Advances in hepatocellular carcinoma (HCC) treatment and patient profiling are driving a shift toward personalized, multimodality management. The enhanced efficacy of locoregional therapies (LRTs) and systemic regimens has expanded treatment options across palliative and curative settings. For patients eligible to curative-intent treatment, adjunctive approaches aim to enhance procedural feasibility and optimize patient outcomes. Bridging and downstaging to liver transplantation, while traditionally relying on intra-arterial therapies are now seeing emerging alternatives such as stereotactic body radiotherapy (SBRT) and systemic agents. In the perioperative setting, immune checkpoint inhibitor (ICI)-based regimens have shown robust pathological response rates and have significantly improved major pathological response and event-free survival for intermediate- to high-risk resectable patients in a recent phase III trial. For incurable disease, treatment intensification via multimodal combinations improves anti-tumor efficacy. Adding ICI-antiangiogenic regimens to transarterial chemoembolization has demonstrated improved response rates and progression-free survival in multiple phase III trials. Systemic-LRT combinations are also being explored in advanced HCC, with a recent phase III trial indicating SBRT's efficacy in this setting. Notably, curative conversion approaches are emerging to enable subsequent curative-intent treatment in select patients that were previously considered incurable. While multimodal care offers significant promise, its complexity necessitates a multidisciplinary approach to patient and treatment selection, and toxicity management. With multidisciplinary guidance, multimodality approaches promise to expand the path to cure for an increasing number of HCC patients.

Transarterial radioembolization (TARE) is an increasingly important technique for treating liver-based malignancies. Personalized treatment planning and dosimetry are not yet possible due to poor imageability of existing TARE agents. This study presents the design and development of a cohort of imageable glass microspheres that are compatible with readily available imaging equipment, including single-photon emission computed tomography (SPECT) and computed tomography (CT). A statistical modelling approach was used to investigate how the addition of holmium (Ho), a high atomic number and high k-edge element, to a Y2O3-Al2O3-SiO2 (YAS) glass matrix impacts material properties such as density, CT imageability, and glass transition temperature (Tg). The microspheres demonstrated excellent radiopacity, with Hounsfield Unit (HU) values ranging up to ~ 19,800 at 70 kVp, high thermal stability, exhibiting Tg values up to 895 °C, no cytotoxic potential, and negligible ion leaching pre- and post-irradiation to 2600 GBq/g Ho-166, supporting their safety and efficacy for locoregional therapies. Statistical modelling elucidated how the fraction of holmium oxide content within the glass matrix impacts density, CT imageability, and Tg. The ability to visualize the microspheres intra- and post-operatively via CT and SPECT imaging, combined with stable radionuclide incorporation and high achievable specific activity, marks a significant advancement in TARE, and represents an opportunity to expand applicability to cancers beyond the liver.

PURPOSE:To determine 6-month interim safety, effectiveness, and multimodal imageability of imageable glass microsphere yttrium-90 (90Y) radioembolization for unresectable hepatocellular carcinoma (HCC) in a first-in-human trial. MATERIALS AND METHODS:Imageable microspheres (Eye90 Microspheres; ABK Biomedical, Halifax, Nova Scotia, Canada), a U.S. Food and Drug Administration (FDA) Breakthrough-Designated Device consisting of glass radiopaque 90Y microspheres visible on computed tomography (CT) and single photon emission CT (SPECT), were used to treat 6 subjects with unresectable HCC. Patients underwent selective (≤2 segments) treatment in a prospective open-label pilot trial. Key inclusion criteria included liver-only HCC, performance status ≤1, total lesion diameter ≤9 cm, and Child-Pugh A status. Prospective partition dosimetry was utilized. Safety (measured by Common Terminology Criteria for Adverse Events [CTCAE] v5), multimodal imageability on CT and SPECT, and 3- and 6-month imaging response by modified Response Evaluation Criteria in Solid Tumors on magnetic resonance (MR) imaging were evaluated. RESULTS:Seven tumors in 6 subjects were treated and followed to 180 days. Administration success was 100%. Microsphere distribution measured by radiopacity on CT correlated with SPECT. Ninety-day target lesion complete response (CR) was observed in 3 of 6 subjects (50%) and partial response (PR) in 2 (33.3%). At 180 days, target lesion CR was maintained in 3 subjects (50%) and PR in 1 (16.7%). Two subjects could not be reassessed, having undergone intervening chemoembolization. All subjects reported adverse events (AEs), and 5 reported AEs related to treatment. There were no treatment-related Grade ≥3 AEs. CONCLUSIONS:Radioembolization using imageable microspheres was safe and effective in 6 subjects with unresectable HCC at 6-month interim analysis. Microsphere distribution by radiopacity on CT correlated with radioactivity distribution by SPECT, providing previously unavailable CT-based tumor targeting information.

Purpose: To compare spatial distributions of radiopaque glass (RG) microspheres, tris-acryl gelatin (TAG) microspheres, and polyvinyl alcohol (PVA) nonspherical foam particles within a planar in vitro microvascular model of the hyperplastic hemiprostate. Materials and Methods: A microvascular model simulating hyperplastic hemiprostate was perfused with a water-glycerin mixture. A microcatheter was positioned distal to the model's prostatic artery origin, and embolic particles (RG, 50 mu m, 100 mu m, and 150 mu m; TAG, 100-300 mu m and 300-500 mu m; and PVA, 90-180 mu m and 180-300 mu m) were administered using a syringe pump. Microscopic imaging and subsequent semantic segmentation were performed to quantify particle distributions within the models. Distal penetrations were quantified statistically via modal analysis of the particle distributions. Results: Maximum distal penetration was observed for RG microspheres of 50 mu m, followed by RG microspheres of 100 mu m and then TAG microspheres of 100-300 mu m and RG microspheres of 150 mu m. TAG microspheres of 300-500 mu m, PVA particles of 90-180 mu m, and PVA particles of 180-300 mu m exhibited the lowest distal penetrations. The distal penetration metrics between groups were significantly different (P < .05) except between TAG microspheres of 100-300 m and RG microspheres of 150 mu m and between PVA particles of 90-180 and 180-300 mu m. Conclusions: Comparing the spatial distributions of embolic particles in an in vitro microvascular model simulating the hyperplastic hemiprostate revealed that noncompressible particles and those with narrower size calibrations and smaller relative diameters exhibited higher degrees of distal packing. The embolization front was less distinct for particles with wider size calibrations, which resulted in smaller, more distal emboli along with larger, more proximal emboli. Both PVA particles and TAG microspheres of 300-500 mu m exhibited relatively low overall distal penetration.

Purpose: To utilize an in vitro microvascular hepatic tumor model to compare the deposition characteristics of glass yttrium-90 microspheres using the dual-syringe (DS) and traditional bolus administration methods.Materials and Methods: The microvascular tumor model represented a 3.5-cm tumor in a 1,400-cm3 liver with a total hepatic flow of 160 mL/min and was dynamically perfused. A microcatheter was placed in a 2-mm artery feeding the tumor model and 2 additional nontarget arteries. Glass microspheres with a diameter of 20-30 mu m were administered using 2 methods: (a) DS delivery at a concentration of 50 mg/mL in either a single, continuous 2-mL infusion or two 1-mL infusions and (b) bolus delivery (BD) of 100 mg of microspheres in a single 3-mL infusion.Results: Overall, the degree of on-target deposition of the microspheres was 85% +/- 11%, with no significant differences between the administration methods. Although the distal penetration into the tumor arterioles was approximately 15 mm (from the second microvascular bifurcation of the tumor model) for all the cases, the distal peak particle counts were significantly higher for the DS delivery case (approximately 5 x 105 microspheres achieving distal deposition vs 2 x 105 for the BD case). This resulted in significantly higher deposition uniformity within the tumor model (90% for the DS delivery case vs 80% for the BD case, alpha = 0.05).Conclusions: The use of this new in vitro microvascular hepatic tumor model demonstrated that the administration method can affect the deposition of yttrium-90 microspheres within a tumor, with greater distal deposition and more uniform tumor coverage when the microspheres are delivered at consistent concentrations using a DS delivery device. The BD adminis-tration method was associated with less favorable deposition characteristics of the microspheres.

Background: Hepatocellular carcinoma (HCC) a leading cause of cancer mortality worldwide and approximately one-third of patients present with intermediate-stage disease. The treatment landscape of intermediate-stage HCC is rapidly evolving due to developments in local, locoregional and systemic therapies. Treatment recom-mendations focused on this heterogenous disease stage and that take into account the Canadian reality are lacking. To address this gap, a pan-Canadian group of experts in hepatology, transplant, surgery, radiation therapy, nuclear medicine, interventional radiology, and medical oncology came together to develop consensus recommendations on management of intermediate-stage HCC relevant to the Canadian context. Methods: A modified Delphi framework was used to develop consensus statements with strengths of recommendation and supporting levels of evidence graded using the AHA/ACC classification system. Tentative consensus statements were drafted based on a systematic search and expert input in a series of iterative feedback cycles and were then circulated via online survey to assess the level of agreement. Results & Conclusion: The pre-defined ratification threshold of 80 % agreement was reached for all statements in the areas of multidisciplinary treatment (n = 4), intra-arterial therapy (n = 14), biologics (n = 5), radiation therapy (n = 3), surgical resection and transplantation (n = 7), and percutaneous ablative therapy (n = 4). These generally reflected an expansion in treatment options due to developments in previously established or emergent techniques, introduction of new and more active therapies and increased therapeutic flexibility. These developments have allowed for greater treatment tailoring and personalization as well as a paradigm shift toward strategies with curative intent in a wider range of disease settings.

Our objective was to demonstrate, through computer simulations, radiation exposure levels from a 90Y contamination event during radioembolization procedures to calculate the radiation doses from various contamination scenarios. We also provide reasonable safety protocols to prevent contamination and minimize radiation exposure during decontamination. Methods: Simulations were performed using the computer code VARSKIN+, version 1.0, to determine the amount of radiation exposure resulting from different contamination scenarios. Results: The annual radiation dose limit to the skin and the lens of the eye was exceeded within 23 s of exposure to a 44-MBq droplet. Double layers of surgical gloves and level 3 gowns provided some attenuation of radiation from 90Y contamination by reducing the dose rate by 39% and 44%, respectively. Two layers of surgical gloves offered the best ratio of radiation protection without compromising dexterity. Conclusion: This study demonstrated that radiation exposures during 90Y spills or contamination events can be considerable. Interventional radiology and nuclear medicine personnel must be mindful of the risks, follow strategies to prevent spills, and be familiar with recommended decontamination procedures for spills in the interventional radiology suite.

Abstract Purpose To perform precision dosimetry in yttrium-90 radioembolization through CT imaging of radiopaque microspheres in a rabbit liver model and to compare extracted dose metrics to those produced from conventional PET-based dosimetry. Materials and methods A CT calibration phantom was designed containing posts with nominal microsphere concentrations of 0.5 mg/mL, 5.0 mg/mL, and 25.0 mg/mL. The mean Hounsfield unit was extracted from the post volumes to generate a calibration curve to relate Hounsfield units to microsphere concentration. A nominal bolus of 40 mg of microspheres was administered to the livers of eight rabbits, followed by PET/CT imaging. A CT-based activity distribution was calculated through the application of the calibration curve to the CT liver volume. Post-treatment dosimetry was performed through the convolution of yttrium-90 dose-voxel kernels and the PET- and CT-based cumulated activity distributions. The mean dose to the liver in PET- and CT-based dose distributions was compared through linear regression, ANOVA, and Bland–Altman analysis. Results A linear least-squares fit to the average Hounsfield unit and microsphere concentration data from the calibration phantom confirmed a strong correlation (r 2 > 0.999) with a slope of 14.13 HU/mg/mL. A poor correlation was found between the mean dose derived from CT and PET (r 2 = 0.374), while the ANOVA analysis revealed statistically significant differences (p < 10−12) between the MIRD-derived mean dose and the PET- and CT-derived mean dose. Bland–Altman analysis predicted an offset of 15.0 Gy between the mean dose in CT and PET. The dose within the liver was shown to be more heterogeneous in CT than in PET with an average coefficient of variation equal to 1.99 and 1.02, respectively. Conclusion The benefits of a CT-based approach to post-treatment dosimetry in yttrium-90 radioembolization include improved visualization of the dose distribution, reduced partial volume effects, a better representation of dose heterogeneity, and the mitigation of respiratory motion effects. Post-treatment CT imaging of radiopaque microspheres in yttrium-90 radioembolization provides the means to perform precision dosimetry and extract accurate dose metrics used to refine the understanding of the dose–response relationship, which could ultimately improve future patient outcomes.

Purpose: Microwave ablation (MWA) has been firmly established as a treatment option for both primary and secondary malignancies of the liver.While modern MWA machines have improved over prior versions, ability to accurately predict the ablation zone remains questionable.One commonly utilized 2450MHz system (Emprint, Medtronic, Minneapolis, MN) provides both in vivo and ex vivo models for ablation zone (AZ) size prediction.The purpose of this abstract is to evaluate which is most accurate.Materials & Methods: Between 1/1/2015 and 2/1/2021 170 patients who underwent 224 ablations with a single MWA system at a single academic center were retrospectively reviewed.The patient's electronic medical records were reviewed to determine patient demographics, treatment variables, and follow up.AZ dimensions were measured at 1 month follow up in the anterior posterior (AP), transverse (TR), and craniocaudal (CC) directions. Results:The cohort consisted of, 123 (123/170, 72.4%) men and 57 (57/170, 27.6%) women with an average age of 64 ± 11.3 years.The mean percentage of predicted for AZ using the in vivo model was 96.5 ± 26.1%, 89.1 ± 31.5%, and 93.1 ± 28.2% in the AP, TR, and CC directions, respectively.While the mean percentage of predicted in the ex vivo model was 96 ± 25.4%, 82 ± 28.6%, and 85.9 ± 26.4% in the AP, TR, and CC directions, respectively.The mean percentage of predicted for 100-watt treatments of ≤5.5 minutes in the in vivo model was 95.4 ± 18.6%, 87.3 ± 26.5% and 89.6 ± 17.6% in the AP, TR, and CC directions, respectively.The mean percentage of predicted for 100watt treatments of ≤5.5 minutes in the ex vivo mode was 103.8 ± 19.8%, 99 ± 26.2% and 102.4 ± 18.6% in the AP, TR, and CC directions respectively.The ex vivo model was significantly more accurate in the AP (103.8 ± 19.8% vs 95.4% ± 18.6%, p = 0.03), TR (99 ± 26.2% vs 87.3 ± 26.5%, p = 0.03), and CC (102.4 ± 18.6% vs 89.6 ± 17.6%, p=0.002) than the in vivo model in this setting.The mean percentage of predicted for 100-watt treatments >5.5 minutes in the in vivo model was 98.3 ± 25.9%, 91.6 ± 31.9%, and 95.2 ± 28.2% in the AP, TR, and CC directions respectively.While the mean percentage of predicted for 100-watt treatments >5.5 minutes in the ex vivo model is 94.7% ± 24.8%, 78.2 ± 27.2%, and 81.3 ± 24.2% in the AP, TR, and CC directions respectively.There was no significant difference in the ability of the in vivo and ex vivo to predict the AP size of the AZ (98.3 ± 25.9% vs 94.7% ± 24.8%, p = 0.13), however, the TR (91.6 ± 31.9% vs 78.2 ± 27.2%, p = 0.001) and CC (95.2 ± 28.2% vs 81.3 ± 24.2%, p< 0.001) were both significantly more accurately predicted by the in vivo as compared to the ex vivo model.Conclusions: The in vivo model, which more realistically recreates the clinical scenario, was more accurate than the ex vivo model in many situations.However, surprisingly the ex vivo model outperformed the in vivo model at some time settings.These findings can help guide users as to which model is best for a given treatment.

The purpose of this study is to perform post-administration dosimetry in yttrium-90 radioembolization through micro-CT imaging of radiopaque microsphere distributions in a porcine renal model and explore the impact of spatial resolution of an imaging system on the extraction of specific dose metrics. Following the administration of radiopaque microspheres to the kidney of a hybrid farm pig, the kidney was explanted and imaged with micro-CT. To produce an activity distribution, 400 MBq of yttrium-90 activity was distributed throughout segmented voxels of the embolized vasculature based on an established linear relationship between microsphere concentration and CT voxel value. This distribution was down-sampled to coarser isotropic grids ranging in voxel size from 2.5 to 15 mm to emulate nominal resolutions comparable to those found in yttrium-90 PET and Bremsstrahlung SPECT imaging. Dose distributions were calculated through the convolution of activity distributions with dose-voxel kernels generated using the GATE Monte Carlo toolkit. Contours were computed to represent normal tissue and target volumes. Dose-volume histograms, dose metrics, and dose profiles were compared to a ground truth dose distribution computed with GATE. The mean dose to the target for all studied voxel sizes was found to be within 5.7% of the ground truth mean dose.D70was shown to be strongly correlated with image voxel size of the dose distribution (r2 = 0.90).D70is cited in the literature as an important dose metric and its dependence on voxel size suggests higher resolution dose distributions may provide new perspectives on dose-response relationships in yttrium-90 radioembolization. This study demonstrates that dose distributions with large voxels incorrectly homogenize the dose by attributing escalated doses to normal tissues and reduced doses in high-dose target regions. High-resolution micro-CT imaging of radiopaque microsphere distributions can provide increased confidence in characterizing the absorbed dose heterogeneity in yttrium-90 radioembolization.

Introduction:Transarterial radioembolization is a treatment for nonresectable, hypervascular liver tumours where yttrium-90-infused microspheres are administered through the arterial vasculature of the liver to selectively target liver tumours. Compared to conventional PET and SPECT imaging, post-procedural CT imaging has the potential to provide superior spatial resolution imaging of microsphere distributions and improve dosimetry estimates. In this paper, we describe a methodology to quantify the inherent radiopacity of glass microspheres using CT. This methodology produces a calibration curve that relates microsphere concentration within a CT voxel to the corresponding change of Hounsfield unit for that voxel. Methods: The radiopaque microspheres under investigation are composed of proprietery blends of yttrium-strontium-gallium-silicate oxide glass similar in size and density to TheraSphere® microspheres. Tissue-equivalent phantoms were designed to determine CT voxel enhancement from uniformly distributed microspheres. Phantoms were imaged with a 128-slice CT scanner to determine the average Hounsfield unit value and with brightfield microscopy to determine the corresponding microsphere concentrations. Results: Hounsfield units (HU) and microsphere concentration (MS/mL) are positively correlated (r2 ≥ 0.930) over a range of CT acquisition parameters. Calibration curve slopes (sensitivities) range from 2.22 × 10−4 to 3.12 × 10−4 HU/MS/ml. Minimum detectable limits are between 1.83 × 105 and 2.54 × 105 MS mL−1. The application of this proposed methodology to recently developed microsphere formulations shows an improvement in correlation (r2 ≥ 0.995), sensitivity (7.53 × 10−4 HU/MS/ml), and minimum detectability (5.39 × 104 MS ml−1). Conclusion: CT has the potential to quantify the radiation dose from the infusion of microspheres for more accurate dosimetry in radioembolization. This finding may improve our understanding of the relationship between absorbed dose and tumour response, which could ultimately translate into improved patient outcomes. Optimization of the prototype microsphere composition to maximize its inherent radiopacity will be an important step in realizing this goal.

Y ttrium-90 (Y-90) transarterial radioembolization (TARE), also known as selective internal radiation therapy (SIRT), has been used for the treatment of primary and secondary liver cancer for decades. This therapy has greatly advanced since the seminal publications on the clinical, technical, and procedural aspects of Y-90 therapy.1-3 Numerous subsequent studies have confirmed the safety and efficacy of Y-90 therapy, resulting in significant growth in its use. Multidisciplinary recognition of the value of Y-90 therapy is highlighted by its inclusion in the National Comprehensive Cancer Network guidelines as a category 2A recommended therapy for colon and rectal cancer liver metastases.4 This, as well as a key institution’s multidisciplinary team’s decision to choose Y-90 as first-line therapy for hepatocellular carcinoma (HCC),5 should lead to continued growth and adoption. This article describes technical and procedural innovations in Y-90 radioembolization and introduces promising next-generation investigational technologies for this well-established and effective therapy.

OBJECTIVE:We aim to define the practice of interventional radiology (IR) in Canada, barriers that have been faced by interventional radiologists, and ways in which the Canadian Interventional Radiology Association (CIRA) have attempted to address these issues.CONCLUSION:IR has faced significant challenges in the Canadian setting. Recognizing the need to address these challenges, leaders in the field of IR in Canada founded the CIRA to serve as our national voice and lobby group.

Considerable efforts have been placed on the development of degradable microspheres for use in transarterial embolization indications. Using the guidance of the U.S. Food and Drug Administration (FDA) special controls document for the preclinical evaluation of vascular embolization devices, this review consolidates all relevant data pertaining to novel degradable microsphere technologies for bland embolization into a single reference. This review emphasizes intended use, chemical composition, degradative mechanisms, and pre-clinical safety, efficacy, and performance, while summarizing the key advantages and disadvantages for each degradable technology that is currently under development for transarterial embolization. This review is intended to provide an inclusive reference for clinicians that may facilitate an understanding of clinical and technical concepts related to this field of interventional radiology. For materials scientists, this review highlights innovative devices and current evaluation methodologies (i.e., preclinical models), and is designed to be instructive in the development of innovative/new technologies and evaluation methodologies.

PURPOSE:To investigate the current status and evolution of both the interventional radiologist's role as a clinician and the practice of interventional radiology (IR) over the past decade in Canada. MATERIALS AND METHODS:In 2015, an online survey was e-mailed to 210 interventional radiologists, including all Canadian active members of the Canadian Interventional Radiology Association (CIRA) and nonmembers who attended CIRA's annual meeting. Comparisons were made between interventional radiologists in academic versus community practice. The results of the 2015 survey were compared with CIRA's national surveys from 2005 and 2010. RESULTS:A total of 102 interventional radiologists responded (response rate 49%). Significantly more academic versus community interventional radiologists performed chemoembolization, transjugular intrahepatic portosystemic shunt, aortic interventions, and arteriovenous malformation embolization (P < .05). Ninety percent of respondents were involved in longitudinal patient care, which had increased by 42% compared with 2005; 46% of interventional radiologists had overnight admitting privileges, compared with 39% in 2010 and 29% in 2005. Eighty-six percent of interventional radiologists accepted direct referrals from family physicians, and 83% directly referred patients to other consultants. Sixty-three percent participated in multidisciplinary tumor board. The main challenges facing interventional radiologists included a lack of infrastructure, inadequate remuneration for IR procedures, and inadequate funding for IR equipment. Significantly more community versus academic interventional radiologists perceived work volume as an important issue facing the specialty in 2015 (60% vs 34%; P = .02). CONCLUSIONS:Over the past decade, many Canadian interventional radiologists have embraced the interventional radiologist-clinician role. However, a lack of infrastructure and funding continue to impede more widespread adoption of clinical IR practice.

Historically, the use of bioactive glasses has been largely devoted to orthopaedic and dental applications. However, the properties which may be derived from glass materials in medical applications is vast. In this chapter, the authors discuss the potential for new formulations of glass for applications in the field of interventional radiology and interventional oncology. This chapter will highlight the benefits, the potential, and the challenges, of developing new glass materials in this field of medicine. This chapter illustrates that this area of glass research is rich with opportunities to discover new formulations and applications for glass materials in medicine, discoveries which may lead to significant advances in the personalization, optimization and standardization of transarterial embolization procedures in areas of oncology and beyond.