Imaging response in the primary index lesion and clinical outcomes following transarterial locoregional therapy for hepatocellular carcinoma.

CONTEXT: Response Evaluation Criteria in Solid Tumors (RECIST) (unidimensional), World Health Organization (WHO) (bidimensional), 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, SETTING, AND PARTICIPANTS: Single-center comprehensive imaging analysis including 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 (kappa 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: Kappa 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) for WHO and 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 the RECIST and WHO guidelines 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.