Evaluation of Post-Stereotactic Body Radiation Therapy Response Assessment for Hepatocellular Carcinoma: An Appraisal of RECIST, m-RECIST and WHO Criteria

Abstract

Response Evaluation Criteria in Solid Tumors (RECIST) is a validated criterion to evaluate response to liver directed therapy in hepatocellular carcinoma (HCC); however, RECIST criteria are inadequate for assessing early response to Stereotactic Body Radiotherapy (SBRT). In this analysis, we evaluated post-treatment response assessment using RECIST, modified-RECIST and World Health Organization (WHO) criteria in patients receiving SBRT for HCC. This retrospective analysis included HCC patients treated with SBRT at two institutions between 2009 and 2016. Included patients had pathologically proven or met radiologic criteria for the diagnosis of HCC and received SBRT. Additionally, only patients with a multiphase contrast liver MR or CT imaging scan in the 6 weeks prior to SBRT and at least one follow-up MR/CT 1-6 months post-SBRT were included in this analysis. For each lesion treated with SBRT, the maximum two diameters, the maximum bidimensional enhancement diameter, the product of the bidimensional diameters and the product of bidimensional enhancement diameters were measured. From these parameters, post-SBRT response was assessed according to RECIST 1.1, mRECIST, and WHO criteria. Fifty-six lesions in 45 patients (32 M, 13 F; mean age: 66.7 ± 7.6 years) were included in this analysis. Twenty-five of these lesions were previously treated with liver-directed therapies. Sixteen lesions were followed with CT and 40 with MR. 14 of the 56 (25%) treated lesions were isointense to the surrounding liver parenchyma in the arterial phase on at least one follow-up examination. Hyperenhancement of the adjacent liver parenchyma was observed for several months post-SBRT. For two lesions previously treated non-SBRT, the SBRT target was a residual tumor at the periphery of the original lesion; in post-SBRT images of these lesions, it was similarly impossible to distinguish between residual tumor and hyperenhancing normal liver parenchyma. The post-SBRT liver parenchymal enhancement limited standard therapeutic response assessment. For RECIST 1.1 and WHO criteria, the lesion diameter evaluation was limited in 1 lesion and pseudoprogression was seen in 2 lesions; with mRECIST criteria, the lesion viability evaluation was limited by isointensity in the arterial phase to the surrounding liver parenchyma in 23 examinations (0-6 months follow-up: 12 exams; 7-12 months follow-up: 7 exams; 13-24 months: 4 exams) and pseudoprogression was seen in 4 lesions. Liver parenchymal changes induced by SBRT may limit post-treatment assessment using current response assessment criteria, especially during early follow-up examinations. New criteria should be evaluated to assess post-SBRT treatment response.