Compliance with radiobiologic principles of radionuclide internal dosimetry is fundamental to the success of 90 Y radioembolization. The artery-specific SPECT/CT partition model is an image-guided personalized predictive dosimetric technique developed by our institution, integrating catheter-directed CT hepatic angiography (CTHA), 99m Tc-macroaggregated albumin SPECT/CT, and partition modeling for unified dosimetry. Catheter-directed CTHA accurately delineates planning target volumes. SPECT/CT tomographically evaluates 99m Tc-macroaggregated albumin hepatic biodistribution. The partition model is validated for 90 Y resin microspheres based on MIRD macrodosimetry. Methods: This was a retrospective analysis of ourearly clinical outcomes for inoperable hepatocellular carcinoma. Mapping hepatic angiography was performed according to standard technique with the addition of catheter-directed CTHA. 99m Tc-MAA planar scintigraphy was used for liver-tolung shunt estimation, and SPECT/CT was used for liver dosimetry. Artery-specific SPECT/CT partition modeling was planned by experienced nuclear medicine physicians. Results: From January to May 2011, 20 arterial territories were treated in 10 hepatocellular carcinoma patients. Median follow-up was 21 wk (95% confidence interval [CI], 12-50 wk). When analyzed strictly as brachytherapy, 90 Y radioembolization planned by predictive dosimetry achieved index tumor regression in 8 of 8 patients, with a median size decrease of 58% (95% CI, 40%-72%). Tumor thrombosis regressed or remained stable in 3 of 4 patients with baseline involvement. The best a-fetoprotein reduction ranged from 32% to 95%. Clinical success was achieved in 7 of 8 patients, including 2 by sublesional dosimetry, in 1 of whom there was radioembolization lobectomy intent. Median predicted mean radiation absorbed doses were 106 Gy (95% CI, 105-146 Gy) to tumor, 27 Gy (95% CI, 22-33 Gy) to nontumorous liver, and 2 Gy (95% CI, 1.3-7.3 Gy) to lungs. Across all patients, tumor, nontumorous liver, and lungs received predicted $91 Gy, #51 Gy, and #16 Gy, respectively, via at least 1 target arterial territory. No patients developed significant toxicities within 3 mo after radioembolization. The median time to best imaging response was 76 d (95% CI, 55-114 d). Median time to progression and overall survival were not reached. SPECT/CT-derived mean tumor-to-normal liver ratios varied widely across all planning target volumes (median, 5.4; 95% CI, 4.1-6.7), even within the same patient. Conclusion: Imageguided personalized predictive dosimetry by artery-specific SPECT/CT partition modeling achieves high clinical success rates for safe and effective 90 Y radioembolization. Asaformofart erial territory-specific point-source brachytherapy, 90 Y radioembolization is always effective when delivered at the right location, in the right dose, and with the right intent. 90 Y radioembolization failure is invariably due to one or a combination of these 3 factors being incorrectly addressed. Responsibility for this triad of factors is ...

ObjectivesYttrium-90 (Y90)-radioembolisation (RE) significantly regresses locally advanced hepatocellular carcinoma and delays disease progression. The current study is designed to deeply interrogate the immunological impact of Y90-RE, which elicits a sustained therapeutic response.DesignTime-of-flight mass cytometry and next-generation sequencing (NGS) were used to analyse the immune landscapes of tumour-infiltrating leucocytes (TILs), tumour tissues and peripheral blood mononuclear cells (PBMCs) at different time points before and after Y90-RE.ResultsTILs isolated after Y90-RE exhibited signs of local immune activation: higher expression of granzyme B (GB) and infiltration of CD8+ T cells, CD56+ NK cells and CD8+ CD56+ NKT cells. NGS confirmed the upregulation of genes involved in innate and adaptive immune activation in Y90-RE-treated tumours. Chemotactic pathways involving CCL5 and CXCL16 correlated with the recruitment of activated GB+CD8+ T cells to the Y90-RE-treated tumours. When comparing PBMCs before and after Y90-RE, we observed an increase in tumour necrosis factor-α on both the CD8+ and CD4+ T cells as well as an increase in percentage of antigen-presenting cells after Y90-RE, implying a systemic immune activation. Interestingly, a high percentage of PD-1+/Tim-3+CD8+ T cells coexpressing the homing receptors CCR5 and CXCR6 denoted Y90-RE responders. A prediction model was also built to identify sustained responders to Y90-RE based on the immune profiles from pretreatment PBMCs.ConclusionHigh-dimensional analysis of tumour and systemic immune landscapes identified local and systemic immune activation that corresponded to the sustained response to Y90-RE. Potential biomarkers associated with a positive clinical response were identified and a prediction model was built to identify sustained responders prior to treatment.

Purpose To compare lesion primary patency and restenosis rates between drug-eluting balloon (DEB) percutaneous transluminal angioplasty (PTA) and conventional balloon PTA (cPTA) in the treatment of arteriovenous fistula (AVF) and arteriovenous graft (AVG) stenosis. Materials and Methods In this prospective study, 119 participants (mean age, 59.2 years; 79 men, 40 women) with failing AVFs (n = 98) or AVGs (n = 21) were randomly assigned to undergo either DEB PTA (n = 59) or cPTA (n = 60) from January 2012 to May 2013. Primary end points were lesion primary patency and restenosis rates at 6 months; secondary outcomes were anatomic and clinical success after PTA, circuit primary patency at 6 months and 1 year, and lesion primary patency at 1 year. Statistical analysis was performed by using the Kaplan-Meier product limit estimator, and hazard ratio was calculated by using Cox proportional hazards regression. Complication rates were assessed in both groups. Results Estimated lesion primary patency in the DEB PTA and cPTA arms was 0.81 and 0.61, respectively, at 6 months (P = .03) and 0.51 and 0.34, respectively, at 1 year (P = .04). Estimated circuit primary patency in the DEB PTA and cPTA arms was 0.76 and 0.56, respectively, at 6 months (P = .048) and 0.45 and 0.32, respectively, at 1 year (P = .16). Restenosis rate was 34.0% (16 of 47) for DEB PTA and 62.9% (22 of 35) for cPTA at 6 months (P = .01). No major complications were noted. Conclusion Drug-eluting balloon angioplasty was effective in prolonging lesion primary patency of dialysis access stenoses at 6 months and 1 year. © RSNA, 2018.