Liver Cancer最新文献

{"title":"Reply to “Methodological Concerns in ‘Prognostic Usefulness of Clinical Complete Response after PD1 InhibitorBased Combination Therapy for Unresectable Hepatocellular Carcinoma’ ”","authors":"Da-Long Yang, Jian-Li Huang, Hong-Gui Qin, Liang Ma, Jian-Hong Zhong","doi":"10.1159/000553001","DOIUrl":"https://doi.org/10.1159/000553001","url":null,"abstract":"","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"58 1","pages":"1-4"},"PeriodicalIF":13.8,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148285684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Definition of Conversion Therapy and Neoadjuvant Therapy for Hepatocellular Carcinoma: A Consensus Guideline from the Japan Liver Cancer Association","authors":"Akihiko Ichida, Ryosuke Tateishi, Etsuro Hatano, Akinobu Taketomi, Minoru Tanabe, Kazuhiro Nouso, Yasunori Minami, Takamichi Murakami, Mitsuo Shimada, Kiyoshi Hasegawa","doi":"10.1159/000552928","DOIUrl":"https://doi.org/10.1159/000552928","url":null,"abstract":"With the advent of novel systemic therapies that provide high response rates, such as lenvatinib, atezolizumab–bevacizumab, durvalumab–tremelimumab, and nivolumab–ipilimumab, treatment strategies for patients with advanced hepatocellular carcinoma (HCC) have markedly evolved, and discussions on conversion therapy—which, broadly speaking, combines these systemic therapies with locoregional modalities—have become commonplace. However, the term “conversion therapy” has not yet been clearly defined, making it difficult to compare treatment outcomes among studies. To address this issue, the Japan Liver Cancer Association established a consensus-based “Working Group on the Definition of Conversion” as an official project of the association. The working group comprised experts in hepatobiliary surgery, hepatology, and radiology, with a rapporteur responsible for drafting and revising the definitions. The group proposed standardized definitions for “conversion surgery,” “neoadjuvant therapy,” and “ablation as conversion therapy,” while recommending that transarterial chemoembolization should not be classified as conversion therapy due to its limited curative potential. The definitions also introduced two key concepts: functional conversion (based on the hepatic functional reserve) and oncological conversion (based on the tumor status). Adoption of these definitions is expected to facilitate appropriate evaluation of pretreatments and outcomes of conversion therapy. Ultimately, these efforts are expected to contribute to refining clinical decision-making, providing a common framework for guideline development and future clinical studies, and improving the outcomes of multidisciplinary treatments for advanced HCC; however, further validation is required.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"20 1","pages":"1-13"},"PeriodicalIF":13.8,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148285613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lenvatinib Added to Nivolumab and Ipilimumab Improves Tumor Control and Progression-Free Survival in Unresectable Hepatocellular Carcinoma","authors":"Kuan-Chang Lai, Chien-An Liu, Hao-Jan Lei, San-Chi Chen","doi":"10.1159/000552861","DOIUrl":"https://doi.org/10.1159/000552861","url":null,"abstract":"Background In CheckMate-9DW, the suboptimal early tumor control of nivolumab–ipilimumab resulted in higher early mortality compared with the sorafenib/lenvatinib arm during the first 12 months. We evaluated whether adding lenvatinib to nivolumab–ipilimumab (NIL) improves outcomes versus nivolumab–ipilimumab (NI). Methods Patients with unresectable HCC treated with NI with or without lenvatinib were retrospectively analyzed. Responses were evaluated by RECIST v1.1, survival outcomes by Kaplan–Meier and inverse probability of treatment weighting (IPTW) adjustment, and multiple sensitivity analyses. Liver function changes were evaluated using the albumin–bilirubin (ALBI) score. Results Among 104 patients, 82 received NI and 22 received NIL. The NIL group demonstrated a higher disease control rate than the NI group (81.8% vs 39.0%; p < 0.01), with similar duration of response (21.4 vs 21.8 months). Median progression-free survival (PFS) was longer with NIL (10.2 vs 3.2 months), but not for overall survival (OS). In the first-line setting, NIL showed a trend toward longer PFS and fewer early deaths within 12 months. After IPTW adjustment and sensitivity analyses, the NIL regimen consistently demonstrated improved PFS (HR 0.44; p < 0.01) without a statistically significant OS benefit. Hypertension, proteinuria and stomatitis were more frequent in the NIL group, while ALBI scores remained stable. Development of immune-related adverse events was associated with improved outcomes. Conclusions This real-world study provides proof-of-concept evidence that incorporating a VEGF inhibitor into dual ICIs therapy is associated with improved tumor control and prolonged PFS, with a potential reduction in early mortality. Prospective studies are warranted to confirm these findings.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"22 1","pages":"1-20"},"PeriodicalIF":13.8,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148285612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissecting the transcriptomic profile of CD163+ macrophages in HCC with VETC+ angiogenesis provides potential targets of treatment","authors":"Camilla De Carlo, Anna Rita Putignano, Reha Akpinar, Barbara Durante, Marika Viatore, Rebecca Polidori, Cristiana Soldani, Barbara Franceschini, Gianluca Basso, Fabio Procopio, Guido Costa, Fabio Grizzi, Luigi Maria Terracciano, Guido Torzilli, Lorenza Rimassa, Ana Lleo, Salvatore Piscuoglio, Charlotte K. Y. Ng, Erica Villa, Sergio Marchini, Federica Marchesi, Luca Di Tommaso","doi":"10.1159/000552648","DOIUrl":"https://doi.org/10.1159/000552648","url":null,"abstract":"HCC is characterized by a highly vascularized tumor microenvironment (TME), with VETC being a distinctive, frequent and prognostically unfavourable type of this vascular TME. VETC+ HCCs show lymphocyte deprivation and enrichment with large, foamy macrophages distributed close to endothelial cells. This study aimed to characterize these macrophages with a spatial transcriptomic approach. We demonstrated that they exhibit a pro-tumor, M2-like tumor-associated macrophages (TAMs) signature (SPP1, ACP5, GPNMB, and FABP5), distinct from those in VETC- cases. They are enriched with specific pathways involved in immunosuppression and angiogenesis. SPP1, ADAM9 and MMP9 were among the genes mostly upregulated. Immunohistochemistry analysis confirmed strong SPP1 expression in TAMs spatially associated with endothelial cells in VETC+ cases. Our findings suggest that M2-like TAMs in VETC+ HCCs contribute to both angiogenesis and immunosuppression. SPP1 and ADAM9 could represent novel therapeutic strategies to reshape TAMs and suppress VETC onset.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"27 1","pages":"1-19"},"PeriodicalIF":13.8,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148285614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atezolizumab Plus Bevacizumab Versus Lenvatinib as First-Line Treatment for Unresectable Hepatocellular Carcinoma Stratified by the CRAFITY Score: An International Multicenter Study","authors":"Masayuki Ueno, Yung-Yeh Su, Atsushi Takai, Yi-Hsiang Huang, Hiroki Morimura, Norihiro Nishijima, Shi-Ming Lin, Ching‑Wei Chang, Satoru Iwamoto, Shu Nagatomo, Hsueh-Chou Lai, Takeshi Mitani, Atsuyuki Ikeda, Yoshito Uenoyama, Makoto Umeda, San-Chi Chen, Chien-Huai Chuang, Shiue-Wei Lai, Teng-Yu Lee, Shigeharu Nakano, Chia-Yen Dai, Tomoyuki Goto, Tung-Hung Su, Ching Sheng Hsu, Ching-Chu Lo, Haruhiko Takeda, Yukio Osaki, Etsuro Hatano, Pei-Chang Lee, Po-Ting Lin, Hung-Wei Wang, Wei-Fan Hsu, Tsung-Hao Liu, Hiroshi Seno","doi":"10.1159/000552808","DOIUrl":"https://doi.org/10.1159/000552808","url":null,"abstract":"Introduction: Atezolizumab plus bevacizumab (Atezo+Bev) is the most widely used first-line treatment for unresectable hepatocellular carcinoma (HCC), while lenvatinib remains a standard alternative. Previous studies suggest limited efficacy of Atezo+Bev in patients with HCC exhibiting a CRAFITY score of 2 (CRP ≥1 mg/dL and AFP ≥100 ng/mL). We conducted an international collaborative study to compare the efficacy of Atezo+Bev and lenvatinib stratified by the baseline CRAFITY score. Methods: We retrospectively analyzed 994 patients who initiated Atezo+Bev or lenvatinib as first-line therapy for unresectable HCC between September 2017 and March 2024 across 11 hospitals in Japan and 13 hospitals in Taiwan. Patients were categorized by baseline CRAFITY score, and progression-free survival (PFS) and overall survival (OS) were compared between treatment groups. Results: The median age of the patients was 71 years, and 770 (77.5%) were male. The baseline CRAFITY score was 0 in 375 patients (37.7%), 1 in 402 patients (40.4%), and 2 in 217 patients (21.8%). In patients with a CRAFITY-0 score, median PFS (10.8 vs. 9.4 months; p = 0.548) and OS (21.1 vs. 29.3 months; p = 0.074) did not differ significantly between Atezo+Bev and lenvatinib. Similar findings were observed in CRAFITY-1 patients, with median PFS of 6.0 vs. 6.1 months (p = 0.943) and OS of 12.7 vs. 15.1 months (p = 0.168). In contrast, among CRAFITY-2 patients, lenvatinib was associated with significantly longer PFS (2.3 vs. 4.4 months; hazard ratio, 0.66; p = 0.017), while OS did not differ significantly between treatments (5.7 vs. 9.1 months; hazard ratio, 0.90; p = 0.586). A significant interaction was observed between CRAFITY score (0/1 vs. 2) and treatment regimen (Atezo+Bev vs. lenvatinib) for PFS (p = 0.002). Consistent findings were observed in adjusted analyses. Conclusion: Lenvatinib was associated with significantly longer PFS than Atezo+Bev in patients with a baseline CRAFITY score of 2. The CRAFITY score may be useful for identifying patients in whom lenvatinib could be considered as a first-line option, and prospective validation is warranted.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"29 1","pages":"1-20"},"PeriodicalIF":13.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148285618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatic Resection Versus Stereotactic Body Radiation Therapy as Initial Local Treatment for BCLC Stage 0 Hepatocellular Carcinoma: A Propensity Score-Weighted Analysis","authors":"Hye In Lee, Jinhong Jung, Gil-Chun Park, Dong-Hwan Jung, Tae-Yong Ha, Deok-Bog Moon, Ki-Hun Kim, Chul-Soo Ahn, Shin Hwang, Ju Hyun Shim, Jin-hong Park, Gi-Won Song, Sang Min Yoon, Sung-Gyu Lee","doi":"10.1159/000552740","DOIUrl":"https://doi.org/10.1159/000552740","url":null,"abstract":"Introduction This study aimed to compare the real-world effectiveness and safety of hepatic resection versus stereotactic body radiation therapy (SBRT) as initial local treatments for Barcelona Clinic Liver Cancer (BCLC) stage 0 hepatocellular carcinoma (HCC). Methods We retrospectively analyzed 537 treatment-naïve patients with single HCC measuring ≤2 cm who underwent hepatic resection (n=450) or SBRT (n=87) between January 2015 and December 2023. Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics between treatment groups. Overall survival (OS) and disease-free survival (DFS) were evaluated using weighted Cox proportional hazards models, while competing-risk models estimated the cumulative incidence of overall and intrahepatic recurrence. Treatment-related adverse events (TRAEs) and longitudinal changes in liver function were also assessed. Results At baseline, patients in the SBRT group were significantly older, had a higher comorbidity burden, and exhibited poorer liver function compared to those in the resection group. Over a median follow-up of 56.8 months (range, 8.3–117.0), the unadjusted 3-year OS rates were 98.8% for resection versus 92.3% for SBRT (hazard ratio [HR] 3.15; p=0.002), and 3-year DFS rates were 80.9% versus 64.9%, respectively (HR 1.58; p=0.026). However, the IPTW-adjusted analysis demonstrated comparable outcomes between treatment groups, with 3-year rates of OS at 98.9% versus 96.2% (HR 1.15; p=0.775), DFS at 79.1% versus 74.1% (HR 1.06; p=0.851), and overall recurrence at 20.9% versus 20.2% (HR 0.96; p=0.906) for resection and SBRT, respectively. Grade ≥3 TRAEs occurred in 31 patients (6.9%) in the resection group and none in the SBRT group. Liver function remained well-preserved in both treatment groups. Conclusion After adjusting for baseline imbalances, SBRT achieved survival outcomes comparable to hepatic resection as initial local therapy, while maintaining an excellent safety profile. These findings suggest that SBRT may serve as a viable alternative for patients with BCLC stage 0 HCC who are suboptimal surgical candidates.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"34 1","pages":"1-24"},"PeriodicalIF":13.8,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148285514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum.","authors":"","doi":"10.1159/000552217","DOIUrl":"https://doi.org/10.1159/000552217","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1159/000549955.].</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13215674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148055187","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":"Erratum.","authors":"","doi":"10.1159/000551913","DOIUrl":"https://doi.org/10.1159/000551913","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1159/000550067.].</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13215675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148055174","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":"Real-World Evidence from a Nationwide Prospective Study of the Efficacy/Safety of Systemic Therapy for Unresectable Hepatocellular Carcinoma: First 1,000 Patients of the PRISM Study.","authors":"Masafumi Ikeda, Shinji Itoh, Daisuke Onozuka, Sadahisa Ogasawara, Tomokazu Kawaoka, Takashi Niizeki, Taro Yamashita, Yasuhito Tanaka, Tomoharu Yamada, Kazushi Numata, Ryosuke Tateishi, Tatsuya Yamashita, Takuji Okusaka, Junji Furuse, Masatoshi Kudo","doi":"10.1159/000552686","DOIUrl":"10.1159/000552686","url":null,"abstract":"<p><strong>Background: </strong>The PRISM study is a nationwide, multicenter, prospective observational study in Japan evaluating the real-world efficacy and safety of systemic therapies for unresectable hepatocellular carcinoma (HCC). HCC patients starting systemic therapy are prospectively enrolled, enabling assessment of outcomes and tolerability across treatment lines. By capturing all patients treated in routine practice, the study is expected to provide a clear picture of the actual treatment outcomes in Japan.</p><p><strong>Methods: </strong>We analyzed the first 1,000 patients enrolled between July 2020 and July 2022, focusing on outcomes of first-line therapy and subsequent patterns. Data on demographics, tumor stage, liver function, regimens, survival, and adverse events (AEs) were prospectively collected and centrally monitored. Survival was estimated by Kaplan-Meier method, and tumor responses were assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST (mRECIST).</p><p><strong>Results: </strong>Of 935 evaluable patients, 82.8% received atezolizumab + bevacizumab (Atezo+Bev) and 15.2% lenvatinib as first-line therapy. Median overall survival and progression-free survival were 21.8 and 7.7 months for Atezo+Bev, respectively, and 20.8 and 6.7 months for lenvatinib, with overall survival numerically longer than that reported in pivotal clinical trials, while progression-free survival remained comparable. Objective response rates were 29.6% (RECIST) and 35.0% (mRECIST) for Atezo+Bev, 24.6% and 35.2% for lenvatinib, and 0% and 6.3% for sorafenib by RECIST and mRECIST, respectively. Grade ≥3 treatment-related AEs occurred in 21.6% and 22.9%, with safety profiles consistent with prior reports. Approximately 50% of patients received second-line therapy, most often lenvatinib after Atezo+Bev and vice versa, with a median progression-free survival of ∼4 months; later-line regimens yielded even shorter benefit.</p><p><strong>Conclusion: </strong>The PRISM study confirms the real-world reproducibility of Atezo+Bev and lenvatinib in Japan, demonstrating their feasibility across diverse patient populations. Ongoing follow-up and subgroup analyses, particularly in special populations, are expected to help optimize long-term outcomes.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13423367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630879","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":"The China Paradox in LEAP-012 Trial.","authors":"Masatoshi Kudo","doi":"10.1159/000552537","DOIUrl":"10.1159/000552537","url":null,"abstract":"","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":"329-336"},"PeriodicalIF":10.5,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13241163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199543","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}