Surrogate endpoint for overall survival in assessment of adjuvant therapies after curative treatment for hepatocellular carcinoma: a re-analysis of meta-analyses of individual patients’ data

Hong-Bo Huan, Li-Li Wu, Wan-Yee Lau, Xu-Dong Wen, Liang Zhang, Da-Peng Yang, Xi-Shu Wang, Ping Bie and Feng Xia _

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Oncotarget. 2017; 8:90291-90300. https://doi.org/10.18632/oncotarget.18853

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Hong-Bo Huan1, Li-Li Wu1, Wan-Yee Lau1,2, Xu-Dong Wen1, Liang Zhang1, Da-Peng Yang1, Xi-Shu Wang1, Ping Bie1 and Feng Xia1

1Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China

2Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China

Correspondence to:

Feng Xia, email: [email protected]

Keywords: hepatocellular carcinoma, overall survival, disease-free survival, surrogate endpoint

Received: April 28, 2017     Accepted: June 20, 2017     Published: June 29, 2017


The gold standard endpoint to evaluate the effect of treatment for hepatocellular carcinoma (HCC) is overall survival (OS), but it requires a longer follow-up period to observe. This study aimed to identify whether disease-free survival (DFS) could be used as a surrogate endpoint for OS to assess the efficacy of adjuvant therapies after curative treatment (surgical resection and ablation) for HCC patients. A systematic review was conducted to identify trials about curative treatment combined with or without adjuvant therapies (interferon, IFN; or transarterial chemoembolization, TACE) for HCC. Total of 2211 patients’ data from 17 trials were analyzed. At the individual study level, DFS was strongly correlated to OS (ρ = 0.988 and 0.930, 95% CI: 0.965–0.996 and 0.806–0.976 for the studies comparing Radiofrequency ablation (RFA) + TACE to RFA alone; and for the studies comparing curative treatment + IFN to curative treatment alone, respectively). At the trial level, the effects of treatment on DFS and OS were also strongly correlated to each other (R = 0.815 and 0.854, 95% CI: 0.536–0.934 and 0.621–0.948, respectively). In conclusion, DFS could be used as a potential surrogate endpoint for OS to assess the effect of adjuvant therapies after curative treatment for HCC.

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