Early arterial stasis during resin-based yttrium-90 radioembolization: incidence and preliminary outcomes

Abstract. Resin Yttrium-90 (Y90) microspheres have historically been infused using sterile water (H 2 O). In 2013, recommendations expanded to allow delivery with 5% dextrose in water (D 5 W). In this retrospective study, we hypothesized that D 5 W would improve Y90 delivery with a lower incidence of stasis. We reviewed 190 resin Y90 infusions using H 2 O (n=137) or D 5 W (n=53). Y90 dosimetry was calculated using the body surface area method. IntroductionYttrium-90 (Y90) microspheres are used to treat patients with primary hepatic and liver-dominant metastatic cancer. The glass and resin Y90 products differ significantly in the density of radionuclide per bead. Glass microspheres have a higher density [2,500 Becquerel (Bq)/bead] of Y90 than resin (50 Bq/bead) (1). The higher Y90 concentration in glass beads allows the delivery of prescribed activity without feeding artery occlusion, a known issue with resin microspheres. From the time of government approval in 2002, the standard technique for infusion of resin microspheres used sterile water (H 2 O) alternating with small aliquots of contrast to evaluate for arterial stasis prior to delivery of the entire dose vial (2,3). While clinical outcomes have resulted in excellent control of hepatic disease, a previous review using H 2 O to inject resin microspheres identified a 20% early stasis rate (4-6).Delivering less than the prescribed Y90 activity has the potential to reduce treatment efficacy or result in earlier time to progression. Therefore, investigation of other injection methods for resin microspheres is required. In 2013, our group began to use 5% dextrose in water (D 5 W) as an alternative to H 2 O (7).The aim of the current study was to measure the incidence of premature stasis using D 5 W in comparison to H 2 O. We hypothesized that D 5 W induces stasis less frequently than H 2 O in a clinical cohort of patients with primary or secondary hepatic malignancy. Materials and methodsClinical setting and patients. Our Institutional Review Board approved this retrospective study. All the procedures performed were in accordance with the ethical standards of the Vanderbilt University School of Medicine and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.We retrospectively reviewed laboratory, radiology and nuclear pharmacy reports of all resin Y90 infusions performed between July, 2013 and July, 2014. Consecutive patients treated after September, 2013, were treated with

Purpose: Treatment efficacy of intra-arterial radioembolization for liver tumors depends on the selective targeting of tumorous tissue. Recent investigations have demonstrated that tumors may receive inadequate doses of radioactivity after radioembolization, due to unfavorable tumor to non-tumor (T/N) uptake ratios of radioactive microspheres. Hepatic arterial infusion of the vasoconstrictor angiotensin II (AT-II) is reported to increase the T/N blood flow ratio. The purpose of this systematic review was to provide a comprehensive overview of the effect of hepatic arterial AT-II on T/N blood flow ratio in patients with hepatic malignancies, and determine its clinical value for radioembolization.Methods: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and MetaAnalyses guidelines. A structured search was performed in the PubMed, EMBASE and Cochrane databases. Only studies that presented data on T/N ratios before and after infusion of AT-II into the hepatic artery, in human patients with hepatic malignancies, were selected. Median T/N ratios before, during and after AT-II infusion, and the median T/N ratio improvement factor were extracted from the selected articles. All data on systemic blood pressure measurements and clinical symptoms were also extracted. Results:The search identified 524 titles of which 5 studies, including a total of 71 patients were considered relevant. Median T/N ratios before infusion of AT-II ranged from 0.4 to 3.4. All studies observed a substantial improvement of the T/N ratio after AT-II infusion, with median improvement factors ranging from 1.8 to 3.1. A transitory increase of systemic blood pressure was observed during AT-II infusion.Conclusions: Infusion of AT-II into the hepatic artery leads to an increase of the tumor to non-tumor blood flow ratio, as measured by T/N uptake ratios. Clinical trials are warranted to assess safety aspects, optimal administration strategy and impact on treatment efficacy during radioembolization.

The primary aim of our study was to compare the need for periinterventional on-demand analgesia when water for injection (WFI) was replaced with glucose 5% (G5) for 90 Y-resin microsphere administration. Methods: Forty-one patients who received 77 radioembolization procedures with G5 (2014-2015) were retrospectively matched with 41 patients (77 radioembolization procedures) who received radioembolization with WFI (2011WFI ( -2014 at our center. The need for on-demand pain medication was chosen as an objective and accessible measure of periprocedural pain experienced by patients. Results: Patients were well matched according to sex, age, tumor type and involvement, and prior antiangiogenic therapies. Periinterventional analgesic requirements were significantly lower for radioembolization procedures performed with G5 than WFI: 5 of 77 (6.5%) versus 29 of 77 (37.7%), P # 0,001, respectively. Early stasis (defined as slowed antegrade flow, before total vascular stasis) occurred in 12 of 154 (7.8%) radioembolization procedures overall and was not different (P # 0.229) between the 2 groups (4/77 [5.2%] vs. 8/77 [10.4%]). Conclusion: Slow pulsatile administration of 90 Y-resin microspheres with WFI is associated with a low rate of stasis. Replacement of WFI with G5 significantly reduces the need for periprocedural analgesia. These data favor the use G5 for 90 Y-resin microsphere implantation in daily practice.Key Words: radioembolization (RE); water for injection (WFI); glucose 5% (G5); peri-procedural analgesia; stasis rate J Nucl Med 2016; 57:1679-1684 DOI: 10.2967/jnumed.115.170779Ast he documented incidence of primary and metastatic liver cancers increases (1,2), treatments using minimally invasive techniques are becoming more common. Radioembolization with 90 Y-resin microspheres is a blood flow-directed therapy enabling intraarterially infused microscopic microspheres (median diameter, 32.5 mm) to lodge within the terminal arteries close to the liver tumors, without passing through the capillary bed (diameter, #7-10 mm) and hence avoiding systemic effects. As observed in explanted whole livers, clusters of 90 Y-resin microspheres gradually assemble after administration and reduce the terminal blood flow but without stopping it completely (3).The dual blood supply of the liver enables the selective treatment of hepatic malignancies via the blood supply-mainly from the hepatic artery-whereas the normal liver parenchyma is perfused mostly by the portal circulation (4). Consequently, a high radiation dose can be delivered safely and effectively to primary and secondary liver tumors by radioembolization, with relative sparing to normal liver tissue (5-10). Radioembolization has been evaluated as both a first-line therapy (11,12) and in the salvage setting for chemoresistant/refractory metastatic colorectal cancer (13-16) and is a recommended salvage treatment by the clinical practice guidelines of the European Society of Medical Oncology (17). Radioembolization has also been extensively evaluated in hepatocellular ca...