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

Articles in Press

Ahsun Riaz 1, Khairuddin Memon 1, Frank H. Miller 1, Paul Nikolaidis 1, Laura M. Kulik 2, Robert J. Lewandowski 1, Robert K. Ryu 1, Kent T. Sato 1, Vanessa L. Gates 1, Mary F. Mulcahy 3, Talia Baker 4, Ed Wang 5, Ramona Gupta 1, Ritu Nayar 6, Al B. Benson III 3, Michael Abecassis 4, Reed Omary 1, Riad Salem 14

Received 15 February 2010; received in revised form 1 October 2010; accepted 6 October 2010. published online 26 November 2010.
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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 the 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 the 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 1.3months (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.

Conclusion
The product of WHO and EASL demonstrated better ROC than the individual guidelines for assessment of tumor response. The EASL×WHO scoring system provides a simple and clinically applicable method of response assessment following locoregional therapies for hepatocellular carcinoma.

Keywords: Hepatocellular carcinoma, Locoregional therapies, Imaging, Pathologic correlation

1 Department of Radiology, Northwestern University, Chicago IL, USA
2 Department of Medicine, Division of Hepatology, Northwestern University, Chicago, IL, USA
3 Department of Medicine, Division of Medical Oncology, Northwestern University, Chicago, IL, USA
4 Department of Surgery, Division of Transplant Surgery, Northwestern University, Chicago, IL, USA
5 Department of Surgery, Section of Biostatistics, Northwestern University, Chicago, IL, USA
6 Department of Pathology, Northwestern University, Chicago, IL, USA

Corresponding author. Address: Interventional Oncology, Department of Radiology, 676N, St. Clair, Suite 800, Chicago, IL 60611, USA. Tel.: +1 312 695 6371; fax: +1 312 695 0654.

PII: S0168-8278(10)00910-4
doi:10.1016/j.jhep.2010.10.004
© 2010 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.

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