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.

Clinical, dosimetric, and reporting considerations for Y-90 glass microspheres in hepatocellular carcinoma: updated 2022 recommendations from an international multidisciplinary working group.

PURPOSE: In light of recently published clinical reports and trials, the TheraSphere Global Dosimetry Steering Committee (DSC) reconvened to review new data and to update previously published clinical and dosimetric recommendations for the treatment of hepatocellular carcinoma (HCC). METHODS: The TheraSphere Global DSC is comprised of health care providers across multiple disciplines involved in the treatment of HCC with yttrium-90 (Y-90) glass microsphere-based transarterial radioembolization (TARE). Literature published between January 2019 and September 2021 was reviewed, discussed, and adjudicated by the Delphi method. Recommendations included in this updated document incorporate both the results of the literature review and the expert opinion and experience of members of the committee. RESULTS: Committee discussion and consensus led to the expansion of recommendations to apply to five common clinical scenarios in patients with HCC to support more individualized efficacious treatment with Y-90 glass microspheres. Existing clinical scenarios were updated to reflect recent developments in dosimetry approaches and broader treatment paradigms evolving for patients presenting with HCC. CONCLUSION: Updated consensus recommendations are provided to guide clinical and dosimetric approaches for the use of Y-90 glass microsphere TARE in HCC, accounting for disease presentation, tumor biology, and treatment intent.

Voxel-based dosimetry predicting treatment response and related toxicity in HCC patients treated with resin-based Y90 radioembolization: a prospective, single-arm study.

BACKGROUND: There is an increasing body of evidence indicating Y90 dose thresholds for tumor response and treatment-related toxicity. These thresholds are poorly studied in resin Y90, particularly in hepatocellular carcinoma (HCC). PURPOSE: To evaluate the efficacy of prospective voxel-based dosimetry for predicting treatment response and adverse events (AEs) in patients with HCC undergoing resin-based Y90 radioembolization. MATERIALS AND METHODS: This correlative study was based on a prospective single-arm clinical trial (NCT04172714), which evaluated the efficacy of low/scout (555 MBq) activity of resin-based Y90 for treatment planning. Partition model was used with goal of tumor dose (TD) > 200 Gy and non-tumoral liver dose (NTLD) < 70 Gy for non-segmental therapies. Single compartment dose of 200 Gy was used for segmentectomies. Prescribed Y90 activity minus scout activity was administered for therapeutic Y90 followed by Y90-PET/CT. Sureplan® (MIM Software, Cleveland, OH) was used for dosimetry analysis. Treatment response was evaluated at 3 and 6 months. Receiver operating characteristic curve determined TD response threshold for objective response (OR) and complete response (CR) as well as non-tumor liver dose (NTLD) threshold that predicted AEs. RESULTS: N = 30 patients were treated with 33 tumors (19 segmental and 14 non-segmental). One patient died before the first imaging, and clinical follow-up was excluded from this analysis. Overall, 26 (81%) of the tumors had an OR and 23 (72%) had a CR. A mean TD of 253 Gy predicted an OR with 92% sensitivity and 83% specificity (area under the curve (AUC = 0.929, p < 0.001). A mean TD of 337 Gy predicted a CR with 83% sensitivity and 89% specificity (AUC = 0.845, p < 0.001). A mean NTLD of 81 and 87 Gy predicted grade 3 AEs with 100% sensitivity and 100% specificity in the non-segmental cohort at 3- and 6-month post Y90, respectively. CONCLUSION: In patients with HCC undergoing resin-based Y90, there are dose response and dose toxicity thresholds directly affecting outcomes. CLINICAL TRIAL NUMBER: NCT04172714.

A global evaluation of advanced dosimetry in transarterial radioembolization of hepatocellular carcinoma with Yttrium-90: the TARGET study.

PURPOSE: To investigate the relationships between tumor absorbed dose (TAD) or normal tissue absorbed dose (NTAD) and clinical outcomes in hepatocellular carcinoma (HCC) treated with yttrium-90 glass microspheres. METHODS: TARGET was a retrospective investigation in 13 centers across eight countries. Key inclusion criteria: liver-dominant HCC with or without portal vein thrombosis, < 10 tumors per lobe (at least one ≥ 3 cm), Child-Pugh stage A/B7, BCLC stages A-C, and no prior intra-arterial treatment. Multi-compartment pre-treatment dosimetry was performed retrospectively. Primary endpoint was the relationship between ≥ grade 3 hyperbilirubinemia (such that > 15% of patients experienced an event) without disease progression and NTAD. Secondary endpoints included relationships between (1) objective response (OR) and TAD, (2) overall survival (OS) and TAD, and (3) alpha fetoprotein (AFP) and TAD. RESULTS: No relationship was found between NTAD and ≥ grade 3 hyperbilirubinemia, which occurred in 4.8% of the 209 patients. The mRECIST OR rate over all lesions was 61.7%; for the target (largest) lesion, 70.8%. Responders and non-responders had geometric mean total perfused TADs of 225.5 Gy and 188.3 Gy (p = 0.048). Probability of OR was higher with increasing TAD (p = 0.044). Higher TAD was associated with longer OS (HR per 100 Gy increase = 0.83, 95% CI: 0.71-0.95; p = 0.009). Increased TAD was associated with higher probability of AFP response (p = 0.046 for baseline AFP ≥ 200 ng/mL). CONCLUSION: Real-world data confirmed a significant association between TAD and OR, TAD and OS, and TAD and AFP response. No association was found between ≥ grade 3 hyperbilirubinemia and NTAD. TRIAL REGISTRATION NUMBER: NCT03295006.

Accuracy and Safety of Scout Dose Resin Yttrium-90 Microspheres for Radioembolization Therapy Treatment Planning: A Prospective Single-Arm Clinical Trial.

PURPOSE: To compare the accuracy and safety of 0.56 GBq resin yttrium-90 (90Y) (scout90Y) microspheres with those of technetium-99m macroaggregated albumin (MAA) in predicting the therapeutic 90Y (Rx90Y) dose for patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This prospective single-arm clinical trial (Clinicaltrials.gov: NCT04172714) recruited patients with HCC. Patients underwent same-day mapping with MAA and scout90Y. Rx90Y activity was administered 3 days after mapping. Using paired t test and Pearson correlation, the tumor-to-normal ratio (TNR), lung shunt fraction (LSF), predicted mean tumor dose (TD), and nontumoral liver dose (NTLD) by MAA and scout90Y were compared with those by Rx90Y. Bland-Altman plots compared the level of agreement between the TNR and LSF of scout90Y and MAA with that of Rx90Y. The safety of scout90Y was evaluated by examining the discrepancy in extrahepatic activity between MAA and scout90Y. RESULTS: Thirty patients were treated using 19 segmental and 14 nonsegmental (ie, 2 contiguous segments or nonsegmental) therapies. MAA had weak LSF, moderate TNR, and moderate TD linear correlation with Rx90Y. Scout90Y had a moderate LSF, strong TNR, strong TD, and very strong NTLD in correlation with those of Rx90Y. Furthermore, the TNR and LSF of scout90Y had a stronger agreement with those of Rx90Y than with those of MAA. In the nonsegmental subgroup, MAA had no significant correlation with the TD and NTLD of Rx90Y, whereas scout90Y had a very strong correlation with both of these factors. In the segmental subgroup, both MAA and scout90Y had a strong linear correlation with the TD and NTLD of Rx90Y. CONCLUSIONS: Compared with MAA, scout90Y is a more accurate surrogate for Rx90Y biodistribution for nonsegmental therapies.

A prospective, multicenter, open-label, single-arm clinical trial design to evaluate the safety and efficacy of 90Y resin microspheres for the treatment of unresectable HCC: the DOORwaY90 (Duration Of Objective Response with arterial Ytrrium-90) study.

BACKGROUND: Selective internal radiation therapy (SIRT) with yttrium-90 (90Y) resin microspheres is an established locoregional treatment option for unresectable hepatocellular carcinoma (HCC), which delivers a lethal dose of radiation to hepatic tumors, while sparing surrounding healthy tissue. DOORwaY90 is a prospective, multicenter, open-label, single arm study, designed to evaluate the safety and effectiveness of 90Y resin microspheres as first-line treatment in patients with unresectable/unablatable HCC. It is unique in that it is the first study with resin microspheres to utilize a personalized 90Y dosimetry approach, and independent review for treatment planning and response assessment. METHODS: Eligibility criteria include unresectable/unablatable HCC, Barcelona Clinic Liver Cancer stage A, B1, B2, or C with a maximal single tumor diameter of ≤ 8 cm, and a sum of maximal tumor diameters of ≤ 12 cm, and at least one tumor ≥ 2 cm (long axis) per localized, modified Response Evaluation Criteria in Solid Tumors. Partition model dosimetry is used to determine the optimal dose; the target mean dose to tumor is ≥ 150 Gy. Patients are assessed at baseline and at regular intervals up until 12 months of treatment for response rates, safety, and quality of life (QoL). Post-treatment dosimetry is used to assess dose delivered to tumor and consider if retreatment is necessary. The co-primary endpoints are best objective response rate and duration of response. Secondary endpoints include grade ≥ 3 toxicity, QoL, and incidence of liver resection and transplantation post SIRT. Target recruitment is 100 patients. DISCUSSION: The results of this trial should provide further information on the potential use of SIRT with 90Y resin microspheres as first-line therapy for unresectable HCC. TRIAL REGISTRATION: Clinicaltrials.gov; NCT04736121; date of 1st registration, January 27, 2021, https://clinicaltrials.gov/ct2/show/NCT04736121 .

Factors modulating 99m Tc-MAA planar lung dosimetry for 90 Y radioembolization.

PURPOSE: To investigate the accuracy and biases of predicted lung shunt fraction (LSF) and lung dose (LD) calculations via 99m Tc-macro-aggregated albumin (99m Tc-MAA) planar imaging for treatment planning of 90 Y-microsphere radioembolization. METHODS AND MATERIALS: LSFs in 52 planning and LDs in 44 treatment procedures were retrospectively calculated, in consecutive radioembolization patients over a 2 year interval, using 99m Tc-MAA planar and SPECT/CT imaging. For each procedure, multiple planar LSFs and LDs were calculated using different: (1) contours, (2) views, (3) liver 99m Tc-MAA shine-through compensations, and (4) lung mass estimations. The accuracy of each planar-based LSF and LD methodology was determined by calculating the median (range) absolute difference from SPECT/CT-based LSF and LD values, which have been demonstrated in phantom and patient studies to more accurately and reliably quantify the true LSF and LD values. RESULTS: Standard-of-care LSF using geometric mean of lung and liver contours had median (range) absolute over-estimation of 4.4 percentage points (pp) (0.9 to 11.9 pp) from SPECT/CT LSF. Using anterior views only decreased LSF errors (2.4 pp median, -1.1 to +5.7 pp range). Planar LD over-estimations decreased when using single-view versus geometric-mean LSF (1.3 vs. 2.6 Gy median and 7.2 vs. 18.5 Gy maximum using 1000 g lung mass) but increased when using patient-specific versus standard-man lung mass (2.4 vs. 1.3 Gy median and 11.8 vs. 7.2 Gy maximum using single-view LSF). CONCLUSIONS: Calculating planar LSF from lung and liver contours of a single view and planar LD using that same LSF and 1000 g lung mass was found to improve accuracy and minimize bias in planar lung dosimetry.

International recommendations for personalised selective internal radiation therapy of primary and metastatic liver diseases with yttrium-90 resin microspheres.

PURPOSE: A multidisciplinary expert panel convened to formulate state-of-the-art recommendations for optimisation of selective internal radiation therapy (SIRT) with yttrium-90 (90Y)-resin microspheres. METHODS: A steering committee of 23 international experts representing all participating specialties formulated recommendations for SIRT with 90Y-resin microspheres activity prescription and post-treatment dosimetry, based on literature searches and the responses to a 61-question survey that was completed by 43 leading experts (including the steering committee members). The survey was validated by the steering committee and completed anonymously. In a face-to-face meeting, the results of the survey were presented and discussed. Recommendations were derived and level of agreement defined (strong agreement ≥ 80%, moderate agreement 50%-79%, no agreement ≤ 49%). RESULTS: Forty-seven recommendations were established, including guidance such as a multidisciplinary team should define treatment strategy and therapeutic intent (strong agreement); 3D imaging with CT and an angiography with cone-beam-CT, if available, and 99mTc-MAA SPECT/CT are recommended for extrahepatic/intrahepatic deposition assessment, treatment field definition and calculation of the 90Y-resin microspheres activity needed (moderate/strong agreement). A personalised approach, using dosimetry (partition model and/or voxel-based) is recommended for activity prescription, when either whole liver or selective, non-ablative or ablative SIRT is planned (strong agreement). A mean absorbed dose to non-tumoural liver of 40 Gy or less is considered safe (strong agreement). A minimum mean target-absorbed dose to tumour of 100-120 Gy is recommended for hepatocellular carcinoma, liver metastatic colorectal cancer and cholangiocarcinoma (moderate/strong agreement). Post-SIRT imaging for treatment verification with 90Y-PET/CT is recommended (strong agreement). Post-SIRT dosimetry is also recommended (strong agreement). CONCLUSION: Practitioners are encouraged to work towards adoption of these recommendations.

Lung shunt and lung dose calculation methods for radioembolization treatment planning.

Radioembolization, also known as selective internal radiation therapy (SIRT), is firmly established in the management of patients with unresectable liver cancers. Advances in normal and tumor liver dosimetry and new knowledge about tumor dose response relationships have helped promote the safe use of higher prescribed doses, consequently transitioning radioembolization from palliative to curative therapy. The lungs are considered a critical organ of risk for radioembolization treatment planning. Unfortunately, lung dosimetry has not achieved similar advances in dose calculation methodology as liver dosimetry. Current estimations of lung dose are dependent on a number of parameters associated with data acquisition and processing algorithms, leading to poor accuracy and precision. Therefore, the efficacy of curative radioembolization may be compromised in patients for whom the lung dose derived using currently available methods unnecessarily limits the desired administered activity to the liver. We present a systematic review of the various methods of determining the lung shunt fraction (LSF) and lung mean dose (LD). This review encompasses pretherapy estimations and post-therapy assessments of the LSF and LD using both 2D planar and 3D SPECT/CT based calculations. The advantages and limitations of each of these methods are deliberated with a focus on accuracy and practical considerations. We conclude the review by presenting a lexicon to precisely describe the methodology used for the estimation of LSF and LD; specifically, category, agent, modality, contour and algorithm, in order to aid in their interpretation and standardization in routine clinical practice.

Yttrium-90 Radioembolization in Intrahepatic Cholangiocarcinoma: A Multicenter Retrospective Analysis.

PURPOSE: To report outcomes of yttrium-90 (90Y) radioembolization in patients with unresectable intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: Retrospective review was performed of 115 patients at 6 tertiary care centers; 92 were treated with resin microspheres (80%), 22 were treated with glass microspheres (19%), and 1 was treated with both. Postintervention outcomes were compared between groups with χ2 tests. Survival after diagnosis and after treatment was assessed by Kaplan-Meier method. RESULTS: Grade 3 laboratory toxicity was observed in 4 patients (4%); no difference in toxicity profile between resin and glass microspheres was observed (P = .350). Clinical toxicity per Society of Interventional Radiology criteria was noted in 29 patients (25%). Partial response per Response Evaluation Criteria In Solid Tumors 1.1 was noted in 25% of patients who underwent embolization with glass microspheres and 3% of patients who were treated with resin microspheres (P = .008). Median overall survival (OS) from first diagnosis was 29 months (95% confidence interval [CI], 21-37 mo) for all patients, and 1-, 3-, and 5-year OS rates were 85%, 31%, and 8%, respectively. Median OS after treatment was 11 months (95% CI, 8-13 mo), and 1- and 3-year OS rates were 44% and 4%, respectively. These estimates were not significantly different between resin and glass microspheres (P = .730 and P = .475, respectively). Five patients were able to undergo curative-intent resection after 90Y radioembolization (4%). CONCLUSIONS: This study provides observational data of treatment outcomes after 90Y radioembolization in patients with unresectable ICC.

Clinical and dosimetric considerations for Y90: recommendations from an international multidisciplinary working group.

The TheraSphere Global Dosimetry Steering Committee was formed in 2017 by BTG International to review existing data and address gaps in knowledge related to dosimetry. This committee is comprised of health care providers with diverse areas of expertise and perspectives on radiation dosimetry. The goal of these recommendations is to optimize glass microspheres radiation therapy for hepatocellular carcinoma while accounting for variables including disease presentation, tumour vascularity, liver function, and curative/palliative intent. The recommendations aim to unify glass microsphere users behind standardized dosimetry methodology that is simple, reproducible and supported by clinical data, with the overarching goal of improving clinical outcomes and advancing the knowledge of dosimetry.

Performance Evaluation of Material Decomposition With Rapid-Kilovoltage-Switching Dual-Energy CT and Implications for Assessing Bone Mineral Density.

OBJECTIVE: The purpose of this article is to quantitatively investigate the accuracy and performance of dual-energy CT (DECT) material density images and to calculate the areal bone mineral density (aBMD) for comparison with dual-energy x-ray absorptiometry (DEXA). MATERIALS AND METHODS: A rapid-kilovoltage-switching DECT scanner was used to create material density images of various two-material phantoms of known concentrations under different experimental conditions. They were subsequently also scanned by single-energy CT and DEXA. The total uncertainty and accuracy of the DECT concentration measurements was quantified by the root-mean-square (RMS) error, and linear regression was performed to evaluate measurement changes under varying scanning conditions. Alterations to accuracy with concentric (anthropomorphic) phantom geometry were explored. The sensitivity of DECT and DEXA to changes in material density was evaluated. Correlations between DEXA and DECT-derived aBMD values were assessed. RESULTS: The RMS error of DECT concentration measurements in air ranged from 9% to 244% depending on the materials. Concentration measurements made off-isocenter or with a different DECT protocol were slightly lower (≈ 5%), whereas measurement in scattering conditions resulted in a reduction of 8-27%. In concentric phantoms, higher-attenuating material in the outer chamber increased measured values of the inner material for all methods. DECT was more sensitive than DEXA to changes in BMD at 2 mg/mL K2HPO4. Measurements of aBMD using DECT and DEXA were highly correlated (R(2) = 0.98). CONCLUSION: DECT material density images were linear in response but prone to poor accuracy and biases. DECT-based aBMD could be used to monitor relative change in bone density.

Characterization of the energy response and backscatter contribution for two electronic personal dosimeter models.

We characterized the energy response of personal dose equivalent (Hp(10) in mrem) and the contribution of backscatter to the readings of two electronic personal dosimeter (EPD) models with radionuclides commonly used in a nuclear medicine clinic. The EPD models characterized were the RADOS RAD-60R, and the SAIC PD-10i. The experimental setup and calculation of EPD energy response was based on ANSI/HPS N13.11-2009. Fifteen RAD-60R and 2 PD-10i units were irradiated using (99m)Tc, (131)I, and (18)F radionuclides with emission energies at 140 keV, 364 keV, and 511 keV, respectively. At each energy, the EPDs output in Hp(10) [mrem] were recorded with 15 inch thick PMMA to simulate backscatter form the torso. Simultaneous free-in-air exposure rate measurements were also performed using two Victoreen ionization survey meters to calculate the expected EPD Hp(10) values per ANSI/HPS N13.11-2009. The energy response was calculated by taking the ratio of the EPD Hp(10) readings with the expected Hp(10) readings and a two-tailed z-test was used to determine the significance of the ratio deviating away from unity. The contribution from backscatter was calculated by taking the ratio of the EPD Hp(10) readings with and without backscatter material. A paired, two-tailed t-test was used to determine the significance of change in EPD Hp(10) readings. The RAD-60R mean energy response at 140 keV was 0.85, and agreed to within 5% and 11% at 364 and 511 keV, respectively. The PD-10i mean energy response at 140 keV was 1.20, and agreed to within 5% at 364 and 511 keV, respectively. On average, in the presence of acrylic, RAD-60R values increased by 32%, 12%, and 14%, at 140, 364, and 511 keV, respectively; all increases were statistically significant. The PD-10i increased by 25%, 19%, and 10% at 140 keV, 364 keV, and 511 keV, respectively; however, only the 140 keV measurement was statistically significant. Although both EPD models performed within the manufacturers' specifications of ± 25% in the energy ranges used, they fell outside of our criteria of 10% at lower energies, suggesting the need to calculate energy-dependent correction factors, depending on the intended EPD use.

90Y SIR-Spheres Activity Measurement with New SIROS D-Vial Delivery Kit.

A new 90Y SIR-Spheres delivery kit (SIROS D-vial and shield) has been introduced with a different physical form from the legacy V-Vial kit. Here, we establish the dose calibrator settings and exposure-rate-to-activity conversion factor to assay 90Y SIR-Spheres activity in the new SIROS kit. Methods: Eight D-vials with initial 90Y activities from 1.2 to 6.6 GBq within acrylic shields were assayed with dose calibrators and exposure-rate meters until activities decayed to approximately 0.1 GBq. The dose calibrator settings resulting in the lowest median activity errors and the best-fit slope of exposure rate versus activity were identified. Results: SIROS D-vial 90Y activity can be accurately and reliably estimated directly using setting 51 × 10 on both the CRC-15R and the CRC-55tR dose calibrators (errors within ±0.5%) and indirectly with an exposure-rate reading at 30 cm using conversion factor 0.664 ± 0.003 GBq/(mR/h) (R 2 = 0.985). Conclusion: Dose calibrator settings and exposure-rate-to-activity conversion factor for 90Y activity assays with new SIROS kit should be updated from legacy V-Vial parameters to avoid an approximately 10% underestimation.

Resin-Based 90 Y Tumor Dose as a Predictor of Duration of Response and Survival in Patients With Surgically Unresectable Hepatocellular Carcinoma : A Prospective Single-Arm Study.

BACKGROUND: Personalized dosimetry improves overall survival (OS) in patients with hepatocellular carcinoma (HCC) treated with glass 90 Y radioembolization. This study evaluated personalized tumor dose (TD) as a predictor of OS, progression-free survival (PFS), and local duration of response (DOR) in patients with surgically unresectable HCC treated with resin 90 Y radioembolization. PATIENTS AND METHODS: This prospective, single-center, single-arm clinical trial (NCT04172714) evaluated the efficacy of scout activity of resin 90 Y versus 99m Tc-MAA for treatment planning. A secondary aim of this study was to evaluate personalized dosimetry as a predictor of OS, PFS, and DOR. Partition dosimetry model was utilized for nonsegmental therapies with targeted TD >200 Gy and nontumoral liver dose <70 Gy. Single compartment dose of 200 Gy was used for segmentectomies. OS, PFS, and local DOR from 90 Y was estimated using Kaplan-Meier estimation with log-rank analysis used to determine predictors of prolonged survival. FINDINGS: Thirty patients with treatment-naive HCC and 33 tumors (19 segmental and 14 nonsegmental) were included. Overall, 18 patients underwent segmental Y90-RE and 12 underwent non-segmental/lobar therapies. The mean 90 Y TD was 493 Gy. The median follow-up since enrollment into the study was 37 months. The mean OS was 32.2 months for the entire cohort. A total of 5 patients underwent orthotopic liver transplantation post 90 Y and were excluded from further survival analysis. The mean OS for the remainder of the cohort was 30.1 months (median not reached). The mean TD >250 Gy resulted in prolonged mean OS and PFS. The median local DOR was 32.7 months with mean TD 330 Gy predicting prolonged DOR. INTERPRETATION: For patients with surgically unresectable HCC treated with resin 90 Y, there is mean TD threshold predicting prolonged OS, PFS, and local DOR. Therefore, there should be further emphasis on personalized dosimetry for optimization of patient outcomes.

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.

Monte Carlo-derived 99m Tc uptake quantification with commercial planar MBI: Tumor and breast activity concentrations.

BACKGROUND: Current molecular breast imaging (MBI) images are limited to qualitative evaluation, not absolute measurement, of 99m Tc uptake in benign and malignant breast tissues. PURPOSE: This work assesses the accuracy of previously-published and newly-proposed tumor and normal breast tissue 99m Tc uptake MBI measurements using simulations of a commercial dual-headed planar MBI system under typical clinical and acquisition protocols. METHODS: Quantification techniques were tested in over 4000 simulated acquisitions of spherical and ellipsoid tumors with clinically relevant uptake conditions using a validated Monte Carlo application of the GE Discovery NM750b system. The evaluated techniques consisted of four tumor total activity methodologies (two single-detector-based and two geometric-mean-based), two tumor MBI volume methodologies (diameter-based and ROI-based), and two normal tissue activity concentration methodologies (single-detector-based and geometric-mean-based). The most accurate of these techniques were then used to estimate tumor activity concentrations and tumor to normal tissue relative activity concentrations (RC). RESULTS: Single-detector techniques for tumor total activity quantification achieved mean (standard deviation) relative errors of 0.2% (4.3%) and 1.6% (4.4%) when using the near and far detector images, respectively and were more accurate and precise than the measured 8.1% (5.8%) errors of a previously published geometric-mean technique. Using these activity estimates and the true tumor volumes resulted in tumor activity concentration and RC errors within 10% of simulated values. The precision of tumor activity concentration and RC when using only MBI measurements were largely driven by the errors in estimating tumor MBI volume using planar images (± 30% inter-quartile range). CONCLUSIONS: Planar MBI images were shown to accurately and reliably be used to estimate tumor total activities and normal tissue activity concentrations in this simulation study. However, volumetric tumor uptake measurements (i.e., absolute and relative concentrations) are limited by inaccuracies in MBI volume estimation using two-dimensional images, highlighting the need for either tomographic MBI acquisitions or anatomical volume estimates for accurate three-dimensional tumor uptake estimates.