Pub Date : 2018-02-09eCollection Date: 2018-01-01DOI: 10.2217/hep-2017-0021
Zachary J Brown, Bernd Heinrich, Tim F Greten
Hepatocellular carcinoma (HCC) is a major health problem worldwide with limited systemic therapies available. Immunotherapy is a fast-moving field that is quickly evolving as a treatment for HCC with three recent clinical trials published treating HCC with immune checkpoint inhibitors with promising results. Checkpoint inhibition may lead to a unique adverse event profile with the potential to cause immune-related adverse events by unbalancing the immune system. Here, we report a case of a 61-year-old male with advanced HCC who developed a shellfish allergy after completing three cycles of combination of tremelimumab and durvalumab therapy.
{"title":"Development of shellfish allergy after exposure to dual immune checkpoint blockade.","authors":"Zachary J Brown, Bernd Heinrich, Tim F Greten","doi":"10.2217/hep-2017-0021","DOIUrl":"https://doi.org/10.2217/hep-2017-0021","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a major health problem worldwide with limited systemic therapies available. Immunotherapy is a fast-moving field that is quickly evolving as a treatment for HCC with three recent clinical trials published treating HCC with immune checkpoint inhibitors with promising results. Checkpoint inhibition may lead to a unique adverse event profile with the potential to cause immune-related adverse events by unbalancing the immune system. Here, we report a case of a 61-year-old male with advanced HCC who developed a shellfish allergy after completing three cycles of combination of tremelimumab and durvalumab therapy.</p>","PeriodicalId":44854,"journal":{"name":"Hepatic Oncology","volume":"5 1","pages":"HEP02"},"PeriodicalIF":5.0,"publicationDate":"2018-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/hep-2017-0021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36558596","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}
Sorafenib has been the only approved systemic treatment of hepatocellular carcinoma (HCC) for almost a decade. Recently, two new drugs showed positive results in two Phase III studies. The RESORCE trial identified regorafenib as a valid second-line treatment for patients progressing to sorafenib, the REFLECT trial showed that lenvatinib is noninferior to sorafenib as front-line treatment. Following these trials, the therapeutic scenario will be dominated by anti-VEGFR drugs, with three different molecules showing a proven anticancer activity. Some open problems still remain and different immunotherapy trials are underway, following promising preliminary results. In this review we analyze: the most recent advancements about patients treated with sorafenib; the results of RESORCE and REFLECT trials; and the ongoing Phase III clinical trials. Finally, we discuss how they could address the current problems and possibly reshape the future of the systemic treatments for HCC.
{"title":"Systemic treatments for hepatocellular carcinoma: challenges and future perspectives.","authors":"Francesco Tovoli, Giulia Negrini, Francesca Benevento, Chiara Faggiano, Elisabetta Goio, Alessandro Granito","doi":"10.2217/hep-2017-0020","DOIUrl":"10.2217/hep-2017-0020","url":null,"abstract":"<p><p>Sorafenib has been the only approved systemic treatment of hepatocellular carcinoma (HCC) for almost a decade. Recently, two new drugs showed positive results in two Phase III studies. The RESORCE trial identified regorafenib as a valid second-line treatment for patients progressing to sorafenib, the REFLECT trial showed that lenvatinib is noninferior to sorafenib as front-line treatment. Following these trials, the therapeutic scenario will be dominated by anti-VEGFR drugs, with three different molecules showing a proven anticancer activity. Some open problems still remain and different immunotherapy trials are underway, following promising preliminary results. In this review we analyze: the most recent advancements about patients treated with sorafenib; the results of RESORCE and REFLECT trials; and the ongoing Phase III clinical trials. Finally, we discuss how they could address the current problems and possibly reshape the future of the systemic treatments for HCC.</p>","PeriodicalId":44854,"journal":{"name":"Hepatic Oncology","volume":"5 1","pages":"HEP01"},"PeriodicalIF":5.0,"publicationDate":"2018-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/hep-2017-0020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36569695","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}
Pub Date : 2017-10-01Epub Date: 2017-11-17DOI: 10.2217/hep-2017-0011
Tim F Greten, Tobias Eggert
Cellular senescence is a stress-induced cell-cycle arrest program that prevents malignant transformation of senescent cells following oncogenic pathway activation and DNA damage. Senescent cells are metabolically active and secrete cytokines and chemokines that shape the function and composition of their microenvironment. These cytokines can recruit immune cells such as lymphocytes and myeloid cells that depending on the context can either promote or inhibit liver tumor development and progression. Accordingly, pharmacologically targeting of secreted cytokines or reprogramming the expression of these cytokines in senescent cells represents a promising approach to skew senescence-associated immune responses toward cancer cell killing.
{"title":"Cellular senescence associated immune responses in liver cancer.","authors":"Tim F Greten, Tobias Eggert","doi":"10.2217/hep-2017-0011","DOIUrl":"https://doi.org/10.2217/hep-2017-0011","url":null,"abstract":"<p><p>Cellular senescence is a stress-induced cell-cycle arrest program that prevents malignant transformation of senescent cells following oncogenic pathway activation and DNA damage. Senescent cells are metabolically active and secrete cytokines and chemokines that shape the function and composition of their microenvironment. These cytokines can recruit immune cells such as lymphocytes and myeloid cells that depending on the context can either promote or inhibit liver tumor development and progression. Accordingly, pharmacologically targeting of secreted cytokines or reprogramming the expression of these cytokines in senescent cells represents a promising approach to skew senescence-associated immune responses toward cancer cell killing.</p>","PeriodicalId":44854,"journal":{"name":"Hepatic Oncology","volume":"4 4","pages":"123-127"},"PeriodicalIF":5.0,"publicationDate":"2017-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/hep-2017-0011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35638296","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}
Pub Date : 2017-10-01Epub Date: 2017-11-17DOI: 10.2217/hep-2017-0014
Peter L Labib, Brian R Davidson, Ricky A Sharma, Stephen P Pereira
Cholangiocarcinoma is a rare and aggressive malignancy of the biliary tract. Complete surgical resection can be curative, but the majority of patients are diagnosed with advanced disease and usually die within a year of diagnosis. Most deaths are attributable to local disease progression rather than distant metastases, supporting the use of locoregional therapies. There is evidence that locoregional therapies can provide local tumor control resulting in increased survival while avoiding some of the side effects of systemic treatments, increasing potential treatment options for patients who may be unsuitable for systemic palliative treatments. This review considers the evidence for locoregional therapies in cholangiocarcinoma, which can be classified into endoscopic, vascular, percutaneous and radiation oncological therapies. Current guidelines do not recommend the routine use of locoregional therapies due to a lack of prospective data, but the results of ongoing trials are likely to increase the evidence base and impact on clinical practice.
{"title":"Locoregional therapies in cholangiocarcinoma.","authors":"Peter L Labib, Brian R Davidson, Ricky A Sharma, Stephen P Pereira","doi":"10.2217/hep-2017-0014","DOIUrl":"10.2217/hep-2017-0014","url":null,"abstract":"<p><p>Cholangiocarcinoma is a rare and aggressive malignancy of the biliary tract. Complete surgical resection can be curative, but the majority of patients are diagnosed with advanced disease and usually die within a year of diagnosis. Most deaths are attributable to local disease progression rather than distant metastases, supporting the use of locoregional therapies. There is evidence that locoregional therapies can provide local tumor control resulting in increased survival while avoiding some of the side effects of systemic treatments, increasing potential treatment options for patients who may be unsuitable for systemic palliative treatments. This review considers the evidence for locoregional therapies in cholangiocarcinoma, which can be classified into endoscopic, vascular, percutaneous and radiation oncological therapies. Current guidelines do not recommend the routine use of locoregional therapies due to a lack of prospective data, but the results of ongoing trials are likely to increase the evidence base and impact on clinical practice.</p>","PeriodicalId":44854,"journal":{"name":"Hepatic Oncology","volume":"4 4","pages":"99-109"},"PeriodicalIF":5.0,"publicationDate":"2017-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777616/pdf/hep-04-99.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35765638","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}
Pub Date : 2017-10-01Epub Date: 2017-11-17DOI: 10.2217/hep-2017-0019
Shreya Sengupta, Neehar D Parikh
Early detection of hepatocellular carcinoma (HCC) leads to improved survival; however, current early detection strategies for HCC surveillance are ineffective. Thus, there has been interest in developing biomarkers to aid in the early detection HCC. In this review, we discuss the five phases of biomarker discovery that are necessary for clinical implementation. We also describe the most promising investigational biomarkers and their phase of discovery. We review several promising technologies for the early detection of HCC, including miRNA, metabolomics and proteomics. Promisingly, there are samples from multiple longitudinal cohorts of patients with cirrhosis in the USA that are being collected in order to validate candidate biomarkers for HCC. A biomarker-based strategy has the potential to become the primary surveillance method for HCC detection.
{"title":"Biomarker development for hepatocellular carcinoma early detection: current and future perspectives.","authors":"Shreya Sengupta, Neehar D Parikh","doi":"10.2217/hep-2017-0019","DOIUrl":"https://doi.org/10.2217/hep-2017-0019","url":null,"abstract":"<p><p>Early detection of hepatocellular carcinoma (HCC) leads to improved survival; however, current early detection strategies for HCC surveillance are ineffective. Thus, there has been interest in developing biomarkers to aid in the early detection HCC. In this review, we discuss the five phases of biomarker discovery that are necessary for clinical implementation. We also describe the most promising investigational biomarkers and their phase of discovery. We review several promising technologies for the early detection of HCC, including miRNA, metabolomics and proteomics. Promisingly, there are samples from multiple longitudinal cohorts of patients with cirrhosis in the USA that are being collected in order to validate candidate biomarkers for HCC. A biomarker-based strategy has the potential to become the primary surveillance method for HCC detection.</p>","PeriodicalId":44854,"journal":{"name":"Hepatic Oncology","volume":"4 4","pages":"111-122"},"PeriodicalIF":5.0,"publicationDate":"2017-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/hep-2017-0019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36465624","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}
Pub Date : 2017-10-01Epub Date: 2017-11-17DOI: 10.2217/hep-2017-0018
Francesco Tovoli, Matteo Renzulli, Alessandro Granito, Rita Golfieri, Luigi Bolondi
Sorafenib has been the only approved systemic therapy for hepatocellular carcinoma until very recently. However, the radiologic assessment of its biological activity is a disputed matter as at least five different criteria have been proposed. In this review, we describe the characteristic of the Response Evaluation Criteria In Solid Tumors (RECIST), European Association for the Study of The Liver (EASL), modified RECIST (mRECIST), Response Evaluation Criteria In the Cancer of the Liver (RECICL) and Choi criteria. The existing comparative studies are reported together with recent pieces of evidence, analyzing the reasons behind the split between recommendations of the scientific societies and regulatory agencies. Future perspectives in the wake of the impending results of the immunotherapy trials are also discussed.
{"title":"Radiologic criteria of response to systemic treatments for hepatocellular carcinoma.","authors":"Francesco Tovoli, Matteo Renzulli, Alessandro Granito, Rita Golfieri, Luigi Bolondi","doi":"10.2217/hep-2017-0018","DOIUrl":"https://doi.org/10.2217/hep-2017-0018","url":null,"abstract":"<p><p>Sorafenib has been the only approved systemic therapy for hepatocellular carcinoma until very recently. However, the radiologic assessment of its biological activity is a disputed matter as at least five different criteria have been proposed. In this review, we describe the characteristic of the Response Evaluation Criteria In Solid Tumors (RECIST), European Association for the Study of The Liver (EASL), modified RECIST (mRECIST), Response Evaluation Criteria In the Cancer of the Liver (RECICL) and Choi criteria. The existing comparative studies are reported together with recent pieces of evidence, analyzing the reasons behind the split between recommendations of the scientific societies and regulatory agencies. Future perspectives in the wake of the impending results of the immunotherapy trials are also discussed.</p>","PeriodicalId":44854,"journal":{"name":"Hepatic Oncology","volume":"4 4","pages":"129-137"},"PeriodicalIF":5.0,"publicationDate":"2017-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/hep-2017-0018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36465625","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}
Surgical resection remains the primary curative treatment option for patients with colorectal liver metastases. While the majority of patients will develop tumor relapse within or outside of the liver after hepatic metastasectomy, a subset of these patients may be amenable to salvage surgical resection. However, outcomes for this approach are not well defined. In this article, we summarize the current evidence for the incidence, feasibility and outcomes of salvage resection for recurrence after initial resection of colorectal liver metastases.
{"title":"Surgical salvage of recurrence after resection of colorectal liver metastases: incidence and outcomes.","authors":"Nuh N Rahbari, Michael I D'Angelica","doi":"10.2217/hep-2017-0002","DOIUrl":"10.2217/hep-2017-0002","url":null,"abstract":"<p><p>Surgical resection remains the primary curative treatment option for patients with colorectal liver metastases. While the majority of patients will develop tumor relapse within or outside of the liver after hepatic metastasectomy, a subset of these patients may be amenable to salvage surgical resection. However, outcomes for this approach are not well defined. In this article, we summarize the current evidence for the incidence, feasibility and outcomes of salvage resection for recurrence after initial resection of colorectal liver metastases.</p>","PeriodicalId":44854,"journal":{"name":"Hepatic Oncology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2017-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095401/pdf/hep-04-25.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35284114","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}
Pub Date : 2017-07-01Epub Date: 2017-10-30DOI: 10.2217/hep-2017-0005
Olaguoke Akinwande, Veer Shah, Abigail Mills, Christopher Noda, Eric Weiner, Gretchen Foltz, Nael Saad
Aim: Compare radioembolization (Y90) and chemoembolization (CE) for the treatment of unresectable intrahepatic cholangiocarcinoma (UICC).
Materials & methods: Institutional Review Board-approved, retrospective search was performed. Forty patients with UICC were treated with either Y90 (n = 25, 39 treatments) or CE (n = 15, 35 treatments). Comparative analysis was performed using Student's t and fisher-exact tests. Multivariable-logistic regression was also performed.
Results: Median ages were 60 and 64 years for CE and Y90 groups, respectively (p = 0.798). Patient variables including age, Eastern Cooperative Oncology Group score, tumor burden, extra-hepatic disease, prior chemotherapy and prior surgery were similar between groups. Adverse events were similar in both groups (CE 20%, Y90 26%; p > 0.9). Overall response rate (CE 6%, Y90 4%; p > 0.9) and disease control rate (CE 46%, Y90 48%; p > 0.9) were statistically similar. Multilogistic regression did not identify any variables that correlated with disease control rate, including Eastern Cooperative Oncology Group score and tumor burden.
Conclusion: Our observation shows that CE and Y90 display similar toxicity and disease control in the treatment of UICC.
{"title":"Chemoembolization versus radioembolization for the treatment of unresectable intrahepatic cholangiocarcinoma in a single institution image-based efficacy and comparative toxicity.","authors":"Olaguoke Akinwande, Veer Shah, Abigail Mills, Christopher Noda, Eric Weiner, Gretchen Foltz, Nael Saad","doi":"10.2217/hep-2017-0005","DOIUrl":"https://doi.org/10.2217/hep-2017-0005","url":null,"abstract":"<p><strong>Aim: </strong>Compare radioembolization (Y90) and chemoembolization (CE) for the treatment of unresectable intrahepatic cholangiocarcinoma (UICC).</p><p><strong>Materials & methods: </strong>Institutional Review Board-approved, retrospective search was performed. Forty patients with UICC were treated with either Y90 (n = 25, 39 treatments) or CE (n = 15, 35 treatments). Comparative analysis was performed using Student's <i>t</i> and fisher-exact tests. Multivariable-logistic regression was also performed.</p><p><strong>Results: </strong>Median ages were 60 and 64 years for CE and Y90 groups, respectively (p = 0.798). Patient variables including age, Eastern Cooperative Oncology Group score, tumor burden, extra-hepatic disease, prior chemotherapy and prior surgery were similar between groups. Adverse events were similar in both groups (CE 20%, Y90 26%; p > 0.9). Overall response rate (CE 6%, Y90 4%; p > 0.9) and disease control rate (CE 46%, Y90 48%; p > 0.9) were statistically similar. Multilogistic regression did not identify any variables that correlated with disease control rate, including Eastern Cooperative Oncology Group score and tumor burden.</p><p><strong>Conclusion: </strong>Our observation shows that CE and Y90 display similar toxicity and disease control in the treatment of UICC.</p>","PeriodicalId":44854,"journal":{"name":"Hepatic Oncology","volume":"4 3","pages":"75-81"},"PeriodicalIF":5.0,"publicationDate":"2017-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/hep-2017-0005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36467822","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}
Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. A careful multidisciplinary assessment of tumor characteristics, liver function and physical status is required for proper therapeutic management. In recent years, several studies have supported the feasibility and benefit of combined therapy in the treatment of single large HCC, defined as those exceeding 3 cm in size. We present a case of combined treatment using radiofrequency ablation followed by trans-arterial chemoembolization with radiopaque embolic beads. The aim of this technical report was to describe the radiologic findings during combined radiofrequency ablation and radiopaque bead embolization, pointing out the differences and the potential advantages of using radiopaque beads compared with non-radiopaque beads. Furthermore, it is also the first report on using radiopaque beads in combined treatment for HCC.
{"title":"'Hug sign': a new radiological sign of intraprocedural success after combined treatment for hepatocellular carcinoma.","authors":"Roberto Iezzi, Maurizio Pompili, Eleonora Brigida Annicchiarico, Matteo Garcovich, Massimo Siciliano, Antonio Gasbarrini, Riccardo Manfredi","doi":"10.2217/hep-2017-0017","DOIUrl":"https://doi.org/10.2217/hep-2017-0017","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. A careful multidisciplinary assessment of tumor characteristics, liver function and physical status is required for proper therapeutic management. In recent years, several studies have supported the feasibility and benefit of combined therapy in the treatment of single large HCC, defined as those exceeding 3 cm in size. We present a case of combined treatment using radiofrequency ablation followed by trans-arterial chemoembolization with radiopaque embolic beads. The aim of this technical report was to describe the radiologic findings during combined radiofrequency ablation and radiopaque bead embolization, pointing out the differences and the potential advantages of using radiopaque beads compared with non-radiopaque beads. Furthermore, it is also the first report on using radiopaque beads in combined treatment for HCC.</p>","PeriodicalId":44854,"journal":{"name":"Hepatic Oncology","volume":"4 3","pages":"69-73"},"PeriodicalIF":5.0,"publicationDate":"2017-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/hep-2017-0017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36467821","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}