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Introduction: Atezolizumab plus bevacizumab (Atez/Bev) is the preferred treatment for advanced hepatocellular carcinoma (HCC). However, biomarkers of therapeutic efficacy have remained unclear. We took a retrospective approach to explore the role of prognostic nutritional index (PNI) for predicting the outcomes of Atez/Bev treatment. Methods: One hundred 25 HCC patients were enlisted; these patients received Atez/Bev treatment and underwent dynamic computerized tomography/magnetic resonance imaging to determine the treatment response on at least one occasion between October 2020 and January 2023, and their PNI before treatment and at the beginning of the second cycle (PNI-2c) was evaluated. Results: During the initial evaluation, 2 (2%), 28 (22%), 70 (56%), and 25 (20%) patients exhibited a complete response, partial response, stable disease, and progressive disease (PD), respectively. Patients with non-PD tended to have higher PNI at baseline and PNI-2c than those with PD (p = 0.245 and 0.122, respectively), with optimal baseline PNI and PNI-2c cut-off values of 42.6 and 40.4, respectively. PNI at baseline could not be used to predict overall survival (OS) or progression-free survival (PFS). However, PNI-2c predicted OS and PFS (PNI-2c ≥ 40.4 vs. < 40.4: 25.3 vs. 16.2 months, p = 0.008 for OS; 12.7 vs. 8.4 months, p = 0.036 for PFS). A multivariate analysis showed a significant association between PNI-2c and OS. Conclusions: PNI-2c is a predictor of prognosis in HCC patients treated with Atez/Bev therapy. Plain Language Summary: Atezolizumab plus bevacizumab (Atez/Bev) is the preferred treatment for advanced hepatocellular carcinoma (HCC). However, biomarkers of therapeutic efficacy have remained unclear. We took a retrospective approach to explore the role of prognostic nutritional index (PNI) for predicting the outcomes of Atez/Bev treatment. 125 HCC patients were enlisted; these patients received Atez/Bev treatment and underwent dynamic computerized tomography/magnetic resonance imaging to determine the treatment response on at least one occasion between October 2020 and January 2023, and their PNI before treatment and at the beginning of the second cycle (PNI-2c) was evaluated. During the initial evaluation, 2 (2%), 28 (22%), 70 (56%), and 25 (20%) patients exhibited a complete response, partial response, stable disease, and progressive disease (PD), respectively. Patients with non-PD tended to have higher PNI at baseline and PNI-2c than those with PD (p = 0.245 and 0.122, respectively), with optimal baseline PNI and PNI-2c cut-off values of 42.6 and 40.4, respectively. PNI at baseline could not be used to predict overall survival (OS) or progression-free survival (PFS). However, PNI-2c predicted OS and PFS (PNI-2c ≥ 40.4 vs. < 40.4: 25.3 vs. 16.2 months, p = 0.008 for OS; 12.7 vs. 8.4 months, p = 0.036 for PFS). A multivariate analysis showed a significant association between PNI-2c and OS. Therefore, PNI-2c is a predictor of prognosis in HCC patients treated with Atez/Bev therapy. [ABSTRACT FROM AUTHOR]

Owing to the high objective response rate of atezolizumab plus bevacizumab (Atez/Bev) for hepatocellular carcinoma (HCC), the concept of sequential conversion to local treatment has recently become mainstream. The conversion concept is mainly applied to Barcelona Clinic for Liver Cancer (BCLC) stage B cases, and radiotherapy is rarely considered as a conversion local treatment. We herein report three patients who were treated with the novel concept of "sequential particle radiotherapy," consisting of Atez/Bev therapy followed by particle radiotherapy (PRT) for HCC with advanced portal vein tumor thrombus (Vp3/4 PVTT). All patients achieved partial response radiologically and were switched to PRT. All patients were recurrence free at 1 year after the introduction of Atez/Bev therapy without any additional treatment. This upcoming combination strategy includes the advocacy of sequential concepts for BCLC stage C cases and the introduction of PRT as a local treatment after Atez/Bev. [ABSTRACT FROM AUTHOR]

Aim: The IMbrave150 trial revealed that atezolizumab plus bevacizumab (AtezoBv) showed a higher objective response rate (ORR) in patients with advanced hepatocellular carcinoma (HCC). Although conversion therapy after AtezoBv has been recently reported, markers predictive of its efficacy, particularly radiological imaging markers, have not yet been identified. The present study focused on tumor morphological appearance on radiological imaging and evaluated whether it could be associated with AtezoBv efficacy. Methods: Ninety‐five intrahepatic lesions in 74 patients who were given AtezoBv for advanced HCC were recruited for evaluation. The lesions were divided into two groups, simple nodular (SN group) and non‐simple nodular (non‐SN group), based on the gross morphology on pretreatment imaging, and retrospectively evaluated for treatment response and other relevant clinical outcomes. Results: Assessing the size of individual tumors after treatment, waterfall plots showed that tumor shrinkage in the non‐SN group including 56 lesions was higher than that in the SN group comprising 39 lesions. The ORR was significantly higher in the non‐SN group (39.3% vs. 15.4%, p = 0.012). Additionally, the median time to nodular progression was longer in the non‐SN group (21.0 months vs. 8.1 months, p = 0.119) compared to the SN group. Six patients with non‐SN lesions underwent sequential local therapy. Conclusions: Atezolizumab plus bevacizumab may show increased therapeutic efficacy in patients with tumors with a higher potential for aggressive oncological behavior, such as non‐SN lesions. Treatment strategies focusing on conversion therapy may be crucial in patients with non‐SN lesions. [ABSTRACT FROM AUTHOR]

Background/Aim: The landscape of treatments for hepatocellular carcinoma (HCC), including immune checkpoint inhibitors, has expanded significantly. However, unresectable HCC patients with portal vein tumor thrombus (PVTT) continue to face a poor prognosis. This investigation examined the survival outcomes and determinants influencing survival rates in advanced HCC patients with PVTT undergoing treatment with atezolizumab plus bevacizumab (ATZ+BEV) or hepatic arterial infusion chemotherapy (HAIC). Patients and Methods: Between December 2003 and June 2023, 48 advanced HCC with PVTT underwent treatment with either ATZ+BEV (16 patients) or HAIC (32 patients). Results: The analysis revealed no significant disparities in overall survival (OS) or treatment efficacy between the ATZ+BEV and HAIC groups (ATZ+BEV: 10.0 months, HAIC: 15.3 months). Treatment with either ATZ+BEV or HAIC resulted in minimal alterations in the ALBI score and preserved hepatic function. Independent prognostic factors for OS, identified via multivariate logistic regression, included serum a-fetoprotein levels >400 ng/ml [hazard ratio (HR)=1.94; p=0.001], the existence of more than five tumors (HR=1.55; p=0.043), and the Child-Pugh score (HR=2.53; p=0.002). Conclusion: This investigation revealed no significant variance in OS and response rates between patients receiving ATZ+BEV and those treated with HAIC. The survival of advanced HCC patients with PVTT is intricately linked to the preservation of liver function, emphasizing the necessity for additional research to enhance treatment approaches for this patient population. [ABSTRACT FROM AUTHOR]

Background Atezolizumab plus bevacizumab (atezo-bev) has been recommended for advanced hepatocellular carcinoma (HCC). High-dose external beam radiotherapy (RT) is recognized for its excellent local tumor control. The efficacy and safety of concurrent atezo-bev with RT for highly advanced HCC has been minimally explored. Methods In this preliminary retrospective study, we assessed patients with highly advanced HCC, characterized by Vp4 portal vein thrombosis or tumors exceeding 50% of liver volume, who received concurrent atezo-bev and RT (group A). Group A included 13 patients who received proton radiation at a dose of 72.6 GyE in 22 fractions, and one patient who received photon radiation at a dose of 54 Gy in 18 fractions. This group was compared with 34 similar patients treated atezo-bev alone as a control (group B). The primary objectives were to evaluate the objective response rate (ORR), overall survival (OS), and safety. Results Baseline characteristics were similar between groups, except for a higher incidence of Vp4 portal vein thrombosis in group A (78.6% vs. 21.4%, P  = .05). Group A achieved a higher ORR (50.0% vs. 11.8%, P  < .01) and a longer OS (not reached vs. 5.5 months, P  = .01) after a median follow-up of 5.2 months. Multivariate analysis indicated that concurrent RT independently favored longer OS (hazard ratio: 0.18; 95% CI, 0.05-0.63, P  < .01). Group A did not increase any grade adverse events (78.6% vs. 58.8%, P  = .19) or severe adverse events of grade ≥ 3 (14.3% vs. 14.7%, P  = .97) compared to group B. Conclusions The concurrent high-dose external beam radiotherapy appears to safely enhance the effectiveness of atezolizumab plus bevacizumab for highly advanced patients with HCC. Further studies are warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Simple Summary: Atezolizumab/bevacizumab (AB) therapy is currently one of the first-line drugs for patients with unresectable hepatocellular carcinoma (u-HCC). Predicting early progressive disease before AB therapy may be beneficial for selecting alternative treatments for patients with u-HCC. Coefficient of variation (CV), as one of the quantitative indicators of signal heterogeneity, in the hepatobiliary phase of Gd-EOB-DTPA-MRI was an independent predictive factor for tumor progression (p = 0.043). Patients with a high CV tended to have shorter PFS than those with a low CV (3.5 vs. 6.7 months, p = 0.071). Quantitative analysis using CV may be useful for predicting tumor progression for AB therapy, contributing to the individualization of therapeutic strategies for patients with u-HCC. Background: This study aimed to examine whether the coefficient of variation (CV) in the hepatobiliary-phase (HBP) of Gd-EOB-DTPA-MRI could be an independent predictive factor for tumor progression. Methods: Patients who underwent Gd-EOB-DTPA-MRI before Atezolizumab/bevacizumab therapy at six affiliated institutions between 2018 and 2022 were included. CV for each patient was calculated as the mean value for up to five tumors larger than 10 mm, and CV of the whole tumor was calculated using LIFEx software. The tumor response was evaluated within 6–10 weeks. The primary endpoint was to investigate the predictive factors, including CV, related to tumor progression using logistic regression analysis. The secondary endpoints were tumor response rate and progression-free survival (PFS) based on CV. Results: Of the 46 enrolled patients, 13 (28.3%) underwent early progressive disease. Multivariate analysis revealed that a high CV (≥0.22) was an independent predictive factor for tumor progression (p = 0.043). Patients with a high CV had significantly frequent PD than those with a low CV (43.5 vs. 13.0%, p = 0.047). Patients with a high CV tended to have shorter PFS than those with a low CV (3.5 vs. 6.7 months, p = 0.071). Conclusion: Quantitative analysis using CV in the HBP of Gd-EOB-DTPA-MRI may be useful for predicting tumor progression for atezolizumab/bevacizumab therapy. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) ranks as the sixth most common malignancy globally, with the majority of patients presenting at the initial diagnosis with locally advanced or metastatic disease, precluding the opportunity for curative surgical intervention. With the exploration and advancement of locoregional treatments, novel molecular-targeted therapies, anti-angiogenic agents, and immunomodulatory drugs, the management of HCC has seen an increase in objective response rates and prolonged duration of response significantly enhancing the potential for conversion to resectable disease in intermediate and advanced-stage unresectable HCC. Herein, we present a case of Barcelona Clinic Liver Cancer stage B unresectable HCC, where after two courses of treatment with transarterial chemoembolization combined with atezolizumab plus bevacizumab significant tumor reduction was achieved. Per Response Evaluation Criteria in Solid Tumors 1.1, partial response culminated in successful curative surgical resection. No drug-related adverse reactions occurred during hospitalization, and there has been no recurrence during the 11-month postoperative follow-up. For patients with Barcelona Clinic Liver Cancer stage B (intermediate-stage) unresectable HCC, the transarterial chemoembolization combined with atezolizumab plus bevacizumab regimen may offer improved therapeutic outcomes leading to a higher success rate of conversion therapy and, thus, improved survival. [ABSTRACT FROM AUTHOR]

Aim: C‐reactive protein (CRP) is both an inflammatory and prognostic marker in various cancers. This study aimed to elucidate the characteristics of CRP and the prognostic factors in patients who were administered with atezolizumab plus bevacizumab (ATZ + BEV) for unresectable hepatocellular carcinoma (HCC). Methods: A total of 213 patients who received ATZ + BEV for HCC from November 2020 to March 2023 at 15 hospitals were enrolled in this retrospective study. The prognosis was analyzed by subdividing the patients based on baseline characteristics, radiologic response, and treatment lines. Accuracy of survival prediction was assessed using CRP, alpha fetoprotein (AFP), C‐reactive protein and alpha fetoprotein in immunotherapy (CRAFITY), and Glasgow Prognostic Score. Results: Compared with patients with baseline CRP <1 mg/dL, those with baseline CRP ≥1 mg/dL (n = 45) had a significantly higher baseline albumin–bilirubin score and AFP levels, significantly lower disease control rate (62.2%), and significantly shorter median overall survival (hazards ratios 2.292; 95% confidence interval 1.313–5.107; log‐rank test, p < 0.001). Multivariate analysis identified CRP ≥1 mg/dL, AFP ≥100 ng/mL, and modified albumin–bilirubin grade as the significant prognostic factors. The baseline CRP, AFP, CRAFITY, and Glasgow Prognostic Score demonstrated higher discrimination for 1‐year survival prediction after first‐line ATZ + BEV administration, compared with beyond second line, with area under the receiver operating characteristic curves of 0.759, 0.761, 0.805, and 0.717, respectively. Conclusions: CRP was a significant biomarker in patients treated with ATZ + BEV for HCC. Elevated CRP levels may indicate aggressive cancer progression and potential resistance to ATZ + BEV therapy. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is often diagnosed in advanced stages. Following sorafenib, lenvatinib (LENV) has been approved as a first‐line treatment option for unresectable HCC. In the past few years, at least 9 large‐scale cohort studies have examined the efficacy and safety of LENV compared to atezolizumab plus bevacizumab (ATE/BEV) in unresectable HCC, but there is currently no direct meta‐analysis conducted for a comprehensive consolidation. To provide the most updated meta‐analysis of the clinical efficacy and safety of ATE/BEV versus LENV for patients with unresectable HCC. Our studies comparing the efficacy and safety of ATE/BEV and LENV in unresectable HCC were systematically searched in PubMed, Embase, and Web of Science from inception to February 2023. Outcomes measured were overall survival (OS), progression‐free survival (PFS), mortality, complete response (CR), partial response (PR), objective response rate (ORR), disease control rate (DCR), progressive disease (PD), stable disease (SD), and adverse events (AEs). Seven eligible studies involving 4428 patients (1569 in the ATE/BEV group and 2859 in the LENV group) were included in the narrative synthesis. All baseline characteristics were similar between the 2 groups except for Child‐Pugh class B. Ultimately, our meta‐analysis showed that the LENV group had longer OS and PFS than the ATE/BEV group. Moreover, patients on LENV were more likely to achieve SD, whereas those on ATE/BEV were more likely to achieve PR. [ABSTRACT FROM AUTHOR]

Background/aim: Unresectable recurrence after curative treatments for hepatocellular carcinoma (HCC) is a life-limited event. Although the IMbrave050 trial (IM050) showed a favorable reduction in recurrence with adjuvant immune-combination chemotherapy, inclusion criteria of the radiofrequency ablation (RFA) group were lower risk than that of the resection group. This study aimed to elucidate the clinical features of patients treated with RFA, which really need adjuvant-chemotherapy. Methods: From 2000 to 2022, 528 patients with Child–Pugh A and HCC within the Milan criteria (MC), who met the IM050 criteria for RFA and undergone resection or RFA, were enrolled (71 years, HCV:HBV:HBV/HCV:alcohol:others = 337:44:5:53:89, multi-tumor = 138, RFA:resection = 309:219). Unresectable recurrence was defined as beyond the MC. Risk factors for recurrence beyond the MC were retrospectively evaluated. Results: Multivariate Cox-hazard analysis showed HCV-positive (HR 1.49), AFP-L3 > 10% (HR 1.75), and DCP > 100 mAU/mL (HR1.80) as significant prognostic factors for recurrence beyond the MC (each P < 0.05). Summing of positive factors (1 point for each) was used for scoring (AD-ON score), which showed increased positive rates for micro-hepatic vein invasion (score 0:1:2:3 = 0%:1.1%:6.6%:15.8%), micro-portal vein invasion (0:1:2:3 = 2.0%:12.1%:14.1%:31.6%), and poor differentiation (0:1:2:3 = 6.0%:6.7%:15.3%:15.8%) in the resection group associated with a greater score (each P < 0.01). In patients treated with RFA, those with greater AD-ON scores showed shorter time to recurrence beyond the MC, recurrence-free time, and overall survival (score 0:1:2:3 = no-estimation:97:66:23 months, 35:27:20:12 months, and 91:82:67:52 months, respectively, each P < 0.05). Conclusion: HCC patients treated by RFA and with a high AD-ON score (≧2) should be considered for aggressive adjuvant-chemotherapy to prolong the period of recurrence beyond the MC. [ABSTRACT FROM AUTHOR]

Aim: Elderly patients are believed to have a reduced immune capacity, which may make immunotherapy less effective. The aim of this study was to compare the therapeutic outcome of atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib (LEN) for advanced hepatocellular carcinoma (HCC) in patients aged 80 years and older. Methods: From March 2018 to July 2022, 170 and 92 elderly patients who received LEN and Atez/Bev as first‐line treatment, respectively, were retrospectively analyzed. Results: The median ages of the Atez/Bev and LEN groups were 83.0 (8.01–86.0) and 83.0 (82.0–86.0) years (p = 0.3), respectively. Men accounted for approximately 70% of the patients in both groups. The objective response rate was 35.9% in the LEN group and 33.7% in the Atez/Bev group (p = 0.8), whereas the disease control rates in the LEN and Atez/Bev groups were 62.9% and 63.0%, respectively (p = 1.0). The median progression‐free survival (PFS) in the LEN and Atez/Bev groups was 6.3 and 7.2 months, respectively, which were not significantly different (p = 0.2). The median overall survival (OS) was 17.9 months in the LEN group and 14.0 months in the Atez/Bev group. This difference was not statistically significant (p = 0.7). In multivariate analyses, the choice of treatment (LEN vs. Atez/Bev) showed no association with PFS or OS. The Atez/Bev group had a significantly higher rate of postprogression treatment (59.0% vs. 35.7%, p = 0.01) and a lower rate of discontinuation due to adverse events (69 [40.6%] vs. 19 [20.7%], p < 0.001) compared to the LEN group. Conclusions: Atezolizumab plus bevacizumab showed comparable effectiveness to LEN in HCC patients aged 80 years and older. Given the results of postprogression treatment and discontinuation due to adverse events, Atez/Bev could serve as a first‐line treatment even for elderly HCC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we evaluated the status and dynamics of peripheral T cell subpopulations in hepatocellular carcinoma (HCC) patients receiving immune checkpoint blockade with atezolizumab plus bevacizumab (Atez/Bev) treatment and explored biomarkers that are predictive of therapeutic response. The results showed that a higher proportion of CD8+ central memory T cells at baseline is associated with tumor inflammation in HCC, as well as with longer progression-free survival in response to Atez/Bev treatment, especially in cases with an increased proportion of CD8+ effector memory T cells after 3 weeks. Our findings suggest that the peripheral T cell subpopulation can serve as a potential noninvasive biomarker predicting benefits from Atez/Bev treatment. The therapeutic benefits of the immunotherapeutic combination of atezolizumab and bevacizumab (Atez/Bev) in hepatocellular carcinoma (HCC) vary. Therapeutic biomarkers might help improve outcomes for HCC patients receiving Atez/Bev therapy. The role of systemic immune profiles in HCC progression also remains unclear. This study aimed to evaluate the status and dynamics of peripheral T cell subpopulations in HCC patients receiving Atez/Bev treatment and to explore biomarkers predictive of a therapeutic response. We enrolled 83 unresectable advanced HCC patients who commenced Atez/Bev treatment at our hospital between October 2020 and June 2022. Peripheral T cell subpopulations in peripheral blood mononuclear cells at baseline and 3 weeks post-treatment were investigated using flow cytometry and compared with those in control samples from 18 healthy individuals. We retrospectively analyzed the association between peripheral T cell subpopulation profiles and clinical outcomes. Baseline peripheral T cell subpopulations could be profiled in 70 patients with sufficient cell counts, among whom 3-week subpopulations could be evaluated in 51 patients. Multivariate analysis showed that a high baseline proportion of CD8+ central memory T (TCM) cells was independently associated with longer progression-free survival (PFS). Further, overall survival (OS) was significantly prolonged in patients with increased CD8+ effector memory T (TEM) cell proportions. In conclusion, TCM proportion at baseline might be a good indicator of the efficacy of Atez/Bev therapy. Furthermore, observation of increasing TEM proportions might be an early predictor of the potential clinical benefits of treatment. [ABSTRACT FROM AUTHOR]

Background & Aims: Tumour microenvironment heterogeneity among different organs can influence immunotherapy responses. Here, we evaluated the impact of differential organ‐specific responses on survival in patients with advanced‐stage hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Atezo/Bev). Methods: We retrospectively analysed 366 consecutive patients with advanced‐stage HCC treated with Atezo/Bev as first‐line systemic treatment. Therapeutic response was assessed using RECIST v1.1. Patients were divided into an intention‐to‐treat (ITT) group (patients treated with ≥1 dose of Atezo/Bev) and a per‐protocol (PP) analysis group (patients with at least one measurable lesion irrespective of location treated with ≥3 doses of Atezo/Bev). Overall response and organ‐specific response at initial and best response were evaluated in the PP group. Responders were defined as patients achieving complete remission or partial response. Initial progressors were defined as patients with progressive disease after three doses of Atezo/Bev. Results: The ITT and PP groups comprised 324 and 236 patients, respectively. In the PP group, the organ‐specific response rate of lung and lymph node (LN) metastases at both initial and best responses were higher than those of intrahepatic lesions and macrovascular tumour thrombosis. Lung and LN‐specific response rates were 21.1% and 23.5%, respectively, at initial response, and 24.7% and 31.4%, respectively, at best response. Both initial pulmonary and lymphatic progressors (adjusted hazard ratios [95% confidence intervals], 6.37 [2.10–19.3], and 8.36 [2.16–32.4], respectively) were independently associated with survival regardless of intrahepatic response. Conclusions: The response of metastatic HCC to the Atezo/Bev regimen may be used to determine whether to continue treatment or switch to second‐line treatment at an early phase of therapy. [ABSTRACT FROM AUTHOR]

Herein, we report the successful treatment using atezolizumab plus bevacizumab of a patient with hepatocellular carcinoma (HCC) with a portal vein tumor thrombus and multiple pulmonary metastases from rectal cancer with microsatellite stability. This patient developed rectal cancer with synchronous pulmonary metastases and HCC. After resecting the primary lesion of the rectal cancer, transcatheter arterial chemoembolization was performed for the HCC. Drug therapy was planned for multiple pulmonary metastases of rectal cancer; however, the early development of recurrent HCC with portal vein tumor thrombus had to be highly prioritized, and atezolizumab plus bevacizumab was introduced. Following the disappearance of the recurrent HCC lesion, the metastatic pulmonary nodules shrunk into scar-like spots. The treatment for both HCC and pulmonary metastases of rectal cancer were considered to result in clinical complete response. [ABSTRACT FROM AUTHOR]

Various locoregional treatments for localized hepatocellular carcinoma (HCC) have been developed. This retrospective study investigated the safety and feasibility of combining on-demand selective locoregional treatment for residual lesions after tumor shrinkage (complete response [CR] oriented) or for solitary or few drug-resistant lesions (progressive disease (PD) salvage) with first-line atezolizumab plus bevacizumab (atezo/bev) for unresectable HCC. Twenty-nine patients with unresectable HCC were included. Fourteen locoregional treatments were performed (CR oriented, 7; PD salvage, 7) in ten patients in the combination-therapy group. All patients in the combination-therapy group successfully achieved a CR or PD salvage status after the planned locoregional treatment. The objective response rate of the combination-therapy group (80.0%) was higher than that of the atezo/bev alone group (21.1%; p = 0.005). Progression-free survival (PFS) and overall survival (OS) were longer in the combination group (medians for PFS and OS not reached) than in the atezo/bev alone group (median PFS, 7.4 months; median OS, 19.8 months) (PFS, p = 0.004; OS, p < 0.001). The albumin–bilirubin score did not change, and no severe complications occurred after locoregional treatment. When performed in a minimally invasive manner, on-demand selective locoregional treatment combined with first-line atezo/bev could be safe and feasible for unresectable HCC.

Atezolizumab plus bevacizumab (AB) and lenvatinib can be alternatively used as first‐line systemic treatment of unresectable hepatocellular carcinoma (HCC). However, no direct comparison of the two regimens has been performed in randomized clinical trials, making the identification of baseline differential predictors of response of major relevance to tailor the best therapeutic option to each patient. Baseline clinical and laboratory characteristics of real‐world AB‐treated HCC patients were analyzed in uni‐ and multivariate analyses to find potential prognostic factors of overall survival (OS). Significant variables were incorporated in a composite score (α‐FAtE) and it was tested for specificity and sensitivity in receiver operating characteristic (ROC) curve and in multivariate analysis for OS. The score was applied in uni‐ and multivariate analyses for OS of a comparable lenvatinib‐treated HCC population. Finally, comparison between treatments was performed in patients with low and high α‐FAtE scores and predictivity estimated by interaction analysis. Time‐to‐progression (TTP) was a secondary endpoint. OS of AB‐treated HCC patients was statistically longer in those with α‐fetoprotein <400 ng/mL (HR 0.62, p =.0407), alkaline phosphatase (ALP) <125 IU/L (HR 0.52, p =.0189) and eosinophil count ≥70/μL (HR 0.46, p =.0013). The α‐FAtE score was generated by the sum of single points attributed to each variable among the above reported. In ROC curve analysis, superior sensitivity and specificity were achieved by the score compared to individual variables (AUC 0.794, p <.02). Patients with high score had longer OS (HR 0.44, p =.0009) and TTP (HR 0.34, p <.0001) compared to low score if treated with AB, but not with lenvatinib. Overall, AB was superior to lenvatinib in high score patients (HR 0.55, p =.0043) and inferior in low score ones (HR 1.75, p =.0227). At interaction test, low α‐FAtE score resulted as negative predictive factor of response to AB (p =.0004). In conclusion, α‐FAtE is a novel prognostic and predictive score of response to first‐line AB for HCC patients that, if validated in prospective studies, could drive therapeutic choice between lenvatinib and AB. [ABSTRACT FROM AUTHOR]

Background: Atezolizumab+bevacizumab (AB) and lenvatinib have been proposed as first-line treatment options for patients with advanced hepatocellular carcinoma (HCC), but comparative efficacy and associated factors are controversial. Materials and methods: This real-world multicenter study analysed patients with HCC who received AB (n=169) or lenvatinib (n=177). Results: First, 1:1 propensity score matching (PSM) was performed, resulting in 141 patients in both the AB and lenvatinib groups. After PSM, overall survival (OS) was better in the AB group than in the lenvatinib group [hazard ratio (HR)=0.642, P=0.009], but progression-free survival (PFS) did not vary between the two groups (HR=0.817, P=0.132). Objective response rate (ORR) was also similar between AB and lenvatinib (34.8% vs. 30.8%, P=0.581). In a subgroup of patients with objective responses (OR, n=78), OS (HR=0.364, P=0.012) and PFS (HR=0.536, P=0.019) were better in the AB group (n=41) than in the lenvatinib group (n=37). Time-to-progression from time of OR was also better in the AB group (HR=0.465, P=0.012). Importantly, residual liver function was a significant factor related to OS in both treatments. Child-Pugh score following cessation of the respective treatments was better in the AB group (n=105) than in the lenvatinib group (n=126) (median 6 versus 7, P=0.008), and proportion of salvage treatment was also higher in the AB group (52.4% versus 38.9%, P=0.047). When we adjusted for residual liver function or salvage treatment, there was no difference in OS between the two treatments. Conclusion: Our study suggests that residual liver function and subsequent salvage treatments are major determinants of clinical outcomes in patients treated with AB and lenvatinib; these factors should be considered in future comparative studies. [ABSTRACT FROM AUTHOR]

Introduction: Systemic therapy is recommended for patients with Child-Pugh A in hepatocellular carcinoma (HCC). We analyzed the outcomes of a cohort of patients with HCC who received either sorafenib (Sor), lenvatinib (Len) or atezolizumab plus bevacizumab (Atezo + Bev) as first-line systemic therapy for HCC, with the aim of identifying prognostic factors for survival. Methods: A total of 825 patients with advanced HCC and Child-Pugh A or B received either Sor, Len or Atezo + Bev as first-line systemic therapy. Liver function was assessed according to the Child-Pugh score and the modified albumin-bilirubin (mALBI) grade. Results: Prognosis was analyzed according to liver function such as Child-Pugh classifications, scores, and mALBI grades that worsened with a decline in liver function (p <0.001 for all). A Child-Pugh score of 7 was a factor significantly associated with OS. In patients with a Child-Pugh score of 7, an mALBI grade of 3 was an independent predictor of OS. In Child-Pugh B patients with HCC, receiving Atezo + Bev was identified as a factor associated with PFS. Conclusion: Determining the hepatic reserve of patients with unresectable HCC might be useful for identifying patents suitable for systemic treatment for HCC. Atezo + Bev might prolong the PFS of patients with a Child-Pugh score of 7. [ABSTRACT FROM AUTHOR]

Aim: Pretreatment peripheral blood markers have value in predicting the treatment outcome of various cancers. In particular, the eosinophil count has recently gained attention. However, no study has reported the influence of the pretreatment eosinophil count on the outcomes of atezolizumab plus bevacizumab (ATZ/BEV), which is the recommended first‐line systemic therapy for unresectable hepatocellular carcinoma (u‐HCC). Methods: We enrolled 114 patients with u‐HCC treated with ATZ/BEV (n = 48) or lenvatinib (n = 66). The patients receiving ATZ/BEV or lenvatinib were divided into two groups by calculating the cutoff value of the pretreatment eosinophil count. The groups were compared regarding the clinicopathological characteristics, outcomes, and incidence of adverse events (AEs). Results: Twenty‐three of 48 patients (47.9%) who received ATZ/BEV therapy were categorized as the ATZ/BEV‐eosinophil‐high group, which had better responses than the ATZ/BEV‐eosinophil‐low group (P = 0.0090). Kaplan–Meier curves revealed a trend toward significantly better progression‐free survival (PFS) in the ATZ/BEV‐eosinophil‐high group than the ATZ/BEV‐eosinophil‐low group (the median PFS: 4.7 months in the ATZ/BEV‐eosinophil‐low group vs 12.6 months in the ATZ/BEV‐eosinophil‐high group; P = 0.0064). Multivariate analysis showed that a low eosinophil count was an independent risk factor for worse PFS after ATZ/BEV therapy (P = 0.0424, hazard ratio: 2.24, 95% confidence interval: 1.02–4.89). AEs (≥ grade 3) were significantly more likely to occur in the ATZ/BEV‐eosinophil‐high group (P = 0.0285). The outcomes did not significantly differ between the LEN‐eosinophil‐high group and the LEN‐eosinophil‐low group. Conclusion: A high pretreatment eosinophil count predicted a better response to ATZ/BEV therapy for u‐HCC and was associated with the incidence of AEs (≥ grade 3). [ABSTRACT FROM AUTHOR]

Various locoregional treatments for localized hepatocellular carcinoma (HCC) have been developed. This retrospective study investigated the safety and feasibility of combining on-demand selective locoregional treatment for residual lesions after tumor shrinkage (complete response [CR] oriented) or for solitary or few drug-resistant lesions (progressive disease (PD) salvage) with first-line atezolizumab plus bevacizumab (atezo/bev) for unresectable HCC. Twenty-nine patients with unresectable HCC were included. Fourteen locoregional treatments were performed (CR oriented, 7; PD salvage, 7) in ten patients in the combination-therapy group. All patients in the combination-therapy group successfully achieved a CR or PD salvage status after the planned locoregional treatment. The objective response rate of the combination-therapy group (80.0%) was higher than that of the atezo/bev alone group (21.1%; p = 0.005). Progression-free survival (PFS) and overall survival (OS) were longer in the combination group (medians for PFS and OS not reached) than in the atezo/bev alone group (median PFS, 7.4 months; median OS, 19.8 months) (PFS, p = 0.004; OS, p < 0.001). The albumin–bilirubin score did not change, and no severe complications occurred after locoregional treatment. When performed in a minimally invasive manner, on-demand selective locoregional treatment combined with first-line atezo/bev could be safe and feasible for unresectable HCC. [ABSTRACT FROM AUTHOR]

Immune-related liver injury (irLI) is commonly observed in patients with cancer treated with immune checkpoint inhibitors (ICIs). We aimed to compare the incidence, clinical characteristics, and outcomes of irLI between patients receiving ICIs for hepatocellular carcinoma (HCC) vs. other solid tumours. Two separate cohorts were included: 375 patients with advanced/unresectable HCC, Child-Pugh A class treated with first-line atezolizumab+bevacizumab from the AB-real study, and a non-HCC cohort including 459 patients treated with first-line ICI therapy from the INVIDIa-2 multicentre study. IrLI was defined as a treatment-related increase of aminotransferase levels after exclusion of alternative aetiologies of liver injury. The incidence of irLI was adjusted for the duration of treatment exposure. In patients with HCC, the incidence of any grade irLI was 11.4% over a median treatment exposure of 4.4 months (95% CI 3.7-5.2) vs. 2.6% in the INVIDIa-2 cohort over a median treatment exposure of 12.4 months (95% CI 11.1-14.0). Exposure-adjusted-incidence of any grade irLI was 22.1 per 100-patient-years in patients with HCC and 2.1 per 100-patient-years in patients with other solid tumours (p <0.001), with median time-to-irLI of 1.4 and 4.7 months, respectively. Among patients who developed irLI, systemic corticosteroids were administered in 16.3% of patients with HCC and 75.0% of those without HCC (p < 0.001), and irLI resolution was observed in 72.1% and 58.3%, respectively (p = 0.362). In patients with HCC, rates of hepatic decompensation and treatment discontinuation due to irLI were 7%. Grade 1-2 irLI was associated with improved overall survival only in patients with HCC (hazard ratio 0.53, 95% CI 0.29-0.96). Despite higher incidence and earlier onset, irLI in patients with HCC is characterised by higher rates of remission and lower requirement for corticosteroid therapy (vs. irLI in other solid tumours), low risk of hepatic decompensation and treatment discontinuation, not negatively affecting oncological outcomes. Immune-related liver injury (irLI) is common in patients with cancer receiving immune checkpoint inhibitors (ICIs), but whether irLI is more frequent or it is associated with a worse clinical course in patients with hepatocellular carcinoma (HCC), compared to other tumours, is not known. Herein, we compared characteristics and outcomes of irLI in two prospective cohorts including patients treated with ICIs for HCC or for other oncological indications. irLI is significantly more common and it occurs earlier in patients with HCC, also after adjustment for duration of treatment exposure. However, outcomes of patients with HCC who developed irLI are not negatively affected in terms of requirement for corticosteroid therapy, hepatic decompensation, treatment discontinuation and overall survival. [Display omitted] • Liver injury related to immune checkpoint inhibitors (irLI) is significantly more common in patients with HCC than other malignancies. • IrLI does not negatively affect outcomes of patients with HCC in terms of treatment discontinuation and hepatic decompensation. • Patients with HCC experiencing grade 1-2 irLI exhibit significantly better overall survival and objective response rates. [ABSTRACT FROM AUTHOR]

Aim: Atezolizumab plus bevacizumab combination therapy (Atezo + Beva) is used as the first‐line therapy for unresectable hepatocellular carcinoma (u‐HCC). Serious adverse events (AEs), including rupture of esophagogastric varices, have been seen during treatment. Therefore, the relationships of efficacy, safety, and portal hypertension (PH) were analyzed. Methods: A total of 146 patients with u‐HCC and Child‐Pugh Scores of 5–7 received Atezo + Beva. Prophylactic treatment for varices was performed for patients with the risk of rupture of varices before the start of Atezo + Beva. A propensity score‐matched cohort was created to minimize the risk of potential confounders. Efficacy was assessed in 41 propensity score‐matched pairs. AEs were assessed between patients without PH (n = 80) and with PH (n = 66). Results: In patients without PH and with PH, median overall survival was 18.4 months and 18.8 months (p = 0.71), and median progression‐free survival was 8.6 months and 5.8 months (p = 0.92), respectively. On the best radiological response evaluation for Response Evaluation Criteria in Solid Tumors, the objective response rate was 31.7% and 26.8% (p = 0.81), respectively. Variceal rupture occurred in three patients with PH, but there were no significant differences in the occurrence of variceal rupture (p = 0.090) and Grade 3–4 AEs between patients without and with PH. Conclusions: No significant differences in efficacy and safety were observed with PH. Prophylactic treatment for varices before the start of Atezo + Beva would allow treatment to continue relatively safely. [ABSTRACT FROM AUTHOR]

Background & Aims: The study goal was to compare the outcomes of patients with intermediate‐stage (Barcelona Clinic Liver Cancer [BCLC]‐B) hepatocellular carcinoma (HCC) who received atezolizumab plus bevacizumab (Atezo/Bev) or lenvatinib (LEN) as first‐line systemic therapy. Methods: A total of 358 patients with BCLC‐B HCC treated with Atezo/Bev (n = 177) or LEN (n = 181) as first‐line systemic therapy were included. Results: The median progression‐free survival (PFS) times in the Atezo/Bev and LEN groups were 10.8 months (95% confidence interval [CI], 7.8–12.6) and 7.3 months (95% CI, 6.3–8.5), respectively (p =.019). In the propensity score‐matched cohort, the median PFS times in the Atezo/Bev (n = 151) and LEN (n = 151) groups were 10.2 months (95% CI, 7.0–12.3) and 6.9 months (95% CI, 5.9–8.1), respectively (p =.020). Restricted mean survival times of PFS were significantly higher in the Atezo/Bev group than in the LEN group at landmarks of 12 and 18 months (p =.031 and.012, respectively). In a subgroup analysis of patients with HCC beyond the up‐to‐seven criteria, the median PFS times in the Atezo/Bev (n = 134) and LEN (n = 117) groups were 10.5 months (95% CI, 7.0–11.8) and 6.3 months (95% CI, 5.5–7.3), respectively (p =.044). Conclusions: The use of Atezo/Bev as first‐line systemic therapy in patients with BCLC‐B HCC is expected to result in good PFS. [ABSTRACT FROM AUTHOR]

Background/Aim: Atezolizumab in combination with bevacizumab is an approved systemic chemotherapy regimen for advanced hepatocellular carcinoma (HCC). However, immune checkpoint inhibitors (ICIs), such as atezolizumab, frequently lead to immune-related adverse events (irAEs). The identification of biomarkers that can predict the occurrence of irAEs is crucial for the optimal management of patients undergoing ICI treatment. Patients and Methods: Between October 2020 and June 2023, we conducted a study involving 69 patients with advanced HCC who received treatment with atezolizumab plus bevacizumab. We conducted an analysis of blood-based biomarkers to identify independent risk factors associated with irAEs. Results: In our study, 12 out of 69 patients (17.4%) experienced irAEs. Our investigation into blood-based biomarkers revealed that a neutrophil--tolymphocyte ratio (NLR) <2.04 at three weeks after the initiation of treatment had high predictive power (area under the curve: 0.77) for irAEs. Furthermore, multivariate logistic analysis identified NLR at three weeks (hazard ratio=0.23; p=0.037) and non-viral infection (hazard ratio=4.47; p=0.037) as independent factors contributing to the occurrence of irAEs. Patients who developed irAEs demonstrated a more favorable overall response rate (75.0% vs. 28.1%, p=0.005), disease control rate (91.6% vs. 52.6%, p=0.016), and progression-free survival (12.1 months vs. 6.0 months, p=0.010) than those who did not experience irAEs. Conclusion: An NLR <2.04 at three weeks after the initiation of treatment may serve as a valuable biomarker for predicting irAEs in patients with HCC undergoing atezolizumab plus bevacizumab therapy. [ABSTRACT FROM AUTHOR]

Abstract Aims The aim of the present study was to elucidate detailed parameters for prediction of prognosis for patients with unresectable hepatocellular carcinoma (uHCC) receiving atezolizumab plus bevacizumab (Atez/Bev) treatment. Methods A total of 719 patients (males 577, median age 74 years) treated with Atez/Bev between September 2020 and January 2023 were enrolled. Factors related to overall survival (OS) were extracted and a prognostic scoring system based on hazard ratio (HR) was created. OS and progression‐free survival (PFS) were retrospectively examined, and the prognostic ability of the newly developed system was compared to CRAFITY score using concordance index (c‐index) and Akaike information criterion (AIC) results. Results Cox‐hazards multivariate analysis showed BCLC classification C/D (HR 1.4; 1 point), AFP ≥100 ng/mL (HR 1.4; 1 point), mALBI 2a (HR 1.7; 1 point), mALBI 2b/3 (HR 2.8; 2 points), and DCP ≥100 mAU/mL (HR 1.6; 1 point) as significant factors. The assigned points were added and used to develop the IMmunotherapy with AFP, BCLC staging, mALBI, and DCP evaluation (IMABALI‐De) scoring system. For IMABALI‐De scores of 0, 1, 2, 3, 4, and 5, OS was not applicable (NA), NA, 26.11, 18.79, 14.07, and 8.32 months, respectively (p

Abstract Aim This retrospective study compared the impact of atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib (LEN) on the liver function in patients with hepatocellular carcinoma. Methods We included 526 patients who received Atez/Bev and 731 who received LEN March 2018 and July 2022 in this study. We conducted a 1:1 propensity‐score‐matched analysis and identified 324 patients in each group for inclusion in the present analysis. Nonlinear mixed‐effects regression models were employed, allowing for the evaluation and inclusion of cases where treatment was interrupted due to disease progression, adverse events, or loss to follow‐up. These models were used to compare the ALBI score between the Atez/Bev and LEN groups. Results Following propensity score matching, the mean ALBI scores in the Atez/Bev and LEN groups were −2.41 ± 0.40 and −2.44 ± 0.42 at baseline, and −2.17 ± 0.56 and −2.19 ± 0.58 at 12 weeks, respectively. Although the ALBI score significantly worsened during treatment in both groups (p

Aim: This retrospective study compared the impact of atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib (LEN) on the liver function in patients with hepatocellular carcinoma. Methods: We included 526 patients who received Atez/Bev and 731 who received LEN March 2018 and July 2022 in this study. We conducted a 1:1 propensity‐score‐matched analysis and identified 324 patients in each group for inclusion in the present analysis. Nonlinear mixed‐effects regression models were employed, allowing for the evaluation and inclusion of cases where treatment was interrupted due to disease progression, adverse events, or loss to follow‐up. These models were used to compare the ALBI score between the Atez/Bev and LEN groups. Results: Following propensity score matching, the mean ALBI scores in the Atez/Bev and LEN groups were −2.41 ± 0.40 and −2.44 ± 0.42 at baseline, and −2.17 ± 0.56 and −2.19 ± 0.58 at 12 weeks, respectively. Although the ALBI score significantly worsened during treatment in both groups (p < 0.001), there was no significant difference in the rate of ALBI score deterioration between the groups (p = 0.06). Subgroup analyses showed that LEN‐treated patients with BCLC advanced stage (p = 0.02) and those who initially received the full dose (p < 0.001) had a significantly greater worsening of ALBI score compared to Atez/Bev. Conclusions: Using a nonlinear mixed‐effects regression approach, which allowed for the inclusion of cases with treatment interruption, we found no significant difference in the trend of liver function deterioration between the Atez/Bev and LEN groups. Caution should be exercised for LEN‐treated patients with BCLC advanced stage or those receiving the full dose of LEN. [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate the cost-effectiveness of atezolizumab plus bevacizumab (atezo-bev) versus sorafenib treatment in Taiwan. Methods: Using sorafenib as the comparator, we developed a partitioned survival model to evaluate the costs and quality-adjusted life year (QALY) of the atezo- bev treatment. The time horizon of the study was 15 years, and the annual discount rate was 3%. We analyzed the incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (INMB) from the treatment effects (determined from the progression-free and overall survival outcomes of the IMbrave150 study), direct medical costs (collected and estimated from the National Health Insurance Research Database, Taiwan), and utility parameters (referred to the NICE technology appraisal guidance), as well as the deterministic sensitivity and probabilistic sensitivity. Results: Compared with sorafenib, the incremental effectiveness of atezo-bev treatment was 1.7 QALY, with an incremental cost of USD 127,607. The ICER was USD 75,192 per QALY, which was less than the predefined willingness to pay in Taiwan. Conclusion: The combined treatment of atezo-bev is cost-effective when compared with sorafenib, which is currently the first-line treatment option for unresectable HCC in Taiwan. [ABSTRACT FROM AUTHOR]

Background: Bevacizumab inhibits vascular endothelial growth factor-A (VEGF-A), though is known to increase bleeding risk as an adverse event (AE). This study examined whether atezolizumab/bevacizumab (Atez/Bev) for unresectable hepatocellular carcinoma (uHCC) can be used for patients with esophageal–gastric varices (EGV). Methods: From October 2020 to December 2022, 506 uHCC patients (median 74 years) underwent an upper gastrointestinal endoscopy examination were enrolled, after exclusion of those with portal vein tumor thrombus (PVTT). Patients with EGV (≧ F1) were defined as EGV positive, and the cohort was divided into non-EGV (n = 355) and EGV (n = 151). Before introducing Atez/Bev, endoscopic treatment was performed, when necessary. Prognosis was evaluated, retrospectively. Results: The EGV group had significantly worse hepatic function, lower platelet count, elevated alpha-fetoprotein, and lower rate of extrahepatic metastasis, and lower rate of first-line use (each P < 0.05) than the other. However, progression-free survival (PFS) was also not a significantly difference between the EGV and non-EGV groups in analyses with (PFS rate at 6/12/18 months: 60%/38%/30% vs. 65%/46%/34%, P = 0.29) or without inverse probability weighting adjustment [median: 10.6 months (95% CI 8.3–14.0) vs. 10.5 months (95% CI 7.8–13.7), P = 0.79]. As for AEs, diarrhea was more frequent in the EGV group (≧ G3: 2.0% vs. 0.3%, P = 0.036), while no significant difference was noted for EGV hemorrhage (≧ G3: 1.3% vs. 0.6%, P = 0.345). Of 28 patients who underwent endoscopic treatments before introducing Atez/Bev, none showed EGV-associated hemorrhage. Conclusions: Atez/Bev might be an effective therapeutic option in patients with EGV, when appropriate endoscopic treatment for EGV is performed. [ABSTRACT FROM AUTHOR]

This text provides an overview of the current therapeutic strategies for hepatocellular carcinoma (HCC) in Japan. The 5-year survival rate for HCC patients has significantly improved over the past 40 years, thanks to advancements in diagnostic techniques and the development of new therapies. The approval of therapeutic agents such as sorafenib, regorafenib, lenvatinib, ramucirumab, and cabozantinib has also contributed to this improvement. The article discusses different treatment strategies for HCC, including the use of molecular-targeted agents after transarterial chemoembolization (TACE) failure and the concept of "TACE unsuitability." Sequential therapies and combination treatments have shown promising results, and ongoing clinical trials are evaluating the combination of TACE with immunotherapy. The article emphasizes the importance of ongoing research in improving treatment outcomes for HCC patients at all stages. [Extracted from the article]

Introduction: Lack of an established methodology for post-progression systemic treatment following atezolizumab plus bevacizumab (Atez/Bev) administration is an important clinical issue. The present study aimed to elucidate the potential of lenvatinib as a second-line treatment option after Atez/Bev failure. Methods: From 2020 to 2022, 101 patients who received lenvatinib as second-line treatment were enrolled (median 72 years, males 77, Child-Pugh A 82, BCLC-A:B:C:D = 1:35:61:4), while 29 treated with another molecular targeting agent (MTA) during the period as second-line treatment were enrolled as controls. The therapeutic efficacy of lenvatinib given as second-line treatment was retrospectively evaluated. Results: Median progression-free survival/median overall survival for all patients was 4.4/15.7 months and for those with Child-Pugh A was 4.7 months/not-reached. When prognosis was compared with patients who received another MTA, there was no significant difference for PFS (3.5 months, p = 0.557) or OS (13.6 months, p = 0.992), and also no significant differences regarding clinical background factors. mRECIST findings showed that objective response and disease control rates in patients treated with lenvatinib were 23.9% and 70.4%, respectively (CR:PR:SD:PD = 3:14:33:21), while those shown by RECIST, ver. 1.1, were 15.4% and 66.2%, respectively (CR:PR:SD:PD = 1:10:36:24). Adverse events (any grade ≥10%) were appetite loss (26.7%) (grade 1:2:3 = 2:15:10), general fatigue (21.8%) (grade 1:2:3 = 3:13:6), protein in urine (16.8%) (grade 1:2:3 = 0:4:13), and hypertension (13.9%) (grade 1:2:3 = 1:8:5). Conclusion: Although lenvatinib treatment might not provide a pseudo-combination immunotherapy effect following Atez/Bev failure, lenvatinib when used as second-line treatment after Atez/Bev failure might be expected to be comparable as compared to its use as first-line treatment. [ABSTRACT FROM AUTHOR]

Aim: The present study focused on Geriatric Nutritional Risk Index (GNRI), which is based on bodyweight and serum albumin, and known as an easy‐to‐use nutritional assessment tool in clinical settings, to elucidate the prognostic predictive ability of GNRI in patients treated with atezolizumab plus bevacizumab (Atez/Bev) for hepatocellular carcinoma (HCC). Methods: A total of 525 HCC patients treated with Atez/Bev, based on their classification of unsuitable status for curative treatments and/or transarterial catheter chemoembolization, were enrolled (Child–Pugh A:B:C = 484:40:1, Barcelona Clinic Liver Cancer stage 0:A:B:C:D = 7:25:192:283:18). Prognosis was evaluated retrospectively using GNRI. Results: Atez/Bev was used in 338 of the present cohort as first‐line systemic chemotherapy (64.4%). Median progression‐free survival based on GNRI indicating normal, mild decline, moderate decline, and severe decline was 8.3, 6.7, 5.3, and 2.4 months, respectively, whereas median overall survival was 21.4, 17.0, 11.5. and 7.3 months, respectively (both p < 0.001). The concordance index (c‐index) values of GNRI for predicting prognosis (progression‐free survival/overall survival) were superior to those of Child–Pugh class and albumin‐bilirubin grade (0.574/0.632 vs. 0.527/0.570 vs. 0.565/0.629). As a subanalysis, muscle volume loss was observed in 37.5% of 256 patients with computed tomography data available. Along with GNRI decline, frequency of muscle volume loss became progressively larger (normal vs. mild vs. moderate vs. severe = 17.6% vs. 29.2% vs. 41.2% vs. 57.9%, p < 0.001), and a GNRI value of 97.8 was predictive of its occurrence (AUC 0.715, 95% CI 0.649–0.781; specificity/sensitivity = 0.644/0.688). Conclusion: These findings indicate that GNRI is an effective nutritional prognostic tool for predicting prognosis and muscle volume loss complication in HCC patients treated with Atez/Bev. [ABSTRACT FROM AUTHOR]

Abstract Aim Atezolizumab plus bevacizumab combination therapy (Atezo + Beva) is used as the first‐line therapy for unresectable hepatocellular carcinoma (u‐HCC). Serious adverse events (AEs), including rupture of esophagogastric varices, have been seen during treatment. Therefore, the relationships of efficacy, safety, and portal hypertension (PH) were analyzed. Methods A total of 146 patients with u‐HCC and Child‐Pugh Scores of 5–7 received Atezo + Beva. Prophylactic treatment for varices was performed for patients with the risk of rupture of varices before the start of Atezo + Beva. A propensity score‐matched cohort was created to minimize the risk of potential confounders. Efficacy was assessed in 41 propensity score‐matched pairs. AEs were assessed between patients without PH (n = 80) and with PH (n = 66). Results In patients without PH and with PH, median overall survival was 18.4 months and 18.8 months (p = 0.71), and median progression‐free survival was 8.6 months and 5.8 months (p = 0.92), respectively. On the best radiological response evaluation for Response Evaluation Criteria in Solid Tumors, the objective response rate was 31.7% and 26.8% (p = 0.81), respectively. Variceal rupture occurred in three patients with PH, but there were no significant differences in the occurrence of variceal rupture (p = 0.090) and Grade 3–4 AEs between patients without and with PH. Conclusions No significant differences in efficacy and safety were observed with PH. Prophylactic treatment for varices before the start of Atezo + Beva would allow treatment to continue relatively safely.

BackgroundAtezolizumab+bevacizumab (AB) and lenvatinib have been proposed as first-line treatment options for patients with advanced hepatocellular carcinoma (HCC), but comparative efficacy and associated factors are controversial.Materials and methodsThis real-world multicenter study analysed patients with HCC who received AB (n=169) or lenvatinib (n=177).ResultsFirst, 1:1 propensity score matching (PSM) was performed, resulting in 141 patients in both the AB and lenvatinib groups. After PSM, overall survival (OS) was better in the AB group than in the lenvatinib group [hazard ratio (HR)=0.642, P=0.009], but progression-free survival (PFS) did not vary between the two groups (HR=0.817, P=0.132). Objective response rate (ORR) was also similar between AB and lenvatinib (34.8% vs. 30.8%, P=0.581). In a subgroup of patients with objective responses (OR, n=78), OS (HR=0.364, P=0.012) and PFS (HR=0.536, P=0.019) were better in the AB group (n=41) than in the lenvatinib group (n=37). Time-to-progression from time of OR was also better in the AB group (HR=0.465, P=0.012). Importantly, residual liver function was a significant factor related to OS in both treatments. Child-Pugh score following cessation of the respective treatments was better in the AB group (n=105) than in the lenvatinib group (n=126) (median 6 versus 7, P=0.008), and proportion of salvage treatment was also higher in the AB group (52.4% versus 38.9%, P=0.047). When we adjusted for residual liver function or salvage treatment, there was no difference in OS between the two treatments.ConclusionOur study suggests that residual liver function and subsequent salvage treatments are major determinants of clinical outcomes in patients treated with AB and lenvatinib; these factors should be considered in future comparative studies.

Chenghao Zhao,&ast; Zhanwang Xiang,&ast; Mingan Li, Haofan Wang, Huan Liu, Huzheng Yan, Mingsheng Huang Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingsheng Huang; Huzheng Yan, Tel/Fax +86-20-85253416, Email huangmsh@mail.sysu.edu.cn; yanhzh8@mail.sysu.edu.cnPurpose: Combined transarterial chemoembolization (TACE) and Lenvatinib (LEN) treatment (LEN-TACE) has been shown to be beneficial. We aimed to evaluate retrospectively Atezolizumab plus Bevacizumab (Atezo/Bev)-TACE compared with LEN-TACE as a first-line therapy for unresectable HCC.Patients and Methods: From October 2020 to October 2022, data from 98 consecutive HCC patients were analyzed. After propensity score matching, two cohorts of 34 patients who received either Atezo/Bev-TACE or LEN-TACE were studied. We compared overall survival (OS), progression-free survival (PFS), duration of response, objective response rate (ORR) and disease control rate (DCR) based on RECIST 1.1 and mRECIST, as well as safety outcome between the two cohorts.Results: The 6-month and 12-month OS rates were 85.3% (95% CI 73.5– 97.0) and 75.4% (95% CI 53.6– 85.7) in the Atezo/Bev-TACE group, and 88.2% (95% CI 76.5– 97.1) and 79.2% (95% CI 63.6– 90.9) in the LEN-TACE group, respectively. The hazard ratio for death in the Atezo/Bev-TACE group compared to the LEN-TACE group was 1.09 (95% CI 0.47– 2.51; P = 0.837). The median PFS was 7.03 months (95% CI 3.89– 10.17) in the Atezo/Bev-TACE group and 6.03 months (95% CI 0– 14.14) in the LEN-TACE group (HR 1.21; 95% CI 0.66– 2.21; P = 0.545). No significant difference in ORR and DCR between the two groups was observed either according to RECIST 1.1 or mRECIST standards. Incidence rates of hand-foot skin reaction (35.3% vs 5.9%, P = 0.003) and proteinuria (17.9% vs 2.9%, P = 0.046) were significantly higher in the LEN-TACE group.Conclusion: Atezo/Bev-TACE and LEN-TACE showed comparable efficacy and safety as first-line therapies for unresectable HCC patients.Keywords: atezolizumab plus bevacizumab, lenvatinib, transarterial chemoembolization, hepatocellular carcinoma, efficacy

Background: This study aimed to examine whether the coefficient of variation (CV) in the hepatobiliary-phase (HBP) of Gd-EOB-DTPA-MRI could be an independent predictive factor for tumor progression. Methods: Patients who underwent Gd-EOB-DTPA-MRI before Atezolizumab/bevacizumab therapy at six affiliated institutions between 2018 and 2022 were included. CV for each patient was calculated as the mean value for up to five tumors larger than 10 mm, and CV of the whole tumor was calculated using LIFEx software. The tumor response was evaluated within 6–10 weeks. The primary endpoint was to investigate the predictive factors, including CV, related to tumor progression using logistic regression analysis. The secondary endpoints were tumor response rate and progression-free survival (PFS) based on CV. Results: Of the 46 enrolled patients, 13 (28.3%) underwent early progressive disease. Multivariate analysis revealed that a high CV (≥0.22) was an independent predictive factor for tumor progression (p = 0.043). Patients with a high CV had significantly frequent PD than those with a low CV (43.5 vs. 13.0%, p = 0.047). Patients with a high CV tended to have shorter PFS than those with a low CV (3.5 vs. 6.7 months, p = 0.071). Conclusion: Quantitative analysis using CV in the HBP of Gd-EOB-DTPA-MRI may be useful for predicting tumor progression for atezolizumab/bevacizumab therapy.

Abstract Background and Aims We aimed to validate the predictive factors for tumor response and the prognostic impact of conversion therapy aimed at cancer‐ and drug‐free states in patients with unresectable hepatocellular carcinoma (u‐HCC) undergoing atezolizumab plus bevacizumab (Atez/Bev) therapy. Methods This retrospective study enrolled 156 patients who were Child‐Pugh class A with u‐HCC treated using Atez/Beva. The profile of objective response was investigated using decision‐tree analysis. Progression‐free, recurrence‐free, and overall survival were assessed. Results The progression‐free and overall survival were 6.1 and 18.0 months, respectively. Objective response and disease control rates were 32.0% and 84.0%, respectively. Decision‐tree analysis revealed that neutrophil‐to‐lymphocyte ratio (NLR)

Abstract Background Treatment of hepatocellular carcinoma (HCC) varies widely depending on the patient's condition. In recent years, combination therapy with immune checkpoint inhibitors has emerged as the treatment of choice due to its superior antitumor effects for unresectable HCC (uHCC). Conversion surgery (CS) after systemic chemotherapy is expected to be an effective treatment strategy for uHCC. Here, we report two cases of uHCC with bilateral porta hepatis invasion, in which atezolizumab plus bevacizumab therapy regressed the tumor invasion of the porta hepatis, followed by CS with R0 resection. Case presentation The first patient—a 71-year-old man with S4 HCC—developed porta hepatis, and the tumor compressed the right portal vein and bile duct. R0 resection with left trihepatectomy was impossible because of insufficient liver function, and combination therapy using atezolizumab and bevacizumab was initiated. After ten courses of treatment, the tumor shrunk with regression of the porta hepatis contact, and segmentectomy of S4 was performed with a sufficient surgical margin. Histopathological findings showed that the primary tumor was mostly necrotic with no residual viable tumor cells. The second patient was a 72-year-old man with an S4 HCC extending to the porta hepatis. The patient’s condition was almost similar to that in the first case and required left tri-segmentectomy with R0 resection; however, insufficient liver function made liver resection impossible. An atezolizumab plus bevacizumab regimen was administered, and after seven courses of treatment, porta hepatis compression regressed, following which left lobectomy was performed with adequate surgical margins. The pathological diagnosis was moderately differentiated HCC, most of which was necrotic, and R0 resection was confirmed. Conclusions Atezolizumab plus bevacizumab therapy has the potential to facilitate radical resection in patients with uHCC.

Abstract Aim To investigate the possible correlation between the development of adverse events (AEs) and prognosis in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Atez/Bev). Methods A total of 286 patients with unresectable HCC treated with Atez/Bev as first‐line systematic therapy were included. Results Regarding treatment‐related AEs, decreased appetite of any grade, proteinuria of any grade, and fatigue of any grade were found with a frequency of ≥20%. Multivariate analysis adjusted for immune‐related liver injury, immune‐related endocrine dysfunction, proteinuria, fatigue, decreased appetite, hypertension, sex, age, Eastern Cooperative Oncology Group performance status, HCC etiology, HCC stage, Child–Pugh score, and α‐fetoprotein showed that hypertension of any grade (hazard ratio [HR], 0.527; 95% confidence interval [CI], 0.326–0.854; p = 0.009) and α‐fetoprotein ≥100 ng/ml (HR, 1.642; 95% CI, 1.111–2.427; p = 0.013) were independently associated with progression‐free survival. Multivariate analysis adjusted for the same AEs showed that fatigue (HR, 2.354; 95% CI, 1.299–4.510; p = 0.010) was independently associated with overall survival. Median progression‐free survival was 6.5 months (95% CI, 5.2–8.1) in patients without hypertension of any grade and 12.6 months (95% CI, 6.7–not available) in patients with hypertension of any grade (p = 0.035). The overall survival was significantly shorter in patients in whom treatment‐related fatigue of any grade was observed (p

Introduction: Systemic treatment is generally recommended for Child-Pugh (CP) A status patients with an unresectable hepatocellular carcinoma (uHCC). This study aimed to elucidate differences regarding therapeutic efficacy between lenvatinib (LEN), a multi-molecular target agent, and atezolizumab plus bevacizumab (Atez/Bev), a newly developed immune-combined therapeutic regimen for CP-B patients affected by uHCC. Methods: From April 2018 to July 2022, 128 patients with uHCC treated with Atez/Bev (n = 29) or LEN (n = 99) as the initial systemic treatment were enrolled (median age 71 years; males 97; CP score 7:8:9 = 94:28:6; median albumin-bilirubin score −1.71). Therapeutic response was evaluated using RECIST, version 1.1. Clinical features and prognosis were retrospectively examined. Results: There were no significant differences between the Atez/Bev and LEN groups in regard to best response (CR:PR:SD:PD = 0:5:12:7 vs. 5:22:25:20, p = 0.415), progression-free survival (PFS) (median 5.0 [95% CI: 2.4–7] vs. 5.5 [95% CI: 3.4–7.9] months, p = 0.332), or overall survival (OS) (5.8 [95% CI: 4.3–11] vs. 8.8 [95% CI: 6.1–12.9] months, p = 0.178). Adverse events (any grade/≥ grade 3) were observed in 72.4%/17.2% (n = 21/5) of patients treated with Atez/Bev and 78.8%/25.3% (n = 78/25) of those treated with LEN (p = 0.46/0.46). Discussion: This retrospective study found no significant differences regarding PFS or OS between CP-B patients given Atez/Bev or LEN as initial systemic treatment for uHCC. [ABSTRACT FROM AUTHOR]

Simple Summary: Atezolizumab plus bevacizumab (Atez/Bev) is the first-line treatment for unresectable advanced hepatocellular carcinoma (HCC). The tumor markers (TMs) for HCC include alpha-fetoprotein (AFP), fucosylated alpha-fetoprotein (AFP-L3), and des-gamma carboxyprothrombin (DCP). A TM score combining these markers has been reported to be useful in predicting HCC prognosis. This retrospective study aimed to evaluate the ability of this previously reported TM score involving AFP, AFP-L3, and DCP as TMs in predicting prognosis and therapeutic efficacy in HCC patients administered Atez/Bev as first-line treatment. The TM score was found to be effective in stratifying overall survival and progression-free survival in 371 patients with unresectable advanced HCC treated with Atez/Bev. The TM score proved to be a simple and useful prognostic marker and therapeutic efficacy indicator for advanced HCC patients administered Atez/Bev as first-line treatment. Aim: This study aimed to evaluate the ability of a previously reported tumor marker (TM) score involving alpha-fetoprotein (AFP), fucosylated AFP (AFP-L3), and des gamma-carboxy prothrombin (DCP) as TMs in predicting the prognosis and therapeutic efficacy in hepatocellular carcinoma (HCC) patients administered atezolizumab plus bevacizumab (Atez/Bev) as first-line treatment. Materials/Methods: The study period covered September 2020 to December 2022 and involved 371 HCC patients treated with Atez/Bev. The values of the TMs AFP, AFP-L3, and DCP were measured upon introducing Atez/Bev. Elevations in the values of AFP (≥100 ng/mL), AFP-L3 (≥10%), and DCP (≥100 mAU/mL) were considered to indicate a positive TM. The number of positive TMs was summed up and used as the TM score, as previously proposed. Hepatic reserve function was assessed using the modified albumin–bilirubin grade (mALBI). Predictive values for prognosis were evaluated retrospectively. Results: A TM score of 0 was shown in 81 HCC patients (21.8%), 1 in 110 (29.6%), 2 in 112 (29.9%), and 3 in 68 (18.3%). The median overall survival (OS) times for TM scores 0, 1, 2, and 3 were not applicable [NA] (95% CI NA-NA), 24.0 months (95% CI 17.8-NA), 16.7 months (95% CI 17.8-NA), and NA (95% CI 8.3-NA), respectively (p < 0.001). The median progression-free survival (PFS) times for TM scores 0, 1, 2, and 3 were 16.5 months (95% CI 8.0-not applicable [NA]), 13.8 months (95% CI 10.6–21.3), 7.7 months (95% CI 5.3–8.9), and 5.8 months (95% CI 3.0–7.6), respectively (p < 0.001). OS was well stratified in mALBI 1/2a and mALBI 2a/2b. PFS was well stratified in mALBI 2a/2b, but not in mALBI 1/2a. Conclusions: The TM score involving AFP, AFP-L3, and DCP as TMs was useful in predicting the prognosis and therapeutic efficacy in terms of OS and PFS in HCC patients administered Atez/Bev as first-line treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: We aimed to compare the prognosis of patients with advanced hepatocellular carcinoma treated with the first-line atezolizumab plus bevacizumab (AB) combination chemotherapy and the less popular locoregional treatment mainly used in East Asia, hepatic artery infusion chemotherapy (HAIC). We conducted a retrospective study with 114 patients treated with AB and 193 patients treated with HAIC and compared the overall survival (OS) and progression-free survival (PFS). Our results showed comparable OS between the two therapy groups; however, PFS was superior in patients treated with AB combination therapy. After compensating for confounding variables via propensity score matching, there was no significant difference in PFS and OS between the two groups. This study aimed to compare the prognosis and characteristics of patients with advanced hepatocellular carcinoma treated with first-line atezolizumab plus bevacizumab (AB) combination therapy and hepatic artery infusion chemotherapy (HAIC). We retrospectively assessed 193 and 114 patients treated with HAIC and AB combination therapy, respectively, between January 2018 and May 2023. The progression-free survival (PFS) of patients treated with AB combination therapy was significantly superior to that of patients treated with HAIC (p < 0.05), but there was no significant difference in overall survival (OS). After propensity score matching, our data revealed no significant differences in OS and PFS between patients who received AB combination therapy and those who received HAIC therapy (p = 0.5617 and 0.3522, respectively). In conclusion, our propensity score study reveals no significant differences in OS and PFS between patients treated with AB combination therapy and those treated with HAIC. [ABSTRACT FROM AUTHOR]

These data support that TACE alone has a limited effect in up-to-seven criteria OUT HCC and confirm that up-to-seven criteria OUT HCC is a TACE-unsuitable patient population, in which LEN-TACE is an extremely effective treatment strategy. Upfront LEN followed by TACE was also associated with better preservation of liver function than TACE alone, suggesting that LEN preceded by TACE is an efficient treatment option for up-to-seven criteria OUT patients who are not suitable for TACE [[13]]. 27 (7): 1110 - 9 16 Kudo M. A Novel treatment strategy for patients with intermediate-stage HCC who are not suitable for TACE: upfront systemic therapy followed by curative conversion. [Extracted from the article]

Background: Multiple bilateral lung metastases secondary to hepatocellular carcinoma (HCC) are mainly treated with molecular therapy. Atezolizumab plus bevacizumab can provide excellent long-term survival for patients with a good response. Case Report: A 67-year-old woman underwent right hepatectomy for a primary solitary HCC, 11 cm in diameter, after portal embolization. After 2 years, she developed bilateral lung metastases with >100 nodules, <1 cm in size. She had no viral hepatitis or liver cirrhosis, and the Child–Pugh Grade was A (5 points). Lenvatinib (12 mg daily) was administered as a first-line treatment and continued for 18 months. The best response was stable disease (SD). Subsequently, intravenous atezolizumab (1,200 mg) plus bevacizumab (15 mg/kg) was administered once every three weeks. The best response was SD, which continued for 26 months. After that, cabozantinib treatment was initiated and discontinued after one cycle. Subsequently, dual immune checkpoint inhibitor treatment (durvalumab + tremelimumab) was administered. She has had multiple, but lung-only, metastases over four years. She has been well as an outpatient with the Child–Pugh Grade of A and a performance status of 0. Conclusion: Even if atezolizumab plus bevacizumab does not induce a good response, a durable SD could prolong survival in patients with metastatic HCC while maintaining liver function and a good quality-of-life. [ABSTRACT FROM AUTHOR]

Background and Aim: The study goal was to compare the outcomes of patients with unresectable hepatocellular carcinoma (HCC) who received atezolizumab plus bevacizumab (Atezo/Bev) as either first‐ or later‐line systemic therapy. Methods: A total of 430 patients with HCC treated with Atezo/Bev at 22 institutions in Japan were included. Patients treated with Atezo/Bev as first‐line therapy for HCC were defined as the first‐line group (n = 268) while those treated with Atezo/Bev as second‐ or later‐line therapy were defined as the later‐line group (n = 162). Results: The median progression‐free survival times in the first‐ and later‐line groups were 7.7 months (95% confidence interval [CI], 6.7–9.2) and 6.2 months (95% CI, 5.0–7.7) (P = 0.021). Regarding treatment‐related adverse events, hypertension of any grade was more common in the first‐line group than in the later‐line group (P = 0.025). Analysis adjusted by inverse probability weighting, including patient and HCC characteristics, showed that the later‐line group (hazard ratio, 1.304; 95% CI, 1.006–1.690; P = 0.045) was significantly associated with progression‐free survival. In patients with Barcelona Clinic Liver Cancer stage B, the median progression‐free survival times in the first‐ and later‐line groups were 10.5 months (95% CI, 6.8–13.8) and 6.8 months (95% CI, 5.0–9.4) (P = 0.021). Among patients with a history of lenvatinib therapy, the median progression‐free survival times in the first‐ and later‐line groups were 7.7 months (95% CI, 6.3–9.2) and 6.2 months (95% CI, 5.0–7.7) (P = 0.022). Conclusion: The use of Atezo/Bev as first‐line systemic therapy in patients with HCC is expected to prolong survival. [ABSTRACT FROM AUTHOR]

Simple Summary: The Barcelona clinic liver cancer (BCLC) system is used widely for staging hepatocellular carcinomas (HCCs). However, it is questionable that for patients classified as BCLC stage C, control of intrahepatic targets using various treatment procedures is not the main topic of discussion, whereas the importance of intrahepatic tumor control in patients with extrahepatic tumor spread is reviewed. Therefore, this study analyzed the data of 64 consecutive BCLC stage C patients with intrahepatic target nodules who received systemic therapy and evaluated the efficacy of the combined use of systemic sequential therapy, including more than two agents, and locoregional treatment administered after initiation of systemic therapy. We showed that the combined use of systemic sequential therapy of more than two agents and locoregional-treatment improved overall survival in BCLC stage C HCC patients with intrahepatic target nodules who had previously received systemic therapy-based treatment. Background: The aim of this study was to evaluate the clinical impact of a combination of systemic sequential therapy and locoregional therapy on the long-term survival of patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC). Methods: Sixty-four consecutive patients with intrahepatic target nodules who had initially received systemic therapy (lenvatinib and atezolizumab plus bevacizumab) were reviewed. The clinical impact of the combined use of systemic sequential therapy and locoregional therapy was evaluated by determining overall survival (OS). The combined use of systemic sequential therapy with more than two agents and locoregional treatment was defined as multidisciplinary combination therapy (MCT), while only systemic sequential therapy and repeated locoregional-treatment was defined as a single treatment procedure (STP). Results: R0 resection, MCT, and STP resulted in significantly better OS compared with no additional treatment (median OS, not reached vs. 18.2 months and 12.6 vs. 8.1 months, respectively; p = 0.002). Multivariate analysis confirmed that the use of R0 resection and MCT were associated with better OS (hazard ratio [HR]; 0.053, p = 0.006 and 0.189, p < 0.001, respectively) compared with that for STP (HR; 0.279, p = 0.003). Conclusions: MCT is may effective in patients with BCLC stage C HCC and intrahepatic target nodules who have previously received systemic therapy-based treatment. [ABSTRACT FROM AUTHOR]