Liver Cancer最新文献

{"title":"Oncological Outcomes and Treatment Strategies for Borderline Resectable Hepatocellular Carcinoma Based on the Oncological Resectability Classification.","authors":"Takashi Hamada, Akihiko Soyama, Hajime Matsushima, Ayaka Kinoshita, Kazushige Migita, Hajime Imamura, Shun Nakamura, Ayaka Satoh, Kohki Kurotaki, Tomohiko Adachi, Ryu Sasaki, Hisamitsu Miyaaki, Susumu Eguchi","doi":"10.1159/000551047","DOIUrl":"10.1159/000551047","url":null,"abstract":"<p><strong>Background: </strong>Although hepatic resection is the most effective curative treatment for hepatocellular carcinoma (HCC) in selected patients, survival outcomes can vary significantly depending on tumor burden and biology. To provide a standardized framework, the oncological resectability classification introduced in 2023 stratifies patients into resectable (R), borderline resectable 1 (BR1), or borderline resectable 2 (BR2). However, the optimal management of patients with BR1 and BR2 in the era of novel systemic therapies remains uncertain. The present study evaluated the surgical validity and treatment strategies for patients with BR1 and BR2, based on this classification.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 184 patients who underwent initial hepatic resection for HCC at Nagasaki University Hospital between 2014 and 2024. Clinical variables, perioperative outcomes, the recurrence-free survival (RFS), and the overall survival (OS) were then compared across the 3 groups: R (<i>n</i> = 149), BR1 (<i>n</i> = 21), and BR2 (<i>n</i> = 14). Subgroup analyses were performed to assess the impact of vascular invasion and preoperative systemic therapy.</p><p><strong>Results: </strong>The 5-year RFS rates were 43.9% for R, 39.3% for BR1, and 20.0% for BR2 (<i>p</i> < 0.001). The 5-year OS rates were 75.1% for R, 76.9% for BR1, and 33.8% for BR2 (<i>p</i> < 0.001). Among BR1 patients without vascular invasion, no cancer-related deaths occurred, and recurrence was largely controllable with repeated hepatectomy, radiofrequency ablation, transarterial chemoembolization, or stereotactic radiotherapy in patients even with recurrence. Conversely, BR1 patients with vascular invasion who underwent upfront surgery exhibited poor survival outcomes, whereas those received preoperative systemic therapy demonstrated at least comparable survival outcomes despite a higher tumor burden, with a lower incidence of cancer-related death. BR2 patients had uniformly poor results regardless of vascular invasion. However, two cases who received systemic therapy before surgery achieved a long-term survival, including one with complete pathological necrosis.</p><p><strong>Conclusions: </strong>BR1 patients, particularly those without vascular invasion, may achieve survival comparable to that of R. In contrast, BR2 patients generally show dismal outcomes with surgery alone, underscoring the necessity of systemic or multimodal approaches. Tailored strategies are essential for optimizing outcomes in patients with borderline resectable HCC.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 1b Study of Botensilimab and Balstilimab in Treatment-Refractory Hepatocellular Carcinoma.","authors":"Anthony B El-Khoueiry, Christopher H Lieu, Ghassan K Abou-Alfa, Apostolia M Tsimberidou, Daruka Mahadevan, Diana L Hanna, Bruno Bockorny, Breelyn A Wilky, Alexis Leal, Justin Stebbing, Manushak Avagyan, Wei Wu, Dhan Chand, Joseph E Grossman, Benny Johnson, Andrea J Bullock","doi":"10.1159/000551630","DOIUrl":"10.1159/000551630","url":null,"abstract":"<p><strong>Introduction: </strong>Botensilimab (BOT) is a fragment crystallizable (Fc)-enhanced multifunctional anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody with differentiated mechanisms of action, designed to extend therapy to cold/poorly immunogenic solid tumors. Patients with hepatocellular carcinoma (HCC) who progress on or after first-line immunotherapy have limited treatment options. Here, we report findings from a phase 1b study of BOT plus balstilimab (BAL; anti-programmed cell death protein 1 [PD-1] antibody) in previously treated patients with HCC.</p><p><strong>Methods: </strong>This is an open-label, nonrandomized, phase 1b, multicenter study of BOT±BAL in patients with advanced solid tumors. The study began with dose escalation (3 + 3 design) then dose expansion with multiple disease-specific cohorts. An expanded cohort of 19 patients with HCC who progressed on or after prior immunotherapy (primarily atezolizumab/bevacizumab) are included in this analysis. Patients with HCC received BOT intravenously at 1 or 2 mg/kg once every 6 weeks for up to 2 years plus BAL intravenously 3 mg/kg once every 2 weeks, for up to 2 years. Endpoints included safety, objective response rate (ORR), disease control rate, duration of response, and progression-free survival (PFS). Overall survival (OS) was an exploratory endpoint.</p><p><strong>Results: </strong>Among 18 efficacy evaluable patients (with ≥1 post-baseline 6-week imaging scan), ORR was 17% (3/18; 95% CI: 4-41), and 18-week clinical benefit rate (a complete or partial response or stable disease) 50% (9/18; 95% CI: 26-74). Median PFS was 4.4 months (95% CI: 1.4-6.9), and median OS was 12.3 months (95% CI: 8.4-21.4). Thirteen patients (68%) experienced any-grade immune-mediated treatment-related adverse events (TRAEs), with 37% (7/19) grade 3. The most common immune-mediated TRAEs included diarrhea/colitis (37% [7/19]; 16% grade 3 [3/19]), hepatitis (21% [4/19]; 16% grade 3 [3/19]), and dermatologic events (21% [4/19]; 5% grade 3 [1/19]). There were no treatment-related deaths or new safety signals outside of the class.</p><p><strong>Conclusions: </strong>The BOT+BAL combination demonstrated durable responses and manageable safety in treatment-refractory patients with HCC previously treated with immunotherapy, supporting further investigation in randomized studies. Despite the small sample size and high percentage of patients with albumin-bilirubin grade 2 liver disease, these results provide early evidence of antitumor activity in a difficult-to-treat disease setting.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13167118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147930774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaging-Based Liver Transplant Eligibility in Hepatocellular Carcinoma: Analysis of 1,094 Patients Using Liver Imaging Reporting and Data System and Asia-Pacific Guideline-Based Criteria.","authors":"Yeongseok Hwang, Subin Heo, Jihyun An, Seong Kyun Na, Seon-Ok Kim, In-Hye Song, Jean-Charles Nault, Gi-Won Song, Sang Hyun Choi, Ju Hyun Shim","doi":"10.1159/000551666","DOIUrl":"10.1159/000551666","url":null,"abstract":"<p><strong>Introduction: </strong>Accurate imaging diagnosis is essential for evaluating liver transplantation (LT) eligibility in hepatocellular carcinoma (HCC) patients. This study investigated whether pre-transplant imaging assessment using the Liver Imaging Reporting and Data System (LI-RADS) and Asia-Pacific guideline-based criteria could effectively predict long-term prognosis when determining LT eligibility.</p><p><strong>Methods: </strong>From a prospective registry, we analyzed 1,094 patients with a preoperative HCC diagnosis who had dynamic CT available within 1 month before LT. LT eligibility was assessed with Milan criteria (MC) and Up-to-Seven criteria (UTS). Imaging evaluation was performed using the LI-RADS, Asian Pacific Association for the Study of the Liver, Japan Society of Hepatology, and Korean Liver Cancer Association-National Cancer Center guidelines. We compared HCC-related mortality using competing risk analysis, overall survival, and prognostic performance between imaging-based and pathologic assessments.</p><p><strong>Results: </strong>The cohort comprised 158 (14.4%) anti-HCC treatment naïve patients and 936 (85.6%) patients who received anti-HCC treatments in the pre-LT setting. No significant difference in HCC-related mortality was observed between patients meeting imaging-based MC and pathological MC (5-year HCC-related mortality: 8.6-8.7% vs. 6.6%; all <i>p</i> > 0.05). Prognostic performance, assessed by 5-year area under the precision-recall curve and integrated Brier score, showed no significant differences between imaging-based MC and pathological MC groups (all <i>p</i> > 0.05). Similar results were observed for overall survival, UTS-based analyses, and pre-LT treatment subgroup analyses. Concordance between imaging-based MC and pathology-based MC was 84.0-84.4%.</p><p><strong>Conclusion: </strong>Although some discordance between imaging-based and pathology-based LT eligibility criteria was observed, pre-transplant imaging provided prognostic stratification comparable to pathology. Given that comprehensive pathological assessment is unattainable before LT, imaging-based evaluation using both LI-RADS and Asia-Pacific guidelines represents a practical and clinically relevant approach for determining LT eligibility.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13249434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148218367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Nivolumab plus Ipilimumab in Advanced Hepatocellular Carcinoma with and without High-Risk Features: An International Multicenter Study.","authors":"Jung Sun Kim, San-Chi Chen, Jeffrey Sum Lung Wong, Beodeul Kang, Ho Yeong Lim, Ilhwan Kim, Hyeyeong Kim, Chansik An, Su Jin Jang, Masatoshi Kudo, David Tai, Chan Kim, Thomas Yau, Hong Jae Chon","doi":"10.1159/000551631","DOIUrl":"10.1159/000551631","url":null,"abstract":"<p><strong>Introduction: </strong>The phase 1/2 CheckMate-040 and the phase 3 CheckMate-9DW trials consistently demonstrated meaningful activity of nivolumab plus ipilimumab (Nivo/Ipi) in previously treated and treatment-naïve patients with advanced HCC. However, patients with ≥50% liver involvement, Vp4 portal vein tumor thrombosis (PVTT), or bile duct invasion were excluded from these trials. We aimed to assess the real-world efficacy and safety of Nivo/Ipi in this high-risk population.</p><p><strong>Methods: </strong>This international, multicenter, retrospective study was conducted in patients with advanced HCC who received Nivo/Ipi at six hospitals in Korea, Hong Kong, Singapore, and Taiwan between 2016 and 2024. Patients with Child-Pugh B/C or ECOG >2 were excluded.</p><p><strong>Results: </strong>Of the 206 patients assessed for eligibility, 145 were included in the final analysis: 44 classified as high risk (Vp4 PVTT, <i>n</i> = 10; ≥50% liver involvement, <i>n</i> = 34; bile duct invasion, <i>n</i> = 7) and 101 as non-high risk. Baseline characteristics were comparable, aside from differences in liver function and high-risk features. Nivo/Ipi was administered as third-line or later-line therapy in 76.6% of patients. The high-risk group exhibited a significantly lower objective response rate (ORR) (12.8% vs. 34.3%) and shorter median progression-free survival (PFS) (1.2 vs. 2.9 months) and overall survival (OS) (3.6 vs. 16.5 months). Among the high-risk features, ≥50% liver involvement was strongly associated with inferior ORR, PFS, and OS, whereas Vp4 PVTT and bile duct invasion alone were not significantly associated with outcomes. A higher intrahepatic tumor burden was also inversely associated with treatment response and survival. Adverse events were more frequent in high-risk patients, particularly hyperbilirubinemia (36.4% vs. 13.9%; grade ≥3: 11.4% vs. 1.0%). On multivariable analysis, ≥50% liver involvement and prior immune-checkpoint inhibitor exposure independently predicted shorter PFS and OS.</p><p><strong>Conclusion: </strong>Extensive liver involvement emerged as the key predictor of poor prognosis, whereas Vp4 PVTT and bile duct invasion were not associated with significantly worse outcomes.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13215676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148055202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Checkpoint Inhibitor Rechallenge in Unresectable Hepatocellular Carcinoma: A Multicenter Efficacy and Safety Study.","authors":"Jing-Kun Chen, Jia-Liang Wei, Zhen-Dong Yang, Shao-Ping Liu, Zhi-Cheng Li, Kang Chen, Chuang Qin, Ze Su, Lin Ye, Shu-Qun Li, Guo-Xing Liu, Jian-Yuan Meng, Ying-Hui Wu, Ting Quan, Jian Li, Zhu-Jian Deng, Da-Long Yang, Jia-Yong Su, Guan-Lin Chen, Cai-Yi Dong, Bin-Yan Gu, Wen-Yang Li, Xiao-Shan Qin, Xiu-Qiong Long, Liang Ma, Jian-Hong Zhong","doi":"10.1159/000551629","DOIUrl":"10.1159/000551629","url":null,"abstract":"<p><strong>Introduction: </strong>Immune checkpoint inhibitors (ICIs) are a standard treatment for unresectable hepatocellular carcinoma, but sometimes they must be discontinued because of resistance or immune-related adverse events. The present study explored whether later resuming ICI therapy in such patients (\"rechallenge\") can improve their prognosis.</p><p><strong>Methods: </strong>Data were retrospectively analyzed for patients treated between March 2019 and May 2024 at 12 medical centers in China. Patients had unresectable hepatocellular carcinoma and were initially treated with ICIs, which were discontinued due to resistance or severe immune-related adverse events and then later resumed. Event-free survival, objective response, and disease control based on RECIST 1.1 criteria, as well as incidence and severity of immune-related adverse events, were assessed separately during first-line ICI (ICI-1) and second-line ICI (ICI-2) therapy.</p><p><strong>Results: </strong>The final analysis included 272 patients (247 men) with a median age of 50 (IQR 43-58) years old at enrollment; ICI-1 was discontinued in 253 patients (93.0%) because of tumor progression. Both ICI-1 and ICI-2 therapies lasted a median of 3.0 months and, for approximately 80% of patients, involved the combination of ICIs and targeted agents rather than ICI monotherapy. During ICI-1 or ICI-2 therapy, respective median event-free survival times were 5.3 (95% CI 4.7-5.9) months and 4.4 (95% CI 3.8-5.0) months, objective response rates were 23.2% and 18.4%, disease control rates were 69.9% and 48.2%, and rates of immune-related adverse events of grades 3-4 were 18.4% and 19.9%. Objective response was observed in 26 patients (9.6%) during both therapy lines, while 10 (12.2%) suffered disease progression during ICI-1 therapy yet achieved partial response during ICI-2 treatment. No deaths due to immune-related adverse events occurred during the study.</p><p><strong>Conclusion: </strong>ICI rechallenge following tumor progression or severe immune-related adverse events can benefit some patients with unresectable hepatocellular carcinoma without posing additional safety risks.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13225850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148149984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multidisciplinary Clinic Approach Improves Immunotherapy Treatment Outcomes in Unresectable Hepatocellular Carcinoma: A Multicentre Retrospective Study.","authors":"Andrea Dalbeni, Alessandra Auriemma, Marco Vicardi, Filippo Cattazzo, Maria Elena Bellucco, Chiara Mazzarelli, Federica Villa, Giulia Dispinzieri, Leonardo Antonio Natola, Caterina Soldà, Sara Lonardi, Luisa Foltran, Sara Torresan, Simone Rota, Tiziana Pressiani, Lorenza Rimassa, David Sacerdoti, Michele Milella","doi":"10.1159/000549738","DOIUrl":"10.1159/000549738","url":null,"abstract":"<p><strong>Introduction: </strong>Given the complexity of managing unresectable hepatocellular carcinoma (HCC), few Italian centres have implemented integrated multidisciplinary clinics (MDTc), where hepatologists and oncologists jointly assess patients. This study aimed to evaluate whether this model improves survival outcomes in patients treated with atezolizumab and bevacizumab (A+B).</p><p><strong>Methods: </strong>In this multicentre retrospective study, 146 patients with cirrhosis and unresectable HCC treated with A+B were included. Based on the outpatient care model, centres were categorized into two groups: those with MDTc and those with standard oncology clinics, where hepatologists were consulted on demand. Primary outcomes were overall survival (OS) and progression-free survival (PFS); secondary outcomes included disease control rate (DCR) and objective response rate (ORR). An inverse probability weighting (IPW) analysis was performed to adjust for baseline imbalances between groups.</p><p><strong>Results: </strong>Seventy-seven (53%) patients were managed in MDTc settings, and 69 (47%) in oncology clinics. Median treatment duration was 6.0 months (IQR 2.0-11.0). Median OS did not significantly differ between groups [19.7 months (95% confidence intervals [CI]: 16.6-23.1) vs. 13.4 months (95% CI: 10.7-19.5); <i>p</i> = 0.07], whereas median PFS was significantly longer in the MDTc group (13.6 months [95% CI: 8.9-NA] vs. 7.7 months [95% CI: 4.9-13.0]; <i>p</i> = 0.02). While ORR was similar, DCR was higher in the MDTc group (70.1% vs. 60.3%; <i>p</i> = 0.05). Patients followed in MDTc remained on first-line therapy significantly longer (8 months [IQR 3-12] vs. 4 months [IQR 1-8]; <i>p</i> = 0.009). Although the overall treatment discontinuation rate did not differ between the two groups, liver-related events were more frequent and accounted for a greater proportion of discontinuations in oncology clinics (40.6% vs. 10.4%; <i>p</i> = 0.04). Furthermore, treatment duration was shorter in patients discontinuing A+B due to liver-related events than other causes (2.5 months [IQR 1.8-6.3] vs. 7.1 months [IQR 3.9-11.2]; <i>p</i> < 0.001). However, in the IPW analysis, the association between MDTc management and clinical outcomes was no longer significant.</p><p><strong>Conclusions: </strong>In patients with unresectable HCC treated with A+B, MDTc management did not significantly improved OS but was associated with better PFS and DCR. These benefits were likely driven by longer treatment duration and lower rates of liver-related decompensation, underscoring the value of integrated hepatologic-oncologic management in this complex population.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13065330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147674760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Multicenter Phase II Study on Atezolizumab plus Bevacizumab Combination Therapy in Patients with Unresectable Hepatocellular Carcinoma and Child-Pugh Classification B Cirrhosis: CHALLENGE Trial.","authors":"Takeshi Terashima, Masafumi Ikeda, Taro Yamashita, Takuji Okusaka, Hiroshi Imaoka, Tomokazu Kawaoka, Satoshi Kobayashi, Sadahisa Ogasawara, Atsushi Hiraoka, Masahito Nakano, Naohiro Okano, Rie Sugimoto, Michihisa Moriguchi, Yoshitaka Inaba, Satoru Shinoda, Makoto Ueno, Masatoshi Kudo, Junji Furuse, Hiroaki Nagano","doi":"10.1159/000551476","DOIUrl":"10.1159/000551476","url":null,"abstract":"<p><strong>Introduction: </strong>Atezolizumab plus bevacizumab combination therapy (atezo + bev) has been successfully developed as a standard of care for patients with unresectable hepatocellular carcinoma (HCC) and Child-Pugh A; however, there is no established treatment for those with Child-Pugh B. This study aimed to evaluate the safety and efficacy of atezo + bev in patients with advanced HCC and Child-Pugh B.</p><p><strong>Methods: </strong>This multicenter, open-label, single-arm, phase II study enrolled patients with advanced HCC and a Child-Pugh score of 7 or 8 who had not received prior systemic therapy. Patients were administered atezolizumab (1,200 mg) plus bevacizumab (15 mg/kg) every 3 weeks. The primary endpoint was the frequency of serious adverse events (SAEs), assuming a threshold SAE of 68.5%. A binomial test with a one-sided significance level of 2.5% was employed for the primary analysis.</p><p><strong>Results: </strong>Among the 31 patients enrolled between December 2021 and April 2023, we set 30 eligible patients as the population for the safety and efficacy analyses. The frequency of SAEs was 23.3% (95% confidence interval [CI]: 9.9-42.3, <i>p</i> < 0.0001). Objective response rates according to RECIST v1.1 and the modified RECIST were 40.0% and 46.7%, respectively. The median progression-free and overall survival were 240 days (95% CI: 176-526 days) and 470 days (95% CI: 256-576 days), respectively. The mean ± SD Child-Pugh scores were 7.2 ± 0.4 at the start of treatment, maintained 7.0 ± 1.0 and 7.0 ± 1.2 at the third and sixth cycles, respectively, and was 7.6 ± 1.7 at the end of treatment.</p><p><strong>Conclusion: </strong>The atezo + bev regimen can be safely administered with demonstrable antitumor effects in patients with unresectable HCC and a Child-Pugh score of 7 or 8. Additional studies are warranted to confirm the usefulness of atezo + bev in this patient group.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13183380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147973461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatic Artery Infusion Chemotherapy for Cholangiocarcinoma in 2025.","authors":"Qi-Feng Chen, Yue Hu, Song Chen, Xiong-Ying Jiang, Ming Zhao","doi":"10.1159/000551430","DOIUrl":"10.1159/000551430","url":null,"abstract":"<p><strong>Background: </strong>Cholangiocarcinoma (CCA), particularly intrahepatic CCA (iCCA), is an aggressive hepatobiliary malignancy with limited therapeutic options and poor prognosis. For unresectable or advanced disease, systemic chemotherapy (SC) with gemcitabine plus cisplatin (GC) has long been the standard of care, and the recent addition of durvalumab to GC has become first-line therapy. However, median overall survival remains approximately ∼1 year, underscoring the need for more effective strategies.</p><p><strong>Summary: </strong>Hepatic arterial infusion chemotherapy (HAIC) has emerged as a promising locoregional approach, leveraging the liver's dual blood supply to deliver high local concentrations of cytotoxic agents while minimizing systemic toxicity. Advances in interventional techniques and chemotherapy protocols have expanded its role, positioning HAIC both as an alternative to SC and as a synergistic partner in multimodal regimens that include targeted therapy and immunotherapy. Importantly, the National Comprehensive Cancer Network (NCCN) now incorporates HAIC as a treatment option for select patients with unresectable iCCA, further endorsing its clinical utility. This integration underscores HAICs evolving role in multimodal therapy, where it can complement other treatment modalities to improve patient outcomes. This review synthesizes recent developments in HAIC for CCA, with emphasis on iCCA. It compares HAIC with SC, explores its integration into multimodal strategies, examines its role within the local treatment paradigm, and addresses clinical challenges such as technical precision, toxicity management, and the need for standardization. Finally, future directions - including biomarker-guided therapy, liquid biopsy, and advanced imaging - are discussed. Collectively, HAIC represents both a clinically relevant treatment option and a platform for precision oncology in CCA.</p><p><strong>Key messages: </strong>(1) HAIC has emerged as a clinically validated and guidelines-supported treatment option that offers superior locoregional control for unresectable iCCA compared to SC alone. (2) The future of iCCA management lies in multimodal integration, where HAIC serves as a foundational platform that can be combined with systemic agents to achieve synergistic antitumor effects. (3) Transitioning from a \"one-size-fits-all\" approach to a precision oncology framework - incorporating molecular profiling and advanced imaging - is essential for refining patient selection and maximizing the survival benefits of HAIC-based strategies.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13171145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147941842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of Patients with Unresectable Hepatocellular Carcinoma in REFLECT Who Achieved Tumor Response or Alpha-Fetoprotein Response When Treated with Lenvatinib.","authors":"Amit Mahipal, Ann-Lii Cheng, Masatoshi Kudo, Adam Burgoyne, Aparna Kalyan, Riccardo Lencioni, Carlos Lopéz Lopéz, Bruno Daniele, Daniel H Palmer, Ari David Baron, Joong-Won Park, Min Ren, Kalgi Mody, Arndt Vogel","doi":"10.1159/000551313","DOIUrl":"10.1159/000551313","url":null,"abstract":"<p><strong>Background: </strong>The phase 3 REFLECT study (NCT01761266) established lenvatinib's noninferiority to sorafenib for unresectable hepatocellular carcinoma (uHCC). This subanalysis examines patients treated with lenvatinib according to the depth of their tumor response and their status as an alpha-fetoprotein (AFP) responder/nonresponder.</p><p><strong>Methods: </strong>Of 478 lenvatinib-treated patients, 194 achieved an objective response by mRECIST per independent imaging review. Patients with tumor response were further categorized by their maximal tumor reduction (assessed every 8 weeks). Patients were also assessed according to their AFP response (≥20% reduction from baseline by week 8) status, including AFP responders (<i>n</i> = 227) and nonresponders (<i>n</i> = 73).</p><p><strong>Results: </strong>Median duration of response in patients with ≥75% (<i>n</i> = 59)/≥50% to <75% (<i>n</i> = 72)/≥30% to <50% (<i>n</i> = 63) tumor reduction was 9.1 months (95% CI: 7.4-9.3)/7.3 months (95% CI: 5.5-7.4)/3.7 months (95% CI: 3.7-5.6), respectively. Median PFS/OS were 11.0 months (95% CI: 9.3-12.9)/23.4 months (95% CI: 14.3-30.1) for ≥75% tumor reduction, 9.2 months (95% CI: 7.4-11.1)/19.8 months (95% CI: 14.1-23.1) for ≥50% to <75% tumor reduction, and 7.4 months (95% CI: 5.5-9.2)/14.4 months (95% CI: 13.1-19.1) for ≥30% to <50% tumor reduction, respectively. Efficacy was improved among AFP responders versus AFP nonresponders (objective response rate: 48.0% versus 13.7%; median PFS, 7.4 months [95% CI: 5.6-7.8] versus 3.5 months [95% CI: 1.9-3.7]; median OS, 13.4 months [95% CI: 11.5-14.3] versus 8.3 months [95% CI: 6.5-10.7]). Patients with baseline AFP levels <400 ng/mL had longer median OS (19.0 months; 95% CI: 14.6-22.5) versus those with ≥400 ng/mL (10.1 months [95% CI: 8.5-11.7]).</p><p><strong>Conclusions: </strong>This analysis highlights the importance of tumor reduction and AFP response as predictors of survival outcomes in lenvatinib-treated patients with uHCC. These data continue to support lenvatinib as an effective first-line treatment option.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147868511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sequential ICI plus Anti-VEGF/TKI with On-Demand TACE beyond RECIST Progression Improves Pathological Response, Resectability, and Survival in Unresectable HCC.","authors":"Masatoshi Kudo","doi":"10.1159/000551332","DOIUrl":"10.1159/000551332","url":null,"abstract":"","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"15 2","pages":"169-177"},"PeriodicalIF":10.5,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}