Boosted selective internal radiation therapy with 90Y-loaded glass microspheres (B-SIRT) for hepatocellular carcinoma patients: a new personalized promising concept

Purpose To evaluate the impact of dosimetry based on MAA SPECT/CT for the prediction of response, toxicity and survival, and for treatment planning in patients with hepatocellular carcinoma (HCC) treated with Y-90-loaded glass microspheres (TheraSphere (R)). Methods TheraSphere (R) was administered to 71 patients with inoperable HCC. MAA SPECT/CT quantitative analysis was used for the calculation of the tumour dose (TD), healthy injected liver dose (HILD), and total injected liver dose. Response was evaluated at 3 months using EASL criteria. Time to progression (TTP) and overall survival (OS) were evaluated using the Kaplan-Meier method. Factors potentially associated with liver toxicity were combined to construct a liver toxicity score (LTS). Results The response rate was 78.8 %. Median TD were 342 Gy for responding lesions and 191 Gy for nonresponding lesions (p<0.001). With a threshold TD of 205 Gy, MAA SPECT/CT predicted response with a sensitivity of 100 % and overall accuracy of 90 %. Based on TD and HILD, 17 patients underwent treatment intensification resulting in a good response rate (76.4 %), without increased grade III liver toxicity. The median TTP and OS were 5.5 months (2-9.5 months) and 11.5 months (2-31 months), respectively, in patients with TD <205 Gy and 13 months (1016 months) and 23.2 months (17.5-28.5 months), respectively, in those with TD >205 Gy (p=0.0015 and not significant). Among patients with portal vein thrombosis (PVT) (n=33), the median TTP and OS were 4.5 months (2-7 months) and 5 months (2-8 months), respectively, in patients with TD <205 Gy and 10 months (6-15.2 months) and 21.5 months (12-28.5months), respectively, in those with TD >205 Gy (p=0.039 and 0.005). The median OS was 24.5 months (18-28.5 months) in PVT patients with TD >205 Gy and good PVT targeting on MAA SPECT/CT. The LTS was able to detect severe liver toxicity (n=6) with a sensitivity of 83 % and overall accuracy of 97 %. Conclusion Dosimetry based on MAA SPECT/CT was able to accurately predict response and survival in patients treated with glass microspheres. This method can be used to adapt the injected activity without increasing liver toxicity, thus defining a new concept of boosted selective internal radiation therapy (B-SIRT). This new concept and LTS enable fully personalized treatment planning with glass microspheres to be achieved.