Abstract

ObjectivesTo develop and validate a deep learning-based overall survival (OS) prediction model in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) plus sorafenib.MethodsThis retrospective multicenter study consisted of 201 patients with treatment-naïve, unresectable HCC who were treated with TACE plus sorafenib. Data from 120 patients were used as the training set for model development. A deep learning signature was constructed using the deep image features from preoperative contrast-enhanced computed tomography images. An integrated nomogram was built using Cox regression by combining the deep learning signature and clinical features. The deep learning signature and nomograms were also externally validated in an independent validation set of 81 patients. C-index was used to evaluate the performance of OS prediction.ResultsThe median OS of the entire set was 19.2 months and no significant difference was found between the training and validation cohort (18.6 months vs. 19.5 months, P = 0.45). The deep learning signature achieved good prediction performance with a C-index of 0.717 in the training set and 0.714 in the validation set. The integrated nomogram showed significantly better prediction performance than the clinical nomogram in the training set (0.739 vs. 0.664, P = 0.002) and validation set (0.730 vs. 0.679, P = 0.023).ConclusionThe deep learning signature provided significant added value to clinical features in the development of an integrated nomogram which may act as a potential tool for individual prognosis prediction and identifying HCC patients who may benefit from the combination therapy of TACE plus sorafenib.

Highlights

  • Almost 80% of patients with hepatocellular carcinoma (HCC) are initially diagnosed at the intermediate or advanced stage, being unqualified for curative treatments such as resection and ablation [1, 2]

  • The median overall survival (OS) and progression-free survival (PFS) of the entire set was 19.2 months and 8.3 months and no significant difference was found between the training and validation cohort (median OS: 18.6 vs. 19.5 months, P = 0.45; median PFS: 8.4 vs. 8.1 months, P = 0.23)

  • The dose reductions and interruptions in 152 (75.6%) patients were mainly due to disease progression and adverse events (AEs)

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Summary

Introduction

Almost 80% of patients with hepatocellular carcinoma (HCC) are initially diagnosed at the intermediate or advanced stage, being unqualified for curative treatments such as resection and ablation [1, 2]. As demonstrated by two controlled randomized trials and the BRIDGE study, transarterial chemoembolization (TACE) is the most common therapeutic option for unresectable hepatocellular carcinoma (HCC), and is recommended for intermediate stage HCC (Barcelona Clinic Liver Cancer (BCLC) stage B) by most guidelines [3,4,5,6,7]. A multikinase inhibitor, was the first oral molecular targeting agent to significantly improve overall survival (OS) and time-to-tumor progression (TTP) in patients with advanced HCC [10, 11]. The TACTIS trial clearly showed that TACE plus sorafenib significantly improved clinical outcomes in patients with unresectable HCC, which indicated that this combination therapy was effective and feasible in routine practice [14]. Biomarkers or models which provide accurate prognosis predictions are still lacking

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