Caren van Roekel

167 Dose-response relationship in 166 Ho-radioembolization the Declaration of Helsinki and were approved by the local research ethics committee. Before study entry, all patients provided written informed consent (6). In HEPAR I and II, multimodality imaging with 18 F-fluorodeoxyglucose (FDG)- PET/CT and multiphasic liver CT were acquired during work-up. A preparatory angiography was performed several days before treatment in which extra- hepatic vessels were coil-embolized if necessary, and a scout dose of 99m Tc- MAA (150 MBq, Technescan LyoMAA ® ; Mallinckrodt Medical B.V., Petten, The Netherlands) was administered to assess the safety and intra-hepatic distribution of subsequent administrations. On the day of treatment, 166 Ho- microspheres were administered as a second scout dose (i.e. 250 MBq) in the morning and as a treatment dose in the afternoon, with 166 Ho-SPECT/CT and MR acquisition after both injections. The total amount of administered activity was adjusted to the targeted liver volume, as measured on CT. In HEPAR II, the aimed absorbed dose was 60 Gy for the treated volume (MIRD mono-compartment method) (7). HEPAR I was a dose-escalation study, in which the aimed absorbed dose was varied between 20 and 80 Gy. Treatment was followed by a post- treatment 166 Ho-SPECT/CT andan FDG-PET/CT at three months follow-up. None of the included patients received concomitant anti-cancer therapies. Included patients for the current study were those who underwent an FDG- PET/CT scan at our hospital at baseline and at three months follow-up, as well as a post-treatment 166 Ho-SPECT/CT as part of the HEPAR I or II studies. Absorbed Dose-Response Evaluation Absorbed dose-response evaluation was performed similarly to what was reported earlier by Van den Hoven et al. (8). The tumor outlines were automatically defined by setting a patient-relative threshold for activity concentration on the baseline FDG-PET/CT scan using the ROVER (ABX GmBH, Radeberg, Germany) software package (9). The threshold was based on the aortic blood pool activity and defined as 2x mean SUV corrected for lean body mass (SUL mean ) (10). Additionally, a volume restriction of 5 mL or more was used. SUL mean and tumor volume were recorded. Total lesion glycolysis (TLG) was calculated by taking the product of SUL mean and tumor volume. The liver was manually delineated on the accompanying low-dose CT, using ROVER. 6

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