Use of an anti-reflux catheter to improve tumor targeting for holmium-166 radioembolization-a prospective, within-patient randomized study

Abstract

Purpose: The objective of this study was to investigate whether the use of an anti-reflux catheter improves tumor targeting for colorectal cancer patients with unresectable, chemorefractory liver metastases (mCRC) treated with holmium-166 (166Ho)-radioembolization.

Materials and methods: In this perspective, within-patient randomized study, left and right hepatic perfusion territories were randomized between infusion with a Surefire® anti-reflux catheter or a standard microcatheter. The primary outcome was the difference in tumor to non-tumor (T/N) activity distribution. Secondary outcomes included the difference in infusion efficiency, absorbed doses, predictive value of 166Ho-scout, dose-response relation, and survival.

Results: Twenty-one patients were treated in this study (the intended number of patients was 25). The median T/N activity concentration ratio with the use of the anti-reflux catheter was 3.2 (range 0.9-8.7) versus 3.6 (range 0.8-13.3) with a standard microcatheter. There was no difference in infusion efficiency (0.04% vs. 0.03% residual activity for the standard microcatheter and anti-reflux catheter, respectively) (95%CI - 0.05-0.03). No influence of the anti-reflux catheter on the dose-response rate was found. Median overall survival was 7.8 months (95%CI 6-13).

Conclusion: Using a Surefire® anti-reflux catheter did not result in a higher T/N activity concentration ratio in mCRC patients treated with 166Ho-radioembolization, nor did it result in improved secondary outcomes measures.

Trial registration: clinicaltrials.gov identifier: NCT02208804.

Keywords: Anti-reflux catheter; Colorectal cancer; Holmium-166; Radioembolization; Surefire.

Conflict of interest statement

ML is a consultant for Boston Scientific and Terumo. MS and AB have served as speakers for BTG and Terumo.

The Department of Radiology and Nuclear Medicine of the UMC Utrecht receives royalties from Quirem Medical and research support from Boston Scientific, Terumo, and Quirem Medical.

No other potential conflicts of interest relevant to this article exist.

Figures

Fig. 1

Schematic representation of within-patient randomized treatment with a standard microcatheter in the right hepatic artery and an anti-reflux catheter in the left hepatic artery. First-generation anti-reflux systems were used until August 2017 and were then replaced by the second-generation anti-reflux systems

Fig. 2

Stepwise process of absorbed-dose estimation after treatment. First, left- and right perfusion territories were manually delineated on the low-dose CT from the baseline [18F]-FDG PET/CT, based on the cone-beam CTs (if available) or the baseline contrast-enhanced CTs. Afterward, tumors were automatically defined on the baseline [18F]-FDG PET/CT using a threshold-based approach. Then, the low-dose CTs of the baseline [18F]-FDG PET/CT and the post-treatment 166Ho-SPECT/CT were coregistered. Using a rigid transformation, the volumes of interest of the tumors and the healthy liver tissue (the left and right perfusion territories) were transferred to the 166Ho-SPECT/CT and absorbed doses were obtained

Fig. 3

Flowchart of study procedures in included patients

Fig. 4

a–d Intention-to-treat analyses of the effect of anti-reflux catheter on T/N activity concentration ratio (a), mean tumor-absorbed dose (b), mean parenchymal-absorbed dose (c), and infusion efficiency (d)

Fig. 5

Relationship between mean tumor-absorbed dose per patient and metabolic response to treatment at a three-month follow-up. The bullets show the mean tumor-absorbed dose per patient. Black vertical lines are the 95%CIs of the mean doses per response category, with the white dot in the middle indicating the mean tumor-absorbed dose per response category. This figure is based on the linear mixed-effects regression model as described in Table 3