Caren van Roekel

164 Chapter 6 ABSTRACT Introduction Holmium-166 ( 166 Ho)-microspheres have recently been approved for clinical use for hepatic radioembolization in the EU. The aim of this study was to investigate the absorbed dose-response relationship and its association with overall survival for 166 Ho-radioembolization in patients with liver metastases. Methods Patients who were treated in the HEPAR I and II studies and who underwent an FDG-PET/CT scan at baseline, a post-treatment 166 Ho-SPECT/CT scan and another FDG-PET/CT scan at three months follow-up, were included for analysis. The post-treatment 166 Ho-microspheres activity distributions were estimated with quantitative SPECT/CT reconstructions using a quantitative Monte Carlo- based reconstructor. Response of each individual tumor was based on the change in total lesion glycolysis (TLG) between baseline and follow-up and categorized in one of four categories, according to the PERCIST criteria, ranging from complete response to progressive disease. Patient level response was grouped according to the average change in TLG per patient. The absorbed dose-response relationship was assessed using a linear mixed-model to account for correlation of tumors within patients. Median overall survival was compared between patients with and without a metabolic liver response, using a log-rank test. Results In total 36 patients with a total of 98 tumors were included. The relation between tumor absorbed dose and both tumor level and patient level response was explored. At a tumor level, a significant difference in geometric mean absorbed dose was found between response categories complete response (232 Gy (95%-confidence interval (CI) 178-303 Gy); n=32) and stable disease (147 Gy (95% CI 113-191 Gy); n= 28), p=0.01. and between complete response and progressive disease (117 Gy (95% CI 87-159 Gy); n=21), p=0.0008). This constitutes a robust absorbed dose-response relationship. At a patient level, a significant difference was found between patients with complete or partial response (210 Gy (95% CI: 161-274 Gy); n=13) and patients with progressive disease (116 Gy (95% CI: 81-165 Gy); n=9), p=0.01. Patients were subsequently