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World J Gastroenterol. Sep 28, 2018; 24(36): 4152-4163
Published online Sep 28, 2018. doi: 10.3748/wjg.v24.i36.4152
Ten years of sorafenib in hepatocellular carcinoma: Are there any predictive and/or prognostic markers?
Giorgia Marisi, Alessandro Cucchetti, Paola Ulivi, Matteo Canale, Giuseppe Cabibbo, Leonardo Solaini, Francesco G Foschi, Serena De Matteis, Giorgio Ercolani, Martina Valgiusti, Giovanni L Frassineti, Mario Scartozzi, Andrea Casadei Gardini
Giorgia Marisi, Paola Ulivi, Matteo Canale, Serena De Matteis, Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola 47014, Italy
Alessandro Cucchetti, Leonardo Solaini, Giorgio Ercolani, Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna 40126, Italy
Alessandro Cucchetti, Leonardo Solaini, Giorgio Ercolani, General and Oncologic Surgery, Morgagni-Pierantoni Hospital, Forlì 47121, Italy
Giuseppe Cabibbo, Section of Gastroenterology, DI.BI.M.I.S., University of Palermo, Palermo 35628, Italy
Francesco G Foschi, Department of Internal Medicine, Degli Infermi Hospital, Faenza 48018, Italy
Martina Valgiusti, Giovanni L Frassineti, Andrea Casadei Gardini, Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola 47014, Italy
Mario Scartozzi, Department of Medical Oncology, University of Cagliari, Cagliari 45698, Italy
Author contributions: All authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of final version.
Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Alessandro Cucchetti, MD, PhD, Adjunct Professor, Surgeon, Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Via Albertoni 15, Granarolo Dell’Emilia, Bologna 40126, Italy. aleqko@libero.it
Telephone: +39-543-731111 Fax: +39-543-739123
Received: July 3, 2018
Peer-review started: July 3, 2018
First decision: July 17, 2018
Revised: August 6, 2018
Accepted: August 24, 2018
Article in press: August 24, 2018
Published online: September 28, 2018
Processing time: 84 Days and 18.1 Hours
Abstract

Sorafenib has been considered the standard of care for patients with advanced unresectable hepatocellular carcinoma (HCC) since 2007 and numerous studies have investigated the role of markers involved in the angiogenesis process at both the expression and genetic level and clinical aspect. What results have ten years of research produced? Several clinical and biological markers are associated with prognosis. The most interesting clinical parameters are adverse events, Barcelona Clinic Liver Cancer stage, and macroscopic vascular invasion, while several single nucleotide polymorphisms and plasma angiopoietin-2 levels represent the most promising biological biomarkers. A recent pooled analysis of two phase III randomized trials showed that the neutrophil-to-lymphocyte ratio, etiology and extra-hepatic spread are predictive factors of response to sorafenib, but did not identify any predictive biological markers. After 10 years of research into sorafenib there are still no validated prognostic or predictive factors of response to the drug in HCC. The aim of the present review was to summarize 10 years of research into sorafenib, looking in particular at the potential of associated clinical and biological markers to predict its efficacy in patients with advanced HCC.

Keywords: Biomarker; Angiopoietin; Neutrophil-to-lymphocyte ratio; Polymorphisms; Sorafenib; MicroRNA; Adverse events; Hepatocellular carcinoma; Vascular endothelial growth factor

Core tip: Sorafenib has been considered the standard of care for patients with advanced unresectable hepatocellular carcinoma, but after 10 years of research into sorafenib response or resistance, there are still no validated prognostic or predictive factors of response.