Pub Date : 2022-06-17eCollection Date: 2022-09-01DOI: 10.1159/000525582
Thomas Yau, David Tai, Stephen Lam Chan, Yi-Hsiang Huang, Su Pin Choo, Chiun Hsu, Tan To Cheung, Shi-Ming Lin, Wei Peng Yong, Joycelyn Lee, Thomas Leung, Tracy Shum, Cynthia S Y Yeung, Anna Yin-Ping Tai, Ada Lai Yau Law, Ann-Lii Cheng, Li-Tzong Chen
Background: Asia has a high burden of hepatocellular carcinoma (HCC) due to the high rates of chronic hepatitis B infection and accounts for 70% of HCC cases globally. In the past 20 years, the systemic treatment landscape of advanced HCC has evolved substantially - from tyrosine kinase inhibitors to immune-oncology agents plus anti-vascular endothelial growth factor agents. The appropriate sequence of therapies has become critical in optimizing patient outcomes given the increase in systemic therapeutic options. This article evaluates the evidence and provides expert recommendations for the use of systemic therapies after first-line treatment in patients with advanced HCC.
Summary: Based on three virtual meetings held in early 2021, a team of 17 experts comprising oncologists, a hepatologist, and a hepatobiliary surgeon from Hong Kong, Singapore, and Taiwan reviewed available data about systemic treatments for HCC after first line and formulated 28 statements. These statements aimed to provide expert guidance on selecting first and subsequent lines of therapies as well as recommending therapies in special circumstances, such as poor liver function, posttransplantation, recent gastrointestinal bleeding, or autoimmune diseases. Data supporting the statements were drawn from clinical trials and real-world studies. The 28 statements were then evaluated anonymously using a 5-point Likert scale, and 24 reached consensus, predefined as achieving 75% agreement. Statements generated covered the selection of first-line systemic therapy, considerations and goals of second-line systemic therapies, treatment selection following first-line therapy, and treatment recommendations following first-line tyrosine kinase inhibitors, immune-oncology monotherapy, or immune-oncology combination therapy. The authors also shared expert opinion on the use of second-line systemic therapy in patients with liver dysfunction, liver transplantation, and recent gastrointestinal or autoimmune disease.
Key messages: These expert statements summarize the latest data and expert opinion on selecting systemic treatment following first-line therapy in patients with unresectable advanced or metastatic HCC.
{"title":"Systemic Treatment of Advanced Unresectable Hepatocellular Carcinoma after First-Line Therapy: Expert Recommendations from Hong Kong, Singapore, and Taiwan.","authors":"Thomas Yau, David Tai, Stephen Lam Chan, Yi-Hsiang Huang, Su Pin Choo, Chiun Hsu, Tan To Cheung, Shi-Ming Lin, Wei Peng Yong, Joycelyn Lee, Thomas Leung, Tracy Shum, Cynthia S Y Yeung, Anna Yin-Ping Tai, Ada Lai Yau Law, Ann-Lii Cheng, Li-Tzong Chen","doi":"10.1159/000525582","DOIUrl":"https://doi.org/10.1159/000525582","url":null,"abstract":"<p><strong>Background: </strong>Asia has a high burden of hepatocellular carcinoma (HCC) due to the high rates of chronic hepatitis B infection and accounts for 70% of HCC cases globally. In the past 20 years, the systemic treatment landscape of advanced HCC has evolved substantially - from tyrosine kinase inhibitors to immune-oncology agents plus anti-vascular endothelial growth factor agents. The appropriate sequence of therapies has become critical in optimizing patient outcomes given the increase in systemic therapeutic options. This article evaluates the evidence and provides expert recommendations for the use of systemic therapies after first-line treatment in patients with advanced HCC.</p><p><strong>Summary: </strong>Based on three virtual meetings held in early 2021, a team of 17 experts comprising oncologists, a hepatologist, and a hepatobiliary surgeon from Hong Kong, Singapore, and Taiwan reviewed available data about systemic treatments for HCC after first line and formulated 28 statements. These statements aimed to provide expert guidance on selecting first and subsequent lines of therapies as well as recommending therapies in special circumstances, such as poor liver function, posttransplantation, recent gastrointestinal bleeding, or autoimmune diseases. Data supporting the statements were drawn from clinical trials and real-world studies. The 28 statements were then evaluated anonymously using a 5-point Likert scale, and 24 reached consensus, predefined as achieving 75% agreement. Statements generated covered the selection of first-line systemic therapy, considerations and goals of second-line systemic therapies, treatment selection following first-line therapy, and treatment recommendations following first-line tyrosine kinase inhibitors, immune-oncology monotherapy, or immune-oncology combination therapy. The authors also shared expert opinion on the use of second-line systemic therapy in patients with liver dysfunction, liver transplantation, and recent gastrointestinal or autoimmune disease.</p><p><strong>Key messages: </strong>These expert statements summarize the latest data and expert opinion on selecting systemic treatment following first-line therapy in patients with unresectable advanced or metastatic HCC.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"11 5","pages":"426-439"},"PeriodicalIF":13.8,"publicationDate":"2022-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8a/55/lic-0011-0426.PMC9485972.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33484259","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}
Pub Date : 2022-06-15eCollection Date: 2022-09-01DOI: 10.1159/000525489
Stephen Lam Chan, Chanisa Chotipanich, Su Pin Choo, Su Wen Kwang, Frankie Mo, Akeanong Worakitsitisatorn, David Tai, Raghav Sundar, David Chee Eng Ng, Kelvin Siu Hoong Loke, Leung Li, Kelvin Kwok Chai Ng, Yong Wei Peng, Simon Chun-Ho Yu
Introduction: This investigator-initiated clinical trial aims to study the efficacy and safety of administering selective internal radiation therapy with resin yttrium-90 microspheres (SIRT) followed by standard chemotherapy in unresectable intrahepatic cholangiocarcinoma (ICC).
Methods: A phase 2 single-arm multicenter study was conducted in patients with unresectable ICC (NCT02167711). SIRT was administered at dose of 120 Gy targeted at tumor followed by commencement of gemcitabine 1,000 mg/m2 and cisplatin 25 mg/m2 on days one and eight of a 21-day cycle. The primary endpoint was overall survival (OS), and the secondary endpoints include progression-free survival (PFS), response rate according to Response Evaluation Criteria in solid tumors 1.1, toxicity, and time from SIRT to commencement of chemotherapy.
Results: Total 31 patients were screened and twenty-four were recruited. All patients completed SIRT and 16 of them underwent subsequent chemotherapy. The median cycle of chemotherapy was 5 (range: 1-8). The median OS was 13.6 months (95% CI: 5.4-21.6) for the intent-to-treat population. Among 16 patients undergoing chemotherapy, the median OS was 21.6 months (95% CI: 7.3-25.2) and the median PFS was 9 months (95% CI: 3.2-13.1). The response rate was 25% (95% CI: 3.8-46.2%), and the disease control rate was 75% (95% CI: 53.8-96.2%). No new safety signal was observed, with fewer than 10% of patients suffering from grade 3 or higher treatment-related adverse events. The median time from SIRT to chemotherapy was 29 (range: 7-42) days. Eight patients could not receive chemotherapy due to rapid progressive disease (n = 4), underlying treatment unrelated comorbidities (n = 2), and withdrawal of consent due to personal reasons (n = 2).
Conclusions: Treatment of SIRT followed by standard gemcitabine and cisplatin chemotherapy is feasible and effective for unresectable ICC. Further studies are required to study the optimal sequence of SIRT and chemotherapy.
{"title":"Selective Internal Radiation Therapy with Yttrium-90 Resin Microspheres Followed by Gemcitabine plus Cisplatin for Unresectable Intrahepatic Cholangiocarcinoma: A Phase 2 Single-Arm Multicenter Clinical Trial.","authors":"Stephen Lam Chan, Chanisa Chotipanich, Su Pin Choo, Su Wen Kwang, Frankie Mo, Akeanong Worakitsitisatorn, David Tai, Raghav Sundar, David Chee Eng Ng, Kelvin Siu Hoong Loke, Leung Li, Kelvin Kwok Chai Ng, Yong Wei Peng, Simon Chun-Ho Yu","doi":"10.1159/000525489","DOIUrl":"https://doi.org/10.1159/000525489","url":null,"abstract":"<p><strong>Introduction: </strong>This investigator-initiated clinical trial aims to study the efficacy and safety of administering selective internal radiation therapy with resin yttrium-90 microspheres (SIRT) followed by standard chemotherapy in unresectable intrahepatic cholangiocarcinoma (ICC).</p><p><strong>Methods: </strong>A phase 2 single-arm multicenter study was conducted in patients with unresectable ICC (NCT02167711). SIRT was administered at dose of 120 Gy targeted at tumor followed by commencement of gemcitabine 1,000 mg/m<sup>2</sup> and cisplatin 25 mg/m<sup>2</sup> on days one and eight of a 21-day cycle. The primary endpoint was overall survival (OS), and the secondary endpoints include progression-free survival (PFS), response rate according to Response Evaluation Criteria in solid tumors 1.1, toxicity, and time from SIRT to commencement of chemotherapy.</p><p><strong>Results: </strong>Total 31 patients were screened and twenty-four were recruited. All patients completed SIRT and 16 of them underwent subsequent chemotherapy. The median cycle of chemotherapy was 5 (range: 1-8). The median OS was 13.6 months (95% CI: 5.4-21.6) for the intent-to-treat population. Among 16 patients undergoing chemotherapy, the median OS was 21.6 months (95% CI: 7.3-25.2) and the median PFS was 9 months (95% CI: 3.2-13.1). The response rate was 25% (95% CI: 3.8-46.2%), and the disease control rate was 75% (95% CI: 53.8-96.2%). No new safety signal was observed, with fewer than 10% of patients suffering from grade 3 or higher treatment-related adverse events. The median time from SIRT to chemotherapy was 29 (range: 7-42) days. Eight patients could not receive chemotherapy due to rapid progressive disease (<i>n</i> = 4), underlying treatment unrelated comorbidities (<i>n</i> = 2), and withdrawal of consent due to personal reasons (<i>n</i> = 2).</p><p><strong>Conclusions: </strong>Treatment of SIRT followed by standard gemcitabine and cisplatin chemotherapy is feasible and effective for unresectable ICC. Further studies are required to study the optimal sequence of SIRT and chemotherapy.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"11 5","pages":"451-459"},"PeriodicalIF":13.8,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4a/17/lic-0011-0451.PMC9485918.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33484709","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}
Introduction: Air pollutants are classified as carcinogens by the International Agency for Research on Cancer. Long-term exposure to ambient particulate matter with an aerodiameter of 2.5 μm or lower (PM2.5) has been reported to be linked with increased mortality due to hepatocellular carcinoma (HCC). However, the effects of air pollutants other than PM2.5 on HCC-related mortality have not been fully investigated. Accordingly, we conducted this study to assess the effect of long-term exposure to air pollutants (PM2.5 and nitrogen dioxide [NO2]) on HCC-related mortality.
Method: In 2005, the Taiwan Liver Cancer Network (TLCN) was established by the National Research Program for Genomic Medicine to recruit liver cancer patients from 5 major medical centers in northern, central, and southern Taiwan. The TLCN had successfully recruited 9,344 patients by the end of 2018. In this study, we included 1,000 patients randomly sampled from the TLCN to assess the effect of exposure to air pollutants on HCC mortality after HCC diagnosis. Daily averages of PM2.5 and NO2 concentrations were retrieved from 77 air quality-monitoring stations and interpolated to the townships of patients' residences by using the Kriging method. The effect of air pollutants on HCC survival was assessed using a Cox proportional hazards model.
Results: A total of 940 patients were included in the analysis. After adjusting for potential confounders and mutually adjusting for co-pollutants, we observed that the hazards ratio (95% confidence interval) for HCC-related mortality for every 1-μg/m3 increase in PM2.5 concentration was 1.11 (1.08-1.14) and that for every 1-ppb increase in NO2 concentration was 1.08 (1.03-1.13).
Conclusion: Our study suggests that long-term exposure to PM2.5 and NO2 was associated with decreased survival time in patients with HCC in Taiwan.
{"title":"Exposure to Air Pollution and Survival in Follow-Up after Hepatocellular Carcinoma.","authors":"Wei-Shan Chin, Shin-Chun Pan, Ching-Chun Huang, Pei-Jer Chen, Yue Leon Guo","doi":"10.1159/000525346","DOIUrl":"10.1159/000525346","url":null,"abstract":"<p><strong>Introduction: </strong>Air pollutants are classified as carcinogens by the International Agency for Research on Cancer. Long-term exposure to ambient particulate matter with an aerodiameter of 2.5 μm or lower (PM<sub>2.5</sub>) has been reported to be linked with increased mortality due to hepatocellular carcinoma (HCC). However, the effects of air pollutants other than PM<sub>2.5</sub> on HCC-related mortality have not been fully investigated. Accordingly, we conducted this study to assess the effect of long-term exposure to air pollutants (PM<sub>2.5</sub> and nitrogen dioxide [NO<sub>2</sub>]) on HCC-related mortality.</p><p><strong>Method: </strong>In 2005, the Taiwan Liver Cancer Network (TLCN) was established by the National Research Program for Genomic Medicine to recruit liver cancer patients from 5 major medical centers in northern, central, and southern Taiwan. The TLCN had successfully recruited 9,344 patients by the end of 2018. In this study, we included 1,000 patients randomly sampled from the TLCN to assess the effect of exposure to air pollutants on HCC mortality after HCC diagnosis. Daily averages of PM<sub>2.5</sub> and NO<sub>2</sub> concentrations were retrieved from 77 air quality-monitoring stations and interpolated to the townships of patients' residences by using the Kriging method. The effect of air pollutants on HCC survival was assessed using a Cox proportional hazards model.</p><p><strong>Results: </strong>A total of 940 patients were included in the analysis. After adjusting for potential confounders and mutually adjusting for co-pollutants, we observed that the hazards ratio (95% confidence interval) for HCC-related mortality for every 1-μg/m<sup>3</sup> increase in PM<sub>2.5</sub> concentration was 1.11 (1.08-1.14) and that for every 1-ppb increase in NO<sub>2</sub> concentration was 1.08 (1.03-1.13).</p><p><strong>Conclusion: </strong>Our study suggests that long-term exposure to PM<sub>2.5</sub> and NO<sub>2</sub> was associated with decreased survival time in patients with HCC in Taiwan.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"11 5","pages":"474-482"},"PeriodicalIF":11.6,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7d/40/lic-0011-0474.PMC9485987.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33484713","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}
Introduction: With the advent of effective systemic therapy, transarterial chemoembolization (TACE) is established as a highly effective locoregional treatment modality for carefully selected patients with hepatocellular carcinoma (HCC). This randomized controlled trial was conducted to clarify whether selective TACE with drug-eluting beads (DEB-TACE) loaded with epirubicin or selective conventional TACE (cTACE) with epirubicin-ethiodized oil might be more effective for obtaining complete response(CR) in patients with HCC.
Methods: Between March 2016 and May 2019, Child-Pugh class A or B patients with unresectable HCC who were scheduled to receive selective TACE were randomly assigned at a 1:1 ratio to the DEB-TACE arm or the cTACE arm. The primary endpoint was the CR rate at 3 months, as evaluated according to the modified Response Evaluation Criteria in Solid Tumors by an independent review committee, and the secondary endpoints were the CR rate at 1 month and incidences of adverse events.
Results: A total of 200 patients (DEB-TACE, 99 patients; cTACE, 101 patients) were enrolled in the study. The CR rates at 3 months and 1 month were significantly higher in the cTACE arm (75.2%, 84.2%) as compared with the DEB-TACE arm (27.6%, 35.7%). However, the frequencies of adverse events of any grade, including pyrexia (DEB-TACE vs. cTACE, 19.4% vs. 45.5%, p = 0.0001), fatigue (5.1% vs. 15.8%, p = 0.0194), malaise (11.1% vs. 25.7%, p = 0.0103), appetite loss (12.1% vs. 28.7%, p = 0.0048), abdominal pain (12.1% vs. 23.8%, p = 0.0423), increased serum bilirubin (22.2% vs. 48.5%, p = 0.0002), hypoalbuminemia (43.4% vs. 60.3%, p = 0.0154), increased serum aspartate aminotransferase (35.7% vs. 81.2%, p < 0.0001), and increased serum alanine aminotransferase (35.7% vs. 77.2%, p < 0.0001), were also significantly higher in the cTACE arm than in the DEB-TACE arm.
Conclusions: Selective cTACE appeared to have higher CR rates for local tumor control as compared to selective DEB-TACE for HCC. However, the frequency of postembolization syndrome was also significantly higher in the cTACE group than in the DEB-TACE group. Thus, to achieve CR, cTACE may be selected over DEB-TACE in patients who can be expected to tolerate postembolization syndrome.
导读:随着有效全身治疗的出现,经动脉化疗栓塞(TACE)被确立为一种高效的局部区域治疗方式,用于精心挑选的肝细胞癌(HCC)患者。这项随机对照试验的目的是阐明,在HCC患者中,是使用表柔比星药物洗脱珠(DEB-TACE)进行选择性TACE治疗,还是使用表柔比星乙化油进行选择性常规TACE治疗更有效。方法:2016年3月至2019年5月期间,Child-Pugh A级或B级不可切除HCC患者计划接受选择性TACE,按1:1的比例随机分配到DEB-TACE组或cace组。主要终点是3个月时的CR率,由独立审查委员会根据修订的实体瘤反应评价标准进行评估,次要终点是1个月时的CR率和不良事件的发生率。结果:共200例患者(DEB-TACE 99例;cTACE, 101例患者)纳入研究。3个月和1个月时,cTACE组的CR率(75.2%,84.2%)明显高于DEB-TACE组(27.6%,35.7%)。然而,任何级别的不良事件发生频率,包括发热(debtace vs. cTACE, 19.4% vs. 45.5%, p = 0.0001)、疲劳(5.1% vs. 15.8%, p = 0.0194)、不适(11.1% vs. 25.7%, p = 0.0103)、食欲减退(12.1% vs. 28.7%, p = 0.0048)、腹痛(12.1% vs. 23.8%, p = 0.0423)、血清胆红素升高(22.2% vs. 48.5%, p = 0.0002)、低白蛋白血症(43.4% vs. 60.3%, p = 0.0154)、血清天门氨酸转氨酶升高(35.7% vs. 81.2%, p < 0.0001)、血清丙氨酸转氨酶升高(35.7% vs 77.2%, p < 0.0001), cace组也显著高于DEB-TACE组。结论:与选择性DEB-TACE治疗HCC相比,选择性cTACE在局部肿瘤控制方面具有更高的CR率。然而,栓塞后综合征的频率在cTACE组也明显高于DEB-TACE组。因此,为了达到CR,对于能够耐受栓塞后综合征的患者,可以选择cTACE而不是DEB-TACE。
{"title":"Conventional or Drug-Eluting Beads? Randomized Controlled Study of Chemoembolization for Hepatocellular Carcinoma: JIVROSG-1302.","authors":"Masafumi Ikeda, Yasuaki Arai, Yoshitaka Inaba, Toshihiro Tanaka, Shunsuke Sugawara, Yoshihisa Kodama, Takeshi Aramaki, Hiroshi Anai, Shinichi Morita, Yoshinori Tsukahara, Hiroshi Seki, Mikio Sato, Kenya Kamimura, Kimei Azama, Masakatsu Tsurusaki, Eiji Sugihara, Masaya Miyazaki, Tatsushi Kobayashi, Miyuki Sone","doi":"10.1159/000525500","DOIUrl":"https://doi.org/10.1159/000525500","url":null,"abstract":"<p><strong>Introduction: </strong>With the advent of effective systemic therapy, transarterial chemoembolization (TACE) is established as a highly effective locoregional treatment modality for carefully selected patients with hepatocellular carcinoma (HCC). This randomized controlled trial was conducted to clarify whether selective TACE with drug-eluting beads (DEB-TACE) loaded with epirubicin or selective conventional TACE (cTACE) with epirubicin-ethiodized oil might be more effective for obtaining complete response(CR) in patients with HCC.</p><p><strong>Methods: </strong>Between March 2016 and May 2019, Child-Pugh class A or B patients with unresectable HCC who were scheduled to receive selective TACE were randomly assigned at a 1:1 ratio to the DEB-TACE arm or the cTACE arm. The primary endpoint was the CR rate at 3 months, as evaluated according to the modified Response Evaluation Criteria in Solid Tumors by an independent review committee, and the secondary endpoints were the CR rate at 1 month and incidences of adverse events.</p><p><strong>Results: </strong>A total of 200 patients (DEB-TACE, 99 patients; cTACE, 101 patients) were enrolled in the study. The CR rates at 3 months and 1 month were significantly higher in the cTACE arm (75.2%, 84.2%) as compared with the DEB-TACE arm (27.6%, 35.7%). However, the frequencies of adverse events of any grade, including pyrexia (DEB-TACE vs. cTACE, 19.4% vs. 45.5%, <i>p</i> = 0.0001), fatigue (5.1% vs. 15.8%, <i>p</i> = 0.0194), malaise (11.1% vs. 25.7%, <i>p</i> = 0.0103), appetite loss (12.1% vs. 28.7%, <i>p</i> = 0.0048), abdominal pain (12.1% vs. 23.8%, <i>p</i> = 0.0423), increased serum bilirubin (22.2% vs. 48.5%, <i>p</i> = 0.0002), hypoalbuminemia (43.4% vs. 60.3%, <i>p</i> = 0.0154), increased serum aspartate aminotransferase (35.7% vs. 81.2%, <i>p</i> < 0.0001), and increased serum alanine aminotransferase (35.7% vs. 77.2%, <i>p</i> < 0.0001), were also significantly higher in the cTACE arm than in the DEB-TACE arm.</p><p><strong>Conclusions: </strong>Selective cTACE appeared to have higher CR rates for local tumor control as compared to selective DEB-TACE for HCC. However, the frequency of postembolization syndrome was also significantly higher in the cTACE group than in the DEB-TACE group. Thus, to achieve CR, cTACE may be selected over DEB-TACE in patients who can be expected to tolerate postembolization syndrome.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"11 5","pages":"440-450"},"PeriodicalIF":13.8,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e1/0e/lic-0011-0440.PMC9485929.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33484258","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}
Pub Date : 2022-06-14eCollection Date: 2022-09-01DOI: 10.1159/000525488
Elia Gigante, Christian Hobeika, Brigitte Le Bail, Valérie Paradis, David Tougeron, Marie Lequoy, Mohamed Bouattour, Jean-Frederic Blanc, Nathalie Ganne-Carrié, Henri Tran, Clémence Hollande, Manon Allaire, Giuliana Amaddeo, Hélène Regnault, Paul Vigneron, Maxime Ronot, Laure Elkrief, Gontran Verset, Eric Trepo, Aziz Zaanan, Marianne Ziol, Massih Ningarhari, Julien Calderaro, Julien Edeline, Jean-Charles Nault
Backgrounds and aims: Even if no systemic treatment is currently validated for unresectable hepatocellular-cholangiocarcinoma (cHCC-CCA), tyrosine kinase inhibitors (TKIs) and platinum-based chemotherapy are frequently used in clinical practice. Our study aims to describe the effectiveness of first-line systemic treatments in patients with cHCC-CCA.
Patients and methods: Patients with histological diagnosis of unresectable or metastatic cHCC-CCA confirmed by a centralized review (WHO classification 2019) and who received systemic treatment from 2009 to 2020 were included retrospectively in 11 centers. The outcomes of patients with cHCC-CCA were compared with patients with hepatocellular carcinoma (HCC) treated by sorafenib (n = 117) and with intrahepatic cholangiocarcinoma (iCCA, n = 94) treated mainly by platinum-based chemotherapy using a frailty Cox model. The efficacy of TKIs and platinum-based chemotherapies in patients with cHCC-CCA was assessed using a doubly robust estimator.
Results: A total of 83 patients with cHCC-CCA were included and were predominantly male (72%) with underlying cirrhosis (55%). 67% of patients had extrahepatic metastases and 31% macrovascular tumor invasion. cHCC-CCAs were more often developed on cirrhosis (55.4%) than iCCA (26.6%) but less frequently than HCC (80.2%) (p < 0.001). Both HCC (36.8% and cHCC-CCA (66.2%) had less frequent extrahepatic metastases than iCCA (81%) (p < 0.001). Unadjusted overall survival (OS) was better in iCCA (13 months) compared to cHCC-CCA (12 months) and HCC (11 months) (p = 0.130). In multivariable analysis, after adjustment by a Cox frailty model, patients with cHCC-CCA had the same survival as HCC and iCCA (HR = 0.67, 95% CI: 0.37-1.22, p = 0.189 and HR = 0.66, 95% CI: 0.43-1.02, p = 0.064, respectively). ALBI score (HR = 2.15; 95% CI: 1.23-3.76; p = 0.009), ascites (HR = 3.45, 95% CI: 1.31-9.03, p = 0.013), and tobacco use (HR = 2.29, 95% CI: 1.08-4.87, p = 0.032) were independently associated with OS in patients with cHCC-CCA. Among patients with cHCC-CCA, 25 patients treated with TKI were compared with 54 patients who received platinum-based chemotherapies. Patients treated with TKI had a median OS of 8.3 months compared to 11.9 months for patients treated with platinum-based chemotherapy (p = 0.86). After a robust doubly adjustment on tumor number and size, vascular invasion, ALBI, MELD, and cirrhosis, the type of treatment did not impact OS (HR = 0.92, 95% CI: 0.27-3.15, p = 0.88) or progression-free survival (HR = 1.24, 95% CI: 0.44-3.49, p = 0.67).
Conclusions: First-line systemic treatments with TKIs or platinum-based chemotherapies have similar efficacy in patients with unresectable/metastatic cHCC-CCA. The ALBI score predicts OS.
{"title":"Systemic Treatments with Tyrosine Kinase Inhibitor and Platinum-Based Chemotherapy in Patients with Unresectable or Metastatic Hepatocholangiocarcinoma.","authors":"Elia Gigante, Christian Hobeika, Brigitte Le Bail, Valérie Paradis, David Tougeron, Marie Lequoy, Mohamed Bouattour, Jean-Frederic Blanc, Nathalie Ganne-Carrié, Henri Tran, Clémence Hollande, Manon Allaire, Giuliana Amaddeo, Hélène Regnault, Paul Vigneron, Maxime Ronot, Laure Elkrief, Gontran Verset, Eric Trepo, Aziz Zaanan, Marianne Ziol, Massih Ningarhari, Julien Calderaro, Julien Edeline, Jean-Charles Nault","doi":"10.1159/000525488","DOIUrl":"https://doi.org/10.1159/000525488","url":null,"abstract":"<p><strong>Backgrounds and aims: </strong>Even if no systemic treatment is currently validated for unresectable hepatocellular-cholangiocarcinoma (cHCC-CCA), tyrosine kinase inhibitors (TKIs) and platinum-based chemotherapy are frequently used in clinical practice. Our study aims to describe the effectiveness of first-line systemic treatments in patients with cHCC-CCA.</p><p><strong>Patients and methods: </strong>Patients with histological diagnosis of unresectable or metastatic cHCC-CCA confirmed by a centralized review (WHO classification 2019) and who received systemic treatment from 2009 to 2020 were included retrospectively in 11 centers. The outcomes of patients with cHCC-CCA were compared with patients with hepatocellular carcinoma (HCC) treated by sorafenib (<i>n</i> = 117) and with intrahepatic cholangiocarcinoma (iCCA, <i>n</i> = 94) treated mainly by platinum-based chemotherapy using a frailty Cox model. The efficacy of TKIs and platinum-based chemotherapies in patients with cHCC-CCA was assessed using a doubly robust estimator.</p><p><strong>Results: </strong>A total of 83 patients with cHCC-CCA were included and were predominantly male (72%) with underlying cirrhosis (55%). 67% of patients had extrahepatic metastases and 31% macrovascular tumor invasion. cHCC-CCAs were more often developed on cirrhosis (55.4%) than iCCA (26.6%) but less frequently than HCC (80.2%) (<i>p</i> < 0.001). Both HCC (36.8% and cHCC-CCA (66.2%) had less frequent extrahepatic metastases than iCCA (81%) (<i>p</i> < 0.001). Unadjusted overall survival (OS) was better in iCCA (13 months) compared to cHCC-CCA (12 months) and HCC (11 months) (<i>p</i> = 0.130). In multivariable analysis, after adjustment by a Cox frailty model, patients with cHCC-CCA had the same survival as HCC and iCCA (HR = 0.67, 95% CI: 0.37-1.22, <i>p</i> = 0.189 and HR = 0.66, 95% CI: 0.43-1.02, <i>p</i> = 0.064, respectively). ALBI score (HR = 2.15; 95% CI: 1.23-3.76; <i>p</i> = 0.009), ascites (HR = 3.45, 95% CI: 1.31-9.03, <i>p</i> = 0.013), and tobacco use (HR = 2.29, 95% CI: 1.08-4.87, <i>p</i> = 0.032) were independently associated with OS in patients with cHCC-CCA. Among patients with cHCC-CCA, 25 patients treated with TKI were compared with 54 patients who received platinum-based chemotherapies. Patients treated with TKI had a median OS of 8.3 months compared to 11.9 months for patients treated with platinum-based chemotherapy (<i>p</i> = 0.86). After a robust doubly adjustment on tumor number and size, vascular invasion, ALBI, MELD, and cirrhosis, the type of treatment did not impact OS (HR = 0.92, 95% CI: 0.27-3.15, <i>p</i> = 0.88) or progression-free survival (HR = 1.24, 95% CI: 0.44-3.49, <i>p</i> = 0.67).</p><p><strong>Conclusions: </strong>First-line systemic treatments with TKIs or platinum-based chemotherapies have similar efficacy in patients with unresectable/metastatic cHCC-CCA. The ALBI score predicts OS.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"11 5","pages":"460-473"},"PeriodicalIF":13.8,"publicationDate":"2022-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ac/9b/lic-0011-0460.PMC9485952.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33484712","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}
We added a comment to the the article by Kim et al.. We first described how the hazard function and commonly used survival function act complementary, although these two functions are mathematically equivalent. Then, we pointed out two notable findings of the present article: 1) a recurrence by metastasis is presumed to occurred constantly at an annualized incidence of 4%-10% until 6 postoperative years; and 2) the annualized recurrence rates between the 5th and 10th postoperative years were between 3%-10% in cirrhotic patients and this figure was comparable to or even lower than the reported annual incidence of HCC in cirrhotic patients (up to 8%). We also pointed out three issues to be paid attention for: 1) the authors amalgamated patients with HBV- and HCV-related HCC together when calculating the hazard function, although the background liver of HCV-related HCC is hypothesized to have a higher carcinogenetic activity than that of HBV-related HCC, at least during the era before the advent of direct-acting antivirals; 2) the authors would have obtained interesting results had they evaluated the risk factors for late-phase recurrence exclusively in patients with HBV infection, including HBV-specific covariates into the analysis; and 3) many investigators may confuse a pathogenic factor with its surrogate marker when interpreting the significance of fibrosis in studies investigating risk factors leading to HCC development.
{"title":"Regarding \"Postresection Period-Specific Hazard of Recurrence as a Framework for Surveillance Strategy in Patients with Hepatocellular Carcinoma: A Multicenter Outcome Study\".","authors":"Hiroshi Imamura, Kiyoshi Hasegawa, Yuji Soejima, Akio Saiura","doi":"10.1159/000525065","DOIUrl":"https://doi.org/10.1159/000525065","url":null,"abstract":"We added a comment to the the article by Kim et al.. \u0000 We first described how the hazard function and commonly used survival function act complementary, although these two functions are mathematically equivalent.\u0000Then, we pointed out two notable findings of the present article: 1) a recurrence by metastasis is presumed to occurred constantly at an annualized incidence of 4%-10% until 6 postoperative years; and 2) the annualized recurrence rates between the 5th and 10th postoperative years were between 3%-10% in cirrhotic patients and this figure was comparable to or even lower than the reported annual incidence of HCC in cirrhotic patients (up to 8%).\u0000 We also pointed out three issues to be paid attention for: 1) the authors amalgamated patients with HBV- and HCV-related HCC together when calculating the hazard function, although the background liver of HCV-related HCC is hypothesized to have a higher carcinogenetic activity than that of HBV-related HCC, at least during the era before the advent of direct-acting antivirals; 2) the authors would have obtained interesting results had they evaluated the risk factors for late-phase recurrence exclusively in patients with HBV infection, including HBV-specific covariates into the analysis; and 3) many investigators may confuse a pathogenic factor with its surrogate marker when interpreting the significance of fibrosis in studies investigating risk factors leading to HCC development.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"11 5","pages":"483-486"},"PeriodicalIF":13.8,"publicationDate":"2022-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/55/1a/lic-0011-0483.PMC9485984.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33484710","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}
Pub Date : 2022-05-10eCollection Date: 2022-06-01DOI: 10.1159/000524977
Masatoshi Kudo
NA
{"title":"Combination Immunotherapy with Anti-PD-1/PD-L1 Antibody plus Anti-VEGF Antibody May Promote Cytotoxic T Lymphocyte Infiltration in Hepatocellular Carcinoma, Including in the Noninflamed Subclass.","authors":"Masatoshi Kudo","doi":"10.1159/000524977","DOIUrl":"https://doi.org/10.1159/000524977","url":null,"abstract":"<jats:p>NA</jats:p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"11 3","pages":"185-191"},"PeriodicalIF":13.8,"publicationDate":"2022-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218634/pdf/lic-0011-0185.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40616546","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}
Hepatocellular carcinoma is one of the leading causes of cancer-related death both in Japan and globally. In the advanced stage, hepatic arterial infusion chemotherapy (HAIC) is one of the most commonly used treatment options for liver cancer in Japan, and implantation of a catheter system (called a port system) in the body is a treatment method that has evolved mainly in Japan. The Guideline Committee of the Japanese Society of Interventional Radiology and the Japanese Society of Implantable Port Assisted Treatment jointly published clinical practice guidelines for HAIC with a port system to ensure its appropriate and safe performance in Japanese in 2018. We have written an updated English version of the guidelines with the aim of making this treatment widely known to experts globally. In this article, the evidence, method, indication, treatment regimen, and maintenance of the system are summarized.
{"title":"Clinical Practice Guidelines for Hepatic Arterial Infusion Chemotherapy with a Port System Proposed by the Japanese Society of Interventional Radiology and Japanese Society of Implantable Port Assisted Treatment.","authors":"Kazuomi Ueshima, Atsushi Komemushi, Takeshi Aramaki, Hideki Iwamoto, Shuntaro Obi, Yozo Sato, Toshihiro Tanaka, Kiyoshi Matsueda, Michihisa Moriguchi, Hiroya Saito, Miyuki Sone, Takuji Yamagami, Yoshitaka Inaba, Masatoshi Kudo, Yasuaki Arai","doi":"10.1159/000524893","DOIUrl":"10.1159/000524893","url":null,"abstract":"<p><p>Hepatocellular carcinoma is one of the leading causes of cancer-related death both in Japan and globally. In the advanced stage, hepatic arterial infusion chemotherapy (HAIC) is one of the most commonly used treatment options for liver cancer in Japan, and implantation of a catheter system (called a port system) in the body is a treatment method that has evolved mainly in Japan. The Guideline Committee of the Japanese Society of Interventional Radiology and the Japanese Society of Implantable Port Assisted Treatment jointly published clinical practice guidelines for HAIC with a port system to ensure its appropriate and safe performance in Japanese in 2018. We have written an updated English version of the guidelines with the aim of making this treatment widely known to experts globally. In this article, the evidence, method, indication, treatment regimen, and maintenance of the system are summarized.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"11 5","pages":"407-425"},"PeriodicalIF":11.6,"publicationDate":"2022-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1f/1d/lic-0011-0407.PMC9485983.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33484715","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}