrospective analysis was conducted on HCC patients treated with TACE plus TKIs and ICIs from January 2018 to February 2023. We compared objective response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) between patients receiving TACE before versus after systemic therapies. Multivariate Cox regression analyses identified potential prognostic factors. Of the 194 patients enrolled, 111 received TACE before systemic therapies, and 83 after. The median age at diagnosis was 52.8 years. There were no significant differences in ORR (40.72% vs. 30.41%, p = 0.989) or DCR (48.45% vs. 35.57%, p = 0.770) between the groups. Likewise, OS (18.73 vs. 18.20 months, p = 0.091) and PFS (11.53 vs. 10.05 months, p = 0.336) were similar regardless of treatment sequence. In the result of Cox analysis, a 20% decrease in AFP from baseline at one month was associated with improved OS (HR = 0.35, 95% CI 0.17–0.70, p = 0.003) and PFS (HR = 0.69, 95% CI 0.49–0.96, p = 0.028). Large tumor size (≥ 10 cm) was a poor prognostic factor for OS (HR = 2.12, 95% CI 1.07–4.21, p = 0.032), and the presence of portal vein tumor thrombus adversely affected PFS (HR = 2.31, 95% CI 1.47–3.62, p < 0.001). The sequencing of TACE and systemic therapies does not significantly impact the prognosis of advanced HCC. A 20% reduction in AFP within one month of treatment commencement emerges as a protective prognostic factor for HCC.Graphical

Role of Immunotherapy in the Management of Advanced Hepatocellular Carcinoma: A Systematic Review.

The most prevalent histologic subtype of primary liver cancer, hepato-cellular carcinoma, is also the third most lethal malignancy worldwide and a significant cause of cancer death. When diagnosed, it is frequently too late for curative therapies. To add to the difficulty, it is resistant to conventional systemic therapies like chemotherapy. Re-cently, more attention has been given to the use of immunotherapy for this condition. Immuno-therapy has had a major impact on the outcome of several malignancies; several studies have revealed the potential role of immunotherapy in advanced hepatocellular carcinoma. To provide an overview of the current literature, justification, and clinical evidence for the use of immuno-therapy in advanced hepatocellular carcinoma, we employed a systematic literature review (SLR) approach in this work. Additionally, we explored the benefits and rationales of various treatment combinations and described the molecular mechanisms behind resistance to a number of immunotherapy drugs. A total of 188 articles from credible journals published be-tween 2013 and August 7, 2023, were screened. Eight of those articles were chosen for in-depth study. This systematic review concluded that the current immunotherapeutic approaches have the potential to improve outcomes for aHCC patients; however, several clinical and biological hurdles have to be overcome, and predictive markers are still eagerly needed. To fully realize the potential of immunotherapy agents and their combination therapies to enhance health outcomes for patients with aHCC, additional investigation and research are required.

Impact of baseline body mass index on the long-term prognosis of advanced hepatocellular carcinoma treated with immunotherapy.

Primary liver cancer is the sixth most common cancer worldwide, with hepatocellular carcinoma (HCC) being the most prevalent form. Despite the current availability of multiple immune or immune combination treatment options, the prognosis is still poor, so how to identify a more suitable population is extremely important. To evaluate the clinical effectiveness of combining lenvatinib with camrelizumab for patients with hepatitis B virus (HBV)-related HCC in Barcelona Clinic Liver Cancer (BCLC) stages B/C, considering various body mass index (BMI) in different categories. Retrospective data were collected from 126 HCC patients treated with lenvatinib plus camrelizumab. Patients were divided into two groups based on BMI: The non-overweight group (BMI < 25 kg/m2, n = 51) and the overweight/obese group (BMI ≥ 25 kg/m2, n = 75). Short-term prognosis was evaluated using mRECIST criteria, with subgroup analyses for non-overweight (BMI: 18.5-24.9 kg/m2), overweight (BMI: 25-30 kg/m2), and obese (BMI ≥ 30 kg/m2) patients. A Cox proportional hazards regression analysis identified independent prognostic factors for overall survival (OS), leading to the development of a column-line graph model. Median progression-free survival was significantly longer in the obese/overweight group compared to the non-overweight group. Similarly, the median OS was significantly prolonged in the obese/overweight group than in the non-overweight group. The objective remission rate and disease control rate for the two groups of patients were, respectively, objective remission rate (5.88% vs 28.00%) and disease control rate (39.22% vs 62.67%). Fatigue was more prevalent in the obese/overweight group, while other adverse effects showed no statistically significant differences (P > 0.05). Subgroup analysis based on BMI showed that obese and overweight patients had better progression-free survival and OS than non-overweight patients, with obese patients showing the best outcomes. Multifactorial regression analysis identified BCLC grade, alpha-fetoprotein level, portal vein tumor thrombosis, and BMI as independent prognostic factors for OS. The column-line graph model highlighted the importance of BMI as a major predictor of patient prognosis, followed by alpha-fetoprotein level, BCLC classification, and portal vein tumor thrombosis. BMI is a long-term predictor of the efficacy of lenvatinib plus camrelizumab, and obese/overweight patients have a better prognosis.

Correspondence on Letter regarding "Transcriptomic signature in advanced hepatocellular carcinoma tissue to predict combination immunotherapy response."

Correspondence on Letter regarding "Transcriptomic signature in advanced hepatocellular carcinoma tissue to predict combination immunotherapy response."

Conversion therapy for hepatocellular carcinoma to improve treatment strategies for intermediate and advanced stages.

This manuscript is based on a case reported by Song et al published in the World Journal of Clinical Cases. Several challenges remain in the field of hepatocellular carcinoma (HCC) conversion therapy. Consequently, only a limited number of patients with HCC accompanied by portal vein tumor thrombosis (PVTT) and hepatic vein tumor thrombosis (HVTT) are eligible for resection. This clinical case demonstrates that considering the complexity of the disease, a multimodal and multidisciplinary approach is essential for managing HCC accompanied by PVTT and HVTT. However, the outcomes of such surgeries remain controversial. In conclusion, research on HCC conversion therapy is extremely useful for improving treatment strategies for intermediate and advanced HCC, which currently have disappointing clinical outcomes.

High-throughput screening identified pacritinib as a promising therapeutic approach to overcome lenvatinib resistance in hepatocellular carcinoma by targeting IRAK1

Lenvatinib resistance presents a significant challenge in the clinical management of advanced hepatocellular carcinoma (HCC). To address this issue, we established lenvatinib resistant HCC cells and performed high-throughput screening using FDA-approved anti-cancer drug library. Through quantitative selective drug sensitivity scoring (sDSS), pacritinib, a well-known JAK inhibitor, emerged as the top candidate, displaying the highest sDSS score among 219 compounds. We further demonstrated that pacritinib reduced the viability of a panel of HCC cell lines in a dose-dependent manner, while exhibiting minimal effects on normal liver cells. Interestingly, pacritinib, but not other JAK inhibitors such as ruxolitinib, upadacitinib, or filgotinib, acted synergistically with lenvatinib in HCC cells. In lenvatinib-resistant HCC cells, pacritinib significantly decreased proliferation and induced apoptosis. Rescue studies using IL-1 receptor-associated kinase 1 (IRAK1) overexpression and knockdown revealed that pacritinib's effects are mediated through IRAK1, with minimal impact on normal liver cells. In a xenograft model of lenvatinib-resistant HCC, oral administration of pacritinib significantly reduced tumor size without affecting body weight. Immunohistochemical analysis of tumor sections revealed that pacritinib reduced Ki67 staining and phosphorylated IRAK1. Our findings suggest that pacritinib may be a promising therapeutic option for the treatment of advanced HCC, particularly in patients who have developed resistance to lenvatinib.

Impact of Etiology on Efficacy Outcomes with Atezolizumab Plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma: A Multinational Retrospective Analysis in Asia-Pacific.

Atezolizumab-bevacizumab is a standard first-line treatment for unresectable hepatocellular carcinoma (uHCC). Given the diversity in HCC etiology and its potential impact on the tumor microenvironment, understanding how different liver disease etiologies affect treatment efficacy is important. We assessed the influence of liver disease etiology on the efficacy of atezolizumab-bevacizumab and evaluated changes in liver function during treatment with atezolizumab-bevacizumab. This study included 390 patients with uHCC treated with first-line atezolizumab-bevacizumab from Asan Medical Center, South Korea, and National Cancer Centre Singapore, Singapore from July 2016 to March 2023. Patients were classified to viral, metabolic dysfunction-associated liver disease (MASLD) and nonviral/non-MASLD groups. Albumin-bilirubin (ALBI) scores were recorded at baseline and every two cycles up to cycle six and at the time of disease progression. The majority of patients presented with viral etiologies (74.1%), and 17.2% had MASLD. Across etiological groups (viral versus MASLD versus nonviral/non-MASLD) no significant differences in objective response rate (23.2% versus 29.9% versus 23.5%, respectively; p = 0.515), progression-free survival (median 5.4 versus 7.7 versus 6.0 months; p = 0.320), and overall survival (18.1 versus 18.9 versus 14.4 months; p = 0.400) were observed. Among the patients with disease progression, ALBI scores at the time of progression were significantly higher than at baseline. Subsequent therapy was administered significantly less often to patients with ALBI grade 3 at disease progression compared with those with ALBI grades 1 or 2 (48.4% versus 78.8%, p = 0.002) CONCLUSIONS: Atezolizumab-bevacizumab demonstrates consistent efficacy regardless of HCC etiology, supporting its use as a first-line treatment across diverse patient populations. Liver function assessments remain crucial for managing therapy and predicting outcomes.

Clinicogenomic predictors of outcomes in patients with hepatocellular carcinoma treated with immunotherapy.

Immune checkpoint inhibitor (ICI) combinations extend overall survival (OS) while anti-PD-1/L1 monotherapy is non-inferior to sorafenib in treatment-naïve, patients with advanced hepatocellular carcinoma (HCC). Clinicogenomic features are posited to influence patient outcomes. The primary objective of this retrospective study was to define the clinical, pathologic, and genomic factors associated with outcomes to ICI therapy in patients with HCC. Patients with histologically confirmed advanced HCC treated with ICI at Memorial Sloan Kettering Cancer Center from 2012 to 2022 were included. Association between clinical, pathological, and genomic characteristics were assessed with univariable and multivariable Cox regression model for progression-free survival (PFS) and OS. Two-hundred and forty-two patients were treated with ICI-based therapy. Patients were predominantly male (82%) with virally mediated HCC (53%) and Child Pugh A score (70%). Median follow-up was 28 months (0.5-78.4). Median PFS for those treated in 1st line, 2nd line and ≥ 3rd line was 4.9 (range: 2.9-6.2), 3.1 (2.3-4.0), and 2.5 (2.1-4.0) months, respectively. Median OS for those treated in 1st line, 2nd line, and ≥ 3rd line was 16 (11-22), 7.5 (6.4-11), and 6.4 (4.6-26) months, respectively. Poor liver function and performance status associated with worse PFS and OS, while viral hepatitis C was associated with favorable outcome. Genetic alterations were not associated with outcomes. Clinicopathologic factors were the major determinates of outcomes for patients with advanced HCC treated with ICI. Molecular profiling did not aid in stratification of ICI outcomes. Future studies should explore alternative biomarkers such as the level of immune activation or the pretreatment composition of the immune tumor microenvironment.

A case of immune checkpoint inhibitor-associated hemophagocytosis after initiation of atezolizumab plus bevacizumab therapy for advanced hepatocellular carcinoma.

A woman in the 70s with a decreased appetite and weight loss (4kg) in the last 3months was referred to our hospital. An enhanced CT scan of the abdomen showed a hepatocellular carcinoma (HCC) of 83mm in diameter of the liver with metastasis to the para-aortic lymph nodes, the left adrenal gland, and the right lower lung lobe (cStage IVb). She was started on atezolizumab + bevacizumab (Atezo-Bev) therapy. A week after the treatment, she began to have a decreased appetite, fever in the 39°C range, subcutaneous bleeding, and a slight headache when walking. So she was urgently admitted to our hospital. We diagnosed her as having a hemophagocytic syndrome and administered 1g steroid pulse therapy for 3days followed by 1mg/kg of prednisone. Her condition began to improve. This is the first case report of a hemophagocytic syndrome in a patient with HCC treated with Atezo-Bev.

Absence of Survival Impact from Hepatitis During Immunotherapy in 193 Patients with Advanced Hepatocellular Carcinoma - An Observational Study from Taiwan.

Hepatitis often occurs after initiating immune checkpoint inhibitor (ICI) treatment. The time and grade of hepatitis after ICI starts and the prognostic role of immune-related hepatitis in patients with advanced hepatocellular carcinoma (aHCC) remain unclear. In this real-world analysis, we enrolled aHCC patients receiving ICIs, documented the highest level of liver enzymes during/after ICIs, and analyzed the survival impact of different hepatitis patterns. One hundred and ninety-three aHCC patients receiving ICIs were recruited. During ICIs, 88.6% of patients experienced aspartate transaminase (AST) elevations (Grade III/IV: 7.8%). For alanine transaminase (ALT), 81.3% had elevated levels (Grade III/IV: 3.6%), and 41.5% of patients had elevated bilirubin levels (Grade 3/4: 6.7%). The median AST, ALT, and total bilirubin values significantly increased after ICI treatment initiated (all p < 0.001) and, similarly, after excluding progressive disease (p = 0.014, p = 0.002, p < 0.001). The median time of hepatitis occurrence is from the 4.0th to 15.9th weeks. Multivariable analysis showed that patterns of liver enzyme change of AST and total bilirubin in patients receiving ICIs significantly correlate to overall survival (OS, p = 0.009 and 0.001, respectively). After ICI termination, patients with elevated bilirubin (p = 0.003) and AST (p = 0.005) would indicate poor survival, with adjustment of viral hepatitis and ICI responses. Hepatitis emerges between the 4th and 20th weeks post-ICI initiation. Changes in liver enzymes during ICI therapy do not directly affect OS, implying the safety of ICI use when corticosteroids are promptly administered if clinically indicated.

The impact of neighborhood socioeconomic deprivation on clinical outcomes for locally advanced and metastatic hepatocellular carcinoma: An incidence-based retrospective cohort study.

108 Background: Prior studies show that socioeconomic status impacts hepatocellular carcinoma (HCC) outcomes. However, these have used larger geographic areas such as zip codes or counties for assessment. Using a statewide cancer registry the Area Deprivation Index (ADI), a granular measure of socioeconomic deprivation (SED), was used to assess receipt of treatment and overall survival (OS) for locally advanced and metastatic HCC. Methods: The incidence-based Florida Cancer Data System was used to identify stage III/IV HCC patients diagnosed from 2007-2015. The ADI was used to measure SED and is a validated dataset that ranks neighborhoods (census block groups) from 1-100 (higher scores = higher deprivation) based on income, education, housing, and other socioeconomic factors. Demographic, tumor, and treatment variables were assessed using descriptive statistics, regression plots, and survival analysis. Chemotherapeutic treatment (CT) included receipt of chemotherapy and/or chemoembolization. Results: The study identified 2,534 eligible patients. Males comprised 80.6% of the cohort. The median age was 63 years. By SED quartile, there were significant differences by age, race, insurance, and receipt of chemotherapy (p&lt;0.05) but no difference by gender, ethnicity, stage, or survival. Overall, 39.1% received chemotherapeutic treatment. However, 41.0% of the lowest-deprivation patients received CT compared to 32.1% in the highest-deprivation cohort (p&lt;0.01). After adjustment for potential confounders, the lowest deprivation quartile had increased odds of CT compared to the highest deprivation quartile (OR 1.47; 95% CI,1.15-1.87). The median OS for the cohort was 4.0 months and was 4.6 and 3.3 months, respectively, for the lowest and highest deprivation quartiles (p&lt;0.01). For patients who received and did not receive CT, the median OS was 8.0 and 2.2 months, respectively (p&lt;0.01). However, there was no difference in median OS by SED for those who received CT (p=0.14). Conclusions: In an incidence-based, statewide cancer registry, the median OS for locally advanced and metastatic HCC remains poor and most patients do not receive CT. While there were differences in receipt of CT by SED, when patients did receive CT, median OS was similar across SED quartiles. These data suggest that SED may impact receipt of treatment and efforts are needed to understand and address treatment disparities. Lowest Deprivation Low Deprivation High Deprivation Highest Deprivation p-Value N=624 N=650 N=589 N=629 Chemotherapeutic treatment 0.001 No 347 (55.6%) 345 (53.1%) 339 (57.6%) 411 (65.3%) Yes 256 (41.0%) 283 (43.5%) 235 (39.9%) 202 (32.1%) Unknown 21 (3.4%) 22 (3.4%) 15 (2.5%) 15 (2.6%) Vital Status 0.93 Alive 41 (5.7%) 44 (5.9%) 43 (6.0%) 44 (6.5%) Dead 682 (94.3%) 695 (94.1%) 673 (94.0%) 632 (93.5%)

Correspondence to editorial on "Sorafenib vs. Lenvatinib in advanced hepatocellular carcinoma after atezolizumab/bevacizumab failure: A real-world study".

Correspondence to editorial on "Sorafenib vs. Lenvatinib in advanced hepatocellular carcinoma after atezolizumab/bevacizumab failure: A real-world study".

Neoadjuvant atezolizumab plus bevacizumab prior liver transplantation for hepatocellular carcinoma☆

Background & AimsThe combination of atezolizumab and bevacizumab offers a novel approach to immunomodulation, showing efficacy as a primary treatment in advanced hepatocellular carcinoma (HCC). Concerns about graft safety and rejection have limited its exploration in the neoadjuvant setting of liver transplantation (LT).This study investigates the clinical efficacy and the safety profile related to the pre-transplant administration of atezolizumab and bevacizumab for HCC. MethodsProspective assessment of 17 patients with HCC treated with neoadjuvant preoperative atezolizumab and bevacizumab prior to LT for HCC, obtained from December 2020 and December 2023 at seven Western transplant centers. ResultsAmong the 17 patients with HCC included in the study, 16 (94.1%) had a tumor burden outside of Milan Criteria (MC). Neoadjuvant loco-regional therapies along with the administration of atezolizumab plus bevacizumab (median:5 months; discontinued at least 4 weeks prior LT), achieved an ORR 94% (Complete response: 59%), downstaging to within MC (82%) and a pathological response at explant examination of 88%. Grade 3-4 TRAE accounted for 17.6% of cases and were manageable. During the 25 months median follow-up period, 2 cases of mild (RAI ≤ 4), biopsy-proven rejection were reported but no instances of severe allograft rejection or graft loss. The 1-year and 3-year post-LT survival rates were 94.2% and 88.2%, respectively. ConclusionsThis study highlights the favorable oncological and survival outcomes from a multicentric cohort of HCC patients treated with atezolizumab and bevacizumab in the pre-LT setting. This immune-based combination was safe in terms of TRAE, and absence of severe post-transplant rejection or graft loss. These preliminary results could pave the way for expanding transplant eligibility criteria in patients at more advanced HCC stages. Impact and Implications•The combination of atezolizumab and bevacizumab in the neoadjuvant setting prior to liver transplantation for hepatocellular carcinoma (HCC) has been limitedly explored despite its potential to enhance anti-tumor response and downstaging due to raising concerns about its safety profile.•Among 17 patients who underwent successful liver transplantation following neoadjuvant atezolizumab/bevacizumab, 82% achieved downstaging to within MC, 94% radiological objective response and 88% pathology response, without drop-outs due to TRAEs or graft loss.•The neoadjuvant combination of atezolizumab plus bevacizumab prior liver transplantation in HCC shows an encouraging safety profile and stands out as a promising pre-transplant optimization treatment adjunct, leading to improved oncological outcomes

Real-world experience of lenvatinib-based therapy in patients with advanced hepatocellular carcinoma

Real-world experience of lenvatinib-based therapy in patients with advanced hepatocellular carcinoma

Prognostic role of serum vascular endothelial growth factor and hepatocyte growth factor post stereotactic body radiation in advanced hepatocellular carcinoma

Prognostic role of serum vascular endothelial growth factor and hepatocyte growth factor post stereotactic body radiation in advanced hepatocellular carcinoma

Efficacy and Safety of Hepatic Arterial Infusion Chemotherapy(HAIC) Combined with PD-1 Inhibitors for Advanced Hepatocellular Carcinoma with Macrovascular Invasion: A Multicenter Propensity Score Matching Analysis.

To investigate the efficacy and safety of HAIC combined with programmed cell death protein-1 (PD1) inhibitors in MVI-positive advanced hepatocellular carcinoma(HCC). From September 2017 to May 2019, we retrospectively collected the clinical data from three medical centers in China pertaining to patients diagnosed with BCLC C stage HCC with MVI and receiving treatment with a combination of HAIC and PD-1 inhibitors treatment or HAIC alone, and we compared the efficacy of HAIC combined with PD-1 inhibitors and HAIC monotherapy. Propensity score matching(PSM) was utilized to adjust for baseline differences between groups. Survival outcomes and tumor response rate were used to assess survival benefits, while the incidence of adverse events was used to evaluate safety. After screening for eligibility, 489 patients diagnosed with HCC and concomitant MVI were enrolled. Of these, 173 patients received treatment combining HAIC with PD-1 inhibitors, while 316 patients underwent HAIC monotherapy. After PSM adjustment, the combination therapy group demonstrate superior survival outcomes. Median overall survival(OS) and progression free survival(PFS) were 31.8 months and 10.8 months, respectively, significantly higher than those in the monotherapy group (OS: 10.0 months; PFS: 6.1 months; both P<0.0001). Moreover, ORR and DCR remained significantly elevated in the combination therapy group (ORR: 44.3% vs 20.4%, P<0.0001; DCR: 89.8% vs 82.0%, P=0.041). Safety profiles indicated no significant differences in adverse event rates between the two treatment groups, encompassing both overall and grade-specific assessments. Compared to HAIC alone, the combination of HAIC with PD-1 inhibitors represents a more promising and effective approach for patients with HCC complicated by macrovascular invasion.

Synergistic activity of Enterococcus Faecium-induced ferroptosis via expansion of IFN-γ+CD8+ T cell population in advanced hepatocellular carcinoma treated with sorafenib

ABSTRACT The gut microbiota plays an important role in the development and treatment of hepatocellular carcinoma (HCC). However, the implication of specific gut microbiota in targeted sorafenib therapy for advanced HCC and the microbiota mode of action, remain to be elucidated. Here, we confirmed that four bacterial genera, Lachnoclostridium, Lachnospira, Enterobacter and Enterococcus, are associated with the therapeutic efficacy of Sorafenib, and that Enterobacter faecium (Efm) plays a crucial role in modulating the sorafenib activity. The effective colonization by Emf induced the IL-12 and IFN-γ production and an increased proportion of IFN-γ+CD8+ T cells in the tumor microenvironment. Finally, exopolysaccharides (EPS) from Efm were the primary inducer to prompt IFN-γ+CD8+ T cells to secrete IFN-γ, which together with sorafenib instigated ferroptosis in HCC cells. Collectively, these results indicate that Efm is a promising probiotics that enhances the efficacy of sorafenib treatment in advanced HCC.