TY - JOUR T1 - First evidence for a dose-response relationship in patients treated with <sup>166</sup>Ho-radioembolization: a prospective study JF - Journal of Nuclear Medicine JO - J Nucl Med DO - 10.2967/jnumed.119.232751 SP - jnumed.119.232751 AU - Remco Bastiaannet AU - Caren van Roekel AU - Maarten L.J. Smits AU - Sjoerd G. Elias AU - Wouter A.C. van Amsterdam AU - Dan T. Doan AU - Jip F. Prince AU - Rutger C.G. Bruijnen AU - Hugo W.A.M. de Jong AU - Marnix G.E.H. Lam Y1 - 2019/10/01 UR - http://jnm.snmjournals.org/content/early/2019/10/10/jnumed.119.232751.abstract N2 - Holmium-166 (166Ho)-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 166Ho-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 166Ho-SPECT/CT scan and another FDG-PET/CT scan at three months follow-up, were included for analysis. The post-treatment 166Ho-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 grouped according to their average change in TLG. Patients with objective response (complete or partial response) exhibited a significantly higher overall survival than non-responding patients (stable or progressive disease) (median 19 months versus 7.5 months; Log-rank; P = 0.01). Conclusion: These results confirm a significant absorbed dose-response relationship in 166Ho-radioembolization. Treatment response is associated with a higher overall survival. ER -