Radioembolization with 90Y Microspheres: Angiographic and Technical Considerations

The anatomy of the mesenteric system and the hepatic arterial bed has been demonstrated to have a high degree of variation. This is important when considering pre-surgical planning, catheterization, and trans-arterial hepatic therapies. Although anatomical variants have been well described, the characterization and understanding of regional hepatic perfusion in the context of radioembolization have not been studied with great depth. The purpose of this review is to provide a thorough discussion and detailed presentation of the angiographic and technical aspects of radioembolization. Normal vascular anatomy, commonly encountered variants, and factors involved in changes to regional perfusion in the presence of liver tumors are discussed. Furthermore, the principles described here apply to all liver-directed transarterial therapies. R.S. and J.-F.G. are consultants for MDS Nordion. R.M., D.L., L.B., and J.I.B. are proctors for Sirtex Medical. A.S.K. has received honoraria from MDS Nordion and Sirtex Medical. This work was not funded.     

Pilot Study of Angiogenic Response to Yttrium-90 Radioembolization with Resin Microspheres

PurposeTo investigate the impact of radioembolization with yttrium-90 resin microspheres on the regulation of angiogenesis through observation of serial changes in a spectrum of angiogenic markers and other cytokines after therapy.Materials and MethodsThis prospective pilot study enrolled 22 patients with liver-dominant disease deriving from biopsy-proven hepatocellular carcinoma (HCC) (n = 7) or metastatic colorectal carcinoma (mCRC) (n = 15). Circulating angiogenic markers were measured from serum samples drawn at baseline and at time points after therapy ranging from 6 hours to 120 days. Using multiplex enzyme-linked immunosorbent assay, several classic angiogenesis factors (vascular endothelial growth factor [VEGF], angiopoietin-2 [Ang-2], basic fibroblast growth factor [bFGF], platelet-derived growth factor subunit BB [PDGF-BB], thrombospondin-1 [Tsp-1]) and nonclassic factors (follistatin, leptin, interleukin [IL]-8) were evaluated.ResultsIncreases in cytokine levels ≥ 50% over baseline were observed in more than half of all patients studied for many cytokines, including classic angiogenic factors such as VEGF, Ang-2, and Tsp-1 as well as nonclassic factors IL-8 and follistatin (range, 36%–82% for all cytokines). Baseline cytokine levels in patients with overall survival (OS) < 6 months differed significantly from patients with longer survival for Ang-2 (P = .033) and IL-8 (P = .041). Patients with OS ≤ 6 months exhibited transient increases in VEGF and PDGF-BB after therapy compared with patients with OS > 6 months.ConclusionsRadioembolization is associated with early transient increases in many angiogenic cytokines. In this small sample size, some of these changes were associated with worse OS. This research has important implications for future studies of radioembolization with antiangiogenic therapy performed during and after the procedure.     

Radioembolization with 90Y Resin Microspheres of Neuroendocrine Liver Metastases: International Multicenter Study on Efficacy and Toxicity

CardioVascular and Interventional Radiology - Radioembolization of liver metastases of neuroendocrine neoplasms (NEN) has shown promising results; however, the current literature is of limited...     

Sequential Use of 90Y Microspheres Radioembolization and 177Lu-Dotatate in Pluri-Metastatic Neuroendocrine Tumors: A Case Report

⁹⁰Y radioembolization and peptide-receptor radionuclide therapy (PRRT) with¹⁷⁷Lu-DOTATATE are both effective treatments for patients with inoperable neuroendocrine metastatic tumors (NET). We report the case of a 72-year-old man with severe functional syndrome due to a metastatic NET. ⁶⁸Ga-DOTATOC positron-emission tomography (PET) revealed high somatostatin receptor expression in a gross liver metastasis, in one abdominal lymph node and in several skeletal lesions. The patient underwent liver radioembolization with ⁹⁰Y-resin microspheres followed by four cycles of PRRT with¹⁷⁷Lu-DOTATATE. After 3 months, a complete remission of the functional syndrome was observed. ⁶⁸Ga-DOTATOC PET demonstrated a complete response for skeletal and lymph nodal lesions with a residual bulky mass in the liver. Therefore a further ⁹⁰Y radioembolization was performed as consolidation treatment for the hepatic lesion. Six months after these combined treatments, ⁶⁸Ga-DOTATOC PET demonstrated complete metabolic response in liver and stable extrahepatic lesions. No significant long-term adverse reactions were registered. To our knowledge, the sequential use of ⁹⁰Y radiembolization before and after PRRT in a liver-dominant advanced NET has not been reported in the literature and this case suggests that these combined treatments can be safe and effective.     

FDG PET/CT as a Prognostic Test After 90Y Radioembolization in Patients With Metastatic Hepatic Disease

ABSTRACT: The purpose of this study was to determine FDG PET/CT utility in predicting patient outcome undergoing Y RE for metastatic liver tumors.Thirty-one patients with metastatic tumors to the liver underwent Y RE between March 15, 2007, and May 5, 2011, at our institution. FDG PET/CT imaging was performed on each patient within 3 months before and after undergoing Y RE. Pretreatment and posttreatment FDG PET/CT were evaluated for SUV, number of liver lesions, and presence of disease outside the liver. The Kaplan-Meier method and Cox proportional hazard modeling was used to evaluate if SUV was a predictor of overall survival.Of the 31 patients, 12 were alive at the end of the study; median survival was 9 months (95% confidence interval, 7-18 months). The 24-month survival rate was 0.28 (95% confidence interval, 0.12-0.48). Kaplan-Meier analysis of preprocedure FDG PET/CT imaging showed no difference in rates of survival by number of lesions observed in the liver (P = 0.114) or presence of disease observed outside the liver (P = 0.719). Cases with new lesions outside the liver after treatment had significantly shorter survival times than cases without new lesions outside the liver (P = 0.002). Cox proportional hazard model showed that SUV levels before and after treatment were not significant predictors of overall survival.The appearance of new lesions outside the liver on FDG PET/CT within 3 months after Y RE was the only statistically significant variable in predicting poor outcome. Absence of new lesions outside the liver on postprocedure FDG PET/CT imaging helps identify patients achieving long-term survival.     

Transarterial Radioembolization with Yttrium-90 Glass Microspheres: Distribution of Residual Activity and Flow Dynamics during Administration

PurposeTo evaluate the microsphere flow dynamics and residual yttrium-90 (⁹⁰Y) activity during and after transarterial radioembolization with glass microspheres and to assess the distribution and predilection sites of residual activity in the administration devices.Materials and MethodsIn this laboratory investigation, after 18 consecutive clinical transarterial radioembolization and 4 ex vivo experimental procedures with ⁹⁰Y glass microspheres, the distribution of residual activity in the administration devices was assessed by activimeter and positron emission tomography (PET)/CT measurements. During ex vivo procedures, microsphere outflow from the administration device was assessed by dynamic scintigraphic measurements.ResultsMean residual activity was 3.4% ± 1.7 (range, 0.9%–8.8%). Calculations showed a negative correlation between relative residual activity and prescribed activity (r = −0.4258, P = .0486) and a positive correlation between absolute residual activity and prescribed activity (r = 0.5345, P = .0104). The main predilection site was the Luer-Lok microcatheter connector. Lower activities were detected in the dose vial. Flow measurements showed that more than 98% of the final injected activity was transferred to the patient with the first 20 mL of saline solution.ConclusionsResidual activity in the standard administration device for glass microsphere radioembolization is considered to be low compared with similar procedures, but is variable. The microsphere flow profile shows an initial peak, resulting in a rapid activity transfer at the beginning of the injection process. The findings may have implications for safe handling of the administration device and for dose calculation of ⁹⁰Y glass microspheres.     

Yttrium-90 Radioembolization with Resin Microspheres without Routine Embolization of the Gastroduodenal Artery

Purpose

To evaluate safety of resin microsphere radioembolization (RE) without prophylactic embolization of the gastroduodenal artery (GDA).

Radioembolization of Symptomatic,Unresectable Neuroendocrine Hepatic Metastases Using Yttrium-90 Microspheres

Purpose  

To evaluate safety, efficacy, and symptom-control of radioembolization in patients with unresectable liver metastases from neuroendocrine tumors (NETLMs).     

Root Cause Analysis of Gastroduodenal Ulceration After Yttrium-90 Radioembolization

Introduction

A root cause analysis was performed on the occurrence of gastroduodenal ulceration after hepatic radioembolization (RE). We aimed to identify the risk factors in the treated population and to determine the specific mechanism of nontarget RE in individual cases.

Methods

The records of 247 consecutive patients treated with yttrium-90 RE for primary (n = 90) or metastatic (n = 157) liver cancer using either resin (n = 181) or glass (n = 66) microspheres were reviewed. All patients who developed a biopsy-proven microsphere-induced gastroduodenal ulcer were identified. Univariate and multivariate analyses were performed on baseline parameters and procedural data to determine possible risk factors in the total population. Individual cases were analyzed to ascertain the specific cause, including identification of the culprit vessel(s) leading to extrahepatic deposition of the microspheres.

Results

Eight patients (3.2 %) developed a gastroduodenal ulcer. Stasis during injection was the strongest independent risk factor (p = 0.004), followed by distal origin of the gastroduodenal artery (p = 0.004), young age (p = 0.040), and proximal injection of the microspheres (p = 0.043). Prolonged administrations, pain during administration, whole liver treatment, and use of resin microspheres also showed interrelated trends in multivariate analysis. Retrospective review of intraprocedural and postprocedural imaging showed a probable or possible culprit vessel, each a tiny complex collateral vessel, in seven patients.

Conclusion

Proximal administrations and those resulting in stasis of flow presented increased risk for gastroduodenal ulceration. Patients who had undergone bevacizumab therapy were at high risk for developing stasis.     

Histological Comparison of Kidney Tissue Following Radioembolization with Yttrium-90 Resin Microspheres and Embolization with Bland Microspheres

Background

Intra-arterial brachytherapy with yttrium-90 (⁹⁰Y) resin microspheres (radioembolization) is a procedure to selectively deliver high-dose radiation to tumors. The purpose of this research was to compare the radioembolic effect of ⁹⁰Y-radioembolization versus the embolic effect of bland microspheres in the porcine kidney model.

Methods

In each of six pigs, ~25–33 % of the kidney volume was embolized with ⁹⁰Y resin microspheres and an equivalent number of bland microspheres in the contralateral kidney. Kidney volume was estimated visually from contrast-enhanced fluoroscopy imaging. Morphologic and histologic analysis was performed 8–9 weeks after the procedure to assess the locations of the microspheres and extent of tissue necrosis from ⁹⁰Y-radioembolization and bland embolization. A semi-quantified evaluation of the non-acute peri-particle and perivascular tissue reaction was conducted. All guidelines for the care and use of animals were followed.

Results

Kidneys embolized with ⁹⁰Y-radioembolization decreased in mass by 30–70 % versus the contralateral kidney embolized with bland microspheres. These kidneys showed significant necrosis/fibrosis, avascularization, and glomerular atrophy in the immediate vicinity of the ⁹⁰Y resin microspheres. By contrast, glomerular changes were not observed, even with clusters of bland microspheres in afferent arterioles. Evidence of a foreign body reaction was recorded in some kidneys with bland microspheres, and subcapsular scarring/infarction only with the highest load (4.96 × 10⁶) of bland microspheres.

Conclusion

This study showed that radioembolization with ⁹⁰Y resin microspheres produces localized necrosis/fibrosis and loss of kidney mass in a porcine kidney model. This result supports the study of ⁹⁰Y resin microspheres for the localized treatment of kidney tumors.

     

90钇玻璃微球治疗肝癌的临床研究

探讨＾９０钇玻璃微球治疗肝癌的临床效果。材料与方法,１９９６年８月至１９９８年５月,应用＾９０钇治疗肝癌１７例,采用含有＾９０钇的三明治疗法：首先注入＾９０钇和超注化碘油悬浮液,然后注入三联合化疗药,最后用明胶海绵颗粒栓塞。对其中１２例施行了经皮股动脉药盒导管系统植入,并对操作技术进行了改进。