Liver Cancer最新文献

{"title":"Early Safety Results from the Phase 3b SIERRA Study of Durvalumab and Tremelimumab as First-Line Treatment for Participants with Unresectable Hepatocellular Carcinoma and a Poor Prognosis.","authors":"Stephen Lam Chan, Masatoshi Kudo, Bruno Sangro, Robin Kate Kelley, Jee Hyun Kim, Binh Pham, Jung Yong Hong, Dirk-Thomas Waldschmidt, Donatella Marino, Jie Xin Joycelyn Lee, René Gerolami, Adam M Burgoyne, Qiao Li, Hitomi Nakamura, Peng Sun, Boris Baur, Lorenza Rimassa","doi":"10.1159/000549955","DOIUrl":"10.1159/000549955","url":null,"abstract":"<p><strong>Introduction: </strong>Subgroups of people with unresectable hepatocellular carcinoma (uHCC) are often excluded from clinical trials due to adverse prognostic factors. The SIERRA (NCT05883644) study assesses the efficacy and safety of STRIDE (Single Tremelimumab Regular Interval Durvalumab) in clinically relevant subgroups of uHCC with poorer prognosis, including participants with more decompensated hepatic function, worse performance status, or more advanced disease than the HIMALAYA (NCT03298451) study.</p><p><strong>Methods: </strong>SIERRA is a phase 3b, single-arm, multicenter study that enrolled participants with uHCC with: Child-Pugh (CP) class of B7 or B8 with Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1, without main trunk portal vein thrombosis (PVT) (CP B7/B8 cohort); CP class A with ECOG PS 2, without main trunk PVT (ECOG PS 2 cohort); or CP class A with ECOG PS 0-1 with evidence of chronic main trunk PVT (Vp4 cohort). Participants received STRIDE (tremelimumab 300 mg plus durvalumab 1,500 mg once followed by durvalumab 1,500 mg every 4 weeks). This preplanned early safety analysis occurred once ∼60 participants had been followed for ≥6 months (data cutoff: September 27, 2024). Co-primary endpoints are incidence of grade 3/4 adverse events (AEs) possibly related to study treatment (PRAEs) within 6 months of treatment initiation and objective response rate. The study is ongoing.</p><p><strong>Results: </strong>This analysis included 98 participants (CP B7/B8 cohort, <i>n</i> = 35; ECOG PS 2 cohort, <i>n</i> = 44; Vp4 cohort, <i>n</i> = 19). Median (Q1-Q3) number of cycles of durvalumab was 4.0 (2.0-8.0). Incidence of grade 3/4 PRAEs occurring within 6 months of treatment was 19.4% (95% confidence interval, 12.1-28.6) overall. Incidence of serious AEs was 32.7%. PRAEs, leading to death, occurred in 2.0% of participants.</p><p><strong>Conclusion: </strong>The safety profile of STRIDE was manageable and consistent with the HIMALAYA study in participants with poorer prognosis than in HIMALAYA.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12830029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052741","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":"Patterns and Prognostic Stratification of Recurrence after Thermal Ablation in Patients with Hepatocellular Carcinoma.","authors":"Chi-Ping Tan, Teng-Yu Lee, I-Cheng Lee, Kuo-Cheng Wu, Chien-An Liu, Nai-Chi Chiu, Shao-Jung Hsu, Pei-Chang Lee, Chi-Jung Wu, Chen-Ta Chi, Jiing-Chyuan Luo, Ming-Chih Hou, Yi-Hsiang Huang","doi":"10.1159/000550105","DOIUrl":"https://doi.org/10.1159/000550105","url":null,"abstract":"<p><strong>Background: </strong>Recurrence rates following thermal ablation for hepatocellular carcinoma (HCC) remain high, but the patterns of recurrence and post-recurrence outcomes are not well characterized. This study aimed to investigate the recurrence patterns and long-term post-recurrence survival (PRS) in patients with HCC after thermal ablation to inform post-recurrence treatment strategy.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 824 patients who underwent thermal ablation for HCC between 2007 and 2023. Recurrence patterns and factors influencing PRS in patients with recurrence within and beyond the Milan criteria were evaluated. An independent cohort of 198 patients served as an external validation cohort for the prognostic models.</p><p><strong>Results: </strong>During a median follow-up of 54.5 months, 536 patients experienced HCC recurrence, with 83.8% within and 16.2% beyond Milan criteria. For patients with recurrence within Milan criteria, early recurrence, recurrent tumor size, AFP, ALBI grade, and FIB-4 score were independent predictors of PRS. In patients with recurrence beyond Milan criteria, diabetes mellitus, macrovascular invasion, AFP, ALBI grade, and FIB-4 score independently predicted PRS. Based on PRS predictors, a risk model stratified patients with recurrence within Milan criteria into four risk groups, with median PRS of 103.7, 65, 48.7, and 28.6 months, respectively (<i>p</i> < 0.001). For recurrence beyond Milan criteria, a separate risk model classified patients into three risk groups, showing median PRS of 70.1, 24.7, and 8.1 months, along with probabilities of successful downstaging of 66.7%, 39.3%, and 0%, respectively (<i>p</i> < 0.001). The external validation results showed that both the Milan-in and Milan-out models demonstrated significant discriminative performance in the validation cohort.</p><p><strong>Conclusions: </strong>PRS in patients with recurrent HCC after thermal ablation is significantly influenced by recurrence patterns, tumor characteristics, and host factors. These findings may guide post-recurrence treatment strategies and optimize the timing of salvage liver transplantation.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12846322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146093050","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":"Proton Radiotherapy Alone versus Combined with Immunotherapies or Tyrosine Kinase Inhibitors for Barcelona Clinic Liver Cancer Stage B or C Hepatocellular Carcinoma.","authors":"Rodney Cheng-En Hsieh, Willy Po-Yuan Chen, Jin-Chiao Lee, Chia-Hsin Lin, Yu-Chen Chang, Chao-Wei Lee, Kun-Ming Chan, Hao-Chien Hung, Tony Kuo, Shen-Yen Lin, Tse-Ching Chen, Ting-Jung Wu, Chung-Wei Su, Hong-Shiue Chou, Chih-Hsien Cheng, Yi-Chung Hsieh, Chen-Yang Huang, Khac Chien Tran, James Welsh, Jason Chia-Hsun Hsieh","doi":"10.1159/000550067","DOIUrl":"10.1159/000550067","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to compare the outcomes of proton radiotherapy alone versus its combination with immuno-oncology agents (Proton-IO) or tyrosine kinase inhibitors (Proton-TKI) in patients with intermediate- to advanced-stage hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>We retrospectively reviewed the medical records of 137 patients with Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC treated with proton radiotherapy at Linkou Chang Gung Memorial Hospital between 2020 and 2023. Patients were stratified into three groups: proton radiotherapy alone (<i>n</i> = 64), Proton-IO (<i>n</i> = 44), and Proton-TKI (<i>n</i> = 29). The most frequently used immuno-oncology agents were atezolizumab-bevacizumab (<i>n</i> = 33) and pembrolizumab (<i>n</i> = 5). Tyrosine kinase inhibitors (TKIs) included lenvatinib (<i>n</i> = 16) and sorafenib (<i>n</i> = 13).</p><p><strong>Results: </strong>With a median follow-up of 30 months, patients in the Proton-IO group were significantly associated with higher 2-year overall survival (OS) rates compared with those receiving Proton-TKI or proton radiotherapy alone (77.0% vs. 47.2% vs. 52.7%; <i>p</i> = 0.002). Proton-IO was also associated with significantly longer time to progression (TTP) and distant metastasis-free survival (DMFS) (2-year TTP: 50.5% vs. 28.1% vs. 24.2%, <i>p</i> = 0.003; 2-year DMFS: 83.4% vs. 61.1% vs. 67.2%, <i>p</i> = 0.027). No significant differences in 2-year local control rates were observed among the treatment groups (97.7% vs. 92.9% vs. 86.8%; <i>p</i> = 0.230). Multivariate analysis identified Proton-IO as an independent predictor of improved OS (<i>p</i> < 0.001), TTP (<i>p</i> < 0.001), and DMFS (<i>p</i> = 0.004). Grade 3-4 upper gastrointestinal (UGI) bleeding was observed in 2 (1.5%) patients (proton monotherapy, <i>n</i> = 1; Proton-IO, <i>n</i> = 1). There were no significant differences among the groups in the incidence of grade ≥3 UGI bleeding, liver toxicity, colitis, rib fractures, or hematologic adverse events.</p><p><strong>Conclusion: </strong>In BCLC stage B/C HCC, proton radiotherapy combined with immunotherapy was significantly associated with higher OS, TTP, and DMFS without an increase in grade ≥3 toxicity compared with proton radiotherapy alone or Proton-TKIs.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12830032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052751","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":"Feasibility and Effectiveness of Liver Transplantation following Immunotherapy in Patients with Hepatocellular Carcinoma.","authors":"Giuliana Amaddeo, Manon Allaire, Maria Stella Franzè, Clément Dupré, Stefano Caruso, Teresa Antonini, Yasmina Chouik, Hélène Regnault, Aurélie Beaufrère, Jose Ursic-Bedoya, Massih Ningarhari, Thomas Uguen, Anaïs Jaillais, Olivier Roux, Lorraine Blaise, René Gerolami, Alina Pascale, Raffaele Brustia, Daniele Sommacale, Jérôme Dumortier, Vincent Leroy","doi":"10.1159/000548608","DOIUrl":"10.1159/000548608","url":null,"abstract":"<p><strong>Introduction: </strong>Immunotherapy is an attractive strategy for downstaging/bridging treatment of hepatocellular carcinoma (HCC) before liver transplantation (LT). This multicentre study reports the feasibility and effectiveness of LT following immunotherapy in a French HCC cohort.</p><p><strong>Methods: </strong>Clinical, biological, and radiological data were collected at the start and end of immunotherapy, and before LT. Outcomes were evaluated through radiological response post-immunotherapy, recurrence risk (R3-alpha-fetoprotein [AFP] score) on explanted livers, and post-LT complications, aiming to assess primary LT success, overall and disease-free survival.</p><p><strong>Results: </strong>Twenty-one HCC patients (17 males; median age 62 years [57-64]) were included in the study. Fourteen (66.7%) patients were BCLC-B, and sixteen (76.2%) received atezolizumab/bevacizumab (median 8.5 cycles [4.7-14]). At the end of immunotherapy, 57.1% met Milan-in criteria, and 95.2% had AFP score ≤2 (<i>p</i> = 0.002). The median interval from last immunotherapy to LT was 5.1 (2.7-9.3) months. All but 3 patients received standard immunosuppression. Explant pathology showed residual tumours in 71.4%, with 47.6% at high recurrence risk according to R3-AFP score. Two patients experienced allograft rejection, and one (4.8%) had HCC recurrence post-LT. Early adverse events occurred in 6 (28.5%) patients, leading to 5 (23.8%) deaths. At 12 months, 71.4% were alive without HCC recurrence. Lower overall survival was linked to pre-LT Child-Pugh B class, absence of prior HCC treatment, fewer than 5 immunotherapy cycles, and early post-LT complications.</p><p><strong>Conclusion: </strong>LT following immunotherapy is feasible in selected HCC patients, although caution is warranted due to the potential but manageable rejection risk. However, high early mortality warrants further investigation in larger prospective series.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12851629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146086476","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":"Comment on the Article \"Curative Treatment after Immunotherapy Leads to Excellent Outcomes in Patients with Hepatocellular Carcinoma\".","authors":"Ji Wu, Xiping Shen","doi":"10.1159/000549974","DOIUrl":"10.1159/000549974","url":null,"abstract":"","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":"646-648"},"PeriodicalIF":10.5,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12823127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030030","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":"Atezolizumab plus Bevacizumab with Transcatheter Arterial Chemoembolization (Sandwich Strategy) versus Atezolizumab plus Bevacizumab Alone in Hepatocellular Carcinoma: A Multicenter Retrospective Study.","authors":"Ko Hashimoto, Tomokazu Kawaoka, Tomoaki Emori, Aiko Tanaka, Yuki Shirane, Ryoichi Miura, Yasutoshi Fujii, Hikaru Nakahara, Kenji Yamaoka, Shinsuke Uchikawa, Hatsue Fujino, Atsushi Ono, Eisuke Murakami, Daiki Miki, C Nelson Hayes, Akira Hiramatsu, Kei Amioka, Michihiro Nonaka, Yasuyuki Aisaka, Kei Morio, Takashi Moriya, Yuji Teraoka, Hirotaka Kono, Yosuke Suehiro, Keiichi Masaki, Kazuki Ohya, Shintaro Takaki, Nami Mori, Keiji Tsuji, Yumi Kosaka, Takashi Nakahara, Hiroshi Aikata, Masataka Tsuge, Shiro Oka","doi":"10.1159/000549979","DOIUrl":"https://doi.org/10.1159/000549979","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to evaluate the effect of sandwiching on-demand transcatheter arterial chemoembolization (TACE) during atezolizumab (Atezo) and bevacizumab (Bev) therapy on overall survival (OS) and progression-free survival (PFS) in patients with unresectable hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>We retrospectively analyzed 398 patients who started Atezo/Bev therapy between October 2020 and April 2024. Overall, 245 patients were included: 51 in the ABC-TACE sandwich group and 194 in the Atezo/Bev alone group. Propensity score matching was performed to balance baseline characteristics, resulting in 49 matched patients per group. OS and PFS were analyzed using the Kaplan-Meier methods, with landmark analysis to adjust for immortal time bias. Multivariate analysis identified independent predictors of OS and PFS.</p><p><strong>Results: </strong>The ABC-TACE sandwich group had significantly longer OS (median, not reached vs. 21.0 months, <i>p</i> < 0.05) and PFS (18.7 months vs. 11.2 months, <i>p</i> < 0.05) than the Atezo/Bev alone group. Landmark analysis showed prolonged OS at multiple time points in the ABC-TACE sandwich group (<i>p</i> < 0.05, <i>p</i> < 0.05, <i>p</i> = 0.078). TACE independently contributed to both OS and PFS. No significant differences in adverse events were observed between the groups. No deterioration in the Child-Pugh score was observed before and after TACE (<i>p</i> = 0.976).</p><p><strong>Conclusion: </strong>Sandwiching TACE during Atezo/Bev therapy may improve survival outcomes for unresectable HCC.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12846315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146092873","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":"Change in Liver Function after Selective Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma: JIVROSG-2001 PRESIDENT-ALBI - A Secondary Analysis of a Multicenter Randomized Controlled Trial.","authors":"Yoshihisa Kodama, Masafumi Ikeda, Yasuaki Arai, Yoshitaka Inaba, Toshihiro Tanaka, Yasunori Arai, Shunsuke Sugawara, Hajime Yamazaki, Takeshi Aramaki, Hiroshi Anai, Shinichi Morita, Yasunari Fujinaga, Hiroshi Seki, Mikio Sato, Kenya Kamimura, Junji Ito, Masakatsu Tsurusaki, Tetsuro Nakazawa, Hiroyuki Tokue, Daisuke Abo, Kenichi Kato, Natsuko Hayashi, Osamu Sato, Miyuki Sone","doi":"10.1159/000549879","DOIUrl":"10.1159/000549879","url":null,"abstract":"<p><strong>Introduction: </strong>Liver function deterioration after transarterial chemoembolization (TACE) may preclude systemic therapy. The JIVROSG-1302 PRESIDENT study, a prospective, randomized controlled trial, showed a significantly higher local complete response rate with selective conventional TACE (cTACE) than with selective TACE using drug-eluting beads (DEB-TACE). However, this study did not assess the changes in liver function after selective TACE. The purpose of this study, JIVROSG-2001 PRESIDENT-ALBI, was to evaluate the change in liver function after selective TACE for unresectable hepatocellular carcinoma (HCC) using the same patient cohort.</p><p><strong>Methods: </strong>The primary endpoint was ALBI grade deterioration rate after 3 months of TACE compared to DEB-TACE and cTACE. Secondary endpoints included the ALBI grade and score change and the identification of risk factors associated with liver function deterioration.</p><p><strong>Results: </strong>A total of 197 patients with unresectable HCC were enrolled in this study. The ALBI grade deterioration rate at 3 months was 11% for the DEB-TACE group and 6% for the cTACE group, with no significant difference (<i>p</i> = 0.203). The mean ALBI score deterioration at 1 and 3 months was 0.06 and 0.02, respectively, and no notable deterioration in liver function was observed. The risk factors for ALBI score deterioration 1 month after selective TACE included large tumor diameter, high number of treated tumors, and treated vessels.</p><p><strong>Conclusions: </strong>Selective TACE, whether DEB-TACE or cTACE, did not significantly impair the liver function. Even with selective TACE, larger tumors, multiple tumors, and a large number of treated blood vessels were associated with worsening liver function 1 month after TACE.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":"567-576"},"PeriodicalIF":10.5,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12799235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970449","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":"Prognostic Usefulness of Clinical Complete Response after PD-1 Inhibitor-Based Combination Therapy for Unresectable Hepatocellular Carcinoma (GUIDANCE006).","authors":"Liang Ma, Da-Long Yang, Teng-Meng Zhong, Qing-Qing Pang, Min Luo, Wen-Feng Li, Yi-He Yan, Kang Chen, Guo-Dong Wang, Fu-Quan Yang, Yong-Cheng Lai, Ming-Song Wu, Xiao-Feng Dong, Yong-Yu Yang, Ning Peng, Jun-Liang Nong, Ze Su, Ya-Qun Yu, Lin Ye, Fan-Jian Zeng, Shao-Ping Liu, Xue-Yao Wang, Hong-Bing Yao, Chuang Qin, Mian-Jing Li, Jie Liu, Yong-Rong Liang, Pei-Sheng Wu, Fu-Xin Li, Shu-Chang Chen, Si-Cong Lu, Zhi-Cheng Li, Zhen Liu, Ping-Ping Guo, Li-Xin Pan, Jian-Hong Zhong","doi":"10.1159/000549844","DOIUrl":"10.1159/000549844","url":null,"abstract":"<p><strong>Background: </strong>Outcomes of patients with unresectable hepatocellular carcinoma (HCC) who achieve clinical complete response (cCR) to PD-1 inhibitor-based combination therapy are unclear. This study aimed to explore whether cCR after combination therapy is an accurate and reliable prognostic indicator and to identify predictors of cCR and pathological complete response that could aid in managing patients with HCC.</p><p><strong>Methods: </strong>Data were analyzed retrospectively for 1,266 patients with initially unresectable HCC who received combination therapy involving PD-1 inhibitors and interventional therapy at 23 medical centers across China between 2019 and 2023. Survival was compared between patients who showed cCR or not after combination therapy, and subgroup analyses differentiated further between patients who experienced pathological complete response or not after combination therapy and patients who subsequently underwent curative hepatectomy or not.</p><p><strong>Results: </strong>Among all patients, 200 (15.8%) achieved cCR after combination therapy, and 360 (28.4%) underwent curative hepatectomy following combination therapy. Survival rates at 3 years were significantly higher among those who achieved cCR after combination therapy than those who did not, whether overall survival (82.4 vs. 35.9%; HR 0.15, 95% CI: 0.12-0.19) or progression-free survival (63.4 vs. 26.4%; HR 0.19, 95% CI: 0.16-0.23). Similar results were obtained with subsets of patients matched through propensity scoring based on baseline characteristics. Patients who underwent hepatectomy showed significantly longer overall and progression-free survival than those who did not; and among those who underwent surgery, cCR after combination therapy was associated with significantly better survival. Multivariable analysis identified the following independent predictors of cCR: α-fetoprotein <400 ng/mL, single tumor, absence of macrovascular invasion, absence of extrahepatic metastasis, and combined with anti-angiogenic agents. cCR correlated strongly with pathological complete response (Φ = 0.633) and independently predicted it (OR 17.43, 95% CI: 5.69-53.35).</p><p><strong>Conclusions: </strong>cCR following PD-1 inhibitor-based combination therapy is associated with excellent survival in patients with unresectable HCC. Such response and the clinical characteristics that predict it may be useful for assessing prognosis after combination therapy.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":"592-610"},"PeriodicalIF":10.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12810982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998665","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":"Pathological Complete Response after Systemic Therapy and Curative Resection in Initially Unresectable Hepatocellular Carcinoma: Feasibility of a Tumor-Free with Drug-Free Strategy.","authors":"Qingyang Lin, Wei Peng, Xi Yu, Fan Xie, Xiaohui Wang, Zihan Song, Ma Luo, Zhenyun Yang, Zili Hu, Yi-Zhen Fu, Jin-Bin Chen, Dandan Hu, Keli Yang, Zhong-Guo Zhou, Minshan Chen, Shunli Shen, Yaojun Zhang, Jun-Cheng Wang","doi":"10.1159/000549793","DOIUrl":"10.1159/000549793","url":null,"abstract":"<p><strong>Introduction: </strong>The outcomes and optimal postoperative management of patients with initially unresectable hepatocellular carcinoma (uHCC) who achieve pathological complete response (pCR) after systemic therapy and curative resection remain undefined.</p><p><strong>Methods: </strong>This multicenter retrospective cohort study included consecutive patients with initially uHCC who received systemic therapy followed by curative resection at three tertiary centers in China between January 2020 and December 2023. The primary outcome was overall survival (OS); secondary endpoints included recurrence-free survival (RFS) and incidence of treatment-related adverse events (AEs).</p><p><strong>Results: </strong>Of the 2,212 patients who underwent conversion surgery, 1,623 (73.4%) received systemic therapy-based regimens; among them, 257 (15.8%) patients achieved pCR and were included in the analysis. The median tumor diameter was 9.0 cm; 39.7% had multifocal tumors, 55.6% presented with macrovascular invasion, and 70.4% were AFP-positive. Most patients (87.2%) received combination regimens based on immune checkpoint inhibitors. Postoperative adjuvant therapy was administered in 88 (34.2%) patients for a median duration of 6.05 months. After a median follow-up of 32.7 months, the 1-, 3-, and 5-year RFS rates were 81.7%, 60.3%, and 58.3%, and OS rates were 98.0%, 91.1%, and 85.5%, respectively. No significant differences in RFS or OS were observed between the adjuvant and active surveillance groups, though AEs occurred more frequent in the adjuvant group. Subgroup analyses failed to identify any population with clear benefit from adjuvant therapy. On multivariate analysis, postoperative alpha-fetoprotein (AFP) positivity was independently associated with inferior RFS and OS.</p><p><strong>Conclusions: </strong>Patients with uHCC who achieve pCR after systemic therapy and curative resection exhibit favorable long-term outcomes. Active surveillance yields comparable survival to adjuvant therapy with reduced toxicity. A \"Tumor-Free with Drug-Free\" strategy may be feasible in patients with normalized postoperative AFP levels, while those with persistent AFP positivity may represent a high-risk subgroup requiring individualized postoperative management.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":"577-591"},"PeriodicalIF":10.5,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12807518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998612","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":"Conversion Resection or Direct Resection for Patients with Intermediate-Stage Hepatocellular Carcinoma: A Multicentre Study.","authors":"Ying Zhou, Haiqing Wang, Jiayi Wu, Junyi Shen, Ji Ma, Qiu Li, Weixia Chen, Wusheng Lu, Xielin Feng, Maolin Yan, Tianfu Wen, Xiaoyun Zhang","doi":"10.1159/000549684","DOIUrl":"10.1159/000549684","url":null,"abstract":"<p><strong>Introduction: </strong>The majority of patients with hepatocellular carcinoma (HCC) are diagnosed at an intermediate stage, and current treatment options are associated with unfavourable overall prognosis. This study aimed to evaluate the efficacy of conversion therapy before resection compared with direct resection or comprehensive therapy alone in patients with intermediate-stage HCC, with a focus on pathological responses and long-term outcomes.</p><p><strong>Methods: </strong>In this multicentre study, 248 patients diagnosed with intermediate-stage HCC between January 2020 and December 2023 were enrolled. Of these, 56 patients received preoperative conversion therapy followed by resection (conversion resection group), 162 underwent direct resection (direct resection group), and 30 received comprehensive therapy alone and did not undergo surgical resection (comprehensive therapy group). Propensity score matching was performed to balance the baseline characteristics, and pathological responses were systematically evaluated.</p><p><strong>Results: </strong>Among conversion resection group, 13 patients (23.2%) achieved a pathological complete response, and 29 (51.8%) achieved a major pathological response. The conversion resection group exhibited significantly lower microvascular invasion rates (17.9% vs. 58.6%, <i>p</i> < 0.001) and higher tumour differentiation grades (<i>p</i> < 0.001). The median recurrence-free survival (RFS) was markedly improved in the conversion resection group (not reached vs. 12.3 months, <i>p</i> < 0.001), with 3-year overall survival (OS) rates of 94.7% vs. 77.6% vs. 43.9% being observed in the conversion resection group, direct resection group and comprehensive therapy group, respectively (<i>p</i> < 0.001). Multivariate analysis identified conversion therapy as an independent prognostic factor for both RFS (HR: 0.241, <i>p</i> < 0.001) and OS (HR: 0.179, <i>p</i> = 0.006).</p><p><strong>Conclusions: </strong>Preoperative conversion therapy could significantly improve pathological responses and long-term survival outcomes in intermediate-stage HCC patients.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":"552-566"},"PeriodicalIF":10.5,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12711257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781621","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}