Imaging Response in the Primary Index Lesion and Clinical Outcomes Following Transarterial Locoregional Therapy for Hepatocellular Carcinoma

Abstract

Context Response Evaluation Criteria in Solid Tumors [RECIST (unidimensional)], World Health Organization [WHO (bi-dimensional)] and European Association for Study of the Liver [EASL (necrosis)] guidelines are commonly used to assess response following therapy for hepatocellular carcinoma (HCC). No universally accepted standard exists. Objectives To evaluate intermethod agreement between these 3 imaging guidelines and to introduce the concept of the “primary index lesion” as a biomarker for response. Design Single-center comprehensive imaging analysis. Setting and Participants 245 consecutive patients with HCC who were treated with chemoembolization or radioembolization between January 2000 and December 2008. Computed tomography and magnetic resonance imaging scans (N=1065) were reviewed to assess response in the “primary index lesion,” defined as the largest tumor targeted during first treatment. Main Outcome Measures Intermethod agreement (k statistics) between RECIST, WHO, and EASL guidelines response; correlation of WHO and EASL response in the primary index lesion with time to progression and survival. Results κ coefficients were 0.86(95% confidence interval [CI],0.80–0.92) between the WHO and RECIST guidelines, 0.24(95% CI, 0.16–0.33) between RECIST and EASL and 0.28 (95% CI, 0.19–0.36) between WHO and EASL. Disease progressed in 96 patients; 113 died. The hazard ratio for time to progression in responders compared with nonresponders was 0.36(95% CI, 0.23–0.57) for WHO, 0.38(95% CI, 0.24–0.58) for RECIST, and 0.38(95% CI, 0.22–0.64) for EASL. Hazard ratios for survival in responders compared with nonresponders in univariate and multivariate analyses were 0.46(95% CI, 0.32–0.67) and 0.55(95% CI, 0.35–0.84); they were 0.36(95% CI, 0.22–0.57) and 0.54(95% CI, 0.34–0.85) for EASL. Hazard ratios for survival in responders vs nonresponders in patients with solitary and multifocal HCC were 0.39 (95% CI, 0.19–0.77) and 0.51 (95% CI, 0.32–0.82) for WHO and 0.26 (95% CI, 0.10–0.67) and 0.47 (95% CI, 0.28–0.79) for EASL. Conclusions Among a group of patients with HCC, agreement for classification of therapeutic response was high between RECIST and WHO, but low between each of these and EASL. Application of these methods to measure response in a primary index lesion resulted in statistically significant correlations with disease progression and survival.

EASL- and mRECIST-Evaluated Responses to Combination Therapy of Sorafenib with Transarterial Chemoembolization Predict Survival in Patients with Hepatocellular Carcinoma

“…The considerably lower response rate assessed using RECIST may be partially due to the longer time for response required by RECIST (7-8 months) compared with EASL (1.6 months) (27). When the subset of patients who experienced CR according to the enhancement criteria was reclassified based on the size criteria, survival was similar between those with PR and SD.…”

Outcomes of Locoregional Tumor Therapy for Patients with Hepatocellular Carcinoma and Transjugular Intrahepatic Portosystemic Shunts

“…Toxicity was assessed at follow-up and retrospectively tabulated according to common terminology criteria for adverse events, version 4.0 [11]. Tumor response on imaging was assessed by measuring the index tumor and categorizing change in tumor size into four categories (complete response, partial response, stable disease, disease progression) as defined by the World Health Organization (WHO) and European association for the study of the liver (EASL) criteria [12][13][14].…”

Number of Target Lesions for EASL and Modified RECIST to Predict Survivals in Hepatocellular Carcinoma Treated with Chemoembolization

“…In addition, mRECIST is a major step forward compared with the previous enhancement method, EASL criteria, in terms that mRECIST not only somewhat simplifies complex EASL criteria, but also provides special recommendations for new lesion and nontarget lesions, such as portal vein thrombosis, lymph node at porta hepatis, ascites, or pleural effusion in detail. EASL and mRECIST guideline have shown superior efficacy for assessing treatment responses and predicting survival outcomes compared with WHO and RECIST guidelines in patients with HCC because enhancement criteria can discriminate patients with better clinical outcomes by tumor necrosis, regardless of shrinkage of entire tumor mass (3,(8)(9)(10)(11)(12).…”