Caren van Roekel

232 Chapter 9 patient, randomized controlled study (Clinicaltrials.gov: NCT02208804) (see also the Consort reporting checklist in the supplemental files). Patients with unresectable, chemorefractory, liver-dominant mCRC were eligible for this study if they had: a pathologically confirmed diagnosis of CRC, hepatic metastases (≥1 cm and measurable on CT) in both the right and left hepatic arterial perfusion territory, a suitable arterial anatomy (not too tortuous vessels, with a large enough diameter to be accessible with the anti-reflux catheter), progressive disease after at least second-line systemic treatment, adequate liver-, renal- and bone marrow function, and a life expectancy of >3 months (see study protocol (15)). All patients provided written informed consent for participation in this study. The institutional review board provided ethical approval and the study was undertaken in accordance with the Declaration of Helsinki. An independent monitor verified all data. Procedures Before treatment, patients underwent 18 F-FDG PET/CT and a dual-phase contrast-enhanced CT. The hepatic arterial anatomy was assessed on the contrast-enhanced CT images and the perfusion territories of the left and right hepatic arteries (or their variants in case of aberrant vascular anatomy) were estimated. Metabolic hepatic tumor burden was assessed on the PET/CT images using ROVER software (ABX, Germany). Pre-treatment activity calculation was done using the standard formula for 166 Ho-microspheres to reach an absorbed dose of 60 Gy in the target volume (in this study the whole liver) (16) : = √ ∗ √ ∗ ) + √ ∗ = 0.2024 ∗ ℎ ℎ ( ) 0,725 ∗ ℎ ( ) 0,425 ( ) = ( − 0,2) + ( + ) ( ) = ( ( ) ∗ ( )) 50 ( ) = ( ) ( ) ( ) ( ) ⁄ ( ) = ( ) ∗ ([ ∗ ( )] + ( )) 49,670 ∗ (1 − ℎ ) ( ) = ℎ ( ) ∗ 3780 ( ) ( ) = ℎ ( ) ∗ 3780 ( ) ( ) = ( ( ) ∗ ( )) 50 ( ) ( ) = ( ( ) ∗ ( )) 16 ( ) ( ) = ( ) ∗ ([ ∗ ( )] + ℎ ℎ ( )) 49.67 ∗ (1 − ℎ ) In which IA is the injected activity and 3780 is the constant specific for 166 Ho. The prescribed activity was split according to the perfusion volume of the left and right hepatic arteries as estimated on pre-treatment contrast-enhanced CT. Before treatment, patients’ perfusion territories were randomized by the investigator between injection with a standard microcatheter and an anti- reflux catheter, using a computer-generated stratified block randomization with difference in tumor burden (above or below 10%) as a stratification factor. The result of randomization was applied for both the 166 Ho-scout and the therapeutic activity (Figure 1).