OBJECTIVE: In this study, we aimed to evaluate the response of the primary and metastatic liver tumors to radioembolization with 90Y glass microspheres and investigate its correlations with dosimetric variables calculated with 90Y PET/MRI.
METHODS: In this ambispective study, 44 patients treated with 90Y glass microspheres and imaged with 90Y PET/MRI were included for analysis. Dosimetric analysis was performed for every perfused lesion using dose-volume histograms. Response was assessed by comparing pre-treatment and follow-up total lesion glycolysis (TLG) values derived from 18F-FDG PET imaging. The relationship between ΔTLG and log-transformed dosimetric variables was analyzed with linear mixed effects regression models. ROC analyses were performed to compare discriminatory power of the variables in predicting response and complete response.
RESULTS: Regression and ROC analyses demonstrated that mean tumor dose and almost all D values were statistically significant predictors of treatment response and complete treatment response. Specifically, D60, D70 and D80 values exhibited significantly higher discriminatory power for predicting treatment response compared to the mean dose (Dmean) delivered to tumor. High specificity cut-off values to predict response were determined as 160.75 Gy for Dmean, 95.50 Gy for D60, 89 Gy for D70, and 59.50 Gy for D80. Similarly, high-specificity cut-off values to predict complete response were 262.75 Gy for Dmean, 173 Gy for D70, 140.5 Gy for D80, and 100 Gy for D90.
CONCLUSIONS: In this study, we demonstrated that voxel-based dosimetry with post-treatment 90Y PET/MRI can predict response to treatment. D60, D70 and D80 variables also did have greater discriminatory power compared to Dmean in prediction of response. In addition, we present high-specificity cut-offs to predict response (CR + PR) and complete response (CR) for both Dmean and several D variables derived from dose-volume histograms.

Selective internal radiation therapy (SIRT) has emerged as a viable endovascular treatment strategy for hepatocellular carcinoma (HCC). According to the Barcelona Clinic Liver Cancer (BCLC) classification, SIRT is currently recommended for early- and intermediate-stage HCC that is unsuitable for alternative locoregional therapies. Additionally, SIRT remains a recommended treatment for patients with advanced-stage HCC and portal vein thrombosis (PVT) without extrahepatic metastasis. Several studies have shown that SIRT is a versatile and promising treatment with a wide range of applications. Consequently, given its favourable characteristics in various scenarios, SIRT could be an encouraging treatment option for patients with HCC across different BCLC stages. Over the past decade, an increasing number of studies have focused on better understanding the prognostic factors associated with SIRT to identify patients who derive the most benefit from this treatment or to refine the optimal technical procedures of SIRT. Several variables can influence treatment decisions, with a growing emphasis on a personalised approach. This review, based on the literature, will focus on the prognostic factors associated with the effectiveness of radioembolization and related complications. By comprehensively analysing these factors, we aimed to provide a clearer understanding of how to optimise the use of SIRT in managing HCC patients, thereby enhancing outcomes across various clinical scenarios.

Medullary thyroid carcinoma (MTC) can often have an indolent course despite distant metastatic disease. Additionally, given that metastatic MTC is incurable and systemic therapies have non-negligeable toxicities, localized treatments are often favored in presence of oligo-progressive disease. Transarterial radioembolization (TARE) with yttrium-90 (Y90) has emerged as a safe and efficacious treatment for nonresectable primary and metastatic liver tumors, yet data supporting its use in metastatic MTC are limited. We present the case of a patient with hereditary MTC and large bilobar liver metastases who demonstrated tumor response and resolution of their paraneoplastic diarrhea following TARE with Y90 microspheres.

OBJECTIVE: 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.
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.

OBJECTIVE: An international survey was conducted by the Cardiovascular Interventional Radiological Society of Europe (CIRSE) to evaluate radioembolization practice and capture opinions on real-world clinical and technical aspects of this therapy.
METHODS: A survey with 32 multiple choice questions was sent as an email to CIRSE members between November and December 2022. CIRSE group member and sister societies promoted the survey to their local members. The dataset was cleaned of duplicates and entries with missing data, and the resulting anonymized dataset was analysed. Data were presented using descriptive statistics.
RESULTS: The survey was completed by 133 sites, from 30 countries, spanning 6 continents. Most responses were from European centres (87/133, 65%), followed by centres from the Americas (22/133, 17%). Responding sites had been performing radioembolization for 10 years on average and had completed a total of 20,140 procedures over the last 5 years. Hepatocellular carcinoma treatments constituted 56% of this total, colorectal liver metastasis 17% and cholangiocarcinoma 14%. New sites had opened every year for the past 20 years, indicating the high demand for this therapy. Results showed a trend towards individualized treatment, with 79% of responders reporting use of personalized dosimetry for treatment planning and 97% reporting routine assessment of microsphere distribution post-treatment. Interventional radiologists played an important role in referrals, being present in the referring multi-disciplinary team in 91% of responding centres.
CONCLUSIONS: This survey provides insight into the current state of radioembolization practice globally. The results reveal the increasing significance placed on dosimetry, evolving interventional techniques and increased technology integration.

Positron Emission Tomography (PET) imaging after 90 Y liver radioembolization is used for both lesion identification and dosimetry. Bayesian penalized likelihood (BPL) reconstruction algorithms are an alternative to ordered subset expectation maximization (OSEM) with improved image quality and lesion detectability. The investigation of optimal parameters for 90 Y image reconstruction of Q.Clear, a commercial BPL algorithm developed by General Electric (GE), in PET/MR is a field of interest and the subject of this study. The NEMA phantom was filled at an 8:1 sphere-to-background ratio. Acquisitions were performed on a PET/MR scanner for clinically relevant activities between 0.7 and 3.3 MBq/ml. Reconstructions with Q.Clear were performed varying the β penalty parameter between 20 and 6000, the acquisition time between 5 and 20 min and pixel size between 1.56 and 4.69 mm. OSEM reconstructions of 28 subsets with 2 and 4 iterations with and without Time-of-Flight (TOF) were compared to Q.Clear with β = 4000. Recovery coefficients (RC), their coefficient of variation (COV), background variability (BV), contrast-to-noise ratio (CNR) and residual activity in the cold insert were evaluated. Increasing β parameter lowered RC, COV and BV, while CNR was maximized at β = 4000; further increase resulted in oversmoothing. For quantification purposes, β = 1000-2000 could be more appropriate. Longer acquisition times resulted in larger CNR due to reduced image noise. Q.Clear reconstructions led to higher CNR than OSEM. A β of 4000 was obtained for optimal image quality, although lower values could be considered for quantification purposes. An optimal acquisition time of 15 min was proposed considering its clinical use.

UNASSIGNED: To describe a pilot study on the use of single-session, high-dose-rate, Food and Drug Administration-cleared, yttrium-90 (Y90) plaque brachytherapy for iris and iridociliary melanoma.
UNASSIGNED: A single-center, clinical case series.
UNASSIGNED: Six consecutive patients were included in this study. Each was diagnosed with an iris or iridociliary melanoma based on clinical examination with or without biopsy.
UNASSIGNED: Each tumor was staged according to the American Joint Committee on Cancer criteria and received Y90 eye plaque brachytherapy. The main variables were tumor size, patient age, sex, and method of diagnosis (clinical or biopsy). Surgical techniques, treatment durations, and ocular side effects were recorded. Local control was defined as a lack of tumor growth or regression determined by clinical examinations, including slit-lamp and gonio photography, as well as high-frequency ultrasound measurements. Toxicity parameters included acute and short-term corneal/scleral change, anterior segment inflammation, and cataract progression.
UNASSIGNED: Local and systemic cancer control, tumor regression, visual acuity, as well as radiation-related normal tissue toxicity.
UNASSIGNED: High-dose-rate Y90 plaque brachytherapy was used to treat small (American Joint Committee on Cancer cT1) category melanomas. Single-surgery high-dose-rate irradiations were performed under anesthesia. Because of short treatment durations, high-dose-rate Y90 did not require the additional procedures used for low-dose-rate plaque (e.g., sutures, amniotic membrane epicorneal buffering, Gunderson flaps, and second surgeries for plaque removal). Only conjunctival recession was used to avoid normal tissue irradiation. High-dose-rate Y90 treatment durations averaged 8.8 minutes (median, 7.9; range, 5.8-12.9). High-dose-rate Y90 brachytherapy was associated with no periorbital, corneal (Descemet folds), or conjunctival edema. There was no acute or short-term anterior uveitis, secondary cataract, scleropathy, radiation retinopathy, maculopathy, or optic neuropathy. The follow-up was a mean of 16.0 (range 12-24) months. Evidence of local control included a lack of expansion of tumor borders (n = 6, 100%), darkening with or without atrophy of the tumor surface (n = 5/6, 83%), and a mean 24.5% reduction in ultrasonographically measured tumor thickness. There were no cases of metastatic disease.
UNASSIGNED: High-dose-rate Y90 brachytherapy allowed for single-surgery, minimally invasive, outpatient irradiation of iris and iridociliary melanomas.
UNASSIGNED: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Objectives Contralateral hypertrophy of non-irradiated liver following Yttrium-90 (90Y) transarterial radioembolization (TARE) is increasingly recognized as an option to facilitate curative surgical resection in patients that would otherwise not be surgical candidates due to a small future liver remnant (FLR). This study aimed to investigate the correlation between patient features and liver hypertrophy and identify potential predictors for liver growth in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) undergoing TARE. Methodology Twenty-three patients with HCC and PVTT were included. Contralateral liver hypertrophy was assessed at six months posttreatment based on CT or MRI imaging. Thirteen patient features were selected for statistical and prediction analysis. Univariate Spearman correlation and analysis of variance (ANOVA) tests were performed. Subsequently, four feature-selection methods based on multivariate analysis were used to improve model generalization performance. The selected features were applied to train linear regression models, with fivefold cross-validation to assess the performance of the predicted models. Results The ratio of disease-free target liver volume to spared liver volume and total liver volume showed the highest correlations with contralateral hypertrophy (P-values = 0.03 and 0.05, respectively). In three out of four feature-selection methods, the feature of disease-free target liver volume to total liver volume ratio was selected, having positive correlations with the outcome and suggesting that more hypertrophy may be expected when more volume of disease-free liver is irradiated. Conclusions Contralateral hypertrophy post-90Y TARE can be an option for facilitating surgical resection in patients with otherwise small FLR.

BACKGROUND: Personalised multi-compartment dosimetry based on [99mTc]Tc-MAA is a valuable tool for planning 90Y radioembolization treatments. The establishment and effective application of dose-effect relationships in yttrium-90 (90Y) radioembolization requires [99mTc]Tc-MAA SPECT quantification ideally independent of clinical site. The purpose of this multi-centre phantom study was to evaluate inter-site variability of [99mTc]Tc-MAA imaging and evaluate a standardised imaging protocol. Data was obtained from the TARGET study, an international, retrospective multi-centre study including 14 sites across 8 countries. The impact of imaging related factors was estimated using a NEMA IQ phantom (representing the liver), and a uniformly filled cylindrical phantom (representing the lungs). Imaging was performed using site-specific protocols and a standardized protocol. In addition, the impact of implementing key image corrections (scatter and attenuation correction) in the site-specific protocols was investigated. Inter-site dosimetry accuracy was evaluated by comparing computed Lung Shunt Fraction (LSF) measured using planar imaging of the cylindrical and NEMA phantom, and contrast recovery coefficient (CRC) measured using SPECT imaging of the NEMA IQ phantom.
RESULTS: Regarding the LSF, inter-site variation with planar site-specific protocols was minimal, as determined by comparing computed LSF between sites (interquartile range 9.6-10.1%). A standardised protocol did not improve variation (interquartile range 8.4-9.0%) but did improve mean accuracy compared to the site-specific protocols (5.0% error for standardised protocol vs 8.8% error for site-specific protocols). Regarding the CRC, inter-system variation was notable for site-specific SPECT protocols and could not be improved by the standardised protocol (CRC interquartile range for 37 mm sphere 0.5-0.7 and 0.6-0.8 respectively), however the standardised protocol did improve accuracy of sphere:background determination. Implementation of key image corrections did improve inter-site variation (CRC interquartile range for 37 mm sphere 0.6-0.7).
CONCLUSIONS: Eliminating sources of variability in image corrections between imaging protocols reduces inter-site variation in quantification. A standardised protocol was not able to improve consistency of LSF or CRC but was able to improve accuracy.

The aim of this study was to evaluate outcomes of transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC) in patients previously treated with transarterial embolization (TAE). In this retrospective study, all HCC patients who received TARE from 1/2012 to 12/2022 for treatment of residual or recurrent disease after TAE were identified. Overall survival (OS) was estimated using the Kaplan-Meier method. Univariate Cox regression was performed to determine significant predictors of OS after TARE. Twenty-one patients (median age 73.4 years, 18 male, 3 female) were included. Median dose to the perfused liver volume was 121 Gy (112-444, range), and 18/21 (85.7%) patients received 112-140 Gy. Median OS from time of HCC diagnosis was 32.9 months (19.4-61.4, 95% CI). Median OS after first TAE was 29.3 months (15.3-58.9, 95% CI). Median OS after first TARE was 10.6 months (6.8-27.0, 95% CI). ECOG performance status of 0 (p = 0.038), index tumor diameter < 4 cm (p = 0.022), and hepatic tumor burden < 25% (p = 0.018) were significant predictors of longer OS after TARE. TARE may provide a survival benefit for appropriately selected patients with HCC who have been previously treated with TAE.