Caren van Roekel

246 Chapter 9 We met several challenges while conducting this innovatively-designed trial. Ultimately, this study was stopped prematurely due to slow accrual and a high drop-out rate. During weekly tumor boards, possible candidates were screened for eligibility. Based on contrast-enhanced CT, many patients were already deemed unsuitable because of their vascular anatomy (mostly because of arteries that were deemed too small or too tortuous for the relatively rigid anti-reflux catheter). Nevertheless, despite careful pre-selection and studying of anatomy before treatment, five included patients (18%) were still excluded during angiography because the desired injection position could not be obtained with the anti-reflux catheter. Positioning was challenging as the catheter sometimes moved forward with the deployment of the anti-reflux system, rendering it difficult to reach a stable injection position. Furthermore, with the use of the anti-reflux catheter, vasospasm occurred very frequently (in 24% of cases), which required the administration of intra-arterial nitroglycerin in most cases. The effect of nitroglycerin on the T/N ratio is unknown. Vasospasms occurred probably because of the relatively rigid catheter shaft and due to contact between the deployed anti-reflux system and the vessel wall. These technical difficulties were most pronounced with the first version of the anti- reflux catheter, as the shaft of the second generation catheter was more flexible and the anti-reflux system could be more easily deployed while maintaining a stable injection position. Strengths of this study were the within-patient randomized study design and the homogenous patient population. The main limitation of this study was the small number of patients, which may have caused potential differences in primary or secondary outcomes to remain undetected. However, in our study, no effect (even a small negative effect) of the anti-reflux catheter on the primary and secondary outcomes was found. Based on our results, it is unlikely that with enough power, a large positive effect of the anti-reflux catheter will be seen. Also, the frequent occurrence of technical adverse events with the anti-reflux catheter likely contributed to the lack of a positive influence on treatment outcomes. The occurrence of vasospasm, for example, probably had an influence on activity distribution. Another limitation is the time between pre-treatment imaging with [ 18 F]-FDG PET/CT and post-treatment 166 Ho-SPECT/ CT. Although much effort was done to limit time between baseline imaging and treatment, an increase of tumor and/or hepatic volume may have occurred,