Alternative Response Criteria (Choi, European association for the study of the liver, and modified Response Evaluation Criteria in Solid Tumors [RECIST]) Versus RECIST 1.1 in patients with advanced hepatocellular carcinoma treated with sorafenib

Abstract

Introduction: Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), may underestimate activity and does not predict survival in patients with hepatocellular carcinoma (HCC) treated with sorafenib. This study assessed the value of alternative radiological criteria to evaluate response in HCC patients treated with sorafenib.

Patients and methods: A retrospective blinded central analysis was performed of computed tomography (CT) scans from baseline and the first tumor evaluation in consecutive patients treated with sorafenib over a 2-year period in a single institution. Four different evaluation criteria were used: Choi, European Association for the Study of the Liver (EASL), modified RECIST (mRECIST), and RECIST 1.1.

Results: Among 82 HCC patients, 64 with Barcelona Clinic Liver Cancer stage B-C were evaluable with a median follow-up of 22 months. Median duration of sorafenib treatment was 5.7 months, and median overall survival was 12.8 months. At the time of the first CT scan, performed after a median of 2.1 months, Choi, EASL, mRECIST, and RECIST 1.1 identified 51%, 28%, 28%, and 3% objective responses, respectively. Responders by all criteria showed consistent overall survival >20 months. Among patients with stable disease according to RECIST 1.1, those identified as responders by Choi had significantly better overall survival than Choi nonresponders (22.4 vs. 10.6 months; hazard ratio: 0.43, 95% confidence interval: 0.15-0.86, p = .0097).

Conclusion: Choi, EASL, and mRECIST criteria appear more appropriate than RECIST 1.1 to identify responders with long survival among advanced HCC patients benefiting from sorafenib.

Keywords: Antiangiogenic agents; Computed tomography; Density; Targeted therapy; Tumor evaluation.

Figure 1.

Baseline and post-treatment evaluation of response using RECIST 1.1 and alternative radiological criteria. Typical example of response evaluation by RECIST 1.1, mRECIST, EASL criteria, and Choi criteria in a patient with hepatocellular carcinoma treated with sorafenib. Abbreviations: EASL, European Association for the Study of the Liver; HU, Hounsfield unit; mRECIST, modified Response Evaluation Criteria in Solid Tumors; RECIST 1.1, Response Evaluation Criteria in Solid Tumors, version 1.1.

Figure 2.

Comparison of freehand and circular ROI delineation of the tumor for density evaluation. (A): Representative examples of target lesions at baseline and postsorafenib using a “circular ROI” placed over the tumor and a “freehand ROI” drawing manually delineating the tumor margins before and after sorafenib. (B): Scatterplot comparing “freehand ROI” and “circular ROI” for the evaluation of tumor density in patients with advanced hepatocellular carcinoma before and after treatment with sorafenib. Abbreviations: HU, Hounsfield unit; ROI, region of interest.

Figure 3.

Kaplan-Meier overall survival of patients with hepatocellular carcinoma treated with sorafenib. (A): Overall survival (solid blue line) and 95% confidence interval (dotted lines) of patients treated with sorafenib. Overall survival was evaluated according to Choi (B), European Association for the Study of the Liver (C), modified Response Evaluation Criteria in Solid Tumors (D), and Response Evaluation Criteria in Solid Tumors, version 1.1 (E). (B–E): Patients with objective responses (green), stable disease (blue), and progressive disease (red). p values compared the three groups using log-rank tests for trends.

Figure 4.

Evaluation of Choi criteria in patients with stable disease by RECIST 1.1. (A): Proportions of patients with objective response, stable disease (SD), and progressive disease using Choi, EASL, and mRECIST among patients with SD according to RECIST 1.1. (B): Kaplan-Meier overall survival of patients with SD by RECIST1.1 is shown in gray. Responders by Choi criteria (green) display significantly higher survival (log-rank test) compared with nonresponders (blue). Abbreviations: EASL, European Association for the Study of the Liver; mRECIST, modified Response Evaluation Criteria in Solid Tumors; OR, objective response; PD, progressive disease; RECIST 1.1, Response Evaluation Criteria in Solid Tumors, version 1.1; SD, stable disease.