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Piscaglia F, Masi G, Martinelli E, Cabibbo G, Di Maio M, Gasbarrini A, Iavarone M, Antonuzzo L, Mazzaferro V, Ballestrero A, Garufi C, Bergamo F, Celsa C, Marino D, Tovoli F, Ponziani FR, Pressiani T, Astolfi C, Gazzoli GC, Ciardiello F, Daniele B, Rimassa L. Atezolizumab plus bevacizumab as first-line treatment of unresectable hepatocellular carcinoma: interim analysis results from the phase IIIb AMETHISTA trial. ESMO Open 2025; 10:104110. [PMID: 39874903 PMCID: PMC11799967 DOI: 10.1016/j.esmoop.2024.104110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 12/05/2024] [Accepted: 12/06/2024] [Indexed: 01/30/2025] Open
Abstract
BACKGROUND The treatment of advanced hepatocellular carcinoma (HCC) with atezolizumab and bevacizumab led to significant improvements in overall survival (OS), progression-free survival (PFS), and response rate compared with sorafenib in the phase III IMbrave150 trial. The etiology of background liver disease can differ between Eastern and Western populations, leading to a potentially different impact of systemic therapies; therefore the unequal representation must be considered in the IMbrave150 trial. To provide further data on the safety and effectiveness of atezolizumab and bevacizumab, the phase IIIb AMETHISTA (Atezolizumab plus bevacizumab in METastatic HCC Italian Safety TriAl) ran in a Western (Italian) population of patients with advanced HCC. The results of the interim analysis are presented in this paper. METHODS AMETHISTA is a multicenter, phase IIIb, single-arm study evaluating the safety and effectiveness of atezolizumab and bevacizumab in an Italian population of patients with systemic treatment-naive HCC (ClinicalTrials.gov: NCT04487067). The primary objective was safety (incidence of grade 3-5 bleeding/hemorrhages). The main secondary objective was effectiveness. RESULTS A total of 152 patients were enrolled and 149 were treated. At the cut-off date, the median observation time was 13.4 months (interquartile range 8.3-15.5 months). The incidence of grade 3-5 bleeding/hemorrhages was 11.4%. Besides, results of other safety endpoints were consistent with the safety profile of atezolizumab plus bevacizumab, and the underlying disease, without any new safety observation. The median OS was 18.2 months (95% confidence interval 15.4 months to not evaluable); the median PFS was 8.5 months (95% confidence interval 7.5-11.2 months). CONCLUSION Results from the interim analysis are consistent with data from the IMbrave150 trial, and further confirm first-line atezolizumab plus bevacizumab as a standard of care for patients with systemic treatment-naive advanced and unresectable HCC.
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Affiliation(s)
- F Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Disease, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - G Masi
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - E Martinelli
- Medical Oncology Unit, Department of Precision Medicine, Università degli Studi della Campania "L. Vanvitelli", Napoli, Italy
| | - G Cabibbo
- Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - M Di Maio
- Department of Oncology, University of Turin, Ordine Mauriziano Hospital, Turin, Italy
| | - A Gasbarrini
- Liver Unit, Internal Medicine and Gastroenterology Center - CEMAD, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of the Sacred Heart, Rome, Italy
| | - M Iavarone
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy; CRC "A. M. and A. Migliavacca" Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - L Antonuzzo
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Clinical Oncology Unit, AOU Careggi, Florence, Italy
| | - V Mazzaferro
- Department of Surgery, Gastro-Intestinal, HPB Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - A Ballestrero
- Department of Internal Medicine and Medical Specialties, University of Genoa, IRCCS Policlinico San Martino Hospital, Genoa, Italy
| | - C Garufi
- Oncology Unit, Azienda Ospedaliera San Camillo-Forlanini, Rome, Italy
| | - F Bergamo
- Oncology 1 Unit, Department of Oncology, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy
| | - C Celsa
- Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy; Department of Surgical, Oncological, and Oral Sciences, University of Palermo, Palermo, Italy
| | - D Marino
- Division of Medical Oncology, Ordine Mauriziano Hospital, Turin, Italy
| | - F Tovoli
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Disease, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - F R Ponziani
- Liver Unit, Internal Medicine and Gastroenterology Center - CEMAD, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of the Sacred Heart, Rome, Italy
| | - T Pressiani
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano (Milan), Italy
| | | | | | - F Ciardiello
- Medical Oncology Unit, Department of Precision Medicine, Università degli Studi della Campania "L. Vanvitelli", Napoli, Italy
| | - B Daniele
- Oncology Unit, Ospedale del Mare, ASL Napoli 1 Centro, Naples, Italy
| | - L Rimassa
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano (Milan), Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, (Milan), Italy.
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Han S, Kim DY, Lim HY, Yoon JH, Ryoo BY, Kim Y, Kim K, Kim BY, Yi SY, Kim DS, Cho DY, Yu J, Kim S, Park JW. Sorafenib for 9,923 Patients with Hepatocellular Carcinoma: An Analysis from National Health Insurance Claim Data in South Korea. Gut Liver 2024; 18:116-124. [PMID: 37334671 PMCID: PMC10791511 DOI: 10.5009/gnl220406] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 01/18/2023] [Accepted: 01/26/2023] [Indexed: 06/20/2023] Open
Abstract
Background/Aims Sorafenib is the standard of care in the management of advanced hepatocellular carcinoma (HCC). The purpose of this study was to investigate the characteristics, treatment patterns and outcomes of sorafenib among HCC patients in South Korea. Methods This population-based retrospective, single-arm, observational study used the Korean National Health Insurance database to identify patients with HCC who received sorafenib between July 1, 2008, and December 31, 2014. A total of 9,923 patients were recruited in this study. Results Among 9,923 patients, 6,669 patients (68.2%) received loco-regional therapy prior to sorafenib, and 1,565 patients (15.8%) received combination therapy with concomitant sorafenib; 2,591 patients (26.1%) received rescue therapy after sorafenib, and transarterial chemoembolization was the most common modality applied in 1,498 patients (15.1%). A total of 3,591 patients underwent rescue therapy after sorafenib, and the median overall survival was 14.5 months compared to 4.6 months in 7,332 patients who received supportive care after sorafenib. The mean duration of sorafenib administration in all patients was 105.7 days; 7,023 patients (70.8%) received an initial dose of 600 to 800 mg. The longest survival was shown in patients who received the recommended dose of 800 mg, subsequently reduced to 400 mg (15.0 months). The second longest survival was demonstrated in patients with a starting dose of 800 mg, followed by a dose reduction to 400-600 mg (9.6 months). Conclusions Real-life data show that the efficacy of sorafenib seems similar to that observed in clinical trials, suggesting that appropriate subsequent therapy after sorafenib might prolong patient survival.
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Affiliation(s)
- Sojung Han
- Department of Internal Medicine, Uijeongbu Eulji Medical Center, Eulji University College of Medicine, Uijeongbu, Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Ho Yeong Lim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Baek-Yeol Ryoo
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yujeong Kim
- Health Insurance Review and Assessment, Wonju, Korea
| | - Kookhee Kim
- Health Insurance Review and Assessment, Wonju, Korea
| | - Bo Yeon Kim
- Health Insurance Review and Assessment, Wonju, Korea
| | - So Young Yi
- Health Insurance Review and Assessment, Wonju, Korea
| | - Dong-Sook Kim
- Health Insurance Review and Assessment, Wonju, Korea
| | - Do-Yeon Cho
- Health Insurance Review and Assessment, Wonju, Korea
| | - Jina Yu
- Health Insurance Review and Assessment, Wonju, Korea
| | - Suhyun Kim
- Health Insurance Review and Assessment, Wonju, Korea
| | - Joong-Won Park
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
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Sacco R, Ramai D, Tortora R, di Costanzo GG, Burlone ME, Pirisi M, Federico P, Daniele B, Silletta M, Gallo P, Cocuzza C, Russello M, Cabibbo G, Rancatore G, Cesario S, Masi G, Marzi L, Mega A, Granito A, Pieri G, Giannini EG, Paolillo R, Gadaleta-Caldarola G, Dadduzio V, Giordano G, Giacomelli L, Papa S, Renzulli M, Maida M, Ghidini M, Borzio M, Facciorusso A. Role of Etiology in Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Counterfactual Event-Based Mediation Analysis. Cancers (Basel) 2023; 15:381. [PMID: 36672330 PMCID: PMC9856921 DOI: 10.3390/cancers15020381] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 12/23/2022] [Accepted: 12/28/2022] [Indexed: 01/11/2023] Open
Abstract
Background: Whether the etiology of underlying liver disease represents a prognostic factor in patients with hepatocellular carcinoma (HCC) treated with lenvatinib is still a matter of debate. This study investigates whether the viral etiology of HCC plays a prognostic role in overall survival (OS). Methods: Data derived from a multicenter series of 313 HCC patients treated with lenvatinib between 2019 and 2022 were analyzed. Actuarial survival estimates were computed using the Kaplan−Meier method and compared with the log-rank test. We performed an event-based counterfactual mediation analysis to estimate direct (chronic inflammation and immunosuppression), indirect (tobacco smoking, alcohol use, illicit drug abuse with injections), and the total effect of viral etiology on OS. Results were expressed as hazard ratio (HR) and 95% CI. Results: Median OS was 21 months (95% CI: 20−23) in the group with other etiologies and 15 months (14−16) in the group with viral etiology (p < 0.0001). The total effect of viral etiology was associated with OS (HR 2.76, 1.32−5.21), and it was mainly explained by the pure direct effect of viral etiology (HR 2.74, 1.15−4.45). By contrast, its total indirect effect was not associated with poorer survival (HR 1.05, 0.82−2.13). These results were confirmed when considering tobacco, alcohol consumption, or injection drug abuse as potential mediators. Median progression-free survival was 9 months (8−10) in patients with other etiologies and 6 months (5−7) in patients with viral etiology (p < 0.0001). No difference in terms of adverse event rate was observed between the two groups. Conclusions: Patients affected by HCC with nonviral etiology treated with lenvatinib exhibit longer survival than those with viral etiology. This finding may have relevance in the treatment decision-making process.
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Affiliation(s)
- Rodolfo Sacco
- Gastroenterology and Endoscopy Unit, Department of Surgical and Medical Sciences, University of Foggia, 71100 Foggia, Italy
| | - Daryl Ramai
- Gastroenterology and Hepatology, University of Utah, Salt Lake City, UT 84112, USA
| | - Raffaella Tortora
- Liver Unit, Department of Transplantation, Cardarelli Hospital, 80100 Naples, Italy
| | | | - Michela Emma Burlone
- Department of Internal Medicine, AOU “Maggiore Della Carità”, 28100 Novara, Italy
| | - Mario Pirisi
- Department of Internal Medicine, AOU “Maggiore Della Carità”, 28100 Novara, Italy
| | - Piera Federico
- Medical Oncology Unit, Ospedale del Mare, 80100 Naples, Italy
| | - Bruno Daniele
- Medical Oncology Unit, Ospedale del Mare, 80100 Naples, Italy
| | - Marianna Silletta
- Division of Medical Oncology, Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy
| | - Paolo Gallo
- Clinical Medicine and Hepatology Unit, Campus Bio-Medico University, 00128 Rome, Italy
| | | | | | - Giuseppe Cabibbo
- Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90121 Palermo, Italy
| | - Gabriele Rancatore
- Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90121 Palermo, Italy
| | - Silvia Cesario
- Unit of Medical Oncology, AOU Pisana, Santa Chiara Hospital, 56121 Pisa, Italy
| | - Gianluca Masi
- Unit of Medical Oncology, AOU Pisana, Santa Chiara Hospital, 56121 Pisa, Italy
| | - Luca Marzi
- Gastroenterology Unit, Bolzano Regional Hospital, 39100 Bolzano, Italy
| | - Andrea Mega
- Gastroenterology Unit, Bolzano Regional Hospital, 39100 Bolzano, Italy
| | - Alessandro Granito
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, S. Orsola-Malpighi Hospital, IRCCS AOU di Bologna, 40121 Bologna, Italy
| | - Giulia Pieri
- Gastroenterology Unit, Department of Internal Medicine, University of Genova, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Policlinico San Martino, 16100 Genova, Italy
| | - Edoardo G. Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genova, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Policlinico San Martino, 16100 Genova, Italy
| | - Rosa Paolillo
- Gastroenterology and Endoscopy Unit, Department of Surgical and Medical Sciences, University of Foggia, 71100 Foggia, Italy
| | | | - Vincenzo Dadduzio
- Medical Oncology Unit, Mons. A.R. Dimiccoli Hospital, 76121 Barletta, Italy
| | - Guido Giordano
- Medical Oncology and Biomolecular Therapy Unit, Department of Surgical and Medical Sciences, University of Foggia, 71100 Foggia, Italy
| | | | | | - Matteo Renzulli
- Department of Radiology, IRCCS AOU di Bologna, 40121 Bologna, Italy
| | - Marcello Maida
- Gastroenterology and Endoscopy Unit, S. Elia-Raimondi Hospital, 93100 Caltanissetta, Italy
| | - Michele Ghidini
- Division of Medical Oncology, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20100 Milano, Italy
| | - Mauro Borzio
- Gastroenterologia ed Endoscopia Digestiva, Centro Diagnostico Italiano, 20100 Milan, Italy
| | - Antonio Facciorusso
- Gastroenterology and Endoscopy Unit, Department of Surgical and Medical Sciences, University of Foggia, 71100 Foggia, Italy
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Rizzo A, Carloni R, Ricci AD, Cusmai A, Laforgia M, Calabrò C, Ungaro V, Oreste D, Sollitto M, Palmiotti G, Brandi G. Treatment-related adverse events of first-line immunotherapy versus sorafenib for advanced hepatocellular carcinoma: a meta-analysis. Expert Opin Drug Saf 2022; 22:323-329. [PMID: 36426773 DOI: 10.1080/14740338.2023.2152793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Affiliation(s)
- Alessandro Rizzo
- Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico “Don Tonino Bello”, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy
| | - Riccardo Carloni
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni - 15, Bologna, Italy
| | - Angela Dalia Ricci
- Medical Oncology Unit, National Institute of Gastroenterology, “Saverio de Bellis” Research Hospital, Castellana Grotte, Italy
| | - Antonio Cusmai
- Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico “Don Tonino Bello”, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy
| | - Mariarita Laforgia
- S.C. Farmacia e U.Ma.C.A., Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Istituto Tumori Giovanni Paolo II-Bari, Bari, Italy
| | - Concetta Calabrò
- S.C. Farmacia e U.Ma.C.A., Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Istituto Tumori Giovanni Paolo II-Bari, Bari, Italy
| | - Valentina Ungaro
- S.C. Farmacia e U.Ma.C.A., Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Istituto Tumori Giovanni Paolo II-Bari, Bari, Italy
| | - Donato Oreste
- Radiology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori Giovanni Paolo II, Bari, Italy
| | - Mario Sollitto
- Radiology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Tumori Giovanni Paolo II, Bari, Italy
| | - Gennaro Palmiotti
- Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico “Don Tonino Bello”, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy
| | - Giovanni Brandi
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni - 15, Bologna, Italy
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Pallozzi M, Di Tommaso N, Maccauro V, Santopaolo F, Gasbarrini A, Ponziani FR, Pompili M. Non-Invasive Biomarkers for Immunotherapy in Patients with Hepatocellular Carcinoma: Current Knowledge and Future Perspectives. Cancers (Basel) 2022; 14:cancers14194631. [PMID: 36230554 PMCID: PMC9559710 DOI: 10.3390/cancers14194631] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 09/18/2022] [Accepted: 09/20/2022] [Indexed: 12/16/2022] Open
Abstract
Simple Summary The search for non-invasive biomarkers is a hot topic in modern oncology, since a tissue biopsy has significant limitations in terms of cost and invasiveness. The treatment perspectives have been significantly improved after the approval of immunotherapy for patients with hepatocellular carcinoma; therefore, the quick identification of responders is crucial to define the best therapeutic strategy. In this review, the current knowledge on the available non-invasive biomarkers of the response to immunotherapy is described. Abstract The treatment perspectives of advanced hepatocellular carcinoma (HCC) have deeply changed after the introduction of immunotherapy. The results in responders show improved survival compared with Sorafenib, but only one-third of patients achieve a significant benefit from treatment. As the tumor microenvironment exerts a central role in shaping the response to immunotherapy, the future goal of HCC treatment should be to identify a proxy of the hepatic tissue condition that is easy to use in clinical practice. Therefore, the search for biomarkers that are accurate in predicting prognosis will be the hot topic in the therapeutic management of HCC in the near future. Understanding the mechanisms of resistance to immunotherapy may expand the patient population that will benefit from it, and help researchers to find new combination regimens to improve patients’ outcomes. In this review, we describe the current knowledge on the prognostic non-invasive biomarkers related to treatment with immune checkpoint inhibitors, focusing on serological markers and gut microbiota.
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Affiliation(s)
- Maria Pallozzi
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Natalia Di Tommaso
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Valeria Maccauro
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Francesco Santopaolo
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Translational Medicine and Surgery Department, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Francesca Romana Ponziani
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Translational Medicine and Surgery Department, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
- Correspondence: (F.R.P.); (M.P.)
| | - Maurizio Pompili
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Translational Medicine and Surgery Department, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
- Correspondence: (F.R.P.); (M.P.)
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Cabibbo G, Aghemo A, Lai Q, Masarone M, Montagnese S, Ponziani FR. Optimizing systemic therapy for advanced hepatocellular carcinoma: the key role of liver function. Dig Liver Dis 2022; 54:452-460. [PMID: 35131176 DOI: 10.1016/j.dld.2022.01.122] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 01/07/2022] [Accepted: 01/09/2022] [Indexed: 12/11/2022]
Abstract
The number of effective systemic therapies for the treatment of advanced hepatocellular carcinoma (HCC) is rapidly increasing, and the advent of immunotherapy has changed the treatment paradigm for these patients, leading to significantly improved survival outcomes. However, many patients with HCC will continue to receive tyrosine kinase inhibitors, partly because of contraindications to immune checkpoint inhibitors. Currently, the best sequential first- and second-line systemic treatment remains elusive. Maintenance of optimal liver function is crucial, it is likely to impinge on temporary or permanent treatment discontinuation, and should also be considered when defining the treatment sequence. Hepatic decompensation, which does not always coincide with disease progression, is part of this complex dynamically evolving system, and must be promptly recognized and adequately managed to allow the patient to continue in the therapeutic course. The purpose of this review is to highlight and summarize the evidence on the efficacy and safety of systemic agents, with a focus on the impact of underlying cirrhosis, and to suggest new clinical outcomes for randomized controlled trials for advanced HCC to better assess the net health benefit in this specific setting.
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Affiliation(s)
- Giuseppe Cabibbo
- Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy.
| | - Alessio Aghemo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Research Hospital IRCCS, Rozzano, Italy
| | - Quirino Lai
- General Surgery and Organ Transplantation, Sapienza University of Rome, Rome, Italy
| | - Mario Masarone
- Internal medicine and Hepatology Division, Department of Medicine, Surgery and Odontostomatology "Scuola Medica Salernitana" - University of Salerno, Baronissi (Salerno), Italy
| | | | - Francesca Romana Ponziani
- Internal Medicine and Gastroenterology - Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy
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An L, Liao H, Yuan K. Efficacy and Safety of Second-line Treatments in Patients with Advanced Hepatocellular Carcinoma after Sorafenib Failure: A Meta-analysis. J Clin Transl Hepatol 2021; 9:868-877. [PMID: 34966650 PMCID: PMC8666373 DOI: 10.14218/jcth.2021.00054] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 04/05/2021] [Accepted: 04/26/2021] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND AND AIMS In the last decade, several second-line therapies followed by sorafenib in patients with advanced hepatocellular carcinoma (HCC) have been reported. But the outcomes were different from each other. This meta-analysis aimed to evaluate the efficacy and safety of the second-line therapies followed by sorafenib in patients with advanced HCC. METHODS Embase (1974 to October 2019) and Ovid MEDLINE (1946 to October 2019) were searched for randomized clinical trials on second-line therapies followed by sorafenib in patients with advanced HCC. The quality of each study was assessed by the modified Jadad scale. Statistical analysis was carried out by RevMan5.3 software. Efficacy and safety were analyzed. Efficacy included overall survival (OS), disease control rate, time to progression, and progression-free survival. RESULTS Eight studies involving 3,173 patients were eligible. No difference in OS was found between the second-line treatment group and the control group (HR=0.87, 95% CI: 0.74-1.01, p=0.06). Disease control rate (relative risk (RR)=1.36, 95% CI: 1.16-1.60, p=0.0002), time to progression (HR=0.64, 95% CI: 0.51-0.81, p=0.0002) and progression-free survival (HR=0.60, 95% CI: 0.46-0.77, p<0.0001) were significantly improved by the second-line therapies. There was a slight difference in adverse events of any grade (RR=1.07, 95% CI: 1.00-1.14, p=0.03) between the two groups. CONCLUSIONS These second-line therapies followed by sorafenib may potentially improve the prognosis in patients with advanced HCC. Compared with other second-line therapies, regorafenib seemed to be more effective.
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Affiliation(s)
- Limin An
- Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, China
| | - Haotian Liao
- Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, China
| | - Kefei Yuan
- Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, China
- Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Correspondence to: Kefei Yuan, Laboratory of Liver Surgery, West China Hospital, Sichuan University, 37 Guoxue lane, Wuhou District, Chengdu, Sichuan 610041, China. ORCID: https://orcid.org/0000-0003-4308-7743. Tel: +86-28-8542-2114, Fax: +86-28-8558-2944, E-mail:
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Tang TY, Daunov K, Lee RT. Case Report: Durable Response to Very Low Dose Tyrosine Kinase Inhibitors in Advanced Hepatocellular Carcinoma. Front Oncol 2021; 11:780798. [PMID: 34976819 PMCID: PMC8716780 DOI: 10.3389/fonc.2021.780798] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 11/29/2021] [Indexed: 12/12/2022] Open
Abstract
The oral tyrosine kinase inhibitors (TKI) sorafenib, regorafenib, and cabozantinib are approved for advanced hepatocellular carcinoma (aHCC) and improve survival. However, patients on these medications frequently require dose reductions or discontinuation due to multiple side effects leading to poor tolerability. Here we report three different aHCC patients with clinical responses outlasting those reported in their corresponding Phase 3 clinical trials on 1/8th the target dose for sorafenib, 1/4th the target dose for regorafenib and 1/6th the target dose for cabozantinib respectively. As these doses are below the minimal recommended doses on the FDA labels, this case series provides a preliminary demonstration that low dose TKI therapy can be effective and patients on TKIs should first assess for clinical response before empirically discontinuing TKI therapy on the basis of tolerating only a low dose.
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Affiliation(s)
- Tin-Yun Tang
- Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
| | - Katherine Daunov
- Division of Hematology and Oncology, University Hospitals Seidman Cancer Center, Cleveland, OH, United States
- Case Western Reserve University School of Medicine, Cleveland, OH, United States
| | - Richard T. Lee
- Division of Hematology and Oncology, University Hospitals Seidman Cancer Center, Cleveland, OH, United States
- Case Western Reserve University School of Medicine, Cleveland, OH, United States
- *Correspondence: Richard T. Lee,
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9
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Panetta JC, Campagne O, Gartrell J, Furman W, Stewart CF. Pharmacokinetically guided dosing of oral sorafenib in pediatric hepatocellular carcinoma: A simulation study. Clin Transl Sci 2021; 14:2152-2160. [PMID: 34060723 PMCID: PMC8604221 DOI: 10.1111/cts.13069] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 03/05/2021] [Accepted: 04/04/2021] [Indexed: 02/01/2023] Open
Abstract
Sorafenib improves outcomes in adult hepatocellular carcinoma; however, hand foot skin reaction (HFSR) is a dose limiting toxicity of sorafenib that limits its use. HFSR has been associated with sorafenib systemic exposure. The objective of this study was to use modeling and simulation to determine whether using pharmacokinetically guided dosing to achieve a predefined sorafenib target range could reduce the rate of HFSR. Sorafenib steady‐state exposures (area under the concentration curve from 0 to 12‐h [AUC0–>12 h]) were simulated using published sorafenib pharmacokinetics at either a fixed dosage (90 mg/m2/dose) or a pharmacokinetically guided dose targeting an AUC0–>12 h between 20 and 55 h µg/ml. Dosages were either rounded to the nearest quarter of a tablet (50 mg) or capsule (10 mg). A Cox proportional hazard model from a previously published study was used to quantify HFSR toxicity. Simulations showed that in‐target studies increased from 50% using fixed doses with tablets to 74% using pharmacokinetically guided dosing with capsules. The power to observe at least 4 of 6 patients in the target range increased from 33% using fixed dosing with tablets to 80% using pharmacokinetically guided with capsules. The expected HFSR toxicity rate decreased from 22% using fixed doses with tablets to 16% using pharmacokinetically guided dosing with capsules. The power to observe less than 6 of 24 studies with HFSR toxicity increased from 51% using fixed dosing with tablets to 88% using pharmacokinetically guided with capsules. Our simulations provide the rationale to use pharmacokinetically guided sorafenib dosing to maintain effective exposures that potentially improve tolerability in pediatric clinical trials.
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Affiliation(s)
- John C Panetta
- Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
| | - Olivia Campagne
- Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
| | - Jessica Gartrell
- Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
| | - Wayne Furman
- Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
| | - Clinton F Stewart
- Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
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10
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Reig M, Forner A, Ávila MA, Ayuso C, Mínguez B, Varela M, Bilbao I, Bilbao JI, Burrel M, Bustamante J, Ferrer J, Gómez MÁ, Llovet JM, De la Mata M, Matilla A, Pardo F, Pastrana MA, Rodríguez-Perálvarez M, Tabernero J, Urbano J, Vera R, Sangro B, Bruix J. Diagnosis and treatment of hepatocellular carcinoma. Update of the consensus document of the AEEH, AEC, SEOM, SERAM, SERVEI, and SETH. Med Clin (Barc) 2021; 156:463.e1-463.e30. [PMID: 33461840 DOI: 10.1016/j.medcli.2020.09.022] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 09/12/2020] [Accepted: 09/15/2020] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver neoplasm and one of the most common causes of death in patients with cirrhosis of the liver. In parallel, with recognition of the clinical relevance of this cancer, major new developments have recently appeared in its diagnosis, prognostic assessment and in particular, in its treatment. Therefore, the Spanish Association for the Study of the Liver (AEEH) has driven the need to update the clinical practice guidelines, once again inviting all the societies involved in the diagnosis and treatment of this disease to participate in the drafting and approval of the document: Spanish Society for Liver Transplantation (SETH), Spanish Society of Diagnostic Radiology (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Association of Surgeons (AEC) and Spanish Society of Medical Oncology (SEOM). The clinical practice guidelines published in 2016 and accepted as National Health System Clinical Practice Guidelines were taken as the reference documents, incorporating the most important recent advances. The scientific evidence and the strength of the recommendation is based on the GRADE system.
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Affiliation(s)
- María Reig
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, IDIBAPS, Universidad de Barcelona, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España
| | - Alejandro Forner
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, IDIBAPS, Universidad de Barcelona, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España
| | - Matías A Ávila
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Programa de Hepatología, Centro de Investigación Médica Aplicada, Universidad de Navarra-IDISNA, Pamplona, España
| | - Carmen Ayuso
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Servicio de Radiodiagnóstico, Hospital Clínic Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Beatriz Mínguez
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Servicio de Hepatología, Hospital Universitario Vall d́Hebron, Grupo de Investigación en Enfermedades Hepáticas (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universidad Autónoma de Barcelona. Barcelona, España
| | - María Varela
- Sección de Hepatología, Servicio de Aparato Digestivo, Hospital Universitario Central de Asturias. Oviedo, España
| | - Itxarone Bilbao
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Servicio de Cirugía Hepatobiliopancreática y Trasplantes Digestivos, Hospital Universitario Vall d'Hebron, Universidad Autónoma de Barcelona. Barcelona, España
| | - José Ignacio Bilbao
- Unidad de Radiología Vascular e Intervencionista, Departamento de Radiodiagnóstico, Clínica Universidad de Navarra, Pamplona, España
| | - Marta Burrel
- Servicio de Radiodiagnóstico, Hospital Clínic Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Javier Bustamante
- Servicio de Gastroenterología y Hepatología, Sección de Hepatología y Trasplante, Hospital Universitario de Cruces, Baracaldo, España
| | - Joana Ferrer
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Cirugía Hepatobiliopancreática, Hospital Clínic, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Miguel Ángel Gómez
- Unidad de Cirugía Hepatobiliopancreática y Trasplantes, Hospital Universitario Virgen del Rocío, Sevilla, España
| | - Josep María Llovet
- Grupo de Investigación Traslacional en Oncología Hepática, Servicio de Hepatología, Hospital Clínic, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Manuel De la Mata
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Unidad Clínica de Aparato Digestivo, Hospital Universitario Reina Sofía, Córdoba, España
| | - Ana Matilla
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Sección de Hepatología, Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Madrid, España
| | - Fernando Pardo
- Servicio de Cirugía Hepatobiliopancreática y Trasplante, Clínica Universidad de Navarra, Pamplona, España
| | - Miguel A Pastrana
- Servicio de Radiodiagnóstico, Hospital Universitario Puerta de Hierro, Universidad Autónoma de Madrid, Madrid, España
| | - Manuel Rodríguez-Perálvarez
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Unidad Clínica de Aparato Digestivo, Hospital Universitario Reina Sofía, Córdoba, España
| | - Josep Tabernero
- Servicio de Oncología Médica, Hospital Universitario Vall d'Hebron, Universidad Autónoma de Barcelona, Barcelona, España
| | - José Urbano
- Unidad de Radiología Vascular e Intervencionista, Servicio de Radiodiagnóstico, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, España
| | - Ruth Vera
- Servicio de Oncología Médica, Complejo hospitalario de Navarra, Navarrabiomed-IDISNA, Pamplona, España
| | - Bruno Sangro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España; Unidad de Hepatología y Área de Oncología HBP, Clínica Universidad de Navarra-IDISNA, Pamplona, España.
| | - Jordi Bruix
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, IDIBAPS, Universidad de Barcelona, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
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Cerrito L, Santopaolo F, Monti F, Pompili M, Gasbarrini A, Ponziani FR. Advances in pharmacotherapeutics for hepatocellular carcinoma. Expert Opin Pharmacother 2021; 22:1343-1354. [PMID: 33637024 DOI: 10.1080/14656566.2021.1892074] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Although hepatocellular carcinoma (HCC) is the most frequent primary liver cancer, there are limited therapeutic options for the advanced stages. Sorafenib was the first tyrosine-kinase inhibitor (TKI) approved for unresectable HCC and remained the only effective choice for a decade. The horizon of systemic treatments drastically expanded in the latest years, opening new interesting possibilities. AREAS COVERED In this manuscript, the authors have analysed the recent advances in pharmacotherapy for HCC, discussing their mechanisms of action, the clinical efficacy and the safety profile of currently available first, second-and third-line treatments. The authors have also analysed the role of immune system modulators, in particular immune checkpoints inhibitors (ICIs), based on the limited data published so far. EXPERT OPINION The emergence of new targeted therapies, such as lenvatinib, have changed the landscape of HCC therapy. Tumor extension, differences in objective response rates and adverse events profiles should be considered to tailor the choice of the first-line agent. Sorafenib remains the most studied drug, with much real-world data available. The efficacy of second line therapies has only been proven in non-responder or sorafenib-intolerant patients. Unfortunately, studies directly comparing the second-line agents regorafenib, ramucirumab and cabozantinib are still lacking.
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Affiliation(s)
- Lucia Cerrito
- Internal Medicine, Gastroenterology And Hepatology, Fondazione Policlinico Universitario Agostino Gemelli Irccs, Università Cattolica Del Sacro Cuore, ROMA, ITALY
| | - Francesco Santopaolo
- Internal Medicine, Gastroenterology And Hepatology, Fondazione Policlinico Universitario Agostino Gemelli Irccs, Università Cattolica Del Sacro Cuore, ROMA, ITALY
| | | | - Maurizio Pompili
- Internal Medicine, Gastroenterology And Hepatology, Fondazione Policlinico Universitario Agostino Gemelli Irccs, Università Cattolica Del Sacro Cuore, ROMA, ITALY
| | - Antonio Gasbarrini
- Internal Medicine, Gastroenterology And Hepatology, Fondazione Policlinico Universitario Agostino Gemelli Irccs, Università Cattolica Del Sacro Cuore, ROMA, ITALY
| | - Francesca Romana Ponziani
- Internal Medicine, Gastroenterology And Hepatology, Fondazione Policlinico Universitario Agostino Gemelli Irccs, Università Cattolica Del Sacro Cuore, ROMA, ITALY
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12
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Facciorusso A, Abd El Aziz MA, Sacco R. Efficacy of Regorafenib in Hepatocellular Carcinoma Patients: A Systematic Review and Meta-Analysis. Cancers (Basel) 2019; 12:36. [PMID: 31877664 PMCID: PMC7017079 DOI: 10.3390/cancers12010036] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Revised: 12/12/2019] [Accepted: 12/15/2019] [Indexed: 12/12/2022] Open
Abstract
Regorafenib showed promising results as a second-line agent after sorafenib failure in hepatocellular carcinoma patients. The aim of this meta-analysis was to evaluate the efficacy and safety of regorafenib in hepatocarcinoma patients. A computerized bibliographic search was performed on the main databases. The primary outcome was overall survival. Secondary outcomes were progression-free survival, tumor response, and the adverse events rate. Outcomes were pooled through a random-effects model and summary estimates were expressed in terms of median and 95% confidence interval or rates, as appropriate. One randomized-controlled trial and seven non-randomized studies with 809 patients were included. The great majority of recruited patients were in Child-Pugh A and ECOG 0 stage. Median overall survival was 11.08 months (9.46-12.71) and sensitivity analyses confirmed this finding, with a median survival ranging from 10.2 to 13.8 months. Duration of regorafenib therapy was 3.58 months, whereas median progression-free survival was 3.24 months (2.68-3.86). The pooled objective response rate was 10.1% (7.8%-12.5%) while the disease control rate was 65.5% (61.3%-69.7%) with no evidence of heterogeneity (I2 = 0%; Diarrhea, fatigue, and hand-foot skin reaction were the most frequent adverse events. The current meta-analysis shows that regorafenib represents a valuable and relatively safe therapeutic option in intermediate/advanced hepatocellular carcinomapatients who progress on sorafenib.
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Affiliation(s)
- Antonio Facciorusso
- Department of Medical Sciences, Section of Gastroenterology, University of Foggia, 71122 Foggia, Italy;
| | - Mohamed A. Abd El Aziz
- Department of Surgery, Faculty of Medicine, University of Arizona, Tucson, AZ 85719, USA; or
- Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA
| | - Rodolfo Sacco
- Department of Medical Sciences, Section of Gastroenterology, University of Foggia, 71122 Foggia, Italy;
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13
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As Clinical Markers, Hand-Foot-Skin Reaction and Diarrhea Can Predict Better Outcomes for Hepatocellular Carcinoma Patients Receiving Transarterial Chemoembolization plus Sorafenib. Can J Gastroenterol Hepatol 2019; 2019:2576349. [PMID: 31815114 PMCID: PMC6877904 DOI: 10.1155/2019/2576349] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Revised: 07/13/2019] [Accepted: 07/28/2019] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Combination therapy of transarterial chemoembolization plus sorafenib (TACE-S) has been proven to be safe and effective for hepatocellular carcinoma (HCC); however, this combination therapy is associated with a high incidence of adverse events (AEs). Our study focused on the relationships between AEs and treatment outcomes and aimed to discover AE-based clinical markers that can predict the survival benefits of combination treatment. METHODS From January 2010 to June 2014, a total of 235 HCC patients treated with TACE-S were retrospectively enrolled. Major sorafenib-related AEs were prospectively recorded, and their correlations with overall survival (OS) were analysed using time-dependent covariate Cox regression analyses. RESULTS The majority of the patients (200, 85.1%) were male, and the median age was 51 years old. After two years of follow-up, the median OS of the study population reached 12.4 months. In all, 218 patients (92.8%) presented at least one AE, and 174 (74.0%) suffered AEs ≥2 grade. Based on time-dependent multivariate analyses, the development of hand-foot skin reaction (HFSR) ≥2 grade (HR = 0.43, 95% CI: 0.32-0.58, P < 0.001) and diarrhoea ≥1 grade (HR = 0.72, 95% CI: 0.53-0.97, P=0.029) were identified as independent predictors of prolonged OS. Moreover, patients who developed both HFSR ≥2 grade and diarrhoea ≥1 grade achieved better outcomes than those patients who developed either or neither of these AEs (HR = 1.51, 95% CI: 1.11-2.06, P=0.009). CONCLUSIONS The development of HFSR ≥2 grade or diarrhoea ≥1 grade during TACE-S treatment indicated prolonged OS, and these AEs should be considered important clinical markers for predicting patient prognoses.
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Ai L, Xu Z, Yang B, He Q, Luo P. Sorafenib-associated hand-foot skin reaction: practical advice on diagnosis, mechanism, prevention, and management. Expert Rev Clin Pharmacol 2019; 12:1121-1127. [PMID: 31679411 DOI: 10.1080/17512433.2019.1689122] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Introduction: Sorafenib is a multitargeted tyrosine kinase inhibitor, which has been mainly used in the treatment of advanced hepatocellular carcinoma and renal cancer. However, hand-foot skin reaction (HFSR), as one of the most common adverse reactions, have hindered its long-term clinical application. At present, the mechanism of its occurrence has not been clearly studied and it leads to the lack of effective means of intervention. This article reviews known mechanism and management methods of HFSR caused by sorafenib.Areas covered: The author reviews HFSR caused by the treatment of sorafenib including the mechanism and management. English language reports located through PubMed are reviewed.Expert opinion: There are some conjectures about the mechanism of HFSR. However, the mechanism of HFSR induced by sorafenib is still unclear at present. In the absence of understanding the mechanism of HFSR, the most common method for clinical treatment of sorafenib-induced HFSR is dose down-regulation or discontinuation of treatment, which affects efficacy and even survival. Future research should focus on the mechanism of HFSR to find out new ways for prevention. Precautionary measures before the occurrence of HFSR can also be studied in the future.
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Affiliation(s)
- Leilei Ai
- Institute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Ziheng Xu
- Institute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Bo Yang
- Institute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Qiaojun He
- Institute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Peihua Luo
- Institute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
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Zhou K, Fountzilas C. Outcomes and Quality of Life of Systemic Therapy in Advanced Hepatocellular Carcinoma. Cancers (Basel) 2019; 11:E861. [PMID: 31234316 PMCID: PMC6627968 DOI: 10.3390/cancers11060861] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2019] [Revised: 06/18/2019] [Accepted: 06/19/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers worldwide; most patients are diagnosed with advanced disease for which there is no known cure. Tremendous progress has been made over the past decade in the development of new agents for HCC, including small-molecule kinase inhibitors such as sorafenib, lenvatinib, cabozantinib, regorafenib, and monoclonal antibodies like ramucirumab, nivolumab, and pembrolizumab. Ideal use of these agents in clinics has improved the long-term outcome of patients with advanced HCC as well as introduced unique toxicities that can affect quality of life. These toxicities usually are thought to be partially related to cirrhosis, a major risk factor for the development of HCC and a pathophysiological barrier complicating the optimal delivery of antineoplastic therapy. Additionally, side effects of medications together with advanced HCC symptoms not only decrease quality of life, but also cause treatment interruptions and dose reductions that can potentially decrease efficacy. Physicians caring for patients with advanced HCC are called to optimally manage HCC along with cirrhosis in order to prolong life while at the same time preserve the quality of life. In this review, we aimed to summarize outcomes and quality of life with the use of modern systemic treatments in advanced HCC and provide a physician reference for treatment toxicity and cirrhosis management.
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Affiliation(s)
- Kehua Zhou
- Catholic Health System Internal Medicine Training Program, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214, USA.
| | - Christos Fountzilas
- Division of Gastrointestinal Medicine, Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
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16
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Wang E, Xia D, Bai W, Wang Z, Wang Q, Liu L, Wang W, Yuan J, Li X, Chen H, Lv Y, Niu J, He C, Guo W, Yin Z, Luo B, Han N, Wang Z, Yu T, Yuan X, Li K, Tie J, Li C, Cai H, Xia J, Fan D, Han G. Hand-foot-skin reaction of grade ≥ 2 within sixty days as the optimal clinical marker best help predict survival in sorafenib therapy for HCC. Invest New Drugs 2019; 37:401-414. [PMID: 30019101 DOI: 10.1007/s10637-018-0640-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2018] [Accepted: 07/09/2018] [Indexed: 12/31/2022]
Abstract
Background & Aims Sorafenib-related adverse events have been reported as clinical surrogates for treatment response in hepatocellular carcinoma (HCC); however, no consensus has been reached regarding the definition of responders. We evaluated the predictive abilities of different definitions for sorafenib response based on treatment-emergent adverse events, aiming to identify the most discriminatory one as a clinical marker. Methods From January 2010 to December 2014, 435 consecutive HCC patients treated with sorafenib were enrolled. Considering the type, severity and timing of adverse events, twelve different categories of sorafenib response were defined. By comparing their discriminatory abilities for survival, an indicative criterion was defined, the prognostic value of which was evaluated by time-dependent multivariate analysis, validated in various subsets and confirmed by landmark analysis. Results Using concordance (C)-index analysis and time-dependent receiver operating characteristic curves, the development of a hand-foot-skin reaction ≥ grade 2 within 60 days of sorafenib initiation (2HFSR60) showed the highest discriminating value. Based on this criterion, 161 (37.0%) sorafenib responders achieved decreased risk of death by 47% (adjusted HR 0.53, 95%CI 0.43-0.67, P < 0.001) and likelihood of progression by 26% (adjusted HR 0.74, 95%CI 0.58-0.96, P = 0.020) compared with non-responders. Notably, 2HFSR60 remained an effective discriminator among most subgroups and had superior predictive ability to previous definitions, even according to the landmark analysis. Conclusions Our study demonstrated that 2HFSR60, with the best discriminatory ability compared to currently available definitions of sorafenib-related adverse events, could be the optimal clinical marker to identify sorafenib responders with decreased risk of death by half.
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Affiliation(s)
- Enxin Wang
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Dongdong Xia
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Wei Bai
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Zhexuan Wang
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Qiuhe Wang
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Lei Liu
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Wenjun Wang
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Jie Yuan
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Xiaomei Li
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Hui Chen
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Yong Lv
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Jing Niu
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Chuangye He
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Wengang Guo
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Zhanxin Yin
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Bohan Luo
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Na Han
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Zhengyu Wang
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Tianlei Yu
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Xulong Yuan
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Kai Li
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Jun Tie
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
| | - Chanjuan Li
- Department of Medical Statistics, Fourth Military Medical University, Xi'an, China
| | - Hongwei Cai
- Information Center, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Jielai Xia
- Department of Medical Statistics, Fourth Military Medical University, Xi'an, China
| | - Daiming Fan
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China
- Xijing Hospital of Digestive Diseases & State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, China
| | - Guohong Han
- Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi'an, 710032, China.
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17
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Wang E, Xia D, Bai W, Yuan J, Li X, Niu J, Yin Z, Xia J, Cai H, Fan D, Han G, Liu L. Tumor Hypervascularity and hand-foot-skin reaction predict better outcomes in combination treatment of TACE and Sorafenib for intermediate hepatocellular carcinoma. BMC Cancer 2019; 19:409. [PMID: 31039750 PMCID: PMC6492437 DOI: 10.1186/s12885-019-5570-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2018] [Accepted: 04/02/2019] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND To validate the robust predictive values of tumor vascularity and hand-foot-skin reaction (HFSR) in combination treatment of transarterial chemoembolization (TACE) and sorafenib for patients with intermediate hepatocellular carcinoma (HCC), and then select the potential candidates who would survive best from such treatment. METHODS A total of 132 treatment-naive patients with intermediate HCC undergoing combination therapy of TACE and sorafenib were recruited between January 2010 and December 2014. The tumor vascularity was defined according to digital subtraction angiography (DSA) and HFSR was assessed by the national cancer institute common terminology criteria for adverse events (NCI-CTCAE). The Mann-Whitney U test was used to assess the correlation between vascularity and radiologic response; time to radiologic progression (TTP) and overall survival (OS) were evaluated using Kaplan-Meier techniques and compared by log-rank test; factors associated with them were evaluated using multivariate Cox regression analysis. RESULTS During a median follow up of 17.3 months, it was revealed that hypervascularity and development of ≥2 grade of HFSR within 60 days after sorafenib initiation were favorable predictors for TTP (HR 0.378, p < 0.001; HR 0.627, p = 0.018) and OS (HR 0.499, p = 0.002; HR 0.555, p = 0.004). The median TTP and OS for patients with both were 12.2 and 29.1 months, which were better than patients with either of them (6.0 months, HR 1.74, p = 0.012; 16.5 months, HR 1.73, p = 0.021), as well as those with neither (2.9 months, HR 3.74, p < 0.001; 11.9 months, HR 3.17, p < 0.001). CONCLUSIONS Tumor hypervascularity and development of ≥2 grade of HFSR within 60 days were favorable predictive factors for the combination treatment of TACE and sorafenib, with both of which the patients survived longest and might be the potential candidates.
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Affiliation(s)
- Enxin Wang
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Dongdong Xia
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Wei Bai
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Jie Yuan
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Xiaomei Li
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Jing Niu
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Zhanxin Yin
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Jielai Xia
- Department of Medical Statistics, Fourth Military Medical University, Xi'an, 710032, China
| | - Hongwei Cai
- Department of Medical Statistics, Fourth Military Medical University, Xi'an, 710032, China
| | - Daiming Fan
- Xijing Hospital of Digestive Diseases & State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, 710032, China
| | - Guohong Han
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China
| | - Lei Liu
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China.
- Cell Engineering Research Center and Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, 169 Changle Road, Xi'an, 710032, China.
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18
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Iezzi R, Pompili M, Rinninella E, Annicchiarico E, Garcovich M, Cerrito L, Ponziani F, De Gaetano A, Siciliano M, Basso M, Zocco MA, Rapaccini G, Posa A, Carchesio F, Biolato M, Giuliante F, Gasbarrini A, Manfredi R. TACE with degradable starch microspheres (DSM-TACE) as second-line treatment in HCC patients dismissing or ineligible for sorafenib. Eur Radiol 2019; 29:1285-1292. [PMID: 30171360 DOI: 10.1007/s00330-018-5692-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Revised: 07/17/2018] [Accepted: 07/31/2018] [Indexed: 02/06/2023]
Abstract
OBJECTIVES To date, there is no approved second-line treatment for patients dismissing sorafenib or ineligible for this treatment, so it would be useful to find an effective alternative treatment option. The aim of our study was to evaluate safety, feasibility and effectiveness of transarterial chemoembolisation with degradable starch microspheres (DSM-TACE) in the treatment of patients with advanced hepatocellular carcinoma (HCC) dismissing or ineligible for multikinase-inhibitor chemotherapy administration (sorafenib) due to unbearable side effects or clinical contraindications. METHODS Forty consecutive BCLC stage B or C patients (31 male; age, 70.6 ± 13.6 years), with intermediate or locally advanced HCC dismissing or ineligible for sorafenib administration, who underwent DSM-TACE treatment cycle via lobar approach were prospectively enrolled. Tumour response was evaluated on multidetector computed tomography based on mRECIST criteria. Primary endpoints were safety, tolerance and overall disease control (ODC); secondary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS Technical success was achieved in all patients. No intra/peri-procedural death/major complications occurred. No signs of liver failure or systemic toxicity were detected. At 1-year follow-up, ODC of 52.5% was registered. PFS was 6.4 months with a median OS of 11.3 months. CONCLUSIONS DSM-TACE is safe and effective as a second-line treatment in HCC patients dismissing or ineligible for sorafenib. KEY POINTS • DSM-TACE is safe and effective as second-line treatment in HCC patients dismissing or ineligible for sorafenib • DSM-TACE allows the temporary occlusion of the smaller arterial vessels, improving overall therapeutic effectiveness by reducing the immediate wash-out of the cytostatic agent • DSM-TACE also decreases the risk of systemic toxicity and post-embolic syndrome.
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Affiliation(s)
- Roberto Iezzi
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy.
| | - Maurizio Pompili
- Dipartimento di Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Emanuele Rinninella
- Dipartimento di Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Eleonora Annicchiarico
- Dipartimento di Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Matteo Garcovich
- Dipartimento di Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Lucia Cerrito
- Dipartimento di Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Francesca Ponziani
- Dipartimento di Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - AnnaMaria De Gaetano
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Massimo Siciliano
- Dipartimento di Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Michele Basso
- Dipartimento di Oncologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Maria Assunta Zocco
- Dipartimento di Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - GianLodovico Rapaccini
- Dipartimento di Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Alessandro Posa
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Francesca Carchesio
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Marco Biolato
- Dipartimento di Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Felice Giuliante
- Dipartimento di Chirurgia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Antonio Gasbarrini
- Dipartimento di Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
| | - Riccardo Manfredi
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00168, Rome, Italy
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Spreafico C, Sposito C, Vaiani M, Cascella T, Bhoori S, Morosi C, Lanocita R, Romito R, Chiesa C, Maccauro M, Marchianò A, Mazzaferro V. Development of a prognostic score to predict response to Yttrium-90 radioembolization for hepatocellular carcinoma with portal vein invasion. J Hepatol 2018; 68:724-732. [PMID: 29331342 DOI: 10.1016/j.jhep.2017.12.026] [Citation(s) in RCA: 113] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2017] [Revised: 12/18/2017] [Accepted: 12/20/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Yttrium-90 transarterial radioembolization (TARE) has shown promising efficacy in the treatment of patients with hepatocellular carcinoma (HCC), associated with portal vein tumor thrombus (PVTT). The aim of this study is to identify prognostic factors for survival in patients with HCC and PVTT undergoing TARE, and build a prognostic classification for these patients. METHODS This is a single center retrospective study conducted over six years (2010-2015), on consecutive patients undergoing TARE. Patients were included if they met the following criteria: presence of at least one measurable HCC, presence of PVTT not occluding the main portal trunk, absence of extrahepatic metastases, Child-Pugh score within B7, Eastern Cooperative Oncology Group performance status 0-1. Uni- and multivariable analysis was used to explore the variables that showed an independent relationship with survival. A prognostic score was then derived, and three prognostic categories were identified. RESULTS A total of 120 patients were included in the study. Median overall survival (OS) was 14.1 months (95% CI 10.7-17.5) and median progression-free survival (PFS) was 6.5 months (95% CI 3.8-9.2). The only variables independently correlated with OS were bilirubin, extension of PVTT and tumor burden. Three prognostic categories were identified: favourable prognosis (0 points), intermediate prognosis (2-3 points) and dismal prognosis (>3 points). Median OS in the three categories was 32.2 months, 14.9 months and 7.8 months respectively (p <0.0001). PFS (p = 0.045) and the risk of liver decompensation (p <0.0001) also significantly differed along the same prognostic categories. CONCLUSIONS Radioembolization with Yttrium-90 is an effective therapy for patients with HCC and PVTT. The proposed prognostic stratification may help to better identify good candidates for the treatment, and those for whom TARE may be futile. LAY SUMMARY Yttrium-90 transarterial radioembolization (TARE) is a microembolic procedure that minimizes alterations to hepatic arterial flow, and thus can be safely performed in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). In this study, we retrospectively evaluated the independent predictors of long-term outcomes in patients with HCC and PVTT treated with TARE. Bilirubin level, extension of PVTT and tumor burden were independently related to post-treatment survival: the combination of these factors allowed us to build a prognostic stratification that may help to better identify good candidates for the treatment, and those for whom TARE may be futile.
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Affiliation(s)
- Carlo Spreafico
- Department of Radiology, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
| | - Carlo Sposito
- Department of Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
| | - Marta Vaiani
- Department of Radiology, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
| | - Tommaso Cascella
- Department of Radiology, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
| | - Sherrie Bhoori
- Department of Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
| | - Carlo Morosi
- Department of Radiology, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
| | - Rodolfo Lanocita
- Department of Radiology, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
| | - Raffaele Romito
- Department of Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
| | - Carlo Chiesa
- Department of Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
| | - Marco Maccauro
- Department of Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
| | - Alfonso Marchianò
- Department of Radiology, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
| | - Vincenzo Mazzaferro
- Department of Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy; University of Milan, Milan, Italy.
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20
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Ponziani FR, Spinelli I, Rinninella E, Cerrito L, Saviano A, Avolio AW, Basso M, Miele L, Riccardi L, Zocco MA, Annicchiarico BE, Garcovich M, Biolato M, Marrone G, De Gaetano AM, Iezzi R, Giuliante F, Vecchio FM, Agnes S, Addolorato G, Siciliano M, Rapaccini GL, Grieco A, Gasbarrini A, Pompili M. Reverse time-dependent effect of alphafetoprotein and disease control on survival of patients with Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma. World J Hepatol 2017; 9:1322-1331. [PMID: 29359015 PMCID: PMC5756721 DOI: 10.4254/wjh.v9.i36.1322] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2017] [Revised: 10/12/2017] [Accepted: 11/11/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) and to ascertain the factors predicting the achievement of disease control (DC). METHODS The cirrhotic patients with BCLC stage C HCC evaluated by the Hepatocatt multidisciplinary group were subjected to the investigation. Demographic, clinical and tumor features, along with the best tumor response and overall survival were recorded. RESULTS One hundred and ten BCLC stage C patients were included in the analysis; the median overall survival was 13.4 mo (95%CI: 10.6-17.0). Only alphafetoprotein (AFP) serum level > 200 ng/mL and DC could independently predict survival but in a time dependent manner, the former was significantly associated with increased risk of mortality within the first 6 mo of follow-up (HR = 5.073, 95%CI: 2.159-11.916, P = 0.0002), whereas the latter showed a protective effect against death after one year (HR = 0.110, 95%CI: 0.038-0.314, P < 0.0001). Only patients showing microvascular invasion and/or extrahepatic spread recorded lower chances of achieving DC (OR = 0.263, 95%CI: 0.111-0.622, P = 0.002). CONCLUSION The BCLC stage C HCC includes a wide heterogeneous group of cirrhotic patients suitable for potentially curative treatments. The reverse and time dependent effect of AFP serum level and DC on patients' survival confers them as useful predictive tools for treatment management and clinical decisions.
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Affiliation(s)
- Francesca Romana Ponziani
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy.
| | - Irene Spinelli
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Emanuele Rinninella
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Lucia Cerrito
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Antonio Saviano
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | | | - Michele Basso
- Department of Oncology, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Luca Miele
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Laura Riccardi
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Maria Assunta Zocco
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | | | - Matteo Garcovich
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Marco Biolato
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Giuseppe Marrone
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Anna Maria De Gaetano
- Department of Bioimaging and Radiological Sciences, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Roberto Iezzi
- Department of Bioimaging and Radiological Sciences, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Felice Giuliante
- Department of Hepatobiliary Surgery, Agostino Gemelli Hospital, Rome 00168, Italy
| | | | - Salvatore Agnes
- Department of Liver Transplant Surgery, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Giovanni Addolorato
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Massimo Siciliano
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Gian Lodovico Rapaccini
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Antonio Grieco
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Antonio Gasbarrini
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Maurizio Pompili
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
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Shriver A, Rudnick S, Intagliata N, Wang A, Caldwell SH, Northup P, Tani CM, Chagas AL, Pfiffer T, Hoff P, Carrilho FJ, Alves de Mattos A. A Randomized Controlled Trial of Procedural Techniques for Large Volume Paracentesis. Ann Hepatol 2017; 16:279-284. [PMID: 28233752 DOI: 10.5604/16652681.1231587] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION The aim of this study is to investigate large volume therapeutic paracentesis using either a z-tract or axial (coxial) technique in a randomized controlled trial. MATERIALS AND METHODS In this randomized, single blind study, patients with cirrhosis undergoing outpatient therapeutic paracentesis were randomized to the z-tract or the modified angular (coaxial) needle insertion technique. Subject and procedure characteristics were compared between the groups with ascites leakage as quantified by need for dressing changes with standardized sized gauze pads as a primary endpoint and subject procedural discomfort, operator preference, and procedure complications as secondary endpoints. RESULTS 72 paracenteses were performed during the study period: 34 to the z-tract and 38 to the coaxial insertion technique. Following exclusions, a total of 61 paracenteses were analyzed: 30 using the z-tract technique and 31 using the coaxial technique. There were equal rates of post-procedural leakage of ascites between groups (13% in both groups, p = 1.00). Using the visual analog scale (0 - 100), there was a statistically significant increase in the subject reported pain score with the z-tract compared with the coaxial method [26.4 (95% CI 18.7 - 34.1) vs. 17.2 (95% CI 10.6 - 23.8), p = 0.04]. Mean physician rated procedure difficulty (1 - 5) was significantly higher for the z-tract versus the coaxial technique [2.1 (95% CI 1.6 - 2.6) vs. 1.5 (95% CI 1.2 - 1.8), p = 0.04]. CONCLUSION When compared to the z-tract technique, the coaxial insertion technique is superior during large volume paracentesis in cirrhosis patients.
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Affiliation(s)
- Amy Shriver
- Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, Virginia, USA
| | - Sean Rudnick
- Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, Virginia, USA
| | - Nicolas Intagliata
- Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, Virginia, USA
| | - Amanda Wang
- University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - Stephen H Caldwell
- Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, Virginia, USA
| | - Patrick Northup
- Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, Virginia, USA
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Abdel-Rahman O, Lamarca A. Development of sorafenib-related side effects in patients diagnosed with advanced hepatocellular carcinoma treated with sorafenib: a systematic-review and meta-analysis of the impact on survival. Expert Rev Gastroenterol Hepatol 2017; 11:75-83. [PMID: 27882800 DOI: 10.1080/17474124.2017.1264874] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Introduction: Clinical markers to predict the benefit from sorafenib in patients diagnosed with hepatocellular carcinoma (HCC) are lacking. A meta-analysis exploring the impact of development of sorafenib-related side effects on survival was conducted. Areas covered: Eligible studies included all clinical studies reporting on the survival/toxicity relationship in sorafenib-treated HCC patients. Data sources included Pub-Med, the Cochrane Controlled Trials Register, and Google scholar. After exclusion of ineligible studies, 16 studies were included in the analysis. Pooled hazard ratio (HR) for overall survival (OS) for patients developing diarrhoea vs. patients who did not was 0.42 (95% confidence interval (CI): 0.30-0.60; p < 0.00001); pooled HR for patients developing hypertension vs. those who did not was 0.46 (95% CI: 0.30-0.70; p = 0.0003); pooled HR for patients developing hand foot skin reaction vs. those who did not was 0.47 (95% CI: 0.35-0.62; p < 0.00001); pooled HR for OS for all types of skin toxicities was 0.51 (95% CI: 0.36-0.72; p = 0.0002); while pooled HR for OS for a combination of selected side effects (hypertension, HFS and diarrhoea) was 0.38 (95% CI: 0.30-0.48; p < 0.00001). No information was available regarding the impact of thyroid dysfunction or proteinuria. Expert commentary: This analysis of data demonstrated that the occurrence of sorafenib-related side effects (such as diarrhoea, hypertension and skin toxicities) is associated with a better OS in sorafenib-treated HCC patients.
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Affiliation(s)
- Omar Abdel-Rahman
- a Clinical Oncology Department, Faculty of Medicine , Ain Shams University , Cairo , Egypt
| | - Angela Lamarca
- b Medical Oncology Department , The Christie NHS Foundation Trust , Manchester , UK
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von Felden J, Schulze K, Gil-Ibanez I, Werner T, Wege H. First- and Second-Line Targeted Systemic Therapy in Hepatocellular Carcinoma-An Update on Patient Selection and Response Evaluation. Diagnostics (Basel) 2016; 6:E44. [PMID: 27916795 PMCID: PMC5192519 DOI: 10.3390/diagnostics6040044] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2016] [Revised: 11/22/2016] [Accepted: 11/23/2016] [Indexed: 12/30/2022] Open
Abstract
Advanced hepatocellular carcinoma (HCC) with vascular invasion and/or extrahepatic spread and preserved liver function, according to stage C of the Barcelona Clinic Liver Cancer (BCLC) classification, has a dismal prognosis. The multi-targeted tyrosine-kinase receptor inhibitor (TKI) sorafenib is the only proven active substance in systemic HCC therapy for first-line treatment. In this review, we summarize current aspects in patient selection and management of side effects, and provide an update on response evaluation during first-line sorafenib therapy. Since second-line treatment options have been improved with the successful completion of the RESORCE trial, demonstrating a survival benefit for second-line treatment with the TKI regorafenib, response monitoring during first-line therapy will be critical to deliver optimal systemic therapy in HCC. To this regard, specific side effects, in particular worsening of arterial hypertension and diarrhea, might suggest treatment response during first-line sorafenib therapy; however, clear predictive clinical markers, as well as laboratory test or serum markers, are not established. Assessment of radiologic response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) is helpful to identify patients who do not benefit from sorafenib treatment.
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Affiliation(s)
- Johann von Felden
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
| | - Kornelius Schulze
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
| | - Ines Gil-Ibanez
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
| | - Tobias Werner
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
| | - Henning Wege
- I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
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24
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Wang W, Bai W, Wang E, Zhao Y, Liu L, Yang M, Cai H, Xia D, Zhang L, Niu J, Yin Z, Zhang Z, Fan D, Xia J, Han G. mRECIST response combined with sorafenib-related adverse events is superior to either criterion alone in predicting survival in HCC patients treated with TACE plus sorafenib. Int J Cancer 2016; 140:390-399. [PMID: 27681592 DOI: 10.1002/ijc.30451] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Accepted: 09/15/2016] [Indexed: 12/11/2022]
Abstract
The mRECIST and dermatologic adverse events (AEs) can be used to assess the patient response to transarterial chemoembolization (TACE) and/or sorafenib for hepatocellular carcinoma (HCC). Here, we aimed to combine the two criteria to stratify the prognosis in patients with unresectable HCC receiving TACE plus sorafenib (TACE-S). In total, 176 consecutive HCC patients treated with TACE-S were enrolled. CT scans and laboratory tests were conducted pretreatment (at baseline, 5-7 days before the TACE-S) and post-treatment (at 1, 2 and 3 months). The radiological response was assessed according to mRECIST. Sorafenib-related AEs were recorded every 2 weeks after oral administration, and patients with dermatologic AEs of Grade 2 or more were defined as dermatologic responders. The earliest time at which mRECIST and dermatologic responses correlated with survival was 2 months after therapy. The mRECIST-dermatologic AE combination assessment stratified patients into three different prognoses; responders on both assessments exhibited the longest median overall survival (OS), followed by responders on one assessment and non-responders on both assessments (30.5, 17.4 and 8.3 months, respectively; p < 0.001). Achieving the highest C-index, the mRECIST-dermatologic AE combination showed better performance in predicting survival than either mRECIST or dermatologic AEs alone. Furthermore, the mRECIST-dermatologic AE combination remained a significant predictor of OS, even when the patients were stratified according to the BCLC stage, ECOG score or alpha-fetoprotein (AFP) value. This study showed that the combination of mRECIST response and dermatologic AEs is superior to either criterion used alone for predicting the survival of HCC patients treated with TACE-S.
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Affiliation(s)
- Wenjun Wang
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Wei Bai
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Enxin Wang
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Yan Zhao
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Lei Liu
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Man Yang
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Hongwei Cai
- Information Center, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Dongdong Xia
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Lei Zhang
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Jing Niu
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Zhanxin Yin
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Zhuoli Zhang
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.,Department of Radiology, Northwestern University, Chicago, IL
| | - Daiming Fan
- State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Jielai Xia
- Department of Medical Statistics, Fourth Military Medical University, Xi'an, China
| | - Guohong Han
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
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25
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Simão A. Hepatocellular Carcinoma: Portuguese Data in Chronic Hepatitis B Patients on Antiviral Therapy and Treatment Results With Sorafenib. GE-PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2016; 23:231-232. [PMID: 28868467 PMCID: PMC5580183 DOI: 10.1016/j.jpge.2016.08.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Adélia Simão
- Internal Medicine A, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
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