Integration of the cancer-related inflammatory response as a stratifying biomarker of survival in hepatocellular carcinoma treated with sorafenib.

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Title: Integration of the cancer-related inflammatory response as a stratifying biomarker of survival in hepatocellular carcinoma treated with sorafenib.
Authors: Howell, J
Pinato, DJ
Ramaswami, R
Arizumi, T
Ferrari, C
Gibbin, A
Burlone, ME
Guaschino, G
Toniutto, P
Black, J
Sellers, L
Kudo, M
Pirisi, M
Sharma, R
Item Type: Journal Article
Abstract: BACKGROUND AND AIMS: Response to sorafenib is highly variable in hepatocellular carcinoma (HCC). Baseline inflammatory parameters and treatment toxicities may improve survival prediction in patients on sorafenib therapy. RESULTS: 442 patients with advanced stage HCC on sorafenib were recruited (follow-up 5096 person-months at risk). 88% had BCLC stage B or greater HCC and 72.3% had Child-Pugh A cirrhosis. On Cox multivariate regression, previously-treated HCC (HR 0.579, 95% CI 0.385-0.872, p=0.009), Cancer of Liver Italian Program (CLIP) score (HR 1.723, 95% CI 1.462-2.047, p<0.0001), baseline red cell distribution width (RDW; HR 1.234, 95% CI 1.115-1.290, p<0.0001) and neutrophil to lymphocyte ratio (NLR; HR 1.218, 95% CI 1.108-1.322, p<0.0001) were significant independent risks for shorter survival, whilst sorafenib-related diarrhoea was associated with prolonged survival (HR 0.533, 95% CI 0.373-0.763, p=0.001). The combination of RD-CLIP score (CLIP score multiplied by RDW) ≥ 70 and no treatment-related diarrhoea had good utility for predicting 3-month survival (AUC of 0.808 (95% CI 0.734-0.882), positive predictive value of 86.4% and negative predictive value of 83.3%), compared with CLIP (AUC=0.642) or BCLC score alone (AUC=0.579). RD-CLIP score ≥ 35 and no treatment-related diarrhoea had an AUC of 0.787 for predicting 12-month survival. METHODS: Patients with HCC were consecutively recruited from three tertiary centres (Japan, Italy and UK) and clinical data were prospectively collected. The primary study endpoint was overall survival (OS) after commencing sorafenib. CONCLUSION: The novel prognostic index of CLIP score combined with inflammatory marker RDW and treatment-related diarrhoea has good accuracy for predicting overall, 3 month and 12 month survival in patients on sorafenib.
Issue Date: 14-Feb-2017
Date of Acceptance: 13-Oct-2016
URI: http://hdl.handle.net/10044/1/45591
DOI: https://dx.doi.org/10.18632/oncotarget.15322
ISSN: 1949-2553
Publisher: Impact Journals
Start Page: 36161
End Page: 36170
Journal / Book Title: Oncotarget
Volume: 8
Copyright Statement: © 2017 Howell et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC-BY https://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
Cell Biology
liver cancer
VEGF inhibitor
CLIP score
BCLC
inflammation
CELL DISTRIBUTION WIDTH
SINGLE-CENTER EXPERIENCE
C-REACTIVE PROTEIN
LYMPHOCYTE RATIO
SKIN TOXICITY
OUTCOMES
CIRRHOSIS
PREDICT
IMPACT
SCORE
Publication Status: Published
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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