Search

[Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

To develop a multidisciplinary consensus for high quality multidisciplinary implementation of brachytherapy using Yttrium-90 (90Y) microspheres transarterial radioembolization (90Y TARE) for primary and metastatic cancers in the liver. Members of the American Brachytherapy Society (ABS) and colleagues with multidisciplinary expertise in liver tumor therapy formulated guidelines for 90Y TARE for unresectable primary liver malignancies and unresectable metastatic cancer to the liver. The consensus is provided on the most recent literature and clinical experience. The ABS strongly recommends the use of 90Y microsphere brachytherapy for the definitive/palliative treatment of unresectable liver cancer when recommended by the multidisciplinary team. A quality management program must be implemented at the start of 90Y TARE program development and follow-up data should be tracked for efficacy and toxicity. Patient-specific dosimetry optimized for treatment intent is recommended when conducting 90Y TARE. Implementation in patients on systemic therapy should account for factors that may enhance treatment related toxicity without delaying treatment inappropriately. Further management and salvage therapy options including retreatment with 90Y TARE should be carefully considered. ABS consensus for implementing a safe 90Y TARE program for liver cancer in the multidisciplinary setting is presented. It builds on previous guidelines to include recommendations for appropriate implementation based on current literature and practices in experienced centers. Practitioners and cooperative groups are encouraged to use this document as a guide to formulate their clinical practices and to adopt the most recent dose reporting policies that are critical for a unified outcome analysis of future effectiveness studies. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [Display omitted] [ABSTRACT FROM AUTHOR]

Purpose: To investigate hepatocellular carcinoma tumor dose-response characteristics based on voxel-level absorbed doses (D) and biological effective doses (BED) using quantitative 90Y-single-photon emission computed tomography (SPECT)/computed tomography (CT) after 90Y-radioembilization with glass microspheres. We also investigated the relationship between normal liver D and toxicities.Methods and Materials: 90Y-radioembolization activity distributions for 34 patients were based on quantitative 90Y-bremsstrahlung SPECT/CT. D maps were generated using a local-deposition algorithm. Contrast-enhanced CT or magnetic resonance imaging scans of the liver were registered to 90Y-SPECT/CT, and all tumors larger than 2.5 cm diameter (53 tumors) were segmented. Tumor mean D and BED (Dmean and BEDmean) and dose volume coverage from 0% to 100% in 10% steps (D0-D100 and BED0-BED100) were extracted. Tumor response was evaluated on follow-up using World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), and modified RECIST (mRECIST) criteria. Differences in dose metrics for responders and nonresponders were assessed using the Mann-Whitney U test. A univariate logistic regression model was used to determine tumor dose metrics that correlated with tumor response. Correlations among tumor size, tumor Dmean, and tumor dose heterogeneity (defined as the coefficient of variation) were assessed.Results: The objective response rates were 14 of 53, 15 of 53, and 30 of 53 for WHO, RECIST, and mRECIST criteria, respectively. WHO and RECIST response statuses did not correlate with D or BED. For mRECIST responders and nonresponders, D and BED were significantly different for Dmean, D20 to D80, BEDmean, and BED0 to BED80. Threshold doses (and the 95% confidence interval) for 50% probability of mRECIST response (D50%) were 160 Gy (123-196 Gy) for Dmean and 214 Gy (146-280 Gy) for BEDmean. Tumor dose heterogeneity significantly correlated with tumor volume. No statistically significant association between Dmean to normal liver and complications related to bilirubin, albumin, or ascites was observed.Conclusions: Hepatocellular carcinoma tumor dose-response curves after 90Y-radioembolization with glass microspheres showed Dmean of 160 Gy and BEDmean of 214 Gy for D50% with a positive predictive value of ∼70% and a negative predictive value of ∼62%. No complications were observed in our patient cohort for normal liver Dmean less than 44 Gy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To quantify differences that exist between dosimetry models used for 90Y selective internal radiation therapy (SIRT).Methods and Materials: Retrospectively, 37 tumors were delineated on 19 post-therapy quantitative 90Y single photon emission computed tomography/computed tomography scans. Using matched volumes of interest (VOIs), absorbed doses were reported using 3 dosimetry models: glass microsphere package insert standard model (SM), partition model (PM), and Monte Carlo (MC). Univariate linear regressions were performed to predict mean MC from SM and PM. Analysis was performed for 2 subsets: cases with a single tumor delineated (best case for PM), and cases with multiple tumors delineated (typical clinical scenario). Variability in PM from the ad hoc placement of a single spherical VOI to estimate the entire normal liver activity concentration for tumor (T) to nontumoral liver (NL) ratios (TNR) was investigated. We interpreted the slope of the resulting regression as bias and the 95% prediction interval (95%PI) as uncertainty. MCNLsingle represents MC absorbed doses to the NL for the single tumor patient subset; other combinations of calculations follow a similar naming convention.Results: SM was unable to predict MCTsingle or MCTmultiple (p>.12, 95%PI >±177 Gy). However, SMsingle was able to predict (p<.012) MCNLsingle, albeit with large uncertainties; SMsingle and SMmultiple yielded biases of 0.62 and 0.71, and 95%PI of ±40 and ± 32 Gy, respectively. PMTsingle and PMTmultiple predicted (p<2E-6) MCTsingle and MCTmultiple with biases of 0.52 and 0.54, and 95%PI of ±38 and ± 111 Gy, respectively. The TNR variability in PMTsingle increased the 95%PI for predicting MCTsingle (bias = 0.46 and 95%PI = ±103 Gy). The TNR variability in PMTmultiple modified the bias when predicting MCTmultiple (bias = 0.32 and 95%PI = ±110 Gy).Conclusions: The SM is unable to predict mean MC tumor absorbed dose. The PM is statistically correlated with mean MC, but the resulting uncertainties in predicted MC are large. Large differences observed between dosimetry models for 90Y SIRT warrant caution when interpreting published SIRT absorbed doses. To reduce uncertainty, we suggest the entire NL VOI be used for TNR estimates when using PM. [ABSTRACT FROM AUTHOR]