Patients with unresectable hepatocellular carcinoma (uHCC) and Child-Pugh grade B face limited treatment options and poor outcomes. This study aims to evaluate whether the effect and safety of combining tyrosine kinase inhibitors (TKIs) with progressive disease (PD)-1 inhibitors in uHCC patients with Child-Pugh B7 (CP7) and B8/9 (CP8/9) differ.

This multicenter retrospective study included 179 uHCC patients with Child-Pugh B (CP7 group: n = 106; CP8/9 group: n = 73), receiving a combination of lenvatinib/sorafenib/other TKIs and PD-1 inhibitors between December 2020 and March 2023. Progression-free survival (PFS) and overall survival (OS) were defined as the primary endpoint. Secondary endpoints included the objective response rate (ORR) and safety.

The median PFS and OS for the entire cohort were 7.3 months (95% confidence intervals [CI]: 6.3-8.3) and 16.0 months (95% CI: 12.9-19.1), respectively. No statistically significant differences were observed between CP7 and CP8/9 groups in PFS (7.8 vs. 6.3 months, p = 0.28), OS (17.8 vs. 14.0 months, p = 0.20), ORR (33.0% vs. 27.4%, p = 0.42), or safety profiles. However, the CP8/9 group had significantly higher rates of TKI dose reductions (46.6% vs. 31.1%, p = 0.04) and discontinuations (57.5% vs. 24.5%, p < 0.001). Notably, 30.2% of patients maintained sustained radiographic responses despite advanced liver dysfunction.

Combining TKIs with PD-1 inhibitors is an effective and well-tolerated option for HCC patients with Child-Pugh B, including those with CP8/9.

The survival outcomes associated with hepatic recompensation in patients with advanced hepatocellular carcinoma (HCC) treated with first-line systemic therapies remain unclear. We compared survival from the initiation of first-line systemic treatments for advanced HCC among patients with compensated, decompensated, and recompensated cirrhosis.

A Latin American multicenter, prospective cohort study was conducted from 2018 to 2024, involving patients with HCC and Child-Pugh class A or B who received systemic therapy. At the time of first-line therapy, patients with cirrhosis were categorised as compensated (never decompensated), decompensated, or recompensated. Cox proportional hazards models were estimated.

Among 306 patients receiving first-line systemic therapy (sorafenib: 60.5%, atezolizumab + bevacizumab: 29.7%, lenvatinib: 9.1%), 240 had cirrhosis, with 30.4% having a history of hepatic decompensation. Of these, 57.5% (95% CI 45.4%-69.0%) achieved hepatic recompensation over a median period of 12 months. At the time of first-line therapy, 69.6% were compensated, 17.5% recompensated, and 12.9% decompensated. Metabolic-associated steatotic liver disease (MASLD) was the most common underlying aetiology in the recompensated group. Median survival was significantly shorter in the decompensated group (8.6 months) compared to the compensated group (17.2 months) [aHR 1.91 (95% CI 1.04-3.5); p = 0.03], without a significant difference between the recompensated and compensated groups [aHR 1.28 (95% CI 0.79-2.1); p = 0.31]. Tumour progression was the primary reason for treatment discontinuation, and similar access to second-line therapies was observed between the compensated and recompensated groups.

Patients with cirrhosis and advanced HCC who achieved hepatic recompensation might benefit from systemic therapies after a cautious observation period.

Current large clinical trials mainly focus on Child-Pugh A (CP-A) stage hepatocellular carcinoma (HCC) patients, with limited data on CP-B patients especially those classified as B8-9, whose treatment needs remain inadequately addressed. This study aims to evaluate the safety efficacy of interventional treatments, with or without targeted-immunotherapy and characteristics of CP-B stage HCC patients receiving.

This single-center retrospective investigation incorporated 119 patients were stratified into two cohorts: the interventional therapy cohort (42) and the combined targeted immunotherapy cohort (77). The clinical data, overall survival (OS), progression-free survival (PFS), and therapeutic efficacy of both groups were meticulously recorded and comprehensively analyzed. Survival disparities were statistically compared employing the Kaplan-Meier survival analysis method and the log-rank test. Tumor remission was appraised in accordance with the RECIST 1.1 and mRECIST criteria. Independent influencing factors were discerned through multifactorial COX regression analysis. Subsequently, survival prediction models were constructed to generate column line graphs, and the safety profiles and adverse events associated with diverse treatment modalities were also evaluated.

119 patients with CP-B grade HCC were included, and the median survival (mOS) of patients who received combination therapy was 21.4 months (vs 13.2, P=0.038) superior to that of interventional therapy, and the median progression-free survival (mPFS) of 12.7 months (vs 10.9 months, P=0.183) was not significantly improved. The OS of patients in group B7 who received combination therapy was 24.6 months (vs 11.9, P=0.006) was superior to that of the intervention, while there was no significant improvement in patients in groups B8-9. The objective remission rate (ORR) was higher in the combination therapy than in the intervention group (RECIST: 32.5% vs 11.9%, P = 0.014; mRECIST: 48.1% vs 23.8%, P = 0.010). Except for Child-Pugh score progression (P = 0.003), there was no significant difference in the occurrence of all-grade and ≥grade 3 adverse events in the combination therapy group compared with the intervention group (P > 0.05).

Interventional therapy combined with targeted and immunotherapy can be a safe and effective treatment for patients with Child-Pugh grade B hepatocellular carcinoma in the setting of controlled liver function impairment.

Systemic therapy represents the standard of care treatment for patients with advanced hepatocellular carcinoma (HCC). Given the increased risk of death from cirrhosis-related complications in patients with advanced liver dysfunction, pivotal phase III trials traditionally limited inclusion to patients with Child-Pugh class A, where death is more likely to be attributed to HCC progression. Therefore, Western guidelines recommend the use of systemic therapies primarily in patients with preserved liver function. However, patients with HCC and Child-Pugh class B are commonly encountered in clinical practice, but due to limited prospective evidence, there is no clear guidance on their optimal management.In this recent advances article, we discuss how the clinical course of cirrhosis can affect eligibility to treatment in the modern era of systemic therapy for HCC, elaborate on strategies to improve liver function in HCC patients by targeting cirrhosis-related and tumour-related factors and summarise the current literature on systemic therapy in HCC patients with Child-Pugh class B. Based on this information, we finally propose a clinical algorithm on how to systematically approach patients with HCC and advanced liver dysfunction in clinical practice.

Over the past years, there has been a remarkable advance in the systemic treatment options for advanced HCC. The overall survival has gradually increased over time, with larger benefits for patients with sensitive tumors and preserved liver function, the latter being an essential condition for the delivery of sequential lines of treatment and optimization of clinical outcomes. With the approval of new first-line agents and the introduction of immune checkpoint inhibitor-based therapies, the treatment landscape of advanced HCC is becoming wider than ever. Atezolizumab plus bevacizumab and, more recently, durvalumab plus tremelimumab have entered the clinical practice and are the current standard of care for treatment-naïve patients, surpassing sorafenib and lenvatinib monopoly. As no head-to-head comparisons are available among all the first-line treatment options, the recommendation for the most appropriate choice and sequence is patient-driven and integrates efficacy data with clinical comorbidities, background liver disease, and the safety profile of available drugs. In addition, predictive biomarkers for successful patients' stratification are yet to be available and constitute the focus of ongoing research. The treatment algorithm is likely to become even more complex since systemic therapeutic approaches are now being translated into earlier stages of the disease, with an impact on the evolution of the sequential treatment of patients with HCC.

In recent years, several global phase III trials have shown that combinations of immune checkpoint inhibitors (ICIs) offer superior efficacy and survival compared to multi-kinase inhibitors, establishing them as the gold standard for treating patients with advanced hepatocellular carcinoma (HCC). This success has led to investigations into expanding the use of immunotherapy into various other settings and populations, including neoadjuvant and adjuvant therapies, patients with decompensated liver function and those awaiting liver transplantation. Despite its proven efficacy, a significant number of patients still develop resistance to immunotherapy, highlighting the need for innovative strategies to address this challenge. Approaches aimed at enhancing tumour immunogenicity, such as combining immunotherapy with transarterial chemoembolization or radiation therapies, show significant promise. Additionally, novel immunotherapeutics - such as triplet therapy, bispecific antibodies, adoptive T-cell therapy and cancer vaccines - are in early development for HCC. These agents have demonstrated potential for synergistic effects with existing ICIs, with initial studies yielding positive outcomes. In this review, we offer our future perspective on immunotherapy, emphasizing emerging indications, novel combination strategies and the development of new immunotherapeutic agents. Overall, the future of immunotherapy in HCC is brimming with extraordinary potential, set to transform the treatment landscape and redefine the possibilities for managing this challenging disease.

Systemic treatment for unresectable hepatocellular carcinoma (HCC) has rapidly advanced, with immune checkpoint inhibitors now the preferred first-line option. However, with multiple agents available and no established treatment sequence, selecting the most suitable second-line (2L) therapy remains challenging. While sorafenib is frequently chosen for 2L treatment, comprehensive data supporting its use is limited. This study evaluates the effectiveness of sorafenib as 2L therapy and factors influencing outcomes following first-line treatment failure in advanced HCC patients.

This is a retrospective, multicenter study, including 81 patients with unresectable HCC from 12 European centers who received sorafenib as 2L treatment. Median overall survival (mOS), median progression-free survival (mPFS), radiological response to treatment, and toxicity were evaluated. Univariable and multivariable analyses were performed to identify potential predictors of clinical benefit.

In this cohort, some patients were treated with 2L sorafenib mOS for 7.4 months (95% CI: 6.6-13.6) and other patients were treated with mPFS for 3.7 months (95% CI: 3.0-4.8). Multivariable analysis revealed the best median OS for patients with CP A and AFP levels < 400 ng/mL (15.5 months). Adverse events (AE) of grade ≥ 3 were reported in 59.4% of patients.

In this real-world cohort of European patients with unresectable HCC, the outcome of sorafenib treatment in the 2L setting was comparable to that of the other established 2L treatment options in patients with preserved liver function and good performance status. This study contributes to the understanding of the role of sorafenib in the 2L setting and underscores the need for further research to identify predictive factors for response and survival in order to optimize treatment algorithms for advanced HCC.

Background/Objectives: Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy. Barcelona Clinic Liver Cancer (BCLC) guidelines recommend antiangiogenic agents with immune checkpoint inhibitors as first-line therapy for advanced HCC. We present our experience of treating HCC patients with Atezolizumab-Bevacizumab, their response rates, adverse events, survival, and response and survival predictors. Methods: This retrospective analysis included HCC patients diagnosed at All India Institute of Medical Sciences, New Delhi, India between July 2021 and April 2024 and receiving at least one dose of Atezolizumab-Bevacizumab. The primary outcome was overall response rate (ORR), comprising complete response (CR) and partial response (PR), as per mRECIST criteria. Secondary outcomes were overall survival (OS), progression-free survival (PFS), and predictors of response and survival. Results: Sixty-three patients were analyzed {mean age: 56.0 + 12.7 years; 82.5% males}. Forty-three (68.2%) patients had BCLC stage C HCC. Thirty-five (55.5%) patients belonged to Child-Pugh class A and 28 (44.5%) belonged to Child-Pugh class B. At 1 year, OS was 39% and PFS was 27%. Among 43 patients with data for radiological response, ORR was 48.8% (CR-9.3% and PR-39.5%) and DCR was 62.7% with stable disease (SD) in 13.9% of patients. PD occurred in 37.2% of patients. AFP response predicted radiological response, while Child-Pugh class and BCLC stage predicted survival. Adverse events were reported in 49.2% of patients. Conclusions: Our study shows slightly lower survival than previous studies with Child-Pugh class being the most important determinant of survival. AFP response predicts radiological response and not survival.

Liver cancer is the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 90% of primary liver cancers. Advances in diagnostic and therapeutic tools, along with improved understanding of their application, are transforming patient treatment. Integrating these innovations into clinical practice presents challenges and necessitates guidance. These clinical practice guidelines offer updated advice for managing patients with HCC and provide a comprehensive review of pertinent data. Key updates from the 2018 EASL guidelines include personalised surveillance based on individual risk assessment and the use of new tools, standardisation of liver imaging procedures and diagnostic criteria, use of minimally invasive surgery in complex cases together with updates on the integrated role of liver transplantation, transitions between surgical, locoregional, and systemic therapies, the role of radiation therapies, and the use of combination immunotherapies at various stages of disease. Above all, there is an absolute need for a multiparametric assessment of individual risks and benefits, considering the patient's perspective, by a multidisciplinary team encompassing various specialties.

Systemic therapy for hepatocellular carcinoma has evolved from sorafenib to now include immune checkpoint blockade, either atezolizumab/bevacizumab or durvalumab/tremelimumab, and soon to include camrelizumab/rivoceranib and nivolumab/ipilimumab. Second-line therapy remains predominantly either a multikinase inhibitor or ramucirumab. Areas of development include testing immune checkpoint-based regimens in the adjuvant setting after surgery, ablation, or transarterial embolization. Also of interest are studies for patients with Child-Pugh B liver function and adding new checkpoint molecules to the current standard platforms.

Various conversion therapy options have become available to patients with unresectable HCC, but which conversion therapy is optimal for which type of patient is controversial. This study compared the efficacy and safety of TACE alone or combined with immune checkpoint and tyrosine kinase inhibitors.

Data were retrospectively compared for patients with initially unresectable HCC who underwent conversion therapy consisting of TACE alone (n=459) or combined with immune checkpoint and tyrosine kinase inhibitors (n=343). Compared to the group that received TACE alone, the group that received triple conversion therapy showed significantly higher rates of overall survival (HR 0.43, 95%CI 0.35-0.53). In addition, triple therapy was associated with significantly longer median progression-free survival (15.9 vs. 8.0 mo, p <0.001). These results were confirmed in matched subsets of patients from each group. However, subgroup analysis confirmed the results only for patients with HCC in intermediate or advanced stages, not in an early stage. Those who received triple conversion therapy had a significantly higher rate of hepatectomy after conversion therapy (36.4 vs. 23.5%, p <0.001). Among those who underwent hepatectomy after conversion therapy, triple therapy was associated with a significantly higher rate of complete tumor response (32.1 vs. 11.1%, p <0.001). However, it was also associated with a significantly higher frequency of serious adverse events (35.6 vs. 27.0%, p =0.009).

Combining TACE with immune checkpoint and tyrosine kinase inhibitors was associated with significantly better survival and conversion efficacy than TACE alone among patients with intermediate or advanced unresectable HCC.

Hepatocellular carcinoma (HCC) is a prevalent malignant tumour worldwide. Depending on the stage of the tumour and liver function, a variety of treatment options are indicated. Traditional radiotherapy and chemotherapy are ineffective against HCC; however, the U.S. Food and Drug Administration (FDA) has approved radiofrequency ablation (RFA), surgical resection, and transarterial chemoembolization (TACE) for advanced HCC. On the other hand, liver transplantation is recommended in the early stages of the disease. Tyrosine kinase inhibitors (TKIs) like lenvatinib and sorafenib, immunotherapy and anti-angiogenesis therapy, including pembrolizumab, bevacizumab, tremelimumab, durvalumab, camrelizumab, and atezolizumab, are other treatment options for advanced HCC. Moreover, to maximize outcomes for patients with HCC, the combination of immune checkpoint inhibitors (ICIs) along with targeted therapies or local ablative therapy is being investigated. This review elaborates on the current status of HCC treatment, outlining the most recent clinical study results and novel approaches.

The impairment of liver function strongly limits the therapeutic options for hepatocellular carcinoma (HCC), and the assessment of liver function is key to finding the appropriate therapy for patients suffering from this disease. Furthermore, preexisting liver dysfunction has a negative impact on the prognosis of patients in addition to the malignant potential of HCC. Hence, defining the optimal treatment of patients with HCC requires a comprehensive examination with liver function being a crucial part of it.

This review will provide an overview of the currently existing methods for evaluating the liver function in patients with HCC. Assessment of liver function includes scoring systems but also functional and technical methods. In addition, the role of these tests in different treatment facilities such as liver resection, transplantation, interventional and systemic therapy is summarized.

A comprehensive pretherapeutic assessment of the liver function includes laboratory-based scoring systems, as well as imaging- and non-imaging-based functional tests. Combining diverse parameters can help to improve the safety and efficacy of HCC therapy particularly in patients with compromised liver function. Future research should focus on optimizing pretherapeutic assessment recommendations for each therapy.

Purpose: We describe the impact of screening on outcomes of patients diagnosed with hepatocellular carcinoma (HCC) in an urban safety-net healthcare system compared to a non-screened cohort diagnosed with HCC. Methods: Patients diagnosed with HCC at John Peter Smith Health Network were identified by querying the hospital tumor registry and allocated to the screened cohort if they had undergone any liver imaging within one year prior to HCC diagnosis, while the remainder were allocated to the non-screened cohort. Kaplan-Meier methods and log-rank tests were used to compare 3-year survival curves from an index date of HCC diagnosis. Cox proportional hazard models were used to calculate unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The Duffy adjustment was used to address lead-time bias. Results: A total of 158 patients were included (n = 53 screened, n = 105 non-screened). The median overall survival (OS) for the screened cohort was 19.0 months (95% CI: 9.9-NA) and that for the non-screened cohort was 5.4 months (95% CI: 3.7-8.5) [HR death (non-screened vs. screened) = 2.4, 95% CI: 1.6-3.6; log rank p < 0.0001]. The benefit of screening remained after adjusting for lead-time bias (HR 2.19, 95% CI 1.4-3.3, p = 0.0002). Conclusions: In an urban safety-net population, screening for HCC was associated with improved outcomes compared to patients diagnosed with HCC outside of a screening protocol.

Cirrhosis represents a significant global health challenge, characterized by high morbidity and mortality rates that severely impact human health. Timely and precise prognostic assessments of liver cirrhosis are crucial for improving patient outcomes and reducing mortality rates as they enable physicians to identify high-risk patients and implement early interventions. This paper features a thorough literature review on the prognostic assessment of liver cirrhosis, aiming to summarize and delineate the present status and constraints associated with the application of traditional prognostic tools in clinical settings. Among these tools, the Child-Pugh and Model for End-Stage Liver Disease (MELD) scoring systems are predominantly utilized. However, their accuracy varies significantly. These systems are generally suitable for broad assessments but lack condition-specific applicability and fail to capture the risks associated with dynamic changes in patient conditions. Future research in this field is poised for deep exploration into the integration of artificial intelligence (AI) with routine clinical and multi-omics data in patients with cirrhosis. The goal is to transition from static, unimodal assessment models to dynamic, multimodal frameworks. Such advancements will not only improve the precision of prognostic tools but also facilitate personalized medicine approaches, potentially revolutionizing clinical outcomes.

This meta-analysis was dedicated to evaluating the effectiveness and safety of Atezolizumab plus Bevacizumab (Atez/Bev) and Lenvatinib (LEN) as first-line systematic therapy for unresectable hepatocellular carcinoma (u-HCC).

The prospective protocol for this study was registered with the PROSPERO (Registration number: CRD42022356874). Literature searches were conducted in PubMed, EMBASE database Cochrane Library, and Web Science to determine all clinical controlled studies that reported Atez/Bev and LEN for treating u-HCC. We. evaluated as primary end-point overall survival (OS) and progression-free survival (PFS), as well as other outcomes such as tumor response and adverse events (AEs).Quality assessment and data extraction of studies were conducted independently by three reviewers. Mean difference (MD) and odds ratio (OR) with 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model. The meta-analysis was performed with RevMan 5.3 software.

12 retrospective cohort studies (RCSs) involving a total of 4948 patients were finally included. The results showed that compared with LEN, Atez/Bev can improve the patient's PFS (HR = 0.80, 95% CI: 0.72 ~ 0.88; p < 0.0001) and reduce the rate of overall AEs (OR = 0.46 95% CI: 0.38 ~ 0.55, p < 0.00001) and grade ≥ 3 AEs (OR = 0.43; 95% CI: 0.36 ~ 0.51, p < 0.00001), while there is no difference between OS and treatment responses rate (objective response rate, disease control rate, complete response, partial response, progressive disease, and stable disease) between two groups. In addition, the subgroup analysis shows that Atez/Bev can promote the OS of patients with viral hepatitis. (HR = 0.79, 95% CI: 0.67 ~ 0.95; p = 0.01), while LEN has an advantage in improving OS in patients with Child-Pugh grade B liver function (HR = 1.98, 95% CI: 1.50 ~ 2.63; p < 0.00001).

Current evidence shows that compared with LEN, Atez/Bev has more advantages in PFS and safety in treating u-HCC and can improve the OS of patients with viral. LEN has advantages in improving the OS of patients with grade B liver function. However, more multicenter randomized controlled experiments are needed in the future to verify our results.

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality in Taiwan. The Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan established HCC management consensus guidelines in 2016 and updated them in 2023. Current recommendations focus on addressing critical issues in HCC management, including surveillance, diagnosis, systemic treatment, and posttreatment monitoring. For surveillance and diagnosis, we updated the guidelines to include the role of protein induced by vitamin K absence or antagonist II (PIVKA-II) and gadoxetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in detecting HCCs. For systemic treatment, the updated guidelines summarize the multiple choices available for targeted therapy, immune checkpoint inhibitors, and a combination of both, especially for those carcinomas refractory to or unsuitable for transarterial chemoembolization. We have added a new section, posttreatment monitoring, that describes the important roles of PIVKA-II and EOB-MRI after HCC therapy, including surgery, locoregional therapy, and systemic treatment. Through this update of the management consensus guidelines, patients with HCC may benefit from optimal diagnosis, therapeutic modalities, and posttreatment monitoring.

Deterioration of liver function is a leading cause of death in patients with advanced hepatocellular carcinoma (HCC). We evaluated the impact of immune checkpoint inhibitor (ICI)-treatment on liver function and outcomes.

HCC patients receiving ICIs or sorafenib between 04/2003 and 05/2024 were included. Liver function (assessed by Child-Pugh score [CPS]) was evaluated at the start of ICI-treatment (baseline, BL) and 3 and 6 months thereafter. A ≥1 point change in CPS was defined as deterioration (-) or improvement (+), while equal CPS points were defined as stable (=).

Overall, 182 ICI-treated patients (66.8 ± 11.8 years; cirrhosis: n = 134, 74%) were included. At BL, median CPS was 5 (IQR: 5-6; CPS-A: 147, 81%). After 3 months, liver function improved/stabilized in 102 (56%) and deteriorated in 61 (34%) patients, while 19 (10%) patients deceased/had missing follow-up (d/noFU). Comparable results were observed at 6 months (+/=: n = 82, 45%; -: n = 55, 30%; d/noFU: n = 45, 25%). In contrast, 54 (34%) and 33 (21%) out of 160 sorafenib patients achieved improvement/stabilization at 3 and 6 months, respectively. Radiological response was linked to CPS improvement/stabilization at 6 months (responders vs. non-responders, 73% vs. 50%; p = 0.007). CPS improvement/stabilization at 6 months was associated with better overall survival following landmark analysis (6 months: +/=: 28.4 [95% CI: 18.7-38.1] versus -: 14.2 [95% CI: 10.3-18.2] months; p < 0.001). Of 35 ICI-patients with CPS-B at BL, improvement/stabilization occurred in 16 (46%) patients, while 19 (54%) patients deteriorated/d/noFU at 3 months. Comparable results were observed at 6 months (CPS +/=: 14, 40%, -: 8, 23%). Importantly, 6/35 (17%) and 9/35 (26%) patients improved from CPS-B to CPS-A at 3 and 6 months.

Radiological response to ICI-treatment was associated with stabilization or improvement in liver function, which correlated with improved survival, even in patients with Child-Pugh class B at baseline.

The efficacy of systemic therapy for unresectable advanced hepatocellular carcinoma (aHCC) has not been proven in patients with Child-Pugh (C-P) B cirrhosis. Nevertheless, in real-world these patients are treated both with tyrosine kinase inhibitors (TKIs) and with metronomic capecitabine (MC). This study aimed to compare sorafenib and MC outcomes versus best supportive care (BSC) in C-P B patients.

Between 2008 and 2020, among 774 C-P B patients with aHCC not amenable/responsive to locoregional treatments, 410 underwent sorafenib, 62 MC, and 302 BSC. The propensity score matching method was used to correct the baseline unbalanced prognostic factors.

In the unmatched population, median OS was 9.7 months in patients treated with sorafenib, 8.0 with MC, and 3.9 months with BSC. In sorafenib vs. BSC-matched patients (135 couples), median OS was 7.3 (4.9-9.6) vs. 3.9 (2.6-5.2) months (p<0.001). ECOG-Performance Status, tumor size, macrovascular invasion, AFP, treatment-naive, and sorafenib were independent predictors of survival. In MC vs. BSC-matched patients (40 couples), median OS was 9.0 (0.2-17.8) vs.3.0 (2.2-3.8) months (p<0.001). Median OS did not differ (p = 0.283) in sorafenib vs. MC-matched patients (55 couples).

C-P B patients with aHCC undergoing BSC have poor survival. Both Sorafenib and MC treatment improve their prognosis.

Hepatocellular carcinoma (HCC) accounts for 85% of liver cancer cases and is the third leading cause of cancer death. Regorafenib is a multi-target inhibitor that dramatically prolongs progression-free survival in HCC patients who have failed sorafenib therapy. However, one of the primary factors limiting regorafenib's clinical utilization is toxicity. Using Clinical Trials.gov and PubMed, we gathered clinical data on regorafenib and conducted a extensive analysis of the medication's adverse reactions and mechanisms. Next, we suggested suitable management techniques to improve regorafenib's effectiveness.

We have reviewed the mechanisms by which regorafenib-induced toxicity occurs and general management strategies through clinical trials of regorafenib. Furthermore, by examining the literature on regorafenib and other tyrosine kinase inhibition, we summarized the mechanics of the onset of regorafenib toxicity and mechanism-based intervention strategies by reviewing the literature related to regorafenib and other tyrosine kinase inhibition.

One of the primary factors restricting regorafenib's clinical utilization and combination therapy is its toxicity reactions. To optimize regorafenib treatment regimens, it is especially important to further understand the specific toxicity mechanisms of regorafenib as a multi-kinase inhibitor.

Hepatocellular carcinoma (HCC) is a lethal malignancy associated with cirrhosis and liver dysfunction. The aim of this study is to characterize a cohort of patients with advanced HCC according to liver function-related variables and evaluate the prognostic significance of Child-Pugh (CP) and albumin-bilirubin (ALBI) scores. A database of 406 HCC patients treated between 2009 and 2023 was retrospectively evaluated. Clinical and laboratory parameters were collected to classify patients into ALBI and CP scores. Survival was estimated using the Kaplan-Meier method and multivariate models were used to evaluate prognosis prediction. In this cohort, 337 (83%) patients were classified as CP-A, while 69 (17%) as CP-B. Additionally, according to ALBI score, 159 (39.2%) individuals were categorised as ALBI-1, 233 (57.4%) as ALBI-2 and 14 (3.4%) as ALBI-3. A statistically significant association between both classifications was observed (p < 0.001). CP and ALBI scores were independently associated with prognosis (Hazard ratio = 2.93 and 1.66, respectively), with better survival for patients with CP-A (versus B) and ALBI-1 (versus -2 and -3). ALBI score showed better predictive performance versus CP (c Harrell´s C index = 0.65 versus 0.62; p = 0.008) and ALBI evolution during the first month of treatment was associated with overall survival. Additionally, ALBI score was able to define distinct prognostic subgroups within CP-A patients. In conclusion, liver function scores, such as ALBI and CP, have a clinically relevant prognostic role in patients with advanced HCC under systemic treatment. ALBI score is a more granular scoring scale than CP, and enables a more precise evaluation of patients with CP-A.

Systemic therapy with atezolizumab and bevacizumab can extend life for patients with advanced hepatocellular carcinoma (HCC). However, there is substantial variability in response to therapy and overall survival. Although current prognostic models have been validated in HCC, they primarily consider covariates that may be reflective of the severity of the underlying liver disease of patients with HCC. We developed and internally validated a classification and regression tree (CART) to identify patient characteristics associated with risks of early mortality, at or before 6 months from treatment initiation.

This retrospective cohort study used the nationwide Flatiron Health electronic health record-derived deidentified database and included patients with a diagnosis of HCC after January 1, 2020, who received initial systemic therapy with atezolizumab and bevacizumab. CART was developed from available baseline clinical and demographic information to predict mortality within 6 months from treatment initiation. Model characteristics were compared to the albumin-bilirubin (ALBI) model and was further validated against a contemporary validation cohort of patients after a data update.

A total of 293 patients were analyzed. The CART identified seven cohorts of patients from baseline demographic and laboratory characteristics. The model had an area under the receiver operating curve (AUROC) of 0.739 (95% CI, 0.683 to 0.794) for predicting 6-month mortality. This model was internally valid and performed more favorably than the ALBI model, which had an AUROC of 0.608 (95% CI, 0.557 to 0.660). The model applied to the contemporary validation cohort (n = 111) had an AUROC of 0.666 (95% CI, 0.506 to 0.826).

Using CART, we identified unique cohorts of patients with HCC treated with atezolizumab and bevacizumab with distinct risks of early mortality. This approach outperformed the ALBI model and used clinical and laboratory characteristics that are readily available to oncologists caring for these patients.

Deaths from the majority of cancers are falling globally, but the incidence and mortality from hepatocellular carcinoma (HCC) is increasing in the United Kingdom and in other Western countries. HCC is a highly fatal cancer, often diagnosed late, with an incidence to mortality ratio that approaches 1. Despite there being a number of treatment options, including those associated with good medium to long-term survival, 5-year survival from HCC in the UK remains below 20%. Sex, ethnicity and deprivation are important demographics for the incidence of, and/or survival from, HCC. These clinical practice guidelines will provide evidence-based advice for the assessment and management of patients with HCC. The clinical and scientific data underpinning the recommendations we make are summarised in detail. Much of the content will have broad relevance, but the treatment algorithms are based on therapies that are available in the UK and have regulatory approval for use in the National Health Service.

More than 800,000 people worldwide are diagnosed with HCC (hepatocellular carcinoma) each year, with approximately 700,000 deaths alone occurring in that same year. Treatment of HCC presents complex therapeutic challenges, particularly in intermediate and advanced stages. LRTs such as transarterial chemoembolization (TACE) and ablations have been the mainstay treatment for early to intermediate-stage HCC, and systemic therapies are used to treat intermediate-late-stage HCC. However, novel literature describing combining LRT with systemic therapies has shown promising results. This review explores recent advances in both liver-directed techniques for hepatocellular carcinoma, including bland transarterial embolization, chemoembolization, radioembolization, and ablative therapies in conjunction as well as with systemic therapies, with a focus on combination therapies, patient selection, procedural technique, periprocedural management, and outcomes. Our findings suggest that LRT combined with systemic therapies is a viable strategy for improving progression-free survival and time to progression for patients with intermediate-to-late-stage HCC. However, further investigation is required to refine treatment protocols and define patient cohorts that would benefit the most.

Limited data exists for the efficacy and outcomes of nivolumab as a second-line treatment for unresectable hepatocellular carcinoma (uHCC). We aimed to assess the efficacy and safety of nivolumab in patients with uHCC who experienced disease progression during sorafenib treatment.

In this retrospective, observational, multicenter study, adult Child-Turcotte-Pugh A/7B patients with uHCC who tolerated sorafenib therapy but showed disease progression switched to second-line intravenous nivolumab (n = 42). A similar number of consecutive, unselected patients who were maintained on sorafenib therapy, regardless of tumoral response or progression, served as historical controls (n = 38). The primary endpoint was overall survival (OS, defined as the time from starting sorafenib in either group up to death due to any cause) and analyzed by intention-to-treat.

The mean age of the overall cohort was 72.4 ± 10.1 years, of whom 87.5% were males and 58.8% had underlying viral etiology. Patients in the two cohorts were similar, except those who received nivolumab had more co-morbidities (70.0% vs. 15.4%), ECOG-2 status (21.4% vs. 15.8%), BCLC stage C (81.0% vs. 47.4%), and extravascular invasion (54.4% vs. 21.8%) (p < 0.05 for all). More patients in the nivolumab arm were Child-Turcotte-Pugh B (35.7% vs. 21.1%, p = 0.15). Median OS was 22.2 months (95% CI: 8.9-49.8) on second-line nivolumab and 11.0 months (95% CI: 3.6-18.4) on sorafenib alone (HR 1.93; 95% CI: 1.1-3.3, p = 0.014). Median OS after starting nivolumab was 10.2 months, and time-to-progression was 4.9 months (95% CI: 3.2-6.3).

Nivolumab is an effective second-line treatment option in patients with uHCC who progress on sorafenib, with significantly improved OS. These early real-life data offer encouraging results, similar to those shown in Phase I/IIa clinical trials. Further investigations are warranted for the use of nivolumab as a monotherapy.