Simon Gray, Angela Lamarca, Mairéad G. McNamara, Julien Edeline, Karen Piper-Hanley, Juan W. Valle, Richard A. Hubner
Hepatocellular carcinoma (HCC) is a growing health concern, with an estimated global incidence of over 1 million by 2025. In its intermediate and advanced stages, HCC remains a challenging condition to treat, despite a recently expanded array of systemic therapies, which continues to grow. Extensive efforts have accordingly been made to identify predictive factors to guide treatment decisions. However, currently, only one predictive biomarker is in widespread clinical use, namely elevated alpha-fetoprotein for second-line systemic therapy with ramucirumab. This article reviews known prognostic and predictive biomarkers for patients with HCC who are treated with locoregional and systemic therapies, including recent controversies around the potential impact of HCC aetiology on the efficacy of systemic therapies.
{"title":"Prognostic and predictive factors for locoregional and systemic therapies in hepatocellular carcinoma","authors":"Simon Gray, Angela Lamarca, Mairéad G. McNamara, Julien Edeline, Karen Piper-Hanley, Juan W. Valle, Richard A. Hubner","doi":"10.1002/lci2.62","DOIUrl":"10.1002/lci2.62","url":null,"abstract":"<p>Hepatocellular carcinoma (HCC) is a growing health concern, with an estimated global incidence of over 1 million by 2025. In its intermediate and advanced stages, HCC remains a challenging condition to treat, despite a recently expanded array of systemic therapies, which continues to grow. Extensive efforts have accordingly been made to identify predictive factors to guide treatment decisions. However, currently, only one predictive biomarker is in widespread clinical use, namely elevated alpha-fetoprotein for second-line systemic therapy with ramucirumab. This article reviews known prognostic and predictive biomarkers for patients with HCC who are treated with locoregional and systemic therapies, including recent controversies around the potential impact of HCC aetiology on the efficacy of systemic therapies.</p>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"4 1","pages":"13-27"},"PeriodicalIF":0.0,"publicationDate":"2022-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.62","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43237249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Omar Fakih, Suraiya S. Haddad, Sophie Walker, Julien Edeline, Florien Estrade, Xin Wang, Angela Lamarca, Mairéad G. McNamara, Juan W. Valle, Richard A. Hubner
Background & Aims
Preserved performance status (PS) and liver function are required for systemic therapy in patients with advanced hepatocellular carcinoma (aHCC). We investigated the frequency of suitability for further systemic therapies following sorafenib in aHCC.
Methods
Demographic, tumour and therapy-related data were collected retrospectively for patients with aHCC who received sorafenib at a UK tertiary referral centre (training cohort), and an independent French centre (validation cohort). The primary endpoint was percentage of patients with Child-Pugh class A (CP-A) liver disease and PS 0–1 after sorafenib discontinuation.
Results
Sorafenib was received by 182 patients. After sorafenib discontinuation, 93 patients (51%) were CP-A and 60 patients (33%) were PS 0–1; 43 patients (24%) were both CP-A and PS 0–1. On multivariable analysis, patients with Albumin-Bilirubin (ALBI) score of 1 at time of sorafenib commencement were more likely to be suitable for post-sorafenib therapy, (44% grade 1 vs 15% grade 2) (OR 3.76, 95%CI 1.72–8.25, P = .0009). In the validation cohort of 216 patients baseline ALBI grade was also significantly associated with suitability for further systemic therapy (P = .008).
Conclusions
Most patients with aHCC are not suitable for further systemic therapy after sorafenib, but those with ALBI grade 1 have a greater likelihood of suitability.
{"title":"ALBI grade predicts suitability for further systemic therapy following sorafenib in patients with advanced hepatocellular carcinoma","authors":"Omar Fakih, Suraiya S. Haddad, Sophie Walker, Julien Edeline, Florien Estrade, Xin Wang, Angela Lamarca, Mairéad G. McNamara, Juan W. Valle, Richard A. Hubner","doi":"10.1002/lci2.61","DOIUrl":"10.1002/lci2.61","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background & Aims</h3>\u0000 \u0000 <p>Preserved performance status (PS) and liver function are required for systemic therapy in patients with advanced hepatocellular carcinoma (aHCC). We investigated the frequency of suitability for further systemic therapies following sorafenib in aHCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Demographic, tumour and therapy-related data were collected retrospectively for patients with aHCC who received sorafenib at a UK tertiary referral centre (training cohort), and an independent French centre (validation cohort). The primary endpoint was percentage of patients with Child-Pugh class A (CP-A) liver disease and PS 0–1 after sorafenib discontinuation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Sorafenib was received by 182 patients. After sorafenib discontinuation, 93 patients (51%) were CP-A and 60 patients (33%) were PS 0–1; 43 patients (24%) were both CP-A and PS 0–1. On multivariable analysis, patients with Albumin-Bilirubin (ALBI) score of 1 at time of sorafenib commencement were more likely to be suitable for post-sorafenib therapy, (44% grade 1 vs 15% grade 2) (OR 3.76, 95%CI 1.72–8.25, <i>P</i> = .0009). In the validation cohort of 216 patients baseline ALBI grade was also significantly associated with suitability for further systemic therapy (<i>P</i> = .008).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Most patients with aHCC are not suitable for further systemic therapy after sorafenib, but those with ALBI grade 1 have a greater likelihood of suitability.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"4 1","pages":"5-12"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.61","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42595039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Charlotte Van Laeken, Thibault Taelman, Sarah Cappuyns, Geert Maleux, Vincent Vandecaveye, Chris Verslype, Christophe Deroose, Jeroen Dekervel
Background and Aims
Radioembolization (RE) for unresectable hepatocellular carcinoma (HCC) can provide clinical benefit for well-selected patients, whilst in others, rapid disease progression is observed. As an alternative for this patient population, new potent systemic treatment options are emerging. We aimed to identify the clinical factors associated with rapid progression following RE and assess the feasibility of starting a systemic treatment after progression.
Methods
A retrospective cohort study of patients with unresectable HCC undergoing RE at a single referral centre between January 2009 and December 2018. Progression-free and overall survival times were calculated. Uni- and multivariate cox regression analysis was used to assess factors associated with poor outcomes. Charts were reviewed for post-progression treatment strategies.
Results
Overall, 116 patients with unresectable HCC were included. Median PFS after RE was 6.7 months (95% CI 3.97–9.37), which varied significantly (P < .001) with Eastern Cooperative Oncology Group Performance Status (EGOC PS) (ECOG 0, 20.9 months [95% CI 8.6–33.2]; ECOG 1, 7.7 months [95% CI 3.1–12.1]; ECOG 2, 4.4 months [95% CI 1.7–7]). This association remained significant after multivariate testing, together with the number of HCC lesions (P = .017) and α-FP (P = .050). Progressive disease after RE occurred in 82 patients, of whom only 40 received subsequent systemic treatment. Again, ECOG PS at the time of progression was significantly better for patients who did receive systemic treatment versus those who did not (P = .002).
Conclusion
Patients with unresectable HCC, impaired general condition and multinodular disease have inferior outcomes after radioembolization. After RE, close monitoring of patient performance status, liver function and cancer control is warranted to allow timely initiation of systemic treatment when indicated.
背景与目的放射栓塞(RE)治疗不可切除的肝细胞癌(HCC)可以为选定的患者提供临床益处，而在其他患者中，观察到疾病的快速进展。作为这一患者群体的替代方案，新的有效的全身治疗方案正在出现。我们的目的是确定与RE后快速进展相关的临床因素，并评估进展后开始全身治疗的可行性。方法回顾性队列研究2009年1月至2018年12月在单个转诊中心接受RE治疗的不可切除HCC患者。计算无进展生存时间和总生存时间。采用单因素和多因素cox回归分析评估与不良预后相关的因素。回顾了进展后治疗策略的图表。结果共纳入116例不可切除HCC患者。RE后的中位PFS为6.7个月(95% CI 3.97-9.37)，与东部肿瘤合作组绩效状态(ECOG) (ECOG 0, 20.9个月[95% CI 8.6-33.2];ECOG 1,7.7个月[95% CI 3.1-12.1];ECOG 2, 4.4个月[95% CI 1.7-7])。在多变量检验后，这种关联仍然显著，包括HCC病变数量(P = 0.017)和α-FP (P = 0.050)。82例患者发生RE后的进展性疾病，其中只有40例接受了后续的全身治疗。同样，接受全身治疗的患者在进展时的ECOG PS明显优于未接受全身治疗的患者(P = 0.002)。结论不可切除的肝细胞癌、全身功能受损及多结节病变患者行放射栓塞治疗后预后较差。RE术后，应密切监测患者的身体状况、肝功能和癌症控制情况，以便在需要时及时开始全身治疗。
{"title":"Clinical factors associated with early disease progression after radioembolization for hepatocellular carcinoma and feasibility of post-progression systemic therapy","authors":"Charlotte Van Laeken, Thibault Taelman, Sarah Cappuyns, Geert Maleux, Vincent Vandecaveye, Chris Verslype, Christophe Deroose, Jeroen Dekervel","doi":"10.1002/lci2.60","DOIUrl":"10.1002/lci2.60","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Radioembolization (RE) for unresectable hepatocellular carcinoma (HCC) can provide clinical benefit for well-selected patients, whilst in others, rapid disease progression is observed. As an alternative for this patient population, new potent systemic treatment options are emerging. We aimed to identify the clinical factors associated with rapid progression following RE and assess the feasibility of starting a systemic treatment after progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective cohort study of patients with unresectable HCC undergoing RE at a single referral centre between January 2009 and December 2018. Progression-free and overall survival times were calculated. Uni- and multivariate cox regression analysis was used to assess factors associated with poor outcomes. Charts were reviewed for post-progression treatment strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, 116 patients with unresectable HCC were included. Median PFS after RE was 6.7 months (95% CI 3.97–9.37), which varied significantly (<i>P</i> < .001) with Eastern Cooperative Oncology Group Performance Status (EGOC PS) (ECOG 0, 20.9 months [95% CI 8.6–33.2]; ECOG 1, 7.7 months [95% CI 3.1–12.1]; ECOG 2, 4.4 months [95% CI 1.7–7]). This association remained significant after multivariate testing, together with the number of HCC lesions (<i>P</i> = .017) and α-FP (<i>P</i> = .050). Progressive disease after RE occurred in 82 patients, of whom only 40 received subsequent systemic treatment. Again, ECOG PS at the time of progression was significantly better for patients who did receive systemic treatment versus those who did not (<i>P</i> = .002).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Patients with unresectable HCC, impaired general condition and multinodular disease have inferior outcomes after radioembolization. After RE, close monitoring of patient performance status, liver function and cancer control is warranted to allow timely initiation of systemic treatment when indicated.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"3 3","pages":"128-136"},"PeriodicalIF":0.0,"publicationDate":"2022-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.60","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42124658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Machine learning and biomarkers in hepatocellular carcinoma: The future is now","authors":"F. Ponziani, E. Giannini, Q. Lai","doi":"10.1002/lci2.67","DOIUrl":"https://doi.org/10.1002/lci2.67","url":null,"abstract":"serum, urine, and tissue samples).","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43330134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carla Pires Amaro, Michael J. Allen, Jennifer J. Knox, Erica S. Tsang, Howard J. Lim, Richard M. Lee-Ying, Kelvin W. Chan, Jessica Qian, Brandon M. Meyers, Alia Thawer, Sulaiman M. S. Al-Saadi, Tina Hsu, Ravi Ramjeesingh, Hatim Karachiwala, Tasnima Abedin, Vincent C. Tam
Background and Aims
A phase 3 trial showed lenvatinib to be effective and safe in the treatment of unresectable hepatocellular carcinoma (HCC), however, its performance in the real world and effect of dosing on survival are unclear.
Methods
From July 2018 to June 2020, HCC patients treated with lenvatinib from 10 Canadian cancer centres were included. Overall survival (OS) and progression-free survival (PFS) were retrospectively analysed and compared across first- and later lines use of lenvatinib. In patients receiving lenvatinib first-line, OS between different mean dose intensities and starting doses were compared.
Results
A total of 220 patients were included, of which 79% received lenvatinib as first-line therapy. For first-line versus later line treatment, median OS was 12.5 versus 11.8 months (P = .83) and median PFS was 7.6 versus 4.6 months (P = .27) respectively. Of patients receiving lenvatinib first-line, 54% started at full dose according to their weight. Median OS for patients starting lenvatinib at full- and reduced-dose was 12.3 and 15.8 months (P = .75) respectively. Median OS for patients with a mean dose intensity >66.7% compared ≤66.7% was 13.7 and 7.7 months (P = .01). In the multivariate analysis, dose intensity (>66.7 vs ≤66.7%) did not predict for OS [HR 0.70, 95% CI 0.42–1.18; P = .18]. The most common side effects were fatigue (59%), hypertension (41%) and decreased appetite (25%).
Conclusions
Lenvatinib appears to be effective in real-world practice regardless of the line of therapy. Dose modifications at the start or during treatment did not appear to significantly affect survival.
{"title":"Dosing, efficacy and safety of lenvatinb in the real-world treatment of hepatocellular carcinoma: Results from a Canadian database","authors":"Carla Pires Amaro, Michael J. Allen, Jennifer J. Knox, Erica S. Tsang, Howard J. Lim, Richard M. Lee-Ying, Kelvin W. Chan, Jessica Qian, Brandon M. Meyers, Alia Thawer, Sulaiman M. S. Al-Saadi, Tina Hsu, Ravi Ramjeesingh, Hatim Karachiwala, Tasnima Abedin, Vincent C. Tam","doi":"10.1002/lci2.59","DOIUrl":"10.1002/lci2.59","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>A phase 3 trial showed lenvatinib to be effective and safe in the treatment of unresectable hepatocellular carcinoma (HCC), however, its performance in the real world and effect of dosing on survival are unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>From July 2018 to June 2020, HCC patients treated with lenvatinib from 10 Canadian cancer centres were included. Overall survival (OS) and progression-free survival (PFS) were retrospectively analysed and compared across first- and later lines use of lenvatinib. In patients receiving lenvatinib first-line, OS between different mean dose intensities and starting doses were compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 220 patients were included, of which 79% received lenvatinib as first-line therapy. For first-line versus later line treatment, median OS was 12.5 versus 11.8 months (<i>P</i> = .83) and median PFS was 7.6 versus 4.6 months (<i>P</i> = .27) respectively. Of patients receiving lenvatinib first-line, 54% started at full dose according to their weight. Median OS for patients starting lenvatinib at full- and reduced-dose was 12.3 and 15.8 months (<i>P</i> = .75) respectively. Median OS for patients with a mean dose intensity >66.7% compared ≤66.7% was 13.7 and 7.7 months (<i>P</i> = .01). In the multivariate analysis, dose intensity (>66.7 vs ≤66.7%) did not predict for OS [HR 0.70, 95% CI 0.42–1.18; <i>P</i> = .18]. The most common side effects were fatigue (59%), hypertension (41%) and decreased appetite (25%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Lenvatinib appears to be effective in real-world practice regardless of the line of therapy. Dose modifications at the start or during treatment did not appear to significantly affect survival.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"3 3","pages":"119-127"},"PeriodicalIF":0.0,"publicationDate":"2022-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.59","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43812995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nishal Ravindran, Amol Agarwal, Feng Li, P. Thuluvath
The guidelines recommend surveillance with liver ultrasound (US) for early detection of hepatocellular carcinoma (HCC). The accuracy of US is operator‐dependent and is limited in those with severe obesity or ascites. Magnetic resonance imaging (MRI) may have higher accuracy for detecting HCC, especially early HCC.
{"title":"Liver ultrasound in cirrhosis is inadequate for hepatocellular carcinoma surveillance compared to magnetic resonance imaging","authors":"Nishal Ravindran, Amol Agarwal, Feng Li, P. Thuluvath","doi":"10.1002/lci2.57","DOIUrl":"https://doi.org/10.1002/lci2.57","url":null,"abstract":"The guidelines recommend surveillance with liver ultrasound (US) for early detection of hepatocellular carcinoma (HCC). The accuracy of US is operator‐dependent and is limited in those with severe obesity or ascites. Magnetic resonance imaging (MRI) may have higher accuracy for detecting HCC, especially early HCC.","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"3 1","pages":"113 - 118"},"PeriodicalIF":0.0,"publicationDate":"2022-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45976239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tuul Purevsambuu, Simona Bota, Florian Hucke, Harald Hofer, Peter Ferenci, Wolfgang Sieghart, Markus Peck-Radosavljevic
Introduction
Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death worldwide with increasing incidence. Effective antiviral treatment for chronic hepatitis C (CHC) became available in the last 7 years but despite the WHO Hepatitis elimination targets, they are not universally available today in all regions for all the patients, indicating still a bleak outlook for CHC-associated HCC in the next decades.
Aim
To assess the HCC incidence in relation to interferon (IFN)-based antiviral treatment response and baseline characteristics of a large cohort of chronic hepatitis C (CHC) patients from a single institution.
Methods
We retrospectively collected data of CHC patients, who were diagnosed between 1989 and 2011 and treated at the AKH-University Hospital of Vienna before the introduction of direct-acting antiviral (DAA) only therapy. We analysed the HCC incidence in patients with a sustained virological response (SVR) and without SVR according to the patients' baseline characteristics.
Results
Our study included 2134 patients, who were treated or not treated with IFN-based antiviral treatment and had long-term follow-up available. The overall HCC incidence in this cohort was 6.2% (132 HCC cases over a median follow-up period of 9 years). According to the baseline fibrosis stage, the overall HCC incidence was: 1.1% in patients with baseline fibrosis stage F0-2, 8.2% in F3 and 20.6% in F4 patients. The HCC incidence was significantly higher in non-SVR and no-treatment group as compared with SVR patients: 12.4% vs 1.9%, P < .0001, 7.3% vs 1.9%, P < .0001. In multivariate analysis, lower platelet count (odds ratio-OR = -0.1, 95% CI: 0.15-0.63), for the SVR group and presence of cirrhosis (OR = 3.6, 95% CI: 1.59-8.17), ALBI grade >=2 (OR = 2.3, 95% CI: 1.0-5.3) for the non-SVR group were independently associated with HCC occurrence. For the group of patients with no treatment, the only predictor for HCC was high baseline alpha-fetoprotein values (OR = 10.2, 95% CI: 2.2-47.9).
Conclusion
The achievement of SVR significantly reduces the risk for HCC occurrence during long-term follow-up. However, the risk remains high in successfully treated patients with low platelet count and in patients who did not achieve SVR with more adv
肝细胞癌(HCC)是全球癌症相关死亡的第二大常见原因，发病率不断上升。慢性丙型肝炎(CHC)的有效抗病毒治疗在过去7年中已经出现，但尽管世卫组织制定了消除肝炎的目标，但目前还没有在所有地区对所有患者普遍提供抗病毒治疗，这表明在未来几十年，慢性丙型肝炎相关HCC的前景仍然黯淡。目的评估来自单一机构的大型慢性丙型肝炎(CHC)患者的HCC发生率与干扰素(IFN)抗病毒治疗反应和基线特征的关系。方法回顾性收集1989年至2011年间诊断并在维也纳akh -大学医院接受直接抗病毒(DAA)治疗前接受治疗的CHC患者的资料。我们根据患者的基线特征分析了有持续病毒学反应(SVR)和没有SVR的患者的HCC发病率。结果本研究纳入了2134例患者，接受或未接受基于干扰素的抗病毒治疗，并进行了长期随访。该队列中HCC的总发病率为6.2%(在9年的中位随访期间有132例HCC)。根据基线纤维化分期，HCC总发病率为:基线纤维化F0-2期患者为1.1%，F3期为8.2%，F4期为20.6%。与SVR患者相比，非SVR组和未治疗组的HCC发生率显著高于SVR组:12.4% vs 1.9%， P <0001, 7.3% vs . 1.9%， P <在多变量分析中，SVR组较低的血小板计数(比值比OR = -0.1, 95% CI: 0.15-0.63)和非SVR组存在肝硬化(OR = 3.6, 95% CI: 1.59-8.17)、ALBI分级>=2 (OR = 2.3, 95% CI: 1.0-5.3)与HCC的发生独立相关。对于未接受治疗的患者组，HCC的唯一预测因子是高基线甲胎蛋白值(OR = 10.2, 95% CI: 2.2-47.9)。结论达到SVR可显著降低肝细胞癌的长期随访风险。然而，在治疗成功的低血小板计数患者和未达到SVR的晚期肝病患者中，风险仍然很高。这些危险因素应在本地区HCC监测决策中予以考虑。
{"title":"Hepatocellular carcinoma incidence in chronic hepatitis C patients according to sustained virological response (SVR) with interferon-based therapies and baseline characteristics","authors":"Tuul Purevsambuu, Simona Bota, Florian Hucke, Harald Hofer, Peter Ferenci, Wolfgang Sieghart, Markus Peck-Radosavljevic","doi":"10.1002/lci2.52","DOIUrl":"10.1002/lci2.52","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death worldwide with increasing incidence. Effective antiviral treatment for chronic hepatitis C (CHC) became available in the last 7 years but despite the WHO Hepatitis elimination targets, they are not universally available today in all regions for all the patients, indicating still a bleak outlook for CHC-associated HCC in the next decades.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To assess the HCC incidence in relation to interferon (IFN)-based antiviral treatment response and baseline characteristics of a large cohort of chronic hepatitis C (CHC) patients from a single institution.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively collected data of CHC patients, who were diagnosed between 1989 and 2011 and treated at the AKH-University Hospital of Vienna before the introduction of direct-acting antiviral (DAA) only therapy. We analysed the HCC incidence in patients with a sustained virological response (SVR) and without SVR according to the patients' baseline characteristics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our study included 2134 patients, who were treated or not treated with IFN-based antiviral treatment and had long-term follow-up available. The overall HCC incidence in this cohort was 6.2% (132 HCC cases over a median follow-up period of 9 years). According to the baseline fibrosis stage, the overall HCC incidence was: 1.1% in patients with baseline fibrosis stage F0-2, 8.2% in F3 and 20.6% in F4 patients. The HCC incidence was significantly higher in non-SVR and no-treatment group as compared with SVR patients: 12.4% vs 1.9%, <i>P</i> < .0001, 7.3% vs 1.9%, <i>P</i> < .0001. In multivariate analysis, lower platelet count (odds ratio-OR = -0.1, 95% CI: 0.15-0.63), for the SVR group and presence of cirrhosis (OR = 3.6, 95% CI: 1.59-8.17), ALBI grade >=2 (OR = 2.3, 95% CI: 1.0-5.3) for the non-SVR group were independently associated with HCC occurrence. For the group of patients with no treatment, the only predictor for HCC was high baseline alpha-fetoprotein values (OR = 10.2, 95% CI: 2.2-47.9).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The achievement of SVR significantly reduces the risk for HCC occurrence during long-term follow-up. However, the risk remains high in successfully treated patients with low platelet count and in patients who did not achieve SVR with more adv","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"3 2","pages":"53-62"},"PeriodicalIF":0.0,"publicationDate":"2022-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.52","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48941417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eleonora Di Carlo, Antonio D'Alessio, Antonella Cammarota, Valentina Zanuso, Tiziana Pressiani, Silvia Bozzarelli, Giuseppe Ferrillo, Giulia Vatteroni, Vittorio Pedicini, Laura Giordano, Nicola Personeni, Lorenza Rimassa
Background & Aims
Treatment of hepatocellular carcinoma (HCC) with immune checkpoint inhibitors (ICIs) is associated with the development of hepatic immune-related adverse events (HIRAEs). We aimed to evaluate the role of baseline hepatic tumour burden, measured with the tumour burden score (TBS), in the development of HIRAEs and survival.
Methods
We conducted a retrospective observational cohort study on 93 patients treated with ICIs at IRCCS Humanitas Research Hospital, of which 42 for advanced HCC (Cohort 1) and 51 for non-HCC cancers with liver metastases developed prior to immunotherapy initiation (Cohort 2). We assessed the baseline tumour burden using TBS: TBS2 = (maximum tumour diameter)2 + (number of liver lesions)2.
Results
In the cohort of patients with HCC, 18 patients (42.86%) developed any grade (G) HIRAEs, of which eight (19.05%) were G ≥ 2. Patients who developed any-grade HIRAEs had a higher median TBS compared to patients with no HIRAEs (10.95 vs 5.85; P = .11). Baseline TBS correlated with the development of any-grade HIRAEs with marginal statistical significance (odds ratio [OR] 1.37, P = .08). Median OS was not influenced by TBS or by the development of HIRAEs.
In the cohort of non-HCC patients, 18 patients (35.29%) developed any-grade HIRAEs, of which three (5.88%) were G ≥ 2. Baseline TBS did not correlate with the development of any-grade HIRAEs (OR 1.01), and median OS was not influenced by TBS or HIRAEs.
Conclusions
Despite the limited sample size and the absence of statistical significance, our study suggested a possible association between baseline TBS and the development of any-grade HIRAEs in the HCC cohort. Future evaluation of larger cohorts is needed to corroborate these findings.
背景,目的使用免疫检查点抑制剂(ICIs)治疗肝细胞癌(HCC)与肝脏免疫相关不良事件(hirae)的发生有关。我们的目的是评估基线肝肿瘤负荷的作用，用肿瘤负荷评分(TBS)来衡量，在HIRAEs的发展和生存中。我们对在IRCCS Humanitas研究医院接受ICIs治疗的93例患者进行了回顾性观察队列研究，其中42例为晚期HCC(队列1)，51例为在免疫治疗开始前发生肝转移的非HCC癌症(队列2)。我们使用TBS评估基线肿瘤负担:TBS2 =(最大肿瘤直径)2 +(肝脏病变数)2。结果HCC患者队列中，18例(42.86%)发生任何(G)级HIRAEs，其中8例(19.05%)为G≥2级。发生任何级别hiae的患者与未发生hiae的患者相比，TBS中位数更高(10.95 vs 5.85;p = .11)。基线TBS与任何级别hiae的发生相关，且具有边际统计学意义(优势比[OR] 1.37, P = .08)。中位OS不受TBS或HIRAEs的影响。在非hcc患者队列中，18例(35.29%)发生了任何级别的hirae，其中3例(5.88%)为G≥2。基线TBS与任何级别HIRAEs的发生均无相关性(OR 1.01)，中位OS不受TBS或HIRAEs的影响。尽管样本量有限且缺乏统计学意义，但我们的研究表明，基线TBS与HCC队列中任何级别hiae的发生之间可能存在关联。未来需要对更大的队列进行评估以证实这些发现。
{"title":"Tumour burden score and immune-related hepatotoxicity in patients with hepatocellular carcinoma or liver metastases treated with immune checkpoint inhibitors","authors":"Eleonora Di Carlo, Antonio D'Alessio, Antonella Cammarota, Valentina Zanuso, Tiziana Pressiani, Silvia Bozzarelli, Giuseppe Ferrillo, Giulia Vatteroni, Vittorio Pedicini, Laura Giordano, Nicola Personeni, Lorenza Rimassa","doi":"10.1002/lci2.51","DOIUrl":"10.1002/lci2.51","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background & Aims</h3>\u0000 \u0000 <p>Treatment of hepatocellular carcinoma (HCC) with immune checkpoint inhibitors (ICIs) is associated with the development of hepatic immune-related adverse events (HIRAEs). We aimed to evaluate the role of baseline hepatic tumour burden, measured with the tumour burden score (TBS), in the development of HIRAEs and survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective observational cohort study on 93 patients treated with ICIs at IRCCS Humanitas Research Hospital, of which 42 for advanced HCC (Cohort 1) and 51 for non-HCC cancers with liver metastases developed prior to immunotherapy initiation (Cohort 2). We assessed the baseline tumour burden using TBS: TBS<sup>2</sup> = (maximum tumour diameter)<sup>2</sup> + (number of liver lesions)<sup>2</sup>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the cohort of patients with HCC, 18 patients (42.86%) developed any grade (G) HIRAEs, of which eight (19.05%) were G ≥ 2. Patients who developed any-grade HIRAEs had a higher median TBS compared to patients with no HIRAEs (10.95 vs 5.85; <i>P</i> = .11). Baseline TBS correlated with the development of any-grade HIRAEs with marginal statistical significance (odds ratio [OR] 1.37, <i>P</i> = .08). Median OS was not influenced by TBS or by the development of HIRAEs.</p>\u0000 \u0000 <p>In the cohort of non-HCC patients, 18 patients (35.29%) developed any-grade HIRAEs, of which three (5.88%) were G ≥ 2. Baseline TBS did not correlate with the development of any-grade HIRAEs (OR 1.01), and median OS was not influenced by TBS or HIRAEs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Despite the limited sample size and the absence of statistical significance, our study suggested a possible association between baseline TBS and the development of any-grade HIRAEs in the HCC cohort. Future evaluation of larger cohorts is needed to corroborate these findings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"3 2","pages":"63-71"},"PeriodicalIF":0.0,"publicationDate":"2022-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.51","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41827309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Giacomo Aimar, Donatella Marino, Clizia Zichi, Teresa Gamba, Andrea Caglio, Francesca De Vita, Elisa Sperti, Massimo Di Maio
In the past years, treatment options for advanced hepatocellular carcinoma (HCC) have thriven. Although globally recognised, the patient-reported outcomes (PROs) are often underused and quality of life (QoL) results are underreported in many phase III trials. We performed a systematic review to describe the prevalence of QoL inclusion and heterogeneity in QoL reporting in published phase III trials of systemic treatment in advanced HCC. Twenty-one publications were identified: 12 (57.1%) in first line setting, eight (38.1%) in second line and only one (4.7%) in second and further lines. In 14 trials (66.6%), Qol was included in the analysis as a secondary or tertiary endpoint but only in nine (47.4%) cases Qol results were published in the main paper. QoL data are lacking in a significant proportion of published phase III trials in advanced HCC. The methodology of QoL analysis is heterogeneous for type of instruments, analysis and presentation of results.
{"title":"Advanced hepatocellular carcinoma: Impact of systemic treatments on health-related quality of life and patient-reported outcomes","authors":"Giacomo Aimar, Donatella Marino, Clizia Zichi, Teresa Gamba, Andrea Caglio, Francesca De Vita, Elisa Sperti, Massimo Di Maio","doi":"10.1002/lci2.50","DOIUrl":"10.1002/lci2.50","url":null,"abstract":"<p>In the past years, treatment options for advanced hepatocellular carcinoma (HCC) have thriven. Although globally recognised, the patient-reported outcomes (PROs) are often underused and quality of life (QoL) results are underreported in many phase III trials. We performed a systematic review to describe the prevalence of QoL inclusion and heterogeneity in QoL reporting in published phase III trials of systemic treatment in advanced HCC. Twenty-one publications were identified: 12 (57.1%) in first line setting, eight (38.1%) in second line and only one (4.7%) in second and further lines. In 14 trials (66.6%), Qol was included in the analysis as a secondary or tertiary endpoint but only in nine (47.4%) cases Qol results were published in the main paper. QoL data are lacking in a significant proportion of published phase III trials in advanced HCC. The methodology of QoL analysis is heterogeneous for type of instruments, analysis and presentation of results.</p>","PeriodicalId":93331,"journal":{"name":"Liver cancer international","volume":"3 2","pages":"90-98"},"PeriodicalIF":0.0,"publicationDate":"2022-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lci2.50","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46866386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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