title: Early sorafenib-related adverse events predict therapy response of TACE plus sorafenib: A multicenter clinical study of 606 HCC patients.
abstract: The purpose of our study was to test the hypothesis that sorafenib-related dermatologic adverse events (AEs) as an early biomarker can predict the long-term outcomes following the combination therapy of transarterial chemoembolization (TACE) plus sorafenib (TACE-S). The intermediate-stage hepatocellular carcinoma patients who received either TACE-S or TACE-alone treatment were consecutively included into analysis. In the TACE-S group, patients with ≥ grade 2 dermatologic AEs within the first month of sorafenib initiation were defined as responders; whereas those with < grade 2 were defined as nonresponders. In the TACE-S group, the median overall survival (OS) of the responders was significantly longer than that of nonresponders (28.9 months vs. 16.8 months, respectively; p = 0.004). Multivariate analysis demonstrated that nonresponders were significantly associated with an increased risk of death compared with responders (HR = 1.9; 95% confidence Interval-CI: 1.3-2.7; p = 0.001). The survival analysis showed that the median OS was 27.9 months (95% CI: 25.0-30.8) among responders treated with TACE-S vs.18.3 months (95% CI: 14.5-22.1) among those who received TACE-alone (p = 0.046). The median time to progression was 13.1 months (95% CI: 4.4-21.8) in the TACE-S group, a duration that was significantly longer than that in the TACE-alone group [5 months (95% CI: 6.4-13.3), p = 0.014]. This study demonstrated that sorafenib-related dermatologic AEs are clinical biomarkers to identify responders from all of the patients for TACE-S therapy. Sorafenib-related dermatologic AEs, clinical biomarkers, can predict the efficacy of TACE-S in future randomized controlled trials.
authors.affiliation: Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Interventional Radiology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Hailiang
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Bai
authors.affiliation: Department of Interventional Radiology and Vascular Surgery, Hunan Provincial People's Hospital, Changsha, China.
authors.forename: Jueshi
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Radiology, Anhui Provincial Hospital, Hefei, China.
authors.forename: Weifu
authors.initials: W
authors.lastname: Lv
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston.
authors.forename: Sonia
authors.initials: S
authors.lastname: Sahu
authors.affiliation: Second Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Guan
authors.affiliation: Department of Hepatobiliary Surgery & Vascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Qin
authors.affiliation: Department of Interventional Medicine, The First Affiliated Hospital of Lanzhou University, Lanzhou, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Interventional Radiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
authors.forename: Weixin
authors.initials: W
authors.lastname: Ren
authors.affiliation: Department of Radiology, The Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Mu
authors.affiliation: Cancer Treatment Center, Baogang Hospital of Inner Mongolia, Baotou, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Interventional Radiology, Hunan Cancer Hospital of Central South University, Changsha, China.
authors.forename: Shanzhi
authors.initials: S
authors.lastname: Gu
authors.affiliation: Department of Interventional Therapy, Tumor Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Yilong
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Zhanxin
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Wengang
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Medical Statistics, Fourth Military Medical University, Xi'an, China.
authors.forename: Yongji
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Radiology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
authors.forename: Rafael
authors.initials: R
authors.lastname: Duran
authors.affiliation: Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.|State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
authors.affiliation: Department of Radiology, Northwestern University, Chicago.
authors.forename: Zhuoli
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Guohong
authors.initials: G
authors.lastname: Han
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D016461:Chemoembolization, Therapeutic / Q000009:adverse effects / Q000379:methods; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D011379:Prognosis; D012189:Retrospective Studies; D000077157:Sorafenib; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
keywords: biomarker; dermatologic adverse events; hepatocellular carcinoma; sorafenib; transarterial chemoembolization