Patient Selection and Activity Planning Guide for Selective Internal Radiotherapy With Yttrium-90 Resin Microspheres

doi:10.1016/j.ijrobp.2010.08.015

International Journal of Radiation OncologyBiologyPhysics

Volume 82, Issue 1, 1 January 2012, Pages 401-407

https://doi.org/10.1016/j.ijrobp.2010.08.015 Get rights and content

Purpose

Selective internal radiotherapy (SIRT) with yttrium-90 (⁹⁰Y) resin microspheres can improve the clinical outcomes for selected patients with inoperable liver cancer. This technique involves intra-arterial delivery of β-emitting microspheres into hepatocellular carcinomas or liver metastases while sparing uninvolved structures. Its unique mode of action, including both ⁹⁰Y brachytherapy and embolization of neoplastic microvasculature, necessitates activity planning methods specific to SIRT.

Methods and Materials

A panel of clinicians experienced in ⁹⁰Y resin microsphere SIRT was convened to integrate clinical experience with the published data to propose an activity planning pathway for radioembolization.

Results

Accurate planning is essential to minimize potentially fatal sequelae such as radiation-induced liver disease while delivering tumoricidal ⁹⁰Y activity. Planning methods have included empiric dosing according to degree of tumor involvement, empiric dosing adjusted for the body surface area, and partition model calculations using Medical Internal Radiation Dose principles. It has been recommended that at least two of these methods be compared when calculating the microsphere activity for each patient.

Conclusions

Many factors inform ⁹⁰Y resin microsphere SIRT activity planning, including the therapeutic intent, tissue and vasculature imaging, tumor and uninvolved liver characteristics, previous therapies, and localization of the microsphere infusion. The influence of each of these factors has been discussed.

Introduction

Selective internal radiotherapy (SIRT) entails the infusion of yttrium-90 (⁹⁰Y) microspheres into the hepatic arterial circulation, from which approximately 80–100% of liver tumor blood flow is derived (1). This interventional technique combines intratumoral brachytherapy with embolization of neoplastic microvasculature by way of the deposition of millions of nonbiodegradable, β-emitting particles. These comprise either resin microspheres with a median diameter of 35 μm (range, 25–45; SIR-Spheres, Sirtex Medical, Lane Cove, Australia) or glass microspheres a median diameter of 25 μm (range, 20–30; TheraSphere, MDS Nordion, Ottawa, ON, Canada).

The clinical effects of SIRT depend on numerous patient-specific factors, including the hepatic arterial flow distribution, vascularity of the target tumor, functional integrity of the uninvolved liver, and relative radiosensitivities of both tissues 1, 2, 3, 4, 5. Several different models are available for planning the tumoricidal radiation doses while preserving the uninvolved liver parenchyma and extrahepatic structures. The present report collated the published evidence and clinical experience to guide patient selection and calculation methods when planning ⁹⁰Y resin microsphere SIRT for unresectable hepatocellular carcinomas (HCCs) or liver metastases.

Section snippets

Methods and Materials

Sirtex Medical supported a meeting of clinicians experienced in ⁹⁰Y resin microsphere SIRT. The appropriate publications were identified using a comprehensive data search and pre-circulated to all participants. A draft report summarizing the group’s proposed recommendations underwent review and revision until consensus had been achieved.

Discussion

Tailoring ⁹⁰Y activity to the clinical circumstances of individual patients remains one of the most testing aspects of SIRT. Effective treatment can transform a patient with a poor prognosis into one suitable for surgical resection or transplantation with curative intent. Nevertheless, the principle underlying ⁹⁰Y microsphere SIRT planning is to preserve patient safety. In appropriate patients, the partition model will provide a more scientifically sound basis for the activity calculations than

Acknowledgments

The contents of the present report were agreed to by the authors at an advisory meeting supported by Sirtex Medical. A freelance medical writer, Peter Hobbins, prepared the first draft and coordinated the author amendments. Each author reviewed and revised the report until a group consensus had been achieved. Although Sirtex Medical was invited to review the draft to ensure technical accuracy, the authors take full responsibility for the contents and expression of the report.

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Dosimetric assessment of Gadolinium-159 for hepatic radioembolization: Tomographic images and Monte Carlo simulation
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A common therapeutic radionuclide used in hepatic radioembolization is yttrium-90 (⁹⁰Y). However, the absence of gamma emissions makes it difficult to verify the post-treatment distribution of ⁹⁰Y microspheres. Gadolinium-159 (¹⁵⁹Gd) has physical properties that are suitable for therapy and post-treatment imaging in hepatic radioembolization procedures. The current study is innovative for conducting a dosimetric investigation of the use of ¹⁵⁹Gd in hepatic radioembolization by simulating tomographic images using the Geant4 application for tomographic emission (GATE) Monte Carlo (MC) simulation. For registration and segmentation, tomographic images of five patients with hepatocellular carcinoma (HCC) who had undergone transarterial radioembolization (TARE) therapy were processed using a 3D slicer. The tomographic images with ¹⁵⁹Gd and ⁹⁰Y separately were simulated using the GATE MC Package. The output of simulation (dose image) was uploaded to 3D slicer to compute the absorbed dose for each organ of interests. ¹⁵⁹Gd were able to provide a recommended dose of 120 Gy to the tumour, with normal liver and lungs absorbed doses close to that of ⁹⁰Y and less than the respective maximum permitted doses of 70 Gy and 30 Gy, respectively. Compared to ⁹⁰Y, ¹⁵⁹Gd requires higher administered activity approximately 4.92 times to achieve a tumour dose of 120 Gy. Thus; this research gives new insights into the use of ¹⁵⁹Gd as a theranostic radioisotope, with the potential to be used as a⁹⁰Y alternative for liver radioembolization.
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Yttrium-90 transarterial radioembolization (TARE) has progressed from a salvage or palliative lobar or sequential bilobar regional liver therapy for patients with advanced disease to a versatile, potentially curative, and often highly selective local treatment for patients across Barcelona Clinic Liver Cancer stages. With this shift, radiation dosimetry has evolved to become more tailored to patients and target lesion(s), with treatment dose and distributions adapted for specific clinical goals (ie, palliation, bridging or downstaging to liver transplantation, converting to surgical resection candidacy, or ablative/curative intent). Data have confirmed that “personalizing” dosimetry yields real-world improvements in tumor response and overall survival while maintaining a favorable adverse event profile. In this review, imaging techniques used before, during, and after TARE have been reviewed. Historical algorithms and contemporary image-based dosimetry methods have been reviewed and compared. Finally, recent and upcoming developments in TARE methodologies and tools have been discussed.
Clinical consensus statement: Selective internal radiation therapy with yttrium 90 resin microspheres for hepatocellular carcinoma in Asia
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Hepatocellular carcinoma (HCC) is subject to different management approaches and guidelines according to Eastern and Western therapeutic algorithms. Use of selective internal radiation therapy (SIRT) with resin yttrium 90 microspheres for HCC has increased in Asia in recent years, without clearly defined indications for its optimal application. The objective of this systematic review and expert consensus statement is to provide guidance and perspectives on the use of SIRT among patients with HCC in Asia.
A systematic literature review identified current publications on HCC management and SIRT recommendations. A group of 10 experts, representing stakeholder specialties and countries, convened between August 2020 and March 2021 and implemented a modified Delphi consensus approach to develop guidelines and indications for use of SIRT for HCC in Asia. Final recommendations were organized and adjudicated based on the level of evidence and strength of recommendation, per approaches outlined by the American College of Cardiology/American Heart Association and Oxford Centre for Evidence-Based Medicine.
The experts acknowledged a general lack of evidence relating to use of SIRT in Asia and identified as an unmet need the lack of phase 3 randomized trials comparing clinical outcomes and survival following SIRT versus other therapies for HCC. Through an iterative process, the expert group explored areas of clinical relevance and generated 31 guidance statements and a patient management algorithm that achieved consensus.
These recommendations aim to support clinicians in their decision-making and to help them identify and treat patients with HCC using SIRT in Asia. The recommendations also highlight areas in which further clinical trials are needed to define the role of SIRT in management of HCC among Asian populations.
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Primary liver cancer, hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), are tumors of poor prognosis where treatment is frequently challenging, especially for inoperable tumors (the majority of the cases). Selective internal radiation therapy (SIRT), mainly using radioactive microspheres, can treat both kinds of tumors. The treatment is provided by injection directly in the hepatic artery, after a treatment simulation to carefully select a suitable candidate. SIRT can be used with good clinical outcomes in several clinical situations, for patients who are not candidates to receive surgery due to general conditions or prior to surgery to facilitate surgery, retracting the tumor from the main vessels or inducing untreated liver hypertrophy to reduce the risk of postoperative liver failure. In a palliative setting, when compared to transarterial chemoembolization (TACE), SIRT provided better results, especially regarding response rates of around 90% with SIRT in comparison to less than 60% with TACE. In well-selected nonoperable patients, SIRT can downstage them to surgery, and then offer a potential curative approach in up to 30% of the patients with unilobar involvement, including patients with portal vein thrombosis, one of the poorest prognosis indicators recognized. SIRT requires a multidisciplinary approach both for the selection of good candidates as well as for the treatment simulation and the treatment itself, where a close collaboration is required between the interventional radiology team and the nuclear medicine team. Recent developments in dosimetry have brought huge improvements in outcomes, especially for HCC where overall survival is more than doubled when using a personalized dosimetry approach in comparison to a standard (i.e., nontailored) dosimetry approach. Based on this evolution, new trials are warranted to better define the role of SIRT using personalized dosimetry in the therapeutic strategy of primary liver disease.
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: Conflict of interest: A. Kennedy is a consultant to Sirtex Medical and has received both research grants and honoraria for continuing medical education activities; S.-C. Wang has acted as a consultant to Sirtex Medical and as a proctor/mentor for Asian centers; R. Salem has served on advisory boards for Sirtex Medical; B. Sangro has received lecture fees from Sirtex Medical; Y. H. Kim, H. K. Lai, W.-Y. Lau, R.-C. Lee, T. Leung, C.-S. Liu, and B. Shuter declare no competing interests.

View full text

Clinical InvestigationPatient Selection and Activity Planning Guide for Selective Internal Radiotherapy With Yttrium-90 Resin Microspheres

Purpose

Methods and Materials

Results

Conclusions

Introduction

Section snippets

Methods and Materials

Discussion

Acknowledgments

Int J Radiat Oncol Biol Phys

J Vasc Interv Radiol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Tech Vasc Interv Radiol

J Vasc Interv Radiol

Am J Transpl

J Vasc Interv Radiol

J Vasc Interv Radiol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

J Vasc Interv Radiol

Ann Oncol

Eur J Surg Oncol

J Vasc Interv Radiol

J Vasc Interv Radiol

J Vasc Interv Radiol

Eur J Surg Oncol

Analysis of the distribution of intra-arterial microspheres in human liver following hepatic yttrium-90 microsphere therapy

Phys Med Biol

Microsphere distribution within a metastatic liver tumour following selective internal radiation therapy

GI Cancer

Dosimetry and dose calculation

Partition model for estimating radiation doses from yttrium-90 microspheres in treating hepatic tumours

Eur J Nucl Med

Dosimetric techniques in 90Y-microsphere therapy of liver cancer: The MIRD equations for dose calculations

J Nucl Med

Clinical Investigation
Patient Selection and Activity Planning Guide for Selective Internal Radiotherapy With Yttrium-90 Resin Microspheres

Dosimetric techniques in ⁹⁰Y-microsphere therapy of liver cancer: The MIRD equations for dose calculations