Role of the EASL, RECIST, and WHO response guidelines alone or in combination for hepatocellular carcinoma: Radiologic-pathologic correlation

Background & Aims: We sought to study receiver-operating characteristics (ROC) of the European Association for the Study of the Liver (EASL), Response Evaluation Criteria in Solid Tumors (RECIST), and World Health Organization (WHO) guidelines for assessing response following locoregional therapies individually and in various combinations. Methods: Eighty-one patients with hepatocellular carcinoma underwent liver explantation following locoregional therapies. Response was assessed using EASL, RECIST, and WHO. Kappa statistics were used to determine inter-method agreement. Uni/multivariate logistic regression analyses were performed to determine the variables predicting complete pathologic necrosis. Numerical values were assigned to the response classes: complete response = 0, partial response = 1, stable disease = 2, and progressive disease = 3. Various mathematical combinations of EASL and WHO were tested to calculate scores and their ROCs were studied using pathological examination of the explant as the gold standard. Results: Median times (95% CI) to the WHO, RECIST, and EASL responses were 5.3 (4-11.5), 5.6 (4-11.5), and 1.3 months (1.2-1.5), respectively. Kappa coefficients for WHO/RECIST, WHO/EASL, and RECIST/EASL were 0.78, 0.28, and 0.31, respectively. EASL response demonstrated significant odds ratios for predicting complete pathologic necrosis on uni/multivariate analyses. Calculated areas under the ROC curves were: RECIST: 0.63, WHO: 0.68, EASL: 0.82, EASL + WHO: 0.82, EASL × WHO: 0.85, EASL + (2 × WHO): 0.79 and (2 × EASL) + WHO: 0.85. An EASL × WHO Score of ≤1 had 90.2% sensitivity for predicting complete pathologic necrosis. Conclusions: The product of WHO and EASL demonstrated better ROC than the individual guidelines for assessment of tumor response. EASL × WHO scoring system provides a simple and clinically applicable method of response assessment following locoregional therapies for hepatocellular carcinoma.