Y-90 PET/MR imaging optimization with a Bayesian penalized likelihood reconstruction algorithm.

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 ß 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 ß = 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 ß parameter lowered RC, COV and BV, while CNR was maximized at ß = 4000; further increase resulted in oversmoothing. For quantification purposes, ß = 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 ß 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.

Imageable Radioembolization Microspheres for Treatment of Unresectable Hepatocellular Carcinoma: Interim Results from a First-in-Human Trial.

PURPOSE: To Describe 6-Month safety, efficacy and multimodal imageability after imageable glass Yttrium-90 radioembolization for unresectable Hepatocellular Carcinoma (HCC) in a First-in Human Trial METHODS: Eye90 microspheres® (Eye90), an FDA Breakthrough Designated Device, are glass radiopaque Y-90 microspheres visible on CT and SPECT/CT. Six subjects with unresectable HCC underwent selective (≤ 2 segments) Eye90 treatment in a prospective open-label pilot trial. Key inclusion criteria included liver only HCC, ECOG ≤ 1, total lesion length ≤ 9 cm and Child-Pugh A. Prospective partition dosimetry was utilized. Safety, biochemistry, toxicity, adverse events (AE), multimodal imageability on CT and SPECT/CT and 3 and 6-month MRI local modified RECIST (mRECIST) response was evaluated. RESULTS: 6 subjects with HCC (7 lesions) were treated with Eye90 and followed to 180 days. Administration success was 100%. Eye90 CT radiopacity distribution correlated with SPECT/CT. Target lesion complete response was observed in 3 of 6 subjects (50%) and partial response in 2 (33.3%). Two subjects could not be assessed at 180 days. At 180 days, target lesion complete response was maintained in 3 subjects (50%) and partial response in 1 (16.7%). All subjects reported AEs, and 5 reported AEs related to treatment. There were no treatment related serious AEs. CONCLUSIONS: Eye90 was safe and effective in six subjects with unresectable HCC up to 6 months. Eye90 was imageable via CT and SPECT/CT with correlation between CT radiopacity and SPECT/CT radioactivity distribution. Eye90 provided previously unavailable CT based tumor targeting information.

Transarterial Radioembolization (TARE) Global Practice Patterns: An International Survey by the Cardiovascular and Interventional Radiology Society of Europe (CIRSE).

PURPOSE: 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. MATERIALS AND 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. CONCLUSION: 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.

High-Dose-Rate Yttrium-90 (90Y) Episcleral Plaque Brachytherapy for Iris and Iridociliary Melanoma.

Purpose: 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. Design: A single-center, clinical case series. Participants: 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. Methods: 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. Main Outcome Measures: Local and systemic cancer control, tumor regression, visual acuity, as well as radiation-related normal tissue toxicity. Results: 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. Conclusions: High-dose-rate Y90 brachytherapy allowed for single-surgery, minimally invasive, outpatient irradiation of iris and iridociliary melanomas. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A comparison of methods for in vivo activity and absorbed dose quantification with PET/CT following yttrium-90 radioembolization.

BACKGROUND: Yttrium-90 (90Y) positron emission tomography (PET)/computed tomography (CT) imaging is increasingly being used to perform tumor (T) and normal liver (NL) voxel dosimetry after 90Y-radioembolization (90Y-RE). Yet, the accuracy of in vivo 90Y-PET/CT imaging, subject to motion blur and co-registration inaccuracies, and 90Y-PET/CT dose quantification, subject to availability of different voxel dosimetry algorithms, are not well understood. PURPOSE: The purpose of this study was to investigate the accuracy of 90Y-PET/CT-based activity estimates following 90Y-RE and characterize differences between 90Y-PET/CT-based voxel dosimetry algorithms. METHODS: Thirty-five patients underwent 90Y-PET/CT imaging after 90Y-RE with TheraSphere. The net administered 90Y activity (Aadmin) was determined using a dose calibrator and pre- and post-procedure exposure rate measurements. The summation of image-based activity (Aimage) was extracted from perfused volume (PV) and 3D-isotropically 2-cm expanded PV contour (PV+2 cm). Absorbed doses were calculated using voxel S-value (VSV), local deposition method (LDM), and LDM with known activity (LDMKA) dosimetry algorithms. Linear regression and Bland-Altman analysis quantified the relationship between Aimage and Aadmin and between mean dose estimates (DLDM, DVSV, DLDM-KA) for PV, T, and perfused NL volumes. RESULTS: While Aadmin and Aimage in PV were highly correlated (R2 > 0.95), the mean bias ± standard error (SE) and (95% limits of agreement, LOA) was significantly non-zero with -22.7 ± 4.7% (± 28.4%). In PV+2 cm, the mean bias ± SE (± LOA) decreased to 1.3 ± 3.4% (± 18.0%) consistent with zero mean error. DLDM and DVSV were highly correlated (R2 > 0.99) for all volumes of interest (VOIs) and the mean bias ± SE (± LOA) was 2.2 ± 0.2% (± 1.0%), 0.7 ± 0.4% (± 2.8%), and 3.2 ± 0.5% (± 2.8%) for PV, T, and NL, respectively. DLDM-KA and DVSV were correlated with R2 = 0.86, 0.80, and 0.86 for PV, T, and NL, respectively. The mean bias ± SE (± LOA) between DLDM-KA and DVSV was significantly non-zero with -19.6 ± 5.1% (± 31.0%), -20.8 ± 4.4% (± 29.0%), and -18.1 ± 5.3% (± 31.1%) for PV, T, and NL, respectively. CONCLUSIONS: The summation of Aimage in PV was underestimated relative to Aadmin. Only by accounting for respiratory motion, limited spatial resolution, and PET/CT co-registration errors through VOI expansion was Aimage, on average, equal to Aadmin. The differences between DLDM and DVSV were not clinically relevant, though DLDM-KA was approximately 20% greater than DVSV. Given the high quantitative accuracy of dose calibrators and challenges associated with accurate 90Y-PET/CT quantification, LDMKA is the preferred algorithm for accurate 90Y-PET/CT-based dosimetry following 90Y-RE.

Contralateral Hypertrophy Post Yttrium-90 Transarterial Radioembolization in Patients With Hepatocellular Carcinoma and Portal Vein Tumor Thrombus.

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.

Outcomes of Y90 Radioembolization for Hepatocellular Carcinoma in Patients Previously Treated with Transarterial Embolization.

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.

Quantitative evaluation of 90Y-PET/CT and 90Y-SPECT/CT-based dosimetry following Yttrium-90 radioembolization.

BACKGROUND: Following yttrium-90 radioembolization (90Y-RE), 90Y-PET/CT and 90Y-SPECT/CT imaging provide the means to calculate the voxelized absorbed dose distribution. Given the widespread use of the two imaging modalities and lack of well-established standardized dosimetry protocols for 90Y-RE, there is a clinical need to systematically investigate and evaluate differences in the performance of voxel-based dosimetry between 90Y-PET/CT and 90Y-SPECT/CT. PURPOSE: To quantitatively analyze and compare 90Y-PET/CT and 90Y-SPECT/CT-based dosimetry following 90Y-RE. METHODS: 90Y-PET/CT and 90Y-SPECT/CT imaging was acquired for 35 patients following 90Y-RE with TheraSphere for the treatment of unresectable hepatocellular carcinoma. Dosimetry was performed using the local deposition method with known activity and the mean dose (Dmean) was calculated for perfused liver volumes (PV), tumors (T), and perfused normal livers (NL). Additionally, the absorbed dose to x% of the volume (Dx, x ∈ $ \in $ [5%, 10%, …, 90%, 95%]) and the volume receiving y Gy (Vy, y ∈ $ \in $ [10 Gy, 20 Gy, …, 190 Gy, 200 Gy]) were calculated for T and NL, respectively. Dose metrics were compared using linear regression, Bland-Altman analysis, and statistical testing. RESULTS: Both 90Y-SPECT/CT and 90Y-PET/CT-based tumor Dmean were strongly correlated (R2 ≥ 0.90) with Dx, excluding metrics on the extrema. Intra-modality comparisons of various Dx and Vy metrics yielded statistically significant differences (ANOVA, p < 0.001) for both90Y-PET/CT and 90Y-SPECT/CT. Based on statistical testing, only Dx metrics separated by greater than 20%-30% coverage, and only Vy metrics separated by greater than 40-70 Gy, reported significant differences. For PV, there was a strong correlation (R2 ≥ 0.99) between Dmean derived separately from 90Y-PET/CT and 90Y-SPECT/CT imaging. The strength of the correlation was slightly reduced for T and NL with R2 = 0.91 and R2 = 0.95, respectively. For PV, the mean bias ± standard error (SE) and 95% limits of agreement (LOA) between Dmean from the two modalities was effectively zero with -0.8 ± 0.4% (± 2.5%). For T and NL, the mean bias ± SE (± LOA) was -14.5 ± 3.7% (± 24%) and 9.4 ± 4.7% (± 27%), respectively. CONCLUSION: The strong correlation between Dmean and Dx suggests information from multiple dose metrics (e.g., D70 and Dmean) is largely redundant when establishing dose-response relationships in 90Y-RE. Dmean is highly correlated between 90Y-PET/CT and 90Y-SPECT/CT-based dosimetry, for all liver VOIs. Relative to 90Y-SPECT/CT, 90Y-PET/CT, on average, yielded higher Dmean to tumors (14%) and lower Dmean to perfused normal livers (9%). Absorbed dose differences for perfused liver volumes between 90Y-SPECT/CT and 90Y-PET/CT were negligible.

Characterizing the voxel-based approaches in radioembolization dosimetry with reDoseMC.

BACKGROUND: Yttrium-90 ( 90 Y $^{90}{\rm {Y}}$ ) represents the primary radioisotope used in radioembolization procedures, while holmium-166 ( 166 Ho $^{166}{\rm {Ho}}$ ) is hypothesized to serve as a viable substitute for 90 Y $^{90}{\rm {Y}}$ due to its comparable therapeutic potential and improved quantitative imaging. Voxel-based dosimetry for these radioisotopes relies on activity images obtained through PET or SPECT and dosimetry methods, including the voxel S-value (VSV) and the local deposition method (LDM). However, the evaluation of the accuracy of absorbed dose calculations has been limited by the use of non-ideal reference standards and investigations restricted to the liver. The objective of this study was to expand upon these dosimetry characterizations by investigating the impact of image resolutions, voxel sizes, target volumes, and tissue materials on the accuracy of 90 Y $^{90}{\rm {Y}}$ and 166 Ho $^{166}{\rm {Ho}}$ dosimetry techniques. METHODS: A specialized radiopharmaceutical dosimetry software called reDoseMC was developed using the Geant4 Monte Carlo toolkit and validated by benchmarking the generated 90 Y $^{90}{\rm {Y}}$ kernels with published data. The decay spectra of both 90 Y $^{90}{\rm {Y}}$ and 166 Ho $^{166}{\rm {Ho}}$ were also compared. Multiple VSV kernels were generated for the liver, lungs, soft tissue, and bone for isotropic voxel sizes of 1 mm, 2 mm, and 4 mm. Three theoretical phantom setups were created with 20 or 40 mm activity and mass density inserts for the same three voxel sizes. To replicate the limited spatial resolutions present in PET and SPECT images, image resolutions were modeled using a 3D Gaussian kernel with a Full Width at Half Maximum (FWHM) ranging from 0 to 16 mm and with no added noise. The VSV and LDM dosimetry methods were evaluated by characterizing their respective kernels and analyzing their absorbed dose estimates calculated on theoretical phantoms. The ground truth for these estimations was calculated using reDoseMC. RESULTS: The decay spectra obtained through reDoseMC showed less than a 1% difference when compared to previously published experimental data for energies below 1.9 MeV in the case of 90 Y $^{90}{\rm {Y}}$ and less than 1% for energies below 1.5 MeV for 166 Ho $^{166}{\rm {Ho}}$ . Additionally, the validation kernels for 90 Y $^{90}{\rm {Y}}$ VSV exhibited results similar to those found in published Monte Carlo codes, with source dose depositions having less than a 3% error margin. Resolution thresholds ( FWHM thresh s ${\rm {FWHM}}_\mathrm{thresh}{\rm {s}}$ ), defined as resolutions that resulted in similar dose estimates between the LDM and VSV methods, were observed for 90 Y $^{90}{\rm {Y}}$ . They were 1.5 mm for bone, 2.5 mm for soft tissue and liver, and 8.5 mm for lungs. For 166 Ho $^{166}{\rm {Ho}}$ , the accuracy of absorbed dose deposition was found to be dependent on the contributions of absorbed dose from photons. Volume errors due to variations in voxel size impacted the final dose estimates. Larger target volumes yielded more accurate mean doses than smaller volumes. For both radioisotopes, the radial dose profiles for the VSV and LDM approximated but never matched the reference standard. CONCLUSIONS: reDoseMC was developed and validated for radiopharmaceutical dosimetry. The accuracy of voxel-based dosimetry was found to vary widely with changes in image resolutions, voxel sizes, chosen target volumes, and tissue material; hence, the standardization of dosimetry protocols was found to be of great importance for comparable dosimetry analysis.

An international phantom study of inter-site variability in Technetium-99m image quantification: analyses from the TARGET radioembolization study.

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). CONCLUSION: 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.

Comparative outcomes of trans-arterial radioembolization in patients with non-alcoholic steatohepatitis/non-alcoholic fatty liver disease-induced HCC: a retrospective analysis.

PURPOSE: Tumorigenesis in NAFLD/NASH-induced HCC is unique and may affect the effectiveness of trans-arterial radioembolization in this population. The purpose of this study was to retrospectively compare the effectiveness of trans-arterial radioembolization for the treatment of hepatocellular carcinoma (HCC) between patients with non-alcoholic steatohepatitis (NASH)/non-alcoholic fatty liver disease (NAFLD) and non-NASH/NAFLD liver disease. MATERIALS AND METHODS: Consecutive patients with HCC who underwent TARE at a single academic institution were retrospectively reviewed. Outcome measures including overall survival (OS), local progression-free survival (PFS), and hepatic PFS as assessed by modified response evaluation criteria in solid tumors (mRECIST) were recorded. Kaplan-Meier and Cox proportional hazard models were utilized to compare progression-free survival and overall survival. RESULTS: 138 separate HCCs in patients treated with TARE between July 2013 and July 2022 were retrospectively identified. Etiologies of HCC included NASH/NAFLD (30/122, 22%), HCV (52/122, 43%), alcoholic liver disease (25/122, 21%), and combined ALD/HCV (14/122, 11%). NASH/NAFLD patients demonstrated a significantly higher incidence of type 2 diabetes mellitus (p < 0.0001). There was no significant difference in overall survival (p = 0.928), local progression-free survival (p = 0.339), or hepatic progression-free survival between the cohorts (p = 0.946) by log-rank analysis. When NASH/NAFLD patients were compared to all combined non-NASH/NAFLD patients, there was no significant difference in OS (HR 1.1, 95% C.I. 0.32-3.79, p = 0.886), local PFS (HR 1.2, 95% C.I. 0.58-2.44, p = 0.639), or hepatic PFS (HR 1.3, 95% C.I. 0.52-3.16, p = 0.595) by log-rank analysis. CONCLUSION: TARE appears to be an equally effective treatment for NASH/NAFLD-induced HCC when compared to other causes of HCC. Further studies in a larger cohort with additional subgroup analyses are warranted.

First Local Experience of Intra-Cavitary Yttrium-90 Citrate Colloid Irradiation via Ommaya Reservoir for Refractory Cystic Craniopharyngioma: a Case Report.

Craniopharyngioma is uncommon benign intracranial tumour that can be cured by surgical resection followed by conventional radiotherapy. However, its anatomical localisation makes the treatment hazardous or impossible. This case report aims to discuss the first local experience of using beta-emitting Yttrium-90 radioisotope in treating a patient with refractory cystic craniopharyngioma. A 43-year-old male who has underlying refractory cystic craniopharyngioma complicated with visual impairment and panhypopituitarism was referred to our nuclear medicine department for intra-cavitary irradiation therapy. Initially, he was presented with blurring of vision and headache which he had two previous resection surgeries of cystic craniopharyngioma. However, due to persistent symptoms, he had Ommaya reservoir shunt inserted for regular aspiration. Despite regular aspiration, his symptoms worsen. He was unsuitable for radiotherapy thus was considered for intra-cystic irradiation with radioisotope. Prior to the therapy, he had pre-therapy assessment with Tc-99 m MAA. He subsequently received Ytrrium-90 citrate colloid of 300 Gy radiation dose to the inner surface of the tumour which complicated with post therapy inflammatory reaction. This first local experience highlights the role of radioisotope as the valuable minimally invasive adjuvant therapy in treating a patient with refractory cystic craniopharyngioma. Further follow-up is necessary to assess the outcome and possible late complications.

Imaging Considerations before and after Liver-Directed Locoregional Treatments for Metastatic Colorectal Cancer.

Colorectal cancer is a leading cause of cancer-related death. Liver metastases will develop in over one-third of patients with colorectal cancer and are a major cause of morbidity and mortality. Even though surgical resection has been considered the mainstay of treatment, only approximately 20% of the patients are surgical candidates. Liver-directed locoregional therapies such as thermal ablation, Yttrium-90 transarterial radioembolization, and stereotactic body radiation therapy are pivotal in managing colorectal liver metastatic disease. Comprehensive pre- and post-intervention imaging, encompassing both anatomic and metabolic assessments, is invaluable for precise treatment planning, staging, treatment response assessment, and the prompt identification of local or distant tumor progression. This review outlines the value of imaging for colorectal liver metastatic disease and offers insights into imaging follow-up after locoregional liver-directed therapy.

Recommendations for the management of yttrium-90 radioembolization in the treatment of patients with colorectal cancer liver metastases: a multidisciplinary review / Recomendaciones para el manejo de la radioembolización con itrio-90 en el tratamiento de pacientes con metástasis hepáticas de cáncer colorrectal: una revisión multidisciplinaria

Purpose: Strategies for the treatment of liver metastases from colon cancer (lmCRC) are constantly evolving. Radioembolization with yttrium 90 (Y-90 TARE) has made significant advancements in treating liver tumors and is now considered a potential option allowing for future resection. This study reviewed the scientific evidence and developed recommendations for using Y-90 TARE as a treatment strategy for patients with unresectable lmCRC. Methods: A multidisciplinary scientific committee, consisting of experts in medical oncology, hepatobiliary surgery, radiology, and nuclear medicine, all with extensive experience in treating patients with ImCRC with Y-90 TARE, led this project. The committee established the criteria for conducting a comprehensive literature review on Y-90 TARE in the treatment of lmCRC. The data extraction process involved addressing initial preliminary inquiries, which were consolidated into a final set of questions. Results: This review offers recommendations for treating patients with lmCRC using Y-90 TARE, addressing four areas covering ten common questions: 1) General issues (multidisciplinary tumor committee, indications for treatment, contraindications); 2) Previous process (predictive biomarkers for patient selection, preintervention tests, published evidence); 3) Procedure (standard procedure); and 4) Post-intervention follow-up (potential toxicity and its management, parameters for evaluation, quality of life). Conclusions: Based on the insights of the multidisciplinary committee, this document offers a comprehensive overview of the technical aspects involved in the management of Y-90 TARE. It synthesizes recommendations for applying Y-90 TARE across various phases of the treatment process.(AU)

The Influence of Additional Treatments on the Survival of Patients Undergoing Transarterial Radioembolization (TARE).

The aim of this study was to present our preliminary experience with transarterial radioembolization (TARE) using Yttrium-90 (90Y), compare the cancer-specific survival (CSS) of patients with hepatocellular carcinoma (HCC) and colorectal cancer (CRC) liver metastases undergoing TARE, and investigate the influence of additional treatments on CSS. Our database was interrogated to retrieve patients who had undergone TARE using Yttrium-90 (90Y) glass or resin microspheres. Kaplan-Meier curves and the log-rank test were employed to conduct survival analysis for the different groups (p < 0.05). Thirty-nine patients were retrieved (sex: 27 M, 12 F; mean age: 63.59 ± 15.66 years): twenty-three with hepatocellular carcinoma (HCC) and sixteen with CRC liver metastasis. Globally, the patients with HCC demonstrated a significantly longer CSS than those with CRC liver metastasis (22.64 ± 2.7 vs. 7.21 ± 1.65 months; p = 0.014). Among the patients with CRC liver metastasis, those receiving TARE and additional concomitant treatments (n = 10) demonstrated a longer CSS than the CRC patients receiving only TARE (9.97 ± 2.21 vs. 2.59 ± 0.24 months; p = 0.06). In the HCC group, there was a trend of a longer CSS in patients (n = 8) receiving TARE and additional treatments (27.89 ± 3.1 vs. 17.69 ± 3.14 months; p = 0.15). Patients with HCC seem to achieve a longer survival after TARE compared to patients with CRC liver metastases. In patients with CRC liver metastases, the combination of TARE and additional concomitant treatments may improve survival.

Techniques to Optimize Radioembolization Tumor Coverage.

Yttrium-90 (Y90) radioembolization has become a major locoregional treatment option for several primary and secondary liver cancers. Understanding the various factors that contribute to optimal tumor coverage including sphere count, embolization techniques, and catheter choice is important for all interventional radiologists while planning Y90 dosimetry and delivery. Here, we review these factors and the evidence supporting current practice paradigms.

Yttrium-90 Episcleral Plaque Brachytherapy for Choroidal Melanoma.

Purpose: To describe the first use of high-dose-rate yttrium-90 disc brachytherapy for choroidal melanoma. Methods: A 72-year-old patient had a cT1-category choroidal melanoma characterized by the presence of orange pigment, increasing subretinal fluid (SRF), and enlarging tumor thickness. It was treated with single-session, light-guided, light-defined yttrium-90-disc brachytherapy. Results: A specialized handheld applicator provided with 4 encircling lights was used to guide plaque placement and localize treatment. Unlike low-dose-rate plaques, high-dose-rate yttrium-90 required only 3 minutes 39 seconds. In this case, treatment did not require episcleral sutures, muscle relocation, outpatient dwell time, or a second surgery. High-dose-rate treatment improved radiation safety by eliminating perioperative exposure to health care personnel, the community, and the family. At the 13-month follow-up, the SRF and tumor thickness were diminished. There was no secondary cataract, radiation retinopathy, maculopathy, or optic neuropathy, and the visual acuity was 20/20. Conclusions: Yttrium-90 brachytherapy allowed for single-surgery, minimally invasive, outpatient irradiation of a choroidal melanoma.

Impact of Hypoxia on Radiation-Based Therapies for Liver Cancer.

Background: Hypoxia, a state of low oxygen level within a tissue, is often present in primary and secondary liver tumors. At the molecular level, the tumor cells' response to hypoxic stress induces proteomic and genomic changes which are largely regulated by proteins called hypoxia-induced factors (HIF). These proteins have been found to drive tumor progression and cause resistance to drug- and radiation-based therapies, ultimately contributing to a tumor's poor prognosis. Several imaging modalities have been developed to visualize tissue hypoxia, providing insight into a tumor's microbiology. Methods: A systematic literature search was conducted in PubMed, EMBASE, Cochrane, and Google Scholar for all reports related to hypoxia on liver tumors. All relevant studies were summarized. Results: This review will focus on the impact of hypoxia on liver tumors and review PET-, MRI-, and SPECT-based imaging modalities that have been developed to predict and assess a tumor's response to radiation therapy, with a focus on liver cancers. Conclusion: While there are numerous studies that have evaluated the impact of hypoxia on tumor outcomes, there remains a relative paucity of data evaluating and quantifying hypoxia within the liver. Novel and developing non-invasive imaging techniques able to provide functional and physiological information on tumor hypoxia within the liver may be able to assist in the treatment planning of primary and metastatic liver lesions.

Linear Boltzmann equation solver for voxel-level dosimetry in radiopharmaceutical therapy: Comparison with Monte Carlo and kernel convolution.

BACKGROUND: With recent interest in patient-specific dosimetry for radiopharmaceutical therapy (RPT) and selective internal radiation therapy (SIRT), an increasing number of voxel-based algorithms are being evaluated. Monte Carlo (MC) radiation transport, generally considered to be the most accurate among different methods for voxel-level absorbed dose estimation, can be computationally inefficient for routine clinical use. PURPOSE: This work demonstrates a recently implemented grid-based linear Boltzmann transport equation (LBTE) solver for fast and accurate voxel-based dosimetry in RPT and SIRT and benchmarks it against MC. METHODS: A deterministic LBTE solver (Acuros MRT) was implemented within a commercial RPT dosimetry package (Velocity 4.1). The LBTE is directly discretized using an adaptive mesh refined grid and then the coupled photon-electron radiation transport is iteratively solved inside specified volumes to estimate radiation doses from both photons and charged particles in heterogeneous media. To evaluate the performance of the LBTE solver for RPT and SIRT applications, 177 Lu SPECT/CT, 90 Y PET/CT, and 131 I SPECT/CT images of phantoms and patients were used. Multiple lesions (2-1052 mL) and normal organs were delineated for each study. Voxel dosimetry was performed with the LBTE solver, dose voxel kernel (DVK) convolution with density correction, and a validated in-house MC code using the same time-integrated activity and density maps as input to the different dose engines. The resulting dose maps, difference maps, and dose-volume-histogram (DVH) metrics were compared, to assess the voxel-level agreement. Evaluation of mean absorbed dose included comparison with structure-level estimates from OLINDA. RESULTS: In the phantom inserts/compartments, the LBTE solver versus MC and DVK convolution demonstrated good agreement with mean absorbed dose and DVH metrics agreeing to within 5% except for the D90 and D70 metrics of a very low activity concentration insert of 90 Y where the agreement was within 15%. In the patient studies (five patients imaged after 177 Lu DOTATATE RPT, five after 90 Y SIRT, and two after 131 I radioimmunotherapy), in general, there was better agreement between the LBTE solver and MC than between LBTE solver and DVK convolution for mean absorbed dose and voxel-level evaluations. Across all patients for all three radionuclides, for soft tissue structures (kidney, liver, lesions), the mean absorbed dose estimates from the LBTE solver were in good agreement with those from MC (median difference < 1%, maximum 9%) and those from DVK (median difference < 5%, maximum 9%). The LBTE and OLINDA estimates for mean absorbed dose in kidneys and liver agreed to within 10%, but differences for lesions were larger with a maximum 14% for 177 Lu, 23% for 90 Y, and 26% for 131 I. For bone regions, the agreement in mean absorbed doses between LBTE and both MC and DVK were similar (median < 11%, max 11%) while for lung the agreement between LBTE and MC (median < 1%, max 8%) was substantially better than between LBTE and DVK (median < 16%, max 33%). Voxel level estimates for soft tissue structures also showed good agreement between the LBTE solver and both MC and DVK with a median difference < 5% (maximum < 13%) for the DVH metrics with all three radionuclides. The largest difference in DVH metrics was for the D90 and D70 metric in lung and bone where the uptake was low. Here, the difference between LBTE and MC had a median value < 14% (maximum 23%) for bone and < 4% (maximum 37%) for lung, while the corresponding differences between LBTE and DVK were < 23% (maximum 31%) and < 67% (maximum 313%), respectively. For a typical patient with a matrix size of 166 × 166 × 129 (voxel size 3 × 3 × 3 mm3 ), voxel dosimetry using the LBTE solver was as fast as ∼2 min on a desktop computer. CONCLUSION: Having established good agreement between the LBTE solver and MC for RPT and SIRT applications, the LBTE solver is a viable option for voxel dosimetry that can be faster than MC. Further analysis is being performed to encompass the broad range of radionuclides and conditions encountered clinically.