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Purpose To evaluate the safety and feasibility of same-day treatment, including the simulation procedure for assessment of intrahepatic and extrahepatic distribution of the microspheres, with holmium-166 (166Ho)-radioembolization. Materials and Methods This was a secondary analysis of patients included in the 4 prospective studies (HEPAR I, HEPAR II, HEPAR PLuS, and SIM) on 166Ho-radioembolization. The technical success rate of the same-day treatment protocol, defined as the number of patients who completed the same-day treatment, was measured. Total in-room time, duration of the scout procedure, time to imaging, and duration of the treatment procedure were recorded. Reasons for discontinuation or adjustment of treatment were identified. Adverse events that occurred during the treatment day were recorded. Results One hundred five of 120 scheduled patients completed the same-day treatment with 166Ho-radioembolization (success rate, 88%). After the simulation procedure, treatment was cancelled in 15 patients because of extrahepatic deposition (n = 8), suboptimal tumor targeting (n = 1), unanticipated vascular anatomy (n = 5), and dissection (n = 1). In another 14 patients, the treatment plan was adjusted. The median total procedure time (ie, simulation, imaging, and treatment) was 6:39 hours:minutes (range, 3:58–9:17 hours:minutes). Back pain was a major same-day treatment-related complaint (n = 28). Conclusion 166Ho-radioembolization as a same-day treatment procedure is feasible in most selected patients, although treatment was adjusted in 12% of patients and cancelled in 12% of patients. This approach might be beneficial for a select patient population, such as patients needing a radiation segmentectomy.

Background and aim Malignant biliary obstruction is an ominous complication of metastatic colorectal cancer (mCRC) that is challenging to solve. Biliary drainage can be performed to relieve symptoms of jaundice, treat cholangitis, or enable palliative systemic therapy. The aim of this study is to evaluate clinical outcomes of biliary drainage of malignant biliary obstruction in mCRC patients. Methods Consecutive patients with malignant biliary obstruction due to mCRC who underwent endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography were included. Patient, disease, and procedural characteristics and outcomes were retrospectively collected from electronic medical records. Radiological data were prospectively reassessed. Main outcome was functional success, i.e. achievement of the intended goal of biliary drainage. Prognostic factors for functional success and survival were assessed. Results Thirty-seven patients were included. Functional success was achieved in 18 (50%) patients. Seventeen (46%) patients experienced adverse events (suspected to be) related to the procedure. Median overall survival after biliary drainage was 61 days (IQR 31–113). No prognostic factors of functional success were identified. Performance status, presence of the primary tumor, ascites, ≥ 5 intrahepatic metastases, estimated hepatic invasion of > 50% and above-median levels of bilirubin and lactate dehydrogenase were significantly associated with poorer survival. Improved survival was seen in patients with technical, functional, or biochemical success, and with subsequent oncologic treatment. Conclusions Functional successful biliary drainage was achieved in half of the patients. Adverse events also occurred in nearly half of the patients. We observed a significantly longer survival in whom biliary drainage allowed palliative oncologic therapy.

166Ho-microspheres have recently been approved for clinical use for hepatic radioembolization in the European Union. The aim of this study was to investigate the absorbed dose-response relationship and its association with overall survival for 166Ho radioembolization in patients with liver metastases. Methods: Patients treated in the HEPAR I and II studies who underwent an 18F-FDG PET/CT scan at baseline, a posttreatment 166Ho SPECT/CT scan, and another 18F-FDG PET/CT scan at the 3-mo follow-up were included for analysis. The posttreatment 166Ho-microsphere activity distributions were estimated with quantitative SPECT/CT reconstructions using a quantitative Monte Carlo-based method. The response of each tumor was based on the change in total lesion glycolysis (TLG) between baseline and follow-up and was placed into 1 of 4 categories, according to the PERCIST criteria, ranging from complete response to progressive disease. Patient-level response was grouped according to the average change in TLG per patient. The absorbed dose-response relationship was assessed using a linear mixed model to account for correlation of tumors within patients. Median overall survival was compared between patients with and without a metabolic liver response, using a log-rank test. Results: Thirty-six patients with a total of 98 tumors were included. The relation between tumor-absorbed dose and both tumor-level and patient-level response was explored. At a tumor level, a significant difference in geometric mean absorbed dose was found between complete response (232 Gy; 95% confidence interval [CI], 178-303 Gy; n = 32) and stable disease (147 Gy; 95% CI, 113-191 Gy; n = 28) ( P = 0.01) and between complete response and progressive disease (117 Gy; 95% CI, 87-159 Gy; n = 21) ( P = 0.0008). This constitutes a robust absorbed dose-response relationship. At a patient level, a significant difference was found between patients with complete or partial response (210 Gy; 95% CI, 161-274 Gy; n = 13) and patients with progressive disease (116 Gy; 95% CI, 81-165 Gy; n = 9) ( P = 0.01). Patients were subsequently grouped according to their average change in TLG. Patients with an objective response (complete or partial) exhibited a significantly higher overall survival than nonresponding patients (stable or progressive disease) (median, 19 mo vs. 7.5 mo; log-rank, P = 0.01). Conclusion: These results confirm a significant absorbed dose-response relationship in 166Ho radioembolization. Treatment response is associated with a higher overall survival.

Purpose: As an alternative to technetium-99m-macroaggregated albumin ( 99mTc-MAA), a scout dose of holmium-166 ( 166Ho) microspheres can be used prior to 166Ho-radioembolization. The use of identical particles for pre-treatment and treatment procedures may improve the predictive value of pre-treatment analysis of distribution. The aim of this study was to analyze the agreement between 166Ho-scout and 166Ho-therapeutic dose in comparison with the agreement between 99mTc-MAA and 166Ho-therapeutic dose. Methods: Two separate scout dose procedures were performed ( 99mTc-MAA and 166Ho-scout) before treatment in 53 patients. First, qualitative assessment was performed by two blinded nuclear medicine physicians who visually rated the agreement between the 99mTc-MAA, 166Ho-scout, and 166Ho-therapeutic dose SPECT-scans (i.e., all performed in the same patient) on a 5-point scale. Second, agreement was measured quantitatively by delineating lesions and normal liver on FDG-PET/CT. These volumes of interest (VOIs) were co-registered to the SPECT/CT images. The predicted absorbed doses (based on 99mTc-MAA and 166Ho-scout) were compared with the actual absorbed dose on post-treatment SPECT. Results: A total of 23 procedures (71 lesions, 22 patients) were included for analysis. In the qualitative analysis, 166Ho-scout was superior with a median score of 4 vs. 2.5 for 99mTc-MAA (p < 0.001). The quantitative analysis showed significantly narrower 95%-limits of agreement for 166Ho-scout in comparison with 99mTc-MAA when evaluating lesion absorbed dose (− 90.3 and 105.3 Gy vs. − 164.1 and 197.0 Gy, respectively). Evaluation of normal liver absorbed dose did not show difference in agreement between both scout doses and 166Ho-therapeutic dose (− 2.9 and 5.5 Gy vs − 3.6 and 4.1 Gy for 99mTc-MAA and 166Ho-scout, respectively). Conclusions: In this study, 166Ho-scout was shown to have a superior predictive value for intrahepatic distribution in comparison with 99mTc-MAA.

Holmium-166 radioembolization is a palliative treatment option for patients with unresectable hepatic malignancies. Its influence on quality of life has not been evaluated yet. Since quality of life is very important in the final stages of disease, the aim of this study was to evaluate the effect of holmium-166 radioembolization on quality of life. Patients with hepatic malignancies were treated with holmium-166 radioembolization in the HEPAR I and II studies. The European Organization for Research and Treatment of Cancer QLQ-C30 and LMC21 questionnaires were used to evaluate quality of life at baseline, 1 week, 6 weeks and at 6, 9 and 12 months after treatment. The course of the global health status and symptom and functioning scales were analyzed using a linear mixed model. Quality of life was studied in a total of 53 patients with a compliance of 94%. Role functioning was the most affected functioning scale. Fatigue and pain were the most affected symptom scales. Changes in almost all categories were most notable at 1 week after treatment. A higher WHO performance score at baseline decreased global health status, physical functioning, role functioning and social functioning and it increased symptoms of fatigue, dyspnea and diarrhea. Quality of life in salvage patients with liver metastases treated with holmium-166 radioembolization was not significantly affected over time, although a striking decline was seen during the first week post-treatment. A WHO performance score > 0 at baseline significantly influenced quality of life. Electronic supplementary material The online version of this article (10.1007/s10585-019-10006-1) contains supplementary material, which is available to authorized users.

Purpose As an alternative to technetium-99m-macroaggregated albumin (99mTc-MAA), a scout dose of holmium-166 (166Ho) microspheres can be used prior to 166Ho-radioembolization. The use of identical particles for pre-treatment and treatment procedures may improve the predictive value of pre-treatment analysis of distribution. The aim of this study was to analyze the agreement between 166Ho-scout and 166Ho-therapeutic dose in comparison with the agreement between 99mTc-MAA and 166Ho-therapeutic dose. Methods Two separate scout dose procedures were performed (99mTc-MAA and 166Ho-scout) before treatment in 53 patients. First, qualitative assessment was performed by two blinded nuclear medicine physicians who visually rated the agreement between the 99mTc-MAA, 166Ho-scout, and 166Ho-therapeutic dose SPECT-scans (i.e., all performed in the same patient) on a 5-point scale. Second, agreement was measured quantitatively by delineating lesions and normal liver on FDG-PET/CT. These volumes of interest (VOIs) were co-registered to the SPECT/CT images. The predicted absorbed doses (based on 99mTc-MAA and 166Ho-scout) were compared with the actual absorbed dose on post-treatment SPECT. Results A total of 23 procedures (71 lesions, 22 patients) were included for analysis. In the qualitative analysis, 166Ho-scout was superior with a median score of 4 vs. 2.5 for 99mTc-MAA (p

Background Dual-energy CT iodine maps are used to detect pulmonary embolism (PE) with CT angiography but require dedicated hardware. Subtraction CT, a software-only solution, results in iodine maps with high contrast-to-noise ratios. Purpose To compare the use of subtraction CT versus dual-energy CT iodine maps to CT angiography for PE detection. Materials and Methods In this prospective study ( https://clinicaltrials.gov , NCT02890706), 274 participants suspected of having PE underwent precontrast CT followed by contrast material-enhanced dual-energy CT angiography between July 2016 and April 2017. Iodine maps from dual-energy CT were derived. Subtraction maps (contrast-enhanced CT minus precontrast CT) were calculated after motion correction. Truth was established by expert consensus. A total of 75 randomly selected participants with and without PE (1:1 ratio) were evaluated by three radiologists and six radiology residents (blinded to final diagnosis) for the presence of PE using three types of CT: CT angiography alone, dual-energy CT, and subtraction CT. The partial area under the receiver operating characteristic curve (AUC) for the clinically relevant specificity region (maximum partial AUC, 0.11) was compared by using multireader multicase variance. A P value less than or equal to .025 was considered indicative of a significant difference due to multiple comparisons. Results There were 35 men and 40 women in the reader study (mean age, 63 years ± 12 [standard deviation]). The pooled sensitivities were not different (P ≥ .31 among techniques) (95% confidence intervals [CIs]: 67%, 89% for CT angiography; 72%, 91% for dual-energy CT; 70%, 91% for subtraction CT). However, pooled specificity was higher for subtraction CT (95% CI: 100%, 100%) than for CT angiography (95% CI: 89%, 97%) or dual-energy CT (95% CI: 89%, 98%) (P < .001). Partial AUCs for the average observer improved equally when adding iodine maps (subtraction CT [0.093] vs CT angiography [0.088], P = .03; dual-energy CT [0.094] vs CT angiography, P = .01; dual-energy CT vs subtraction CT, P = .68). Average reading times were equivalent (range, 97-101 seconds; P ≥ .41) among techniques. Conclusion Subtraction CT iodine maps had greater specificity than CT angiography alone in pulmonary embolism detection. Subtraction CT had comparable diagnostic performance to that of dual-energy CT, without the need for dedicated hardware. © RSNA, 2019 Online supplemental material is available for this article.

PURPOSE: To study the effectiveness of prophylactic embolization of hepaticoenteric arteries to prevent gastrointestinal complications during radioembolization. METHODS: A PubMed, Embase and Cochrane literature search was performed. We included studies assessing both a group of patients with and without embolization. RESULTS: Our search revealed 1401 articles of which title and abstract were screened. Finally, eight studies were included investigating 1237 patients. Of these patients, 456 received embolization of one or more arteries. No difference was seen in the incidence of gastrointestinal complications in patients with prophylactic embolization of the gastroduodenal artery (GDA), right gastric artery (RGA), cystic artery (CA) or hepatic falciform artery (HFA) compared to patients without embolization. Few complications were reported when microspheres were injected distal to the origin of these arteries or when reversed flow of the GDA was present. A high risk of confounding by indication was present because of the non-randomized nature of the included studies. CONCLUSION: It is advisable to restrict embolization to those hepaticoenteric arteries that originate distally or close to the injection site of microspheres. There is no conclusive evidence that embolization of hepaticoenteric arteries influences the risk of complications.

Radioembolization is an established treatment modality that has been subjected to many improvements over the last decade. Developments are occurring at a high pace, affecting patient selection and treatment. The aim of this review is therefore to provide an overview of current practice, with a focus on recent developments in the field of radioembolization. Several practical issues and recommendations in the application of radioembolization will be discussed, ranging from patient selection to treatment response and future applications.

Rationale: Radioembolization of liver malignancies with holmium-166 (166Ho) microspheres has been shown safe in a phase 1 dose-escalation study. The purpose of this study was to investigate the efficacy of 166Ho radioembolization. Methods: In this prospective single-arm study, 56 patients were enrolled, all with liver metastases refractory to systemic therapy and ineligible for surgical resection. Radioembolization was performed with a projected average absorbed dose of 60 Gy to the liver (equal to 3.8 GBq/kg liver tissue). The primary outcome was tumor response of two target lesions on triphasic liver CT scans, 3 months after therapy using RECIST 1.1 criteria. Secondary outcomes included overall tumor response, response on (18)F-FDG-PET/CT, time to imaging progression, overall survival, toxicity, quality of life, and quantification of the microspheres on SPECT and MRI. Results: Between May 2012 and March 2015, 38 eligible patients were treated, one of whom was not evaluable. In 27/37 (73%) patients, the target lesions showed complete response, partial response or stable disease (disease control) at three months (95% confidence interval [CI], 57 to 85%). Disease control in the whole liver was achieved in 18/37 (49%) of patients (95% CI, 33 to 64%). The median overall survival was 14.5 months (95% CI, 8.6 to 22.8 months). For colorectal cancer patients (n = 23), the median overall survival was 13.4 months (95% CI, 8.2 - 15.7 months). Grade 3 or 4 toxic events after treatment (according to CTCAE v4.03 criteria) included abdominal pain (in 18% of patients), nausea (8%), ascites (3%), fatigue (3%), gastric stenosis (3%), hepatic failure (3%), liver abscesses (3%), paroxysmal atrial tachycardia (3%), thoracic pain (3%), upper gastrointestinal hemorrhage (3%), and vomiting (3%). On SPECT/CT, 166Ho could be quantified with high accuracy and precision, with a mean overestimation of 9.3±7.1% in the liver. Conclusion: Radioembolization with 166Ho microspheres induced a tumor response with an acceptable toxicity profile in salvage patients with liver metastases.

Radioembolization of liver malignancies with

Radiation pneumonitis is a rare but serious complication of radioembolic therapy of liver tumours. Estimation of the mean absorbed dose to the lungs based on pretreatment diagnostic 99mTc-macroaggregated albumin (99mTc-MAA) imaging should prevent this, with administered activities adjusted accordingly. The accuracy of 99mTc-MAA-based lung absorbed dose estimates was evaluated and compared to absorbed dose estimates based on pretreatment diagnostic 166Ho-microsphere imaging and to the actual lung absorbed doses after 166Ho radioembolization. This prospective clinical study included 14 patients with chemorefractory, unresectable liver metastases treated with 166Ho radioembolization. 99mTc-MAA-based and 166Ho-microsphere-based estimation of lung absorbed doses was performed on pretreatment diagnostic planar scintigraphic and SPECT/CT images. The clinical analysis was preceded by an anthropomorphic torso phantom study with simulated lung shunt fractions of 0 to 30 % to determine the accuracy of the image-based lung absorbed dose estimates after 166Ho radioembolization. In the phantom study, 166Ho SPECT/CT-based lung absorbed dose estimates were more accurate (absolute error range 0.1 to −4.4 Gy) than 166Ho planar scintigraphy-based lung absorbed dose estimates (absolute error range 9.5 to 12.1 Gy). Clinically, the actual median lung absorbed dose was 0.02 Gy (range 0.0 to 0.7 Gy) based on posttreatment 166Ho-microsphere SPECT/CT imaging. Lung absorbed doses estimated on the basis of pretreatment diagnostic 166Ho-microsphere SPECT/CT imaging (median 0.02 Gy, range 0.0 to 0.4 Gy) were significantly better predictors of the actual lung absorbed doses than doses estimated on the basis of 166Ho-microsphere planar scintigraphy (median 10.4 Gy, range 4.0 to 17.3 Gy; p

PURPOSE: In intra-arterial hepatic radioembolization using Holmium-166 (166 Ho)-microspheres, an predicted lung absorbed dose of more than 30 Gy is a contra-indication for therapy. Therefore, scout imaging by means of quantitative SPECT of the lungs after a low dose pretreatment session is essential. Earlier we showed the superiority of Monte Carlo-based iterative SPECT reconstructions over conventional reconstructions due to its quantitative nature, required for dosimetry, at the cost of substantial computation times. In clinical routine, however, the limited available time between scout imaging and therapy constrains its application. To reduce computation times, we investigated the minimum number of iterations required to guarantee a clinical acceptable accuracy in lung dose estimation using patient and phantom data. METHODS: 166 Ho scout SPECT data (range: 222-283 MBq) were used from 10 patients. SPECT images were Monte Carlo-based OSEM reconstructed (effective iterations: 240). Additionally, the 4D XCAT anthropomorphic phantom was used to mimic studies with an injected scout activity of 250 MBq and with varying lung absorbed doses ranging from 0.9 to 225 Gy for a therapeutic dosage of 15 GBq. These studies were reconstructed in the same way as the patient data, and were also reconstructed using a clinically available, standard OSEM algorithm for comparison. Lung absorbed dose was determined using VOI analysis as a function of iterations. RESULTS: The estimated lung absorbed dose in nine patients ranged upon MC-based OSEM convergence from 0 to 0.26 Gy for a therapeutic dosage. One patient had an estimated lung absorbed dose in case treatment was proceeded of 20.3 Gy upon convergence or 18.4 Gy after 40 iterations (-9%). The phantom data showed that the lung absorbed dose upon OSEM convergence was underestimated by 15% as compared to the actual simulated lung dose, and the dose after 40 iterations was underestimated by 9% as compared to the dose upon convergence. Both underestimations were irrespective of the magnitude of the lung absorbed dose (0.9 to 225 Gy) and thus can be easily corrected for. The quantitative accuracy of the MC-based OSEM reconstructions (40 iterations, before convergence) outperformed the clinical OSEM reconstruction while estimating the lung dose. CONCLUSIONS: The number of effective iterations necessary for quantitative estimation of the lung dose using MC-based OSEM can be reduced from 240 to 40. The resulting sixfold reduction in calculation time enables processing of the scout images before therapy administration. This article is protected by copyright. All rights reserved.

Background An anti-reflux catheter (ARC) may increase the tumor absorbed dose during radioembolization (RE) by elimination of particle reflux and its effects on hemodynamics. Since the catheter is fixed in a centro-luminal position, it may also increase the predictive accuracy of a scout dose administration before treatment. The purpose of the SIM trial is to compare the effects of ARC use during RE with holmium-166 (166Ho) microspheres in patients with colorectal liver metastases (CRLM), with the use of a standard end-hole microcatheter. Methods/Design A within-patient randomized controlled trial (RCT) will be conducted in 25 patients with unresectable chemorefractory liver-dominant CRLM. Study participants will undergo a 166Ho scout dose procedure in the morning and a therapeutic procedure in the afternoon. The ARC will be randomly allocated to the left/right hepatic artery, and a standard microcatheter will be used in the contralateral artery. SPECT/CT imaging will be performed for quantitative analyses of the microsphere distribution directly after the scout and treatment procedure. Baseline and follow-up investigations include 18F-FDG-PET + liver CT, clinical and laboratory examinations. The primary endpoint is the comparison of tumor to non-tumor (T/N) activity ratio in both groups. Secondary endpoints include comparisons of mean absorbed dose in tumors and healthy liver tissue, infusion efficiency, the predictive value of 166Ho scout dose for tumor response. In the entire cohort, a dose-response relationship, clinical toxicity, and overall survival will be assessed. The sample was determined for the expectation that the ARC will increase the T/N ratio by 25 % (mean T/N ratio 2.0 vs. 1.6). Discussion The SIM trial is a within-patient RCT that will assess whether 166Ho RE treatment can be optimized by using an ARC. Trial registration The SIM trial is registered at clinicaltrials.gov (NCT02208804). Registered on 31 July 2014. Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1643-3) contains supplementary material, which is available to authorized users.

Purpose: To optimize a C-arm computed tomography (CT) protocol for radioembolization (RE), specifically for extrahepatic shunting and parenchymal enhancement. Materials and Methods: A prospective development study was performed per IDEAL recommendations. A literature-based protocol was applied in patients with unresectable and chemorefractory liver malignancies undergoing an angiography before radioembolization. Contrast and scan settings were adjusted stepwise and repeatedly reviewed in a consensus meeting. Afterwards, two independent raters analyzed all scans. A third rater evaluated the SPECT/CT scans as a reference standard for extrahepatic shunting and lack of target segment perfusion. Results: Fifty scans were obtained in 29 procedures. The first protocol, using a 6 s delay and 10 s scan, showed insufficient parenchymal enhancement. In the second protocol, the delay was determined by timing parenchymal enhancement on DSA power injection (median 8 s, range 4–10 s): enhancement improved, but breathing artifacts increased (from 0 to 27 %). Since the third protocol with a 5 s scan decremented subjective image quality, the second protocol was deemed optimal. Median CNR (range) was 1.7 (0.6–3.2), 2.2 (−1.4–4.0), and 2.1 (−0.3–3.0) for protocol 1, 2, and 3 (p = 0.80). Delineation of perfused segments was possible in 57, 73, and 44 % of scans (p = 0.13). In all C-arm CTs combined, the negative predictive value was 95 % for extrahepatic shunting and 83 % for lack of target segment perfusion. Conclusion: An optimized C-arm CT protocol was developed that can be used to detect extrahepatic shunts and non-perfusion of target segments during RE.

In patients undergoing hepatic radioembolization for metastatic colorectal adenocarcinoma, increased lung shunt fraction is predictive of significantly decreased survival but demonstrates only a weak correlation with serum carcinoembryonic antigen levels and tumor-to-liver volume ratio and no correlation to the presence or absence of extrahepatic metastatic disease.

Radioembolisation is generally preceded by a scout dose of technetium-99m-macroaggregated albumin to estimate extrahepatic shunting of activity. Holmium-166 microspheres can be used as a scout dose (±250 MBq) and as a therapeutic dose. The general toxicity of a holmium-166 scout dose (166Ho-SD) and safety concerns of an accidental extrahepatic deposition of 166Ho-SD were investigated. All patients who received a 166Ho-SD in our institute were reviewed for general toxicity and extrahepatic depositions. The absorbed dose in extrahepatic tissue was calculated on SPECT/CT and correlated to clinical toxicities. In total, 82 patients were included. No relevant clinical toxicity occurred. Six patients had an extrahepatic deposition of 166Ho-SD (median administered activity 270 MBq). The extrahepatic depositions (median activity 3.7 MBq) were located in the duodenum (3x), gastric fundus, falciform ligament and the lesser curvature of the stomach, and were deposited in a median volume of 15.3 ml, which resulted in an estimated median absorbed dose of 3.6 Gy (range 0.3–13.8 Gy). No adverse events related to the extrahepatic deposition of the 166Ho-SD occurred after a median follow-up of 4 months (range 1–12 months). These results support the safety of 250 MBq 166Ho-SD in a clinical setting. • A holmium-166 scout dose is safe in a clinical setting. • Holmium-166 scout dose is a safe alternative for 99m Tc-MAA for radioembolisation work-up. • Holmium-166 scout dose potentially has several benefits over 99m Tc-MAA for radioembolisation work-up.

UNLABELLED: Before (166)Ho radioembolization, a small batch of the same type of microspheres is administered as a scout dose instead of the conventional (99m)Tc-macroaggregated albumin ((99m)Tc-MAA). The (166)Ho scout dose provides a more accurate and precise lung shunt assessment. However, in contrast to (99m)Tc-MAA, an unintended extrahepatic deposition of this β-emitting scout dose could inflict radiation damage, the extent of which we aimed to quantify in this study. METHODS: All patients eligible for radioembolization in our institute between January 2011 and March 2014 were reviewed. Of the extrahepatic depositions of (99m)Tc-MAA on SPECT, the amount and volume were measured. These were used to calculate the theoretic absorbed dose in the case a (166)Ho scout dose had been used. The extrahepatic activity was measured as the sum of all voxels of the deposition. Volumes were measured using a threshold technique including all voxels from the maximum voxel intensity up to a certain percentage. The threshold needed to obtain the true volume was studied in a phantom study. RESULTS: In the phantom study, a threshold of 40% was found to overestimate the volume, with the consequence of underestimating the absorbed dose. Of 160 patients, 32 patients (34 cases) of extrahepatic deposition were identified. The depositions contained a median of 1.3% (range, 0.1%-19.5%) of the administered activity in a median volume of 6.8 mL (range, 1.1-42 mL). The use of a scout dose of 250 MBq of (166)Ho microspheres in these cases would theoretically have resulted in a median absorbed dose of 6.0 Gy (range, 0.9-374 Gy). The dose exceeded a limit of 49 Gy (reported in 2013) in 2 of 34 cases (5.9%; 95% confidence interval, 0.7%-20.1%) or 2 of 160 (1.3%; 95% confidence interval, 0.1%-4.7%) of all patients. In these 2 patients with a large absorbed dose (112 and 374 Gy), the culprit vessel was identified in 1 case. CONCLUSION: Extrahepatic deposition of a (166)Ho scout dose seems to be theoretically safe in most patients. Its safety in clinical practice is being evaluated in ongoing clinical trials.

Purpose To assess the radiation exposure to individuals coming from patients after treatment with holmium-166 ( 166 Ho) microspheres. Materials and Methods Holmium-166 radioembolization (RE) with escalating whole-liver doses of 20 Gy, 40 Gy, 60 Gy, and 80 Gy was administered to 15 patients. Exposure rates (μSv/h) from patients were measured at 1.0 m distance from a lateral and frontal position at 0, 3, 6, 24, and 48 hours after infusion. The total effective dose equivalent (TEDE) to a maximally exposed contact was calculated in accordance with guidelines of the U.S. Nuclear Regulatory Commission (NRC). Results were extrapolated to a whole-liver dose of 60 Gy used in future treatments. Results The median exposure rate at discharge, 48 hours after infusion, measured from a lateral position was 26 μSv/h (range, 7–45 μSv/h). Extrapolated to a whole-liver dose of 60 Gy, none of the exposure rates for the NRC contact scenario, at any time, frontal or lateral, would lead to a TEDE > 5 mSv; all patients may be released directly after treatment. Release after 6 hours is possible without contact restrictions for patients who received up to 7 GBq. Conclusions The TEDE to a contact of patients treated with 166 Ho RE would not exceed the NRC limit of 5 mSv. Contact restrictions 6 hours after treatment are unnecessary for infused activities

Controversy exists over the need to take precautionary measures during hepatic radioembolization to minimize the risk of radiation-induced cholecystitis. Strategies for a variety of clinical scenarios are discussed on the basis of a literature review. Precautionary measures are unnecessary in the majority of patients and should be taken only when single photon-emission computed tomography (CT; SPECT)/CT shows a significant concentration of technetium-99m macroaggregated albumin in the gallbladder wall. In this case report with quantitative SPECT analysis, it is illustrated how an adjustment of the catheter position can effectively reduce the absorbed dose of radiation delivered to the gallbladder wall by more than 90%.

Radiation pneumonitis is a rare but serious complication of radioembolic therapy of liver tumours. Estimation of the mean absorbed dose to the lungs based on pretreatment diagnostic (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) imaging should prevent this, with administered activities adjusted accordingly. The accuracy of (99m)Tc-MAA-based lung absorbed dose estimates was evaluated and compared to absorbed dose estimates based on pretreatment diagnostic (166)Ho-microsphere imaging and to the actual lung absorbed doses after (166)Ho radioembolization.This prospective clinical study included 14 patients with chemorefractory, unresectable liver metastases treated with (166)Ho radioembolization. (99m)Tc-MAA-based and (166)Ho-microsphere-based estimation of lung absorbed doses was performed on pretreatment diagnostic planar scintigraphic and SPECT/CT images. The clinical analysis was preceded by an anthropomorphic torso phantom study with simulated lung shunt fractions of 0 to 30 % to determine the accuracy of the image-based lung absorbed dose estimates after (166)Ho radioembolization.In the phantom study, (166)Ho SPECT/CT-based lung absorbed dose estimates were more accurate (absolute error range 0.1 to -4.4 Gy) than (166)Ho planar scintigraphy-based lung absorbed dose estimates (absolute error range 9.5 to 12.1 Gy). Clinically, the actual median lung absorbed dose was 0.02 Gy (range 0.0 to 0.7 Gy) based on posttreatment (166)Ho-microsphere SPECT/CT imaging. Lung absorbed doses estimated on the basis of pretreatment diagnostic (166)Ho-microsphere SPECT/CT imaging (median 0.02 Gy, range 0.0 to 0.4 Gy) were significantly better predictors of the actual lung absorbed doses than doses estimated on the basis of (166)Ho-microsphere planar scintigraphy (median 10.4 Gy, range 4.0 to 17.3 Gy; p 0.001), (99m)Tc-MAA SPECT/CT imaging (median 2.5 Gy, range 1.2 to 12.3 Gy; p 0.001), and (99m)Tc-MAA planar scintigraphy (median 5.5 Gy, range 2.3 to 18.2 Gy; p 0.001).In clinical practice, lung absorbed doses are significantly overestimated by pretreatment diagnostic (99m)Tc-MAA imaging. Pretreatment diagnostic (166)Ho-microsphere SPECT/CT imaging accurately predicts lung absorbed doses after (166)Ho radioembolization.

Intra-arterial radioembolization with yttrium-90 microspheres is a safe and effective treatment option for patients with unresectable liver tumors. Pretreatment coil embolization of extrahepatic vessels is recommended to avoid extrahepatic deposition of radioactive microspheres. A novel infusion system with an expandable tip, the Surefire Infusion System (SIS), has recently been developed to minimize reflux. We report three cases of radioembolization with the use of the SIS. In all cases, yttrium-90 radioembolization was performed successfully without coil embolization of extrahepatic vessels. In all patients, positron emission tomography-computed tomography confirmed intrahepatic biodistribution of the microspheres in all targeted liver segments, and no extrahepatic deposition. With the use of the SIS, the need for coil embolization of extrahepatic vessels might be eliminated, and treatment may be extended to patients who were previously deemed unfit.

To compare right gastric (RGA) and segment 4 artery (A4) origin detection rates during radioembolisation workup between early and late arterial phase liver CT protocols. 100 consecutive patients who underwent liver CT between May 2012–January 2015 with early or late arterial phase protocol (n = 50 each, 10- vs. 20-s post-threshold delay) were included. RGA/A4 origin detection rates, assessed by two raters, and contrast-to-noise ratio (CNR) of the hepatic artery relative to the portal vein were compared between the protocols. The first–second rater scored the RGA origin as visible in 58–65 % (specific proportion of agreement 82 %, κ = 0.62); A4 origin in 96–89 % (94 %, κ = 0.54). Thirty-six percent of RGA origins not detectable by DSA were identified on CT. Origin detection rates were not significantly different for early/late arterial phases. Mean CNR was higher in the early arterial phase protocol (1.7 vs. 1.2, p

Aim To assess the technical feasibility and clinical outcome of percutaneous transluminal angioplasty (PTA) with and without stent placement for treatment of buttock claudication caused by internal iliac artery (IIA) stenosis. Methods Between September 2001 and July 2011, thirty-four patients with buttock claudication underwent endovascular treatment. After angiographic lesion evaluation PTA with or without stent placement was performed. Technical success was recorded. Clinical outcome post-treatment was assessed at three months post-intervention and was classified as: 1) complete relief of symptoms, 2) partial relief, or 3) no relief of symptoms. Complications during follow-up were recorded. Results Forty-four lesions in 34 symptomatic patients were treated with PTA. Eight lesions were treated with additional stent placement. Technical success was achieved in 40/44 lesions (91%). Three procedure-related minor complications occurred, i.e. asymptomatic conservatively treated intimal dissections. After a median of 2.9 months, patients experienced no relief of symptoms in 7/34 cases (21%), partial relief in 14/34 cases (41%), and complete relief in 13/34 cases (38%). Six patients required a reintervention during follow-up. Conclusion Endovascular treatment of IIA stenosis has a high technical success rate and a low complication rate. Complete or partial relief of symptoms is achieved in the majority (79%) of patients.

Purpose Quality of life (QoL) is an important outcome measure for palliative treatment options like radioembolization (RE) of liver tumors. Several studies have shown a trend towards a decrease in overall QoL after 90Y RE (1-6). The purpose of this study was to evaluate the QoL after RE with 166Ho microspheres; a new imageable particle for RE. Materials and Methods QoL was evaluated in patients with unresectable, chemorefractory liver metastases who were enrolled in a phase 1 dose-escalation clinical trial (7). Patients were enrolled between November 30, 2009 and September 19, 2011. Patients were treated with 166Ho RE in cohorts of three patients with escalating whole-liver absorbed doses of 20, 40, 60 and 80 Gy. QoL was assessed using the global health status and QoL score of the validated European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-LMC21 questionnaires at baseline and at 6 and 12 weeks after treatment. Results 15 patients underwent 166Ho RE. QoL could be assessed in 14 patients, because one patient developed brain metastases and did not comply with follow-up. Compared with baseline values, the mean QoL score at 6 weeks after treatment had decreased by 13 points for the whole group (from 75.6 to 62.5, p=0.053) and by 14 points at 12 weeks to a mean score of 61.9 (p=0.048). There was a difference in decrease in QoL scores between patients with progressive disease and patients with response to treatment, favouring responders, respectively -18.8 versus -5.6 points at 6 weeks (p=0.31). Decrease in QoL scores was most prominent in high dose cohorts: -8 (20 Gy), 3 (40 Gy), -13 (60 Gy), -39 (80 Gy) at 6 weeks. Conclusion Overall QoL decreased in patients with liver metastases after treatment with 166Ho RE. Patients with progressive disease and patients treated with high liver absorbed doses show the greatest decrease in QoL. References 1. Van Hazel G, et al. J Surg Oncol. 2004. 2. Gray B, et al. Ann Oncol. 2001. 3. Cosimelli M, et al. Br J Cancer. 2010. 4. Kalinowski M, et al. Digestion. 2009. 5. Mancini R, et al. In Vivo. 2006. 6. Steel J, et al. Psychooncology. 2004. 7. Smits ML, et al. Lancet Oncol. 2012

Purpose Holmium-166 ( 166 Ho) microspheres have been developed for radioembolization (RE) of liver tumors. The radiation emission of 166 Ho-microspheres outside the body can raise concerns regarding radiation safety after RE. The purpose of this study was to perform an external dose assessment for patients treated with 166 Ho-RE. Materials and Methods In the phase 1 HEPAR study (Holmium Embolization Particles for Arterial Radiotherapy), the safety and toxicity profile of 166 Ho-RE was evaluated in fifteen patients with unresectable, chemorefractory liver metastases (1). Patients (mean liver volume 2.1 L, range 1.5 L - 3.6 L) were treated with a mean net infused activity of 5.1 GBq (SD 2.9). Radiation dose rates were measured at 1 m distance from a right lateral and frontal position using a portable dose rate meter (Radiagem 2000, CANBERRA, Meriden, Ct.). The measurements were done 0, 3, 6, 24, and 48 hours after infusion, and corrected to an aimed whole-liver absorbed dose of 60 Gy, which is used in subsequent phase 2 treatments. A total effective dose equivalent (TEDE) was calculated in accordance with published guidelines of the U.S. Nuclear Regulatory Commission (NRC) (2). Results The mean dose rate at discharge, 48 hours after infusion, measured from 1 m distance from a right lateral position was 6.4 μSv/h (SD 3.8). Assuming invariable presence, the mean TEDE was 0.25 mSv (SD 0.15). When adjusted to a whole-liver absorbed dose of 60 Gy, the mean dose rate in the air at 1 m immediately after treatment was 30.9 μSv/h (SD 13.2), corresponding to a mean TEDE of 1.19 mSv (SD 0.51). None of the corrected dose rates, at any time, measured from either frontal or lateral position, would have led to a TEDE above 5 mSv. Conclusion TEDE of patients treated with 166 Ho-RE aimed at a 60 Gy whole-liver absorbed dose, will not exceed the NRC limit (3) of 5 mSv to another individual: not even when discharged immediately after treatment. Patients are to be provided with written instructions as to keep the exposure to other individuals as low as reasonably achievable. References 1. Smits MLJ, et al., Lancet Oncol 2012;13:1025-34. 2. NRC, Regulatory Guide 8.39, April 1997. 3. NRC, NRC-10 CFR 35.75.