Serum HMGB1 concentrations at 4\xa0weeks is a useful predictor of extreme poor prognosis for advanced hepatocellular carcinoma treated with sorafenib and hepatic arterial infusion chemotherapy

Kazuhiko Masuda,Tomokazu Kawaoka,Michio Imamura,Masaki Kitajima ,Hiromi Kan,Yizhou Zhang,Daiki Miki,Takashi Nakahara,Atsushi Ono,Hatsue Fujino,Yoshiiku Kawakami,Tomoki Kobayashi,Yuji Teraoka,Kana Daijo,Hidenori Ochi,Hiroshi Aikata,Masataka Tsuge,Hiromi Abe‐Chayama ,Akira Hiramatsu,C Nelson Hayes,Kei Morio,Takuro Uchida,Yuko Nagaoki,Grace Naswa Makokha,Yuki Nakamura-Inagaki,Kazuaki Chayama

doi:10.1007/s00535-017-1348-8

Abstract

BackgroundBiomarkers predicting the response to the anticancer treatment and prognosis in patients with advanced hepatocellular carcinoma (HCC) are required. Recently, high mobility group box 1 (HMGB1) was reported to promote HCC progression and be associated with poor prognosis for patients with HCC. The purpose of this study was to assess serum HMGB1 concentrations before and during sorafenib treatment or hepatic arterial infusion chemotherapy (HAIC) and to explore the ability of serum HMGB1 concentrations to predict prognosis.MethodsSerum HMGB1 concentrations were measured in 71 and 72 patients with advanced HCC treated with sorafenib and HAIC, respectively, to assess their usefulness for prediction of the response to the treatment and prognosis.ResultsMultivariate analysis identified high HMGB1 at 4 weeks (P = 0.001), high α-fetoprotein (AFP) at baseline (P = 0.025), tumor liver occupying rate (P = 0.009) and modified RECIST (mRECIST, P < 0.0001) as independent predictors of poor overall survival in sorafenib treatment. High HMGB1 at 4 weeks (P = 0.025), vascular invasion to the hepatic vein (Vv) (P = 0.009), mRECIST (P < 0.0001) and Child-Pugh B (P = 0.004) were identified as independent predictors of poor overall survival in HAIC treatment. The concentrations of HMGB1 at baseline and 4 weeks were not correlated with conventional tumor markers and progressive disease assessed by mRECIST at 8 weeks.ConclusionsThese results suggest that serum HMGB1 at 4 weeks after the start of treatment might be a useful biomarker with added value to the conventional tumor marker and radiologic responses to predict poor overall survival in patients with advanced HCC treated with sorafenib or HAIC.

Highlights

Primary liver cancer is the second leading cause of cancerrelated deaths worldwide [1]
Background Biomarkers predicting the response to the anticancer treatment and prognosis in patients with advanced hepatocellular carcinoma (HCC) are required
These results suggest that serum high mobility group box 1 (HMGB1) at 4 weeks after the start of treatment might be a useful biomarker with added value to the conventional tumor marker and radiologic responses to predict poor overall survival in patients with advanced HCC treated with sorafenib or hepatic arterial infusion chemotherapy (HAIC)

Summary

Introduction

Primary liver cancer is the second leading cause of cancerrelated deaths worldwide [1]. Sorafenib has demonstrated survival benefits and is the current standard drug for systemic treatment in patients with advanced unresectable HCC [4, 5]. Several studies have indicated that HAIC improves survival in patients with advanced HCC in the absence of distant metastasis, with an increase in response rate from 20.8% up to 52% [6,7,8,9,10,11,12,13]. J Gastroenterol (2018) 53:107–118 predictors of poor overall survival in sorafenib treatment. High HMGB1 at 4 weeks (P = 0.025), vascular invasion to the hepatic vein (Vv) (P = 0.009), mRECIST (P \ 0.0001) and Child-Pugh B (P = 0.004) were identified as independent predictors of poor overall survival in HAIC treatment. The concentrations of HMGB1 at baseline and 4 weeks were not correlated with conventional tumor markers and progressive disease assessed by mRECIST at 8 weeks

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