Jip F. Prince

Posttreatment PET-CT-Confirmed Intrahepatic Radioembolization Performed Without Coil Embolization, by Using the Antireflux Surefire Infusion System

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.

⁹⁰Y 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.

Radioembolization: Is Prophylactic Embolization of Hepaticoenteric Arteries Necessary? A Systematic Review

PurposeTo study the effectiveness of prophylactic embolization of hepaticoenteric arteries to prevent gastrointestinal complications during radioembolization.MethodsA PubMed, Embase and Cochrane literature search was performed. We included studies assessing both a group of patients with and without embolization.ResultsOur 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.ConclusionIt 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.

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

Before 166Ho radioembolization, a small batch of the same type of microspheres is administered as a scout dose instead of the conventional 99mTc-macroaggregated albumin (99mTc-MAA). The 166Ho scout dose provides a more accurate and precise lung shunt assessment. However, in contrast to 99mTc-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 99mTc-MAA on SPECT, the amount and volume were measured. These were used to calculate the theoretic absorbed dose in the case a 166Ho 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 166Ho 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 166Ho scout dose seems to be theoretically safe in most patients. Its safety in clinical practice is being evaluated in ongoing clinical trials.

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%.

Endovascular Treatment of Internal Iliac Artery Stenosis in Patients with Buttock Claudication

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.

Efficacy of radioembolization with holmium-166 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.

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.

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 (166Ho) 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 166Ho 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.

Accessory Left Gastric Artery from Left Hepatic Artery is a Potential Risk for Radioembolization Complications

While prophylactic embolization of hepaticoenteric arteries may not be necessary in the majority of patients who have been referred for yttrium-90 (Y) radioembolization (RE), it is important to note that some patients have hepaticoenteric arteries that should be coil embolized to prevent gastrointestinal complications due to inadvertent extrahepatic deposition of activity. In general, the rate of gastrointestinal complications after RE is low in both embolized and non-embolized patient cohorts [1]. No evidence in favor of routine performance of prophylactic embolization could be found. However, when microspheres are injected proximal to the origin of a hepaticoenteric artery (with the exception of the cystic artery and hepatic falciform artery), it is advised to embolize this artery during pre-treatment angiography. A left gastric artery originating from the left hepatic artery is one of those distal hepaticoenteric arteries that should be embolized before treatment. Significant extrahepatic deposition of microspheres may otherwise occur. To illustrate the importance of C-arm CT during pretreatment angiography, we have included a patient with a left gastric artery originating from the left hepatic artery (Fig. 1). To prevent gastrointestinal complications and unnecessary extra procedures, it is important to use pre-treatment imaging work-up, including contrast-enhanced arterial phase CT and C-arm CT during angiography, to accurately guide treatment strategy. In a cohort of 118 patients, Ishigami et al. compared pretreatment multiphase contrast-enhanced CT and CT during angiography with intra-arterial injection of contrast as the standard of reference. A left gastric artery from the left hepatic artery was found in 25/118 patients (21 %). The sensitivity, specificity, and accuracy of pre-treatment multiphase contrast-enhanced CT to detect a left gastric artery originating from the left hepatic artery were 72 %, 99 %, and 93 %, respectively. Conventional digital subtraction angiography imaging had a sensitivity, specificity, and accuracy of 88 %, 98 %, and 96 %, respectively [2]. It may be hypothesized that the sensitivity of pre-treatment multiphase contrast-enhanced CT to detect small aberrant arteries may be increased by using a shorter delay than the 45-second delay that was used in this study [3]. In conclusion, a left gastric artery originating from the left hepatic artery is a fairly common variant finding. Pretreatment imaging and imaging during angiography workup may help to prevent unnecessary extra procedures, as well as inadvertent gastrointestinal complications.