Clinical practice in radioembolization of hepatic malignancies: A survey among interventional centers in Europe

doi:10.1016/j.ejrad.2012.04.004

European Journal of Radiology

Volume 81, Issue 7, July 2012, Pages e804-e811

https://doi.org/10.1016/j.ejrad.2012.04.004 Get rights and content

Abstract

Objectives

A survey was conducted to give an overview about the practice of radioembolization in malignant liver tumors by European centers.

Methods

A questionnaire of 23 questions about the interventional center, preinterventional patient evaluation, the radioembolization procedure and aftercare were sent to 45 European centers.

Results

The response rate was 62.2% (28/45). The centers performed 1000 (median = 26) radioembolizations in 2009 and 1292 (median = 40) in 2010. Most centers perform preinterventional evaluation and radioembolization on an inpatient basis. An arterioportal shunt not amendable to preinterventional embolization is considered a contraindication. During preinterventional angiography, the gastroduodenal artery is embolized by 71%, the right gastric artery by 59%, and the cystic artery by 41%. In case of bilobar disease, yttrium-90 microspheres are infused into the common hepatic artery (14%) or separately into left and right hepatic artery (86%). 33% prefer a time interval between right and left liver lobe radioembolization to prevent radiation induced liver disease. 43% of the respondents do not prescribe prophylactic medication after radioembolization. In case of iatrogenic manipulation to the biliary duct system most centers perform radioembolization with prophylactic antibiotics.

Conclusions

Despite standardization of the procedure, there are some differences in how radioembolization of liver tumors is performed in Europe.

Introduction

Radioembolization (RE) or selective internal radiation therapy (SIRT) is a new form of embolizing particle brachytherapy for treating primary and secondary liver malignancies [1]. RE is performed by transarterial administration of embolic radioactive particles for selectively depositing a high tumoricidal radiation dose in the target lesion, which is preferably supplied by arterial blood, while maximally sparing normal liver parenchyma, which is mostly supplied through the portal vein. Commercially two different microspheres for yttrium-90 RE are available: glass Y-90 microspheres (TheraSpheres^®, MDS Nordion, Kantana, Canada), and resin Y-90 microspheres (SIR-Spheres^®, SIRTEX Medical, Lane Cove, Australia). Both have the approval of the Food and Drug Administration (FDA) and European Authorities for treatment of primary (hepatocellular (HCC) and cholangiocarcinoma (CC)) and secondary hepatic malignancies (metastasis). Although one may assume that standardization of the logistic and technical procedure before, during, and after radioembolization has reached a high level by now [2], the complexity of the procedure has probably given rise to some differences as well. Modifications of therapeutic procedures can be expected to arise from different clinical experiences and attitudes of the interventional radiologists performing RE, the therapeutic focus of the center offering the procedure, and the legal or regional framework. To identify, analyze, and discuss such differences, we developed a questionnaire to collect data on how hepatic RE is performed in Europe. The questions relate to four issues: the center performing the intervention, preinterventional patient evaluation, the RE procedure itself, and patient aftercare. The questionnaire was sent to 45 interventional radiology centers in Europe. Here we present the results of our analysis of a total of 28 (62.2%) questionnaires that were completed and returned.

Section snippets

The questionnaire

The questionnaire consists of a total of 23 questions on how RE is performed, covering the clinical procedure from preinterventional patient evaluation to aftercare (Table 1). The first set of questions pertains to details of the department performing RE, the second and longest part concerns patient evaluation, the third part deals with the intervention itself (administration of microspheres and other periprocedural aspects), and the fourth and last set of questions is on patient aftercare. The

Results

Twenty-eight of the 45 European centers included in the mail survey completed and returned the questionnaire, corresponding to a response rate of 62.2% (28/45). Some centers did not answer all questions, which is why we do not have information from all 28 centers on some of the questions.

Discussion

Our response rate of 62.2% is on the order of the average response rate of 60% reported for medical questionnaires by Asch et al. [3]. Hence, our data can be regarded as being of generally accepted validity. Caution is in order, though, because the answers given in a questionnaire reflect the opinions of the respondents and not necessarily the “correct” answers. The following discussion focuses on questions that might have been unclear on retrospective analysis and should have been phrased

Conclusion

Hepatic radioembolization is an effective treatment option for patients with primary or secondary liver tumors not amenable to surgery or local ablation. While the complex treatment procedure is increasingly being standardized through a growing body of studies and certification of radiologists by the two manufacturers, SIRTEX and MDS Nordion, our survey has revealed some considerable differences in therapeutic practices among the centers performing radioembolization in Europe.

Acknowledgment

We would like to thank Ms Herwig for translating the manuscript.

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The origin of RGA is highly variable and has been reported to arise from the CHA or its first order branch. Embolization of the RGA before radioembolization is unanimously recommended in the literature (Salem and Thurston, 2006; Powerski et al., 2012). The GDA is almost always a branch of the CHA (92–95%) as also observed in the present study (Lipshutz, 1917; Michels, 1951).
To describe the hepatic arterial anatomy in detail, tracing the individual hepatic arteries from their origin, extrahepatic course, branching to their segmental territorial supply as applicable to the vascular mapping for hepatic endovascular procedures.
The study was conducted on 100 formalin fixed adult cadaveric livers. The hepatic arterial anatomy was dissected from the origin of hepatic arteries up to their segmental branching.
The origin of hepatic arteries was standard in 72% and aberrant in 28% livers. In livers with standard origin, extrahepatic branching of the main hepatic artery was close to the hepatic hilum in 48% and was in the lower part of the hepatoduodenal ligament in 24% livers. The pattern of extrahepatic branching in each type was three and five respectively. Aberrant arterial anatomy was broadly categorized into three groups. The mapping of segmental arterial vascularization of individual hepatic arteries in each type was also done.
In the present study, an attempt was made to systematically describe the complex hepatic arterial anatomy in a clinically applicable fashion. High variability was seen in the hepatic arterial anatomy at each level, a lot of which could not be included in the current classification systems. The information provided is an important prerequisite for performing accurate intra-arterial hepatic interventions.
Feasibility of Boosted Radioembolization for Hepatocellular Carcinoma Larger than 5 cm
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To address the feasibility of yttrium-90 (⁹⁰Y) glass microspheres administered at a boosted dose in large hepatocellular carcinomas (HCCs).
From July 2016 to August 2017, 20 patients who underwent ⁹⁰Y radioembolization for treatment-naïve HCC met the following inclusion criteria: (i) nodular tumor, (ii) tumor size > 5 cm, (iii) Barcelona Clinic Liver Cancer stage A/B disease, (iv) target perfused tissue dose > 150 Gy, and (v) all tumors treated in 1 session of radioembolization. Follow-up radiologic findings and clinical outcomes were retrospectively reviewed until May 2018. Tumor response was determined per modified Response Evaluation Criteria In Solid Tumors.
Mean total radiation activity infused was 4.96 GBq ± 1.82 (median, 4.88 GBq; range, 1.63–9.15 GBq). Mean target perfused tissue dose was 263.5 Gy ± 95.2 (median, 241.6 Gy; range, 156.2–550.6 Gy). The mean number of vials used per treatment was 4.15 ± 1.4 (median, 4; range, 2–7). Complete response rates were 25% at 1 month and 60% at 3 months. Complete response of the primary index tumor was achieved in 16 patients (80%) based on best tumor response. Local progression–free survival and progression-free survival rates were 94.1% and 85.0% at 6 mo and 94.1% and 74.7% at 1 year, respectively. Four patients (20%) had symptomatic (n = 3) or asymptomatic (n = 1) benign biliary strictures.
Radioembolization with a boosted dose in patients with large HCCs may show favorable tumor response, but with considerable biliary complications.
Safety of Radioembolization in the Setting of Angiographically Apparent Arterioportal Shunting
2018, Journal of Vascular and Interventional Radiology
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Yttrium-90 microsphere dosimetry may be affected by variable vascular conduit caliber, tumor neovascularity, portal and hepatic venous shunting, and nonuniform intralesional vascular saturation (8,14). Transarterial chemoembolization has been described as less effective in the setting of APS due to nontarget embolization (12); consequently, this notion has been applied to yttrium-90 administration (8,15). Theoretically, shunts larger than the particle size of 20–60 microns (16) may conceptually bypass the tumor and irradiate unaffected liver parenchyma and the lungs (17).
To retrospectively analyze adverse events (AE) in patients with hepatocellular carcinoma (HCC) treated with yttrium-90 radioembolization in the setting of angiographically apparent arterioportal shunts (APSs).
Thirty-two patients with HCC underwent radioembolization with APSs from January 2011 to September 2016, totaling 34 administrations using resin (6) and glass (28) microspheres. APSs were graded angiographically as segmental (9), ipsilobar (15), contralobar (7), or main portal (2), according to portal perfusion. Tumors were categorized as solitary (9), multifocal (7), or infiltrative (16). Both unilobar (25) and bilobar (7) disease was treated. Child Pugh Score was A (22), B (10), or C (2), with a median Model for End-Stage Liver Disease (MELD)/Na-MELD of 8/8.5. Median procedure dose was 132.6 Gy. AEs were graded using Combined Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST).
CTCAE grade ≥3 AEs were observed in 22% of patients. Barcelona Clinic Liver Cancer (BCLC) C patients with nonsegmental shunts who received lobar administrations had a grade ≥3 AE rate of 38% compared with the remaining cohort, which was 12% (P = .076). No events were reported in patients with segmental shunts (P = .023). Imaging analysis revealed mRECIST complete response (17), partial response (13), stable disease (3), and progressive disease (1). Overall survival at 6 months and 12 months was 72% and 57%, respectively.
Radioembolization in the setting of APS may have a higher AE profile than reported literature when BCLC-C patients with nonsegmental shunts receive lobar administrations. Segmental shunts are generally well tolerated.
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Radioembolization (RE) of liver tumors is performed using yttrium-90-loaded microspheres semiselectively injected through a catheter placed in a hepatic artery. A few weeks to a few days before the radioactive microspheres are injected, a patient scheduled for this procedure needs to have an angiographic evaluation with coil and/or plug embolization of any hepatoenteral and hepatopancreatic branches and determination of the hepatopulmonary shunt (HPS) fraction [1]. Branches not supplying the liver need to be occluded before RE to prevent microsphere migration and complications such as radiation ulcer [2].
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Selective internal radiation therapy (SIRT) is based on the intra-arterial administration of microspheres with the beta emitter 90-yttrium (90Y). It is increasingly used as a treatment for unresectable liver tumours.1–13 Due to the almost exclusive arterial blood supply of the tumours but the dual (portal venous > arterial) blood supply of normal liver tissue, the intra-arterial administration of 90Y allows local tumour therapy with partial sparing of healthy liver tissue.
To assess the effect of gastroduodenal artery (GDA) occlusion prior to selective internal radiation therapy (SIRT) with regards to arterial hepato-intestinal collateralization (HIC).
Six hundred and six patients were scheduled for SIRT between 2006 and 2012 at University Hospital Essen, Germany. Digital subtraction angiography (DSA) followed by administration of 99m-technetium labelled human serum albumin microspheres (^99mTc-HSAM) and single-photon emission computed tomography combined with computed tomography (SPECT/CT) was initially performed. Depending on vascular anatomy and hepatic tumour load, GDA coil embolization was considered. In subsequent ^99mTc-HSAM rescans or therapeutic DSA, HIC and its consequences for SIRT were analysed.
The GDA was occluded in 86 of 606 patients (14%). Twenty-two of these 86 patients did not undergo SIRT due to the patients' clinical status or SIRT contraindications. In 28 of the remaining 64 patients, newly apparent or reopened HIC were seen either at the site of the proximal GDA (n = 21) or in the periphery of the hepatic arteries (n = 7). In 25 of these 28 patients, the HIC could be occluded or the catheter position could be changed achieving a safe ⁹⁰Y application. However, due to the newly visible HIC in three of 28 patients, SIRT was regarded as unsafe and was abandoned.
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Clinical practice in radioembolization of hepatic malignancies: A survey among interventional centers in Europe

Abstract

Objectives

Methods

Results

Conclusions

Introduction

Section snippets

The questionnaire

Results

Discussion

Conclusion

Acknowledgment

Journal of Vascular and Interventional Radiology

Journal of Clinical Epidemiology

Seminars in Radiation Oncology

Journal of Vascular and Interventional Radiology

Journal of Vascular and Interventional Radiology

Journal of Vascular and Interventional Radiology

International Journal of Radiation Oncology, Biology, Physics

Journal of Vascular and Interventional Radiology

International Journal of Radiation Oncology, Biology, Physics

Minimally invasive tumor ablation in the liver

Anasthesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie