The superior predictive value of 166Ho-scout compared with 99mTc-macroaggregated albumin prior to 166Ho-microspheres radioembolization in patients with liver metastases.

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.

Evaluation of the Safety and Feasibility of Same-Day Holmium-166 -Radioembolization Simulation and Treatment of Hepatic Metastases.

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.

Safety analysis of holmium-166 microsphere scout dose imaging during radioembolisation work-up: A cohort study.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: These results support the safety of 250 MBq 166Ho-SD in a clinical setting. KEY POINTS: • 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.

Liver CT for vascular mapping during radioembolisation workup: comparison of an early and late arterial phase protocol.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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 < 0.001). CONCLUSION: A 10-s delay arterial phase CT protocol does not significantly improve detection of small intra- and extrahepatic branches. RGA origin detection requires further optimization, whereas A4/MHA origin detection is adequate, with good inter-rater reproducibility. CT remains important for preprocedural planning, because it may reveal arterial anatomy not discernible on DSA. KEY POINTS: • An early arterial phase does not significantly improve RGA and A4/MHA origin detection. • RGA origin detection (58-65 %) on CT is still suboptimal. • 36 % of RGA origins undetectable on DSA can be identified on CT. • A4/MHA origin detection (89-96 %) on CT is excellent. • Inter-rater reproducibility is good for RGA and A4/MHA origin detection on CT.

(99m)Tc-MAA overestimates the absorbed dose to the lungs in radioembolization: a quantitative evaluation in patients treated with ¹66Ho-microspheres.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Radiation-induced cholecystitis after hepatic radioembolization: do we need to take precautionary measures?

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 emission from patients treated with holmium-166 radioembolization.

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 < 7 GBq.

Lung Mean Dose Prediction in Transarterial Radioembolization (TARE): Superiority of [166Ho]-Scout Over [99mTc]MAA in a Prospective Cohort Study.

PURPOSE: Radiation pneumonitis is a serious complication of radioembolization. In holmium-166 ([166Ho]) radioembolization, the lung mean dose (LMD) can be estimated (eLMD) using a scout dose with either technetium-99 m-macroaggregated albumin ([99mTc]MAA) or [166Ho]-microspheres. The accuracy of eLMD based on [99mTc]MAA (eLMDMAA) was compared to eLMD based on [166Ho]-scout dose (eLMDHo-scout) in two prospective clinical studies. MATERIALS AND METHODS: Patients were included if they received both scout doses ([99mTc]MAA and [166Ho]-scout), had a posttreatment [166Ho]-SPECT/CT (gold standard) and were scanned on the same hybrid SPECT/CT system. The correlation between eLMDMAA/eLMDHo-scout and LMDHo-treatment was assessed by Spearman's rank correlation coefficient (r). Wilcoxon signed rank test was used to analyze paired data. RESULTS: Thirty-seven patients with unresectable liver metastases were included. During follow-up, none developed symptoms of radiation pneumonitis. Median eLMDMAA (1.53 Gy, range 0.09-21.33 Gy) was significantly higher than median LMDHo-treatment (0.00 Gy, range 0.00-1.20 Gy; p < 0.01). Median eLMDHo-scout (median 0.00 Gy, range 0.00-1.21 Gy) was not significantly different compared to LMDHo-treatment (p > 0.05). In all cases, eLMDMAA was higher than LMDHo-treatment (p < 0.01). While a significant correlation was found between eLMDHo-scout and LMDHo-treatment (r = 0.43, p < 0.01), there was no correlation between eLMDMAA and LMDHo-treatment (r = 0.02, p = 0.90). CONCLUSION: [166Ho]-scout dose is superior in predicting LMD over [99mTc]MAA, in [166Ho]-radioembolization. Consequently, [166Ho]-scout may limit unnecessary patient exclusions and avoid unnecessary therapeutic activity reductions in patients eligible for radioembolization. TRAIL REGISTRATION: NCT01031784, registered December 2009. NCT01612325, registered June 2012.

Clinical Outcomes of Biliary Drainage in Patients with Malignant Biliary Obstruction Caused by Colorectal Cancer Metastases.

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.

Quality of life in patients with liver tumors treated with holmium-166 radioembolization.

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.

First Evidence for a Dose-Response Relationship in Patients Treated with 166Ho Radioembolization: A Prospective Study.

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.

Accuracy of SPECT/CT-based lung dose calculation for Holmium-166 hepatic radioembolization before OSEM convergence.

PURPOSE: In intra-arterial hepatic radioembolization using Holmium-166 (166 Ho) microspheres, a predicted lung-absorbed dose of more than 30 Gy is a contraindication 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 for a therapeutic dosage of 20.3 Gy upon MC-based OSEM 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.

Efficacy of Radioembolization with 166Ho-Microspheres in Salvage Patients with Liver Metastases: A Phase 2 Study.

Radioembolization of liver malignancies with 166Ho-microspheres has been shown to be 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. The primary outcome was a response by 2 target lesions on triphasic liver CT scans 3 mo after therapy, as assessed using RECIST, version 1.1. Secondary outcomes included overall tumor response, 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 (73%) of 37 patients, the target lesions showed complete response, partial response, or stable disease (disease control) at 3 mo (95% confidence interval [CI], 57%-85%). The median overall survival was 14.5 mo (95% CI, 8.6-22.8 mo). For colorectal cancer patients (n = 23), the median overall survival was 13.4 mo (95% CI, 8.2-15.7 mo). Grade 3 or 4 toxic events after treatment (according to the Common Terminology Criteria for Adverse Events, version 4.03) 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, 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: Is Prophylactic Embolization of Hepaticoenteric Arteries Necessary? A Systematic Review.

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.

Use of C-Arm Cone Beam CT During Hepatic Radioembolization: Protocol Optimization for Extrahepatic Shunting and Parenchymal Enhancement.

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.

Surefire infusion system versus standard microcatheter use during holmium-166 radioembolization: study protocol for a randomized controlled trial.

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.

Safety of a Scout Dose Preceding Hepatic Radioembolization with 166Ho Microspheres.

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 ß-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.

9°Y Hepatic Radioembolization: An Update on Current Practice and Recent Developments.

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.