Prospective Trial Using Internal Pair-Production Positron Emission Tomography to Establish the Yttrium-90 Radioembolization Dose Required for Response of Hepatocellular Carcinoma

Abstract

Toprospectively assess the threshold dose for objective response of hepatocellular carcinoma (HCC), using 90Y internal pair-production positron emission tomography (PET) to quantify the radiation dose delivered to hepatic tumors after radioembolization. A prospective study was performed under institutional review board approval from 2012 to 2014. Thirty-five patients with primary and secondary liver tumors undergoing 90Y treatment were recruited. Eight patients did not meet inclusion criteria, and 27 patients with HCC were included for analysis. Time-of-flight PET imaging was performed immediately after radioembolization and voxel values converted into 90Y activity. The radioembolization dose was calculated from PET images, and image segmentation was performed with volumetric analysis of dose deposition within tumors. Radiographic response was assessed on follow-up imaging. Treated HCC showed 84% objective response, 11% stable disease, and 5% progressive disease according to modified RECIST 1.1 response criteria. Responders had a higher median 90Y tumor dose than nonresponders (225Gy vs 83Gy, P < .01). Logistic regression models show tumor dose (P=.002) strongly predicted objective response. All nonresponders had tumor dose <200Gy. No statistical difference for patient age, tumor volume, multifocal or extrahepatic disease, portal vein invasion, or injected 90Y activity was found between responders and nonresponders. Hepatocellular carcinoma that resulted in objective response after radioembolization had a greater median tumor dose of 225Gy, compared with 83Gy in nonresponders. Delivered tumor dose can be assessed by PET and significantly impacts treatment response in HCC.