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Survival Outcome Analysis of Stereotactic Body Radiotherapy and Immunotherapy (SBRT-IO) versus SBRT-alone in Unresectable Hepatocellular Carcinoma (HCC) 立体定向放疗和免疫治疗(SBRT-IO)与单用sbrt治疗不可切除肝细胞癌的生存结局分析
1区 医学
Liver Cancer Pub Date : 2023-10-01 DOI: 10.1159/000533425
Chi Leung Chiang, Francis Ann Shing Lee, Kenneth Sik Kwan Chan, Venus Wan Yan Lee, Keith Wan Hang Chiu, Ryan Lok Man Ho, John Ka Shun Fong, Natalie Sean Man Wong, Winnie Wing Ling Yip, Cynthia Sin Yu Yeung, Vince Wing Hang Lau, Man Kwan, Feng-Ming Spring Kong, Albert Chi Yan Chan
{"title":"Survival Outcome Analysis of Stereotactic Body Radiotherapy and Immunotherapy (SBRT-IO) versus SBRT-alone in Unresectable Hepatocellular Carcinoma (HCC)","authors":"Chi Leung Chiang, Francis Ann Shing Lee, Kenneth Sik Kwan Chan, Venus Wan Yan Lee, Keith Wan Hang Chiu, Ryan Lok Man Ho, John Ka Shun Fong, Natalie Sean Man Wong, Winnie Wing Ling Yip, Cynthia Sin Yu Yeung, Vince Wing Hang Lau, Man Kwan, Feng-Ming Spring Kong, Albert Chi Yan Chan","doi":"10.1159/000533425","DOIUrl":"https://doi.org/10.1159/000533425","url":null,"abstract":"<b><i>Introduction:</i></b> While combination of stereotactic body radiotherapy (SBRT) and immunotherapy are promising, their efficacy and safety have not been compared with SBRT-alone in patients with unresectable hepatocellular carcinoma (HCC). <b><i>Methods:</i></b> This retrospective study included 100 patients with nonmetastatic, unresectable HCC in two hospitals. Eligible patients had tumor nodules ≤3 and Child-Pugh liver function score of A5 to B7. Seventy patients received SBRT-alone, and 30 patients underwent combined SBRT and immunotherapy (SBRT-IO). Overall survival (OS), time to progression (TTP), overall response rate (ORR), and toxicity were analyzed. We adjusted for the potential confounding factors using propensity score matching. <b><i>Results:</i></b> The median tumor size was 7.3 cm (range, 2.6–18 cm). Twenty-five (25%) of patients had vascular invasion. Before propensity score matching, the 1-year and 3-year OS rate was 89.9% and 59.8% in the SBRT-IO group and 75.7% and 42.3% in SBRT-alone group (<i>p</i> = 0.039). After propensity score matching (1:2), 25 and 50 patients were selected from the SBRT-IO and SBRT-alone group. The 1-year and 3-year OS was 92.0% and 63.9% in the SBRT-IO group versus 74.0% and 43.3% in the SBRT-alone group (<i>p</i> = 0.034). The 1-year and 3-year TTP was better in SBRT-IO group (1-year: 68.9% vs. 58.9% and 3-year: 61.3% vs. 32.5%, <i>p</i> = 0.057). The ORR of 88% (complete response [CR]: 56%, partial response [PR]: 22%) in SBRT-IO arm was significantly better than 50% (CR: 20%, PR: 30%) in the SBRT-alone arm (<i>p</i> = 0.006). Three patients (12%) developed ≥grade 3 immune-related treatment adverse events (<i>n</i> = 2 hepatitis, <i>n</i> = 1 dermatitis) leading to permanent treatment discontinuation. <b><i>Conclusion:</i></b> Adding immunotherapy to SBRT resulted in better survival with manageable toxicities. Prospective randomized trial is warranted.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"42 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135660816","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}
引用次数: 0
PHOCUS: A Phase 3, Randomized, Open-Label Study of Sequential Treatment with Pexa-Vec (JX-594) and Sorafenib in Patients with Advanced Hepatocellular Carcinoma PHOCUS:Pexa-Vec(JX-594)和索拉非尼对晚期肝细胞癌患者进行序贯治疗的 3 期随机、开放标签研究
IF 13.8 1区 医学
Liver Cancer Pub Date : 2023-09-30 DOI: 10.1159/000533650
G. Abou-Alfa, Peter R. Galle, Yee Chao, Joseph Erinjeri, Jeong Heo, M. Borad, Angelo Luca, James M. Burke, Adina Pelusio, Delphine Agathon, Monika Lusky, C. Breitbach, S. Qin, Edward Gane
{"title":"PHOCUS: A Phase 3, Randomized, Open-Label Study of Sequential Treatment with Pexa-Vec (JX-594) and Sorafenib in Patients with Advanced Hepatocellular Carcinoma","authors":"G. Abou-Alfa, Peter R. Galle, Yee Chao, Joseph Erinjeri, Jeong Heo, M. Borad, Angelo Luca, James M. Burke, Adina Pelusio, Delphine Agathon, Monika Lusky, C. Breitbach, S. Qin, Edward Gane","doi":"10.1159/000533650","DOIUrl":"https://doi.org/10.1159/000533650","url":null,"abstract":"Introduction: Intratumoral administration of pexa-vec (pexastimogene devacirepvec), an oncolytic and immunotherapeutic vaccinia virus, given to patients with hepatocellular carcinoma (HCC), is associated with both local and distant tumor responses. We hypothesized subsequent treatment with sorafenib could demonstrate superior efficacy. Methods: This random phase III open-label study evaluated the sequential treatment with pexa-vec followed by sorafenib compared to sorafenib in patients with advanced HCC and no prior systemic treatment. The primary endpoint is overall survival (OS). Key secondary endpoints included time to progression (TTP), progression-free survival, overall response rate (ORR), and disease control rate (DCR). Safety was assessed in all patients who received ≥1 dose of study treatment. Results: The study was conducted at 142 sites in 16 countries. From December 30, 2015, to the interim analysis on August 2, 2019, 459 patients were randomly assigned (pexa-vec plus sorafenib: 234, sorafenib: 225). At the interim analysis, the median OS was 12.7 months (95% CI: 9.89, 14.95) in the pexa-vec plus sorafenib arm and 14.0 months (95% CI: 11.01, 18.00) in the sorafenib arm. This led to the early termination of the study. The median TTP was 2.0 months (95% CI: 1.77, 2.96) and 4.2 months (95% CI: 2.92, 4.63); ORR was 19.2% (45 patients) and 20.9% (47 patients); and DCR was 50.0% (117 patients) and 57.3% (129 patients) in the pexa-vec plus sorafenib and sorafenib arms, respectively. Serious adverse events were reported in 117 (53.7%) patients in the pexa-vec plus sorafenib and 77 (35.5%) patients in the sorafenib arm. Liver failure was the most frequently reported in both groups. Conclusion: Sequential pexa-vec plus sorafenib treatment did not demonstrate increased clinical benefit in advanced HCC and fared worse compared to sorafenib alone. The advent of the added value of checkpoint inhibitors should direct any further development of oncolytic virus therapy strategies.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"57 1","pages":""},"PeriodicalIF":13.8,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139333543","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}
引用次数: 0
Incidence and predictors of esophagogastric varices bleeding in patients with hepatocellular carcinoma in lenvatinib lenvatinib治疗肝癌患者食管胃静脉曲张出血的发生率和预测因素
1区 医学
Liver Cancer Pub Date : 2023-09-14 DOI: 10.1159/000534127
Massimo Iavarone, Eleonora Alimenti, Toshifumi Tada, Shigeo Shimose, Goki Suda, Changhoon Yoo, Caterina Soldà, Fabio Piscaglia, Giulia Tosetti, Fabio Marra, Caterina Vivaldi, Fabio Conti, Marta Schirripa, Hideki Iwamoto, Takuya Sho, So Heun Lee, Mario Domenico Rizzato, Matteo Tonnini, Margherita Rimini, Claudia Campani, Gianluca Masi, Francesco Foschi, Mariangela Bruccoleri, Takumi Kawaguchi, Takashi Kumada, Atsushi Hiraoka, Masanori Atsukawa, Shinya Fukunishi, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Takeshi Hatanaka, Satoru Kakizaki, Kazuhito Kawata, Fujimasa Tada, Hideko Ohama, Norio Itokawa, Tomomi Okubo, Taeang Arai, Michitaka Imai, Atsushi Naganuma, Andrea Casadei-Gardini, Pietro Lampertico
{"title":"Incidence and predictors of esophagogastric varices bleeding in patients with hepatocellular carcinoma in lenvatinib","authors":"Massimo Iavarone, Eleonora Alimenti, Toshifumi Tada, Shigeo Shimose, Goki Suda, Changhoon Yoo, Caterina Soldà, Fabio Piscaglia, Giulia Tosetti, Fabio Marra, Caterina Vivaldi, Fabio Conti, Marta Schirripa, Hideki Iwamoto, Takuya Sho, So Heun Lee, Mario Domenico Rizzato, Matteo Tonnini, Margherita Rimini, Claudia Campani, Gianluca Masi, Francesco Foschi, Mariangela Bruccoleri, Takumi Kawaguchi, Takashi Kumada, Atsushi Hiraoka, Masanori Atsukawa, Shinya Fukunishi, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Takeshi Hatanaka, Satoru Kakizaki, Kazuhito Kawata, Fujimasa Tada, Hideko Ohama, Norio Itokawa, Tomomi Okubo, Taeang Arai, Michitaka Imai, Atsushi Naganuma, Andrea Casadei-Gardini, Pietro Lampertico","doi":"10.1159/000534127","DOIUrl":"https://doi.org/10.1159/000534127","url":null,"abstract":"<b><i>Introduction:</i></b> Lenvatinib is indicated for the forefront treatment of advanced hepatocellular carcinoma (aHCC), but its use may be limited by the risk of esophagogastric varices (EGV) bleeding. This study assessed the prevalence, predictors, and complications of EGV in aHCC patients treated with lenvatinib. <b><i>Methods:</i></b> In this multicenter international retrospective study, cirrhotic patients treated with lenvatinib for aHCC, were enrolled if upper-gastrointestinal endoscopy was available within 6 months before treatment. Primary endpoint was the incidence of EGV bleeding during lenvatinib therapy; secondary endpoints were predictors for EGV bleeding, prevalence, and risk factors for the presence of EGV and high-risk EGV at baseline, as well as impact of EGV bleeding on patients’ survival. <b><i>Results:</i></b> 535 patients were enrolled in the study (median age: 72 years, 78% male, 63% viral etiology, 89% Child-Pugh A, 16% neoplastic portal vein thrombosis [nPVT], 56% Barcelona Clinic Liver Cancer-C): 234 had EGV (44%), 70 (30%) were at high risk and 59 were on primary prophylaxis. During lenvatinib treatment, 17 patients bled from EGV (3 grade 5), the 12-month cumulative incidence being 3%. The only baseline independent predictor of EGV bleeding was the presence of baseline high-risk EGV (hazard ratio: 6.94, 95% confidence interval [CI]: 2.23–21.57, <i>p</i> = 0.001). In these patients the 12-month risk was 17%. High-risk varices were independently associated with Child-Pugh B score (odds ratio [OR]: 2.12; 95% CI: 1.08–4.17, <i>p</i> = 0.03), nPVT (OR: 2.54; 95% CI: 1.40–4.61, <i>p</i> = 0.002), and platelets &amp;lt;150,000/μL (OR: 2.47; 95% CI: 1.35–4.50, <i>p</i> = 0.003). <b><i>Conclusion:</i></b> In hepatocellular carcinoma patients treated with lenvatinib, the risk of EGV bleeding was mostly low but significant only in patients with high-risk EGV at baseline.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134973088","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}
引用次数: 0
MRI Using Gadoxetic Acid in the Work-Up of Liver Nodules Not Conclusively Benign in Budd-Chiari Syndrome: A Prospective Long-Term Follow-Up 在Budd-Chiari综合征非决定性良性肝结节的MRI检查中使用Gadoxetic酸:一项前瞻性长期随访
1区 医学
Liver Cancer Pub Date : 2023-08-18 DOI: 10.1159/000533598
Angeles García-Criado, Jordi Rimola, Susana Seijo, Anna Darnell, Ernest Belmonte, Victor Sapena, Julián Moreno-Rojas, Valeria Pérez, Virginia Hernández-Gea, Carmen Ayuso, Maria Reig, Juan Carlos García-Pagán, Jordi Bruix
{"title":"MRI Using Gadoxetic Acid in the Work-Up of Liver Nodules Not Conclusively Benign in Budd-Chiari Syndrome: A Prospective Long-Term Follow-Up","authors":"Angeles García-Criado, Jordi Rimola, Susana Seijo, Anna Darnell, Ernest Belmonte, Victor Sapena, Julián Moreno-Rojas, Valeria Pérez, Virginia Hernández-Gea, Carmen Ayuso, Maria Reig, Juan Carlos García-Pagán, Jordi Bruix","doi":"10.1159/000533598","DOIUrl":"https://doi.org/10.1159/000533598","url":null,"abstract":"<b><i>Introduction:</i></b> The incidence of hepatocellular carcinoma (HCC) in Budd-Chiari syndrome (BCS) is unknown and there is no validated diagnostic work-up to define the liver nodules with arterial phase hyperenhancement (APHE), suggesting malignancy. This prospective study evaluates HCC incidence in a Western cohort of patients with BCS and assesses the performance of MRI with hepatobiliary contrast (HB-MRI) for nodule characterization. <b><i>Methods:</i></b> Patients with BCS followed in our hospital were prospectively evaluated by MRI with extracellular contrast (EC-MRI). Nodules with APHE categorized as non-conclusively benign by 2 radiologists were studied by HB-MRI and reviewed by 2 radiologists blinded to the EC-MRI results. A new EC-MRI 1 year later and clinical, analytical, and sonographic follow-up every 6 months for a median of 10 years was performed. <b><i>Results:</i></b> A total of 55 non-conclusively benign nodules with APHE were detected at EC-MRI in 41 patients. While 32 of them were suggestive of HCC by EC-MRI, all the 55 nodules showed increased uptake of hepatobiliary contrast. An unequivocal central scar was seen in 12/55 nodules at HB-MRI regardless of it was not detected on the EC-MRI. None of the nodules was hypointense in the hepatobiliary phase (HBP). HCC was not detected during a median of 10 years of follow-up. <b><i>Conclusions:</i></b> Detection of nodules with APHE is frequent in patients with BCS, but HCC is rare in Western patients with BCS. While EC-MRI may detect nodules suggesting malignancy, the identification of contrast uptake in the HBP at HB-MRI may help categorize them as benign.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"26 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136214853","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}
引用次数: 0
All Stages of Hepatocellular Carcinoma Patients Benefit from Systemic Therapy Combined with Locoregional Therapy. 所有阶段的肝细胞癌患者都受益于系统治疗和局部治疗。
IF 11.6 1区 医学
Liver Cancer Pub Date : 2023-08-12 eCollection Date: 2023-10-01 DOI: 10.1159/000533493
Masatoshi Kudo
{"title":"All Stages of Hepatocellular Carcinoma Patients Benefit from Systemic Therapy Combined with Locoregional Therapy.","authors":"Masatoshi Kudo","doi":"10.1159/000533493","DOIUrl":"10.1159/000533493","url":null,"abstract":"","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"12 5","pages":"395-404"},"PeriodicalIF":11.6,"publicationDate":"2023-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10603619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71412865","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}
引用次数: 0
Risk Factors for Early Onset of Proteinuria in Patients Receiving Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma. 接受阿特唑单抗加贝伐单抗治疗不可切除肝癌患者早发性蛋白尿的危险因素
IF 13.8 1区 医学
Liver Cancer Pub Date : 2023-08-01 DOI: 10.1159/000528145
Yuwa Ando, Tomokazu Kawaoka, Masanari Kosaka, Yuki Shirane, Yusuke Johira, Ryoichi Miura, Serami Murakami, Shigeki Yano, Kei Amioka, Kensuke Naruto, Yumi Kosaka, Shinsuke Uchikawa, Kenichiro Kodama, Hatsue Fujino, Takashi Nakahara, Atushi Ono, Eisuke Murakami, Masami Yamauchi, Wataru Okamoto, Shoichi Takahashi, Michio Imamura, Hiroshi Aikata
{"title":"Risk Factors for Early Onset of Proteinuria in Patients Receiving Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma.","authors":"Yuwa Ando,&nbsp;Tomokazu Kawaoka,&nbsp;Masanari Kosaka,&nbsp;Yuki Shirane,&nbsp;Yusuke Johira,&nbsp;Ryoichi Miura,&nbsp;Serami Murakami,&nbsp;Shigeki Yano,&nbsp;Kei Amioka,&nbsp;Kensuke Naruto,&nbsp;Yumi Kosaka,&nbsp;Shinsuke Uchikawa,&nbsp;Kenichiro Kodama,&nbsp;Hatsue Fujino,&nbsp;Takashi Nakahara,&nbsp;Atushi Ono,&nbsp;Eisuke Murakami,&nbsp;Masami Yamauchi,&nbsp;Wataru Okamoto,&nbsp;Shoichi Takahashi,&nbsp;Michio Imamura,&nbsp;Hiroshi Aikata","doi":"10.1159/000528145","DOIUrl":"https://doi.org/10.1159/000528145","url":null,"abstract":"<p><strong>Introduction: </strong>Proteinuria is one of the adverse events of atezolizumab plus bevacizumab combination therapy (Atezo + Bev) and can cause interruption in the use of Bev. However, the risk factors for proteinuria in patients with hepatocellular carcinoma (HCC) who are receiving Atezo + Bev have not yet been investigated. The aim of this study was to identify the risk factors for early onset of proteinuria in Atezo + Bev for patients with unresectable HCC.</p><p><strong>Methods: </strong>Sixty-four patients with Child-Pugh scores of 5-7, an Eastern Cooperative Oncology Group performance status of 0 or 1, and low level of proteinuria (1+ or less on a dipstick test and urine protein-to-creatinine ratio (UPCR) less than 2.0 g/g Cr) at the initiation of therapy were analyzed. The level of proteinuria was evaluated based on the Common Terminology Criteria for Adverse Events version 5.0. We adopted the UPCR for the quantitative test instead of a 24-h urine collection. The incidence of proteinuria and changes in liver function were retrospectively investigated.</p><p><strong>Results: </strong>The cumulative incidence of proteinuria over a 24-week period was 34.4%. Multivariate analysis showed that a low estimated glomerular filtration rate (hazard ratio [HR], 3.807; 95% confidence interval [CI], 1.579-9.180; <i>p</i> = 0.003), treatment for hypertension (HR, 6.224; 95% CI, 1.614-24.010; <i>p</i> = 0.008), and high systolic blood pressure (SBP) (HR, 2.649; 95% CI, 1.133-6.194; <i>p</i> = 0.025) were risk factors for proteinuria. Serum albumin levels and albumin-bilirubin scores in patients with proteinuria worsened. In addition, a mean SBP ≥135 mm Hg during treatment was the only risk factor for the development of severe proteinuria (UPCR >2 g/g Cr).</p><p><strong>Conclusion: </strong>Our study found that controlling blood pressure is extremely important for the management of proteinuria in patients with HCC who are receiving Atezo + Bev.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"12 3","pages":"251-261"},"PeriodicalIF":13.8,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1f/7b/lic-0012-0251.PMC10433089.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10049724","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}
引用次数: 2
Relationship of Atezolizumab plus Bevacizumab Treatment with Muscle Volume Loss in Unresectable Hepatocellular Carcinoma Patients: Multicenter Analysis. 阿特唑单抗加贝伐单抗治疗与不可切除肝细胞癌患者肌肉体积损失的关系:多中心分析
IF 13.8 1区 医学
Liver Cancer Pub Date : 2023-08-01 DOI: 10.1159/000527402
Atsushi Hiraoka, Takashi Kumada, Toshifumi Tada, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Noritomo Shimada, Kazuhito Kawata, Atsushi Naganuma, Masaki Kaibori, Takaaki Tanaka, Hideko Ohama, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Michitaka Imai, Yohei Koizumi, Shinichiro Nakamura, Kouji Joko, Hiroko Iijima, Hisashi Kosaka, Yoichi Hiasa, Masatoshi Kudo
{"title":"Relationship of Atezolizumab plus Bevacizumab Treatment with Muscle Volume Loss in Unresectable Hepatocellular Carcinoma Patients: Multicenter Analysis.","authors":"Atsushi Hiraoka,&nbsp;Takashi Kumada,&nbsp;Toshifumi Tada,&nbsp;Masashi Hirooka,&nbsp;Kazuya Kariyama,&nbsp;Joji Tani,&nbsp;Masanori Atsukawa,&nbsp;Koichi Takaguchi,&nbsp;Ei Itobayashi,&nbsp;Shinya Fukunishi,&nbsp;Kunihiko Tsuji,&nbsp;Toru Ishikawa,&nbsp;Kazuto Tajiri,&nbsp;Hironori Ochi,&nbsp;Satoshi Yasuda,&nbsp;Hidenori Toyoda,&nbsp;Chikara Ogawa,&nbsp;Takashi Nishimura,&nbsp;Takeshi Hatanaka,&nbsp;Satoru Kakizaki,&nbsp;Noritomo Shimada,&nbsp;Kazuhito Kawata,&nbsp;Atsushi Naganuma,&nbsp;Masaki Kaibori,&nbsp;Takaaki Tanaka,&nbsp;Hideko Ohama,&nbsp;Kazuhiro Nouso,&nbsp;Asahiro Morishita,&nbsp;Akemi Tsutsui,&nbsp;Takuya Nagano,&nbsp;Norio Itokawa,&nbsp;Tomomi Okubo,&nbsp;Taeang Arai,&nbsp;Michitaka Imai,&nbsp;Yohei Koizumi,&nbsp;Shinichiro Nakamura,&nbsp;Kouji Joko,&nbsp;Hiroko Iijima,&nbsp;Hisashi Kosaka,&nbsp;Yoichi Hiasa,&nbsp;Masatoshi Kudo","doi":"10.1159/000527402","DOIUrl":"https://doi.org/10.1159/000527402","url":null,"abstract":"<p><strong>Background/aim: </strong>There is no known report regarding the relationship of atezolizumab plus bevacizumab (Atez/Bev) treatment with muscle volume loss (MVL) in unresectable hepatocellular carcinoma (u-HCC) patients. This study aimed to elucidate the clinical relationship between MVL and Atez/Bev.</p><p><strong>Materials/methods: </strong>From September 2020 to December 2021, 229 u-HCC patients treated with Atez/Bev and with muscle volume data obtained by computed tomography at the baseline available were analyzed (median age, 74 years; males, 186 (81.2%); ECOG PS 0/1, 221 (96.5%); HCV:HBV:alcohol:others = 81:33:40:75; Child-Pugh A, 212 (92.6%); modified albumin-bilirubin (mALBI) grade 1:2a:2b = 79:60:90; BCLC 0:A:B:C = 1:24:87:117; median observation period, 6.8 months). Japan Society of Hepatology criteria were used for definition of MVL and prognostic factors were retrospectively evaluated.</p><p><strong>Results: </strong>Multivariate Cox-hazard analysis of prognostic factors for progression-free survival (PFS) showed elevated alpha-fetoprotein (AFP) (≥100 ng/mL) (HR 1.848, 95% CI 1.264-2.702, <i>p</i> = 0.002), mALBI grade (≥2a) (HR 1.563, 95% CI 1.035-2.359, <i>p</i> = 0.034), and MVL (HR 1.479, 95% CI 1.020-2.144, <i>p</i> = 0.039) as significant factors. For overall survival (OS), significant factors included elevated AFP (≥100 ng/mL) (HR 3.564, 95% CI 1.856-6.844, <i>p</i> < 0.001), mALBI grade (≥2a) (HR 3.451, 95% CI 1.580-7.538, <i>p</i> = 0.002), and MVL (HR 2.119, 95% CI 1.150-3.904, <i>p</i> = 0.016). Patients with MVL (MVL group, <i>n</i> = 91) showed worse PFS than those without (non-MVL group, <i>n</i> = 138) (median PFS 5.3 vs. 7.6 months, <i>p</i> = 0.025), while the MVL group showed worse OS (<i>p</i> = 0.038), though neither reached the median survival time.</p><p><strong>Conclusion: </strong>MVL may be a clinical factor related to poor prognosis in patients receiving Atez/Bev treatment for u-HCC.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"12 3","pages":"209-217"},"PeriodicalIF":13.8,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3a/91/lic-0012-0209.PMC10433099.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10406206","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}
引用次数: 3
Adjuvant Atezolizumab-Bevacizumab after Resection or Ablation for Hepatocellular Carcinoma. 阿特唑单抗-贝伐单抗在肝细胞癌切除术或消融后的辅助治疗。
IF 13.8 1区 医学
Liver Cancer Pub Date : 2023-08-01 DOI: 10.1159/000531225
Masatoshi Kudo
{"title":"Adjuvant Atezolizumab-Bevacizumab after Resection or Ablation for Hepatocellular Carcinoma.","authors":"Masatoshi Kudo","doi":"10.1159/000531225","DOIUrl":"https://doi.org/10.1159/000531225","url":null,"abstract":"Hepatic resection and radiofrequency ablation (RFA)/ microwave ablation are well-established curative treatments for hepatocellular carcinoma (HCC); however, the disease often recurs [1, 2]. Pathological studies of resected HCC specimens reported that microscopic intrahepatic metastases are present in about 10% of patients with a solitary HCC measuring 2 cm or less. Microvascular invasion is also present in about 27% of patients [3]. Based on these facts, it is believed that there is a certain risk of recurrence of intrahepatic metastasis, even for a single nodule measuring 2 cm or less. Furthermore, the larger the tumor, or the presence of multiple HCCs larger than 2 cm, increases the risk of intrahepatic metastasis and microvascular invasion, and therefore the risk of intrahepatic metastatic recurrence [4, 5]. There are two patterns of recurrence after curative treatment: early and late. Early recurrence involves mainly intrahepatic metastasis via the portal vein, while late recurrence has a more multicentric etiology [2]. About 80% of HCCs recur 5 years after RFA or resection [6]. The main reason for the poor prognosis associated with HCC is frequent recurrence, even after curative treatment. Repeated TACE to treat recurrence worsens liver function in many cases, resulting in death from liver failure. Conversely, if HCC recurrence after curative treatment can be suppressed, the prognosis should improve dramatically. Several adjuvant trials have been conducted to inhibit recurrence, but all yielded negative results [7–9]. To date, representative clinical trials of adjuvants that help to prevent recurrence include a trial of Vitamin K [7], the NIK-333 trial that used retinoid [8], and the STORM trial","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"12 3","pages":"189-197"},"PeriodicalIF":13.8,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f4/57/lic-2023-0012-0003-531225.PMC10360452.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10291505","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}
引用次数: 2
Genomic and Immune Features in an Intrahepatic Cholangiocarcinoma Patient with Microsatellite Instability-High Suffered Rapid Acquired Resistance to PD-1 Inhibitor. 微卫星不稳定-高水平肝内胆管癌患者PD-1抑制剂快速获得性耐药的基因组和免疫特征
IF 13.8 1区 医学
Liver Cancer Pub Date : 2023-08-01 DOI: 10.1159/000530273
Zhuo Cheng, Tianmei Zeng, Guang Yang, Di Liu, Zhi Zheng, Zhengang Yuan
{"title":"Genomic and Immune Features in an Intrahepatic Cholangiocarcinoma Patient with Microsatellite Instability-High Suffered Rapid Acquired Resistance to PD-1 Inhibitor.","authors":"Zhuo Cheng,&nbsp;Tianmei Zeng,&nbsp;Guang Yang,&nbsp;Di Liu,&nbsp;Zhi Zheng,&nbsp;Zhengang Yuan","doi":"10.1159/000530273","DOIUrl":"https://doi.org/10.1159/000530273","url":null,"abstract":"<p><strong>Introduction: </strong>Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive liver malignancy with poor prognosis. Recently, the development of immune checkpoint inhibitors (ICIs), such as programmed cell death 1 (PD-1) inhibitors, has emerged as a promising strategy in multiple tumor types, including ICC. Microsatellite instability-high (MSI-H) is an important biomarker for ICIs in solid tumors. The response rate in patients with MSI-H is significantly higher than in those with microsatellite stability/microsatellite instability-low. And approximately 80-90% of the patients with MSI-H could maintain sustained clinical benefits once they had an initial response. However, some patients could have primary resistance at the beginning, and some might have acquired resistance after long-term treatment.</p><p><strong>Case presentation: </strong>We present the case of an ICC patient with MSI-H who suffered rapid progression after a short-term remission with camrelizumab, a kind of PD-1 inhibitor, as second-line treatment. The patient's genomic and immune features were analyzed by next-generation sequencing and multiplex immunofluorescence staining to explore the possible mechanisms of the rapidly acquired resistance of ICIs in this MSI-H case.</p><p><strong>Conclusion: </strong>The genomic and immunohistochemical analysis showed that TGFBR2 mutation, loss of HLA B44 supertype, carrying B62 supertype, and increased PD-L1<sup>+</sup> cells, macrophages, and Tregs in the tumor microenvironment might be related to the nonsustain benefit of ICIs in this MSI-H patient.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"12 3","pages":"281-288"},"PeriodicalIF":13.8,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a5/df/lic-2023-0012-0003-530273.PMC10427924.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10603731","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}
引用次数: 0
Drug-Off Criteria in Patients with Hepatocellular Carcinoma Who Achieved Clinical Complete Response after Combination Immunotherapy Combined with Locoregional Therapy. 联合免疫治疗和局部治疗后达到临床完全反应的肝癌患者的药物禁用标准。
IF 11.6 1区 医学
Liver Cancer Pub Date : 2023-07-28 eCollection Date: 2023-09-01 DOI: 10.1159/000532023
Masatoshi Kudo
{"title":"Drug-Off Criteria in Patients with Hepatocellular Carcinoma Who Achieved Clinical Complete Response after Combination Immunotherapy Combined with Locoregional Therapy.","authors":"Masatoshi Kudo","doi":"10.1159/000532023","DOIUrl":"10.1159/000532023","url":null,"abstract":"","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"12 4","pages":"289-296"},"PeriodicalIF":11.6,"publicationDate":"2023-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71412862","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}
引用次数: 0
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