PMID- 30180810 OWN - NLM STAT- MEDLINE DCOM- 20181024 LR - 20181202 IS - 1471-230X (Electronic) IS - 1471-230X (Linking) VI - 18 IP - 1 DP - 2018 Sep 4 TI - Transarterial chemoembolization plus sorafenib for the management of unresectable hepatocellular carcinoma: a systematic review and meta-analysis. PG - 138 LID - 10.1186/s12876-018-0849-0 [doi] LID - 138 AB - BACKGROUND: Transarterial chemoembolization (TACE) is the recommended treatment for hepatocellular carcinoma (HCC) patients at Barcelona Clinic Liver Cancer (BCLC) B-stage, whereas sorafenib is an orally administered small molecule target drug for BCLC C-stage. This updated systemic review and meta-analysis focuses on identifying the efficacy of the combination of TACE with sorafenib, which remains controversial despite years of exploration. METHODS: PubMed, EMBASE, Scopus and the Cochrane Library were systematically reviewed to search for studies published from January 1990 to May 2017. Studies focusing on the efficacy of combination therapy for unresectable HCC were eligible. The hazard ratio (HR) with 95% confidence intervals (95% CIs) for time to progression (TTP), overall survival (OS), disease control rate (DCR) and aetiology were collected. The data were then analysed through fixed/random effects meta-analysis models with STATA 13.0. The incidence and severity of treatment-related adverse events (AEs) were also evaluated. RESULTS: Twenty-seven studies were included. Thirteen non-comparative studies reported median OS (ranging from 18.5 to 20.4 months), median TTP (ranging from 7 to 13.9 months) and DCR (ranging from 18.4 to 95%). Fourteen comparative studies provided median OS (ranging from 7.0 to 29.7 months) and median TTP (ranging from 2.6 to 10.2 months). Five comparative studies provided DCR (ranging from 32 to 97.2%). Forest plots showed that combination therapy significantly improved TTP (HR = 0.66, 95% CI 0.50-0.81, P = 0.002) rather than OS (HR = 0.63, 95% CI 0.55-0.71, P = 0.058), compared to TACE alone. DCR increased significantly in the combination therapy group (OR = 2.93, 95% CI 1.59-5.41, P = 0.005). Additional forest plots were drawn and no significant differences were observed with regard to survival outcome among various aetiologies. Forest plots for separate analysis of regions showed the HR for TTP was 0.62 (95% CI 0.45-0.79, P = 0.002) in the Asian countries group, and 0.82 (95% CI 0.59-1.05, P = 0.504)) in western countries. The HR for OS was 0.61 (95% CI 0.48-0.75, P = 0.050) in the Asian countries group and was 0.88 (95% CI 0.56-1.20, P = 0.845) in western countries. These data may indicate positive TTP outcome in Asian patients but not in European patients while no positive findings regarding OS were observed in either region. The most common AEs included fatigue, hand-foot skin reaction, diarrhoea and hypertension. CONCLUSIONS: Combination therapy may benefit unresectable HCC patients in terms of prolonged TTP and DCR. More well-designed studies are needed to investigate its superiority for OS. FAU - Li, Lin AU - Li L AD - Department of Gastroenterology, Tangdu Hospital, Military Medical University of PLA Airforce (Fourth Military Medical University), 1 Xinsi Road, Xi'an, 710038, China. FAU - Zhao, Wenzhuo AU - Zhao W AD - Department of Gastroenterology, Tangdu Hospital, Military Medical University of PLA Airforce (Fourth Military Medical University), 1 Xinsi Road, Xi'an, 710038, China. FAU - Wang, Mengmeng AU - Wang M AD - Department of Drug and Equipment, Aeromedicine Identification and Training Centre of Air Force, Lintong District, Xi'an, China. FAU - Hu, Jie AU - Hu J AD - Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Military Medical University of PLA Airforce (Fourth Military Medical University), Xi'an, China. FAU - Wang, Enxin AU - Wang E AD - Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Military Medical University of PLA Airforce (Fourth Military Medical University), Xi'an, China. FAU - Zhao, Yan AU - Zhao Y AD - Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, China. yanzhao211@163.com. FAU - Liu, Lei AU - Liu L AUID- ORCID: 0000-0002-1479-0192 AD - Department of Gastroenterology, Tangdu Hospital, Military Medical University of PLA Airforce (Fourth Military Medical University), 1 Xinsi Road, Xi'an, 710038, China. 18700972783@163.com. AD - Cell Engineering Research Center and Department of Cell Biology, State Key Laboratory of Cancer Biology, Military Medical University of PLA Airforce), Xi'an, China. 18700972783@163.com. LA - eng GR - 81702999/National Natural Science Foundation of China/ GR - 2017SF-208/Health and Family Planning commission of Shaanxi province/ PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review DEP - 20180904 PL - England TA - BMC Gastroenterol JT - BMC gastroenterology JID - 100968547 RN - 0 (Antineoplastic Agents) RN - 0 (Phenylurea Compounds) RN - 25X51I8RD4 (Niacinamide) RN - 9ZOQ3TZI87 (Sorafenib) SB - IM MH - Antineoplastic Agents/adverse effects/*therapeutic use MH - Carcinoma, Hepatocellular/pathology/*therapy MH - *Chemoembolization, Therapeutic/adverse effects MH - Combined Modality Therapy MH - Disease Progression MH - Humans MH - Liver Neoplasms/*therapy MH - Neoplasm Staging MH - Niacinamide/adverse effects/*analogs & derivatives/therapeutic use MH - Phenylurea Compounds/adverse effects/*therapeutic use MH - Sorafenib MH - Survival Analysis MH - Time Factors PMC - PMC6124009 OTO - NOTNLM OT - Hepatocellular carcinoma OT - Meta-analysis OT - Sorafenib OT - Systemic review OT - Transarterial chemoembolization COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Not applicable. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/09/06 06:00 MHDA- 2018/10/26 06:00 PMCR- 2018/09/04 CRDT- 2018/09/06 06:00 PHST- 2017/09/09 00:00 [received] PHST- 2018/07/23 00:00 [accepted] PHST- 2018/09/06 06:00 [entrez] PHST- 2018/09/06 06:00 [pubmed] PHST- 2018/10/26 06:00 [medline] PHST- 2018/09/04 00:00 [pmc-release] AID - 10.1186/s12876-018-0849-0 [pii] AID - 849 [pii] AID - 10.1186/s12876-018-0849-0 [doi] PST - epublish SO - BMC Gastroenterol. 2018 Sep 4;18(1):138. doi: 10.1186/s12876-018-0849-0.