Transarterial Radioembolization (TARE) Global Practice Patterns: An International Survey by the Cardiovascular and Interventional Radiology Society of Europe (CIRSE)

Commentary on: Transarterial Radioembolization (TARE) Global Practice Patterns: An International Survey by the Cardiovascular and Interventional Radiology Society of Europe (CIRSE).

Carotid Artery Angioplasty and Stent Placement: Quality Improvement Guidelines to Ensure Stroke Risk Reduction

This study evaluates outcomes for patients with unresectable colorectal liver metastases (CRLM) undergoing hepatic artery infusion chemotherapy (HAI) and transarterial radioembolization (TARE). The most common liver-directed therapies for unresectable CRLM include HAI and TARE. In this retrospective cohort study, patients with unresectable CRLM treated with HAI at one high-volume center were compared with patients treated with TARE at five other institutions. Propensity score matching was performed within lines of chemotherapy received prior to treatment (treatment-naïve; 1-line; 2-lines; 3-4 lines) using baseline demographics, extrahepatic disease (EHD), prior chemotherapy, disease-free interval, and interval from primary diagnosis to HAI/TARE. Overall survival (OS) analysis was conducted to compare the matched groups. A total of 708 HAI patients and 481 TARE patients were identified. The majority of patients (84%) received chemotherapy prior to HAI/TARE. HAI patients were younger (median age:54 vs. 62) and more likely to have evidence of EHD at time of treatment (65% vs. 60%). Of the 493 patients who received 1-line of chemotherapy, 166 (34%) were matched. Among matched patients who received 1-line (HAI:83, TARE:83) or 2-lines of chemotherapy (HAI:80, TARE:80), TARE patients had a significantly increased risk of all-cause mortality compared to HAI [HR:1.46 (95%CI:1.02-2.08) and HR:1.96 (95%CI:1.32-2.89)]. More frequent conversion to resection and use of concurrent systemic chemotherapy were also seen in the HAI cohort. Among matched patients who received 3-4 lines of chemotherapy (HAI:50, TARE:50), there was no difference in OS between HAI and TARE [HR:0.88 (95%CI:0.57-1.35)] and rate of conversion to surgery was 4% for both groups. Within matched cohorts stratified by lines of therapy, there appear to be differences in survival for patients treated with HAI and TARE after first or second-line chemotherapy. Outcomes after TARE and HAI are not significantly different in the refractory setting.

308 Background: Trans-arterial radioembolization (TARE) is a treatment option for patients with intrahepatic cholangiocarcinoma (ICC). The CIRSE Registry for SIR-Spheres Therapy (CIRT) is the first European prospective multi-centre observational study designed to evaluate the clinical outcomes of patients treated with TARE with SIR-Spheres Y90 resin microspheres for ICC in the multi-institutional real-life clinical setting. The study was conducted by the Cardiovascular and Interventional Radiological Society of Europe (CIRSE). Methods: Patients were enrolled prospectively between Jan 2015 and 31 Dec 2017. Eligible patients were adults treated with TARE with Y90 resin microspheres for ICC. Data on baseline characteristics and treatment intention/clinical context and dosimetry were collected, as well as follow-up data (every 3 months; for 24 months after treatment), including overall survival (OS), (hepatic) progression-free survival [(h)PFS], safety and Global Health Status (GHS, using the European Organisation for the Research and Treatment of Cancer QLQ-C30). Results: 120 patients were included from 18 sites in 8 European countries. Median age was 63 years (range: 29-86) and 54.2% were male. Median tumour to liver percentage was 12.8%. Median prescribed activity was 1.32 GBq for whole liver treatments (n = 49), 1.20 GBq for right lobe treatments (n = 56) and 0.82 GBq for left lobe treatments (n = 51). 97.5% of the delivered activity was within 90% of the prescribed activity. TARE treatment as a first line (L1) global strategy was applied in 39.1%, 27.4% as second line (after systemic therapy). Treatment intention was predominantly palliative (69.2%) or tumour shrinkage (20.8%). Median OS was 14.7 months (95% confidence interval (CI) 10.9 – 17.9). Median PFS was 5.7 months (95% CI 3.9 – 7.5), whereas hPFS was 6.2 months (95% CI 4.1 – 8.5). Mean GHS was 59.3 at baseline, 61.0 after 3 months, 56.0 at 6 months, 54.4 at 9 months and 63.0 after 1 year. Severe adverse events (grade 3 and 4) were found in 13 (10.8%) patients: (abdominal pain 3.3%, fatigue 1.7%, gastrointestinal ulceration 0.8%, gastritis 0.8%, radiation cholecystitis 0.8%, radiation-induced liver disease 1.7%, other 5.8%). Detailed subgroup analyses are currently being performed. Updated data describing OS, PFS and hPFS for L1 TARE vs TARE after systemic chemotherapy, as well as prognostic factors for OS, PFS and hPFS will be shown. Conclusions: The results from this large prospective multi-centre observational study shows that in the real-world context, TARE is applied early and successfully in the treatment pathway. TARE is shown to be an effective and safe treatment with no meaningful deterioration of quality of life. Clinical trial information: NCT02305459.

Histopathologic Changes after Yttrium-90 Radioembolization of Colorectal Liver Metastases: A Pilot Feasibility Study

[Purpose] Transarterial radioembolization (TARE) is an established treatment modality for patients with unresectable liver cancer. However, a better understanding of treatment parameters that influence microsphere distribution could further improve the therapy. This systematic review examines and summarizes the available evidence on intraprocedural parameters that influence the microsphere distribution during TARE as investigated by in vivo, ex vivo, in vitro and in silico studies. [Methods] A standardized search was performed in Medline, Embase and Web of Science to identify all published articles investigating microsphere distribution or dynamics during TARE. Studies presenting original research on parameters influencing the microsphere distribution during TARE were included. [Results] A total of 42 studies reporting a total of 11 different parameters were included for narrative analysis. The investigated studies suggest that flow distribution is not a perfect predictor of microsphere distribution. Increasing the injection velocity may help increase the similarity between flow and microsphere distributions. Furthermore, the microsphere distributions are very sensitive to the radial and axial catheter position. [Conclusion] The most promising parameters for future research which can be controlled in the clinic appear to be microsphere injection velocity as well as the axial catheter position. Up to now, many of the included studies do not take clinical feasibility into account, limiting the translation of results to clinical settings. Future research should therefore focus on the applicability of in vivo, in vitro, or in silico research to patient specific scenarios to improve the efficacy of radioembolization as treatment for liver cancer.

To experimentally investigate the behavior of a clinically used microcatheter during transarterial radioembolization (TARE) microsphere injection in a successively bifurcating in vitro model. A symmetrical phantom was developed which bifurcated 3 times into 8 outlets. A blood-mimicking fluid was pumped through the phantom using a physiological representative waveform. Holmium-165 microspheres were injected in a pulsed manner at 3 different locations using a standard microcatheter and a rigid counterpart with same dimensions as a control. Motion of the catheter was studied with a top- and side-view camera on the phantom. Microspheres were collected at each outlet and their distribution over the 8 outlets was analyzed. Due to the pulsatile flow in the phantom, strengthened by the pulsatile microsphere injection, the clinical catheter showed maximum displacements of 0.87 mm within a vessel with a diameter of 3.6 mm. This motion resulted in a different microsphere distribution for the clinical catheter compared with the rigid counterpart (75.9% vs 49.4% of the microspheres went to outlet 1-4, respectively). In this in vitro model, the motion of the clinical catheter affected distribution of microspheres. Since the pulsatile administration of microspheres resulted in increased motion of the clinical catheter, standardizing microsphere administration could be beneficial to reduce interprocedural differences in TARE. Our study demonstrated that microsphere distribution during transarterial radioembolization (TARE) is affected by catheter motion. Furthermore, increased catheter motion was observed as a result of the injection profile. Predictive tools such as the contrast CBCT and scout dose use different injection profiles compared to therapeutic TARE injections, potentially altering catheter tip behaviour and microsphere distribution, which could compromise their predictive values. Additionally, current TARE microsphere injection guidelines provide limited details, which may lead to variability across institutes and interventional radiologists. Standardizing injection techniques could reduce catheter motion variability and may facilitate more consistent and predictable microsphere distribution patterns.

BACKGROUNDTwo-stage hepatectomy (TSH) is a well-established surgical technique, used to treat bilateral colorectal liver metastases (CRLM) with a small future liver remnant (FLR). However, in classical TSH, drop-out is reported to be around 25%-40%, due to insufficient FLR increase or progression of disease. Trans-arterial radioembolization (TARE) has been described to control locally tumor growth of liver malignancies such as hepatocellular carcinoma, but it has been also reported to induce a certain degree of contralateral liver hypertrophy, even if at a lower rate compared to portal vein embolization or ligation.CASE SUMMARYHerein we report the case of a 75-year-old female patient, where TSH and TARE were combined to treat bilateral CRLM. According to computed tomography (CT)-scan, the patient had a hepatic lesion in segment VI-VII and two other confluent lesions in segment II-III. Therefore, one-stage posterior right sectionectomy plus left lateral sectionectomy (LLS) was planned. The liver volumetry estimated a FLR of 38% (segments I-IV-V-VIII). However, due to a more than initially planned, extended right resection, simultaneous LLS was not performed and the patient underwent selective TARE to segments II-III after the first surgery. The CT-scan performed after TARE showed a reduction of the treated lesion and a FLR increase of 55%. Carcinoembryonic antigen and CA 19.9 decreased significantly. Nearly three months later after the first surgery, LLS was performed and the patient was discharged without any postoperative complications.CONCLUSIONAccording to this specific experience, TARE was used to induce liver hypertrophy and simultaneously control cancer progression in TSH settings for bilateral CRLM.

Transarterial radioembolisation (TARE) is a treatment for liver malignancies, involving the injection of radioactive microspheres in the hepatic artery (HA). Tumour-to-nontumour uptake varies among patients, possibly influenced by patient-specific blood flow profiles. To examine the impact of HA blood flow rate and high microsphere dosages on microsphere distribution in normal liver parenchyma, ex vivo magnetic resonance imaging (MRI)-guided machine perfusion experiments were conducted in porcine livers. Porcine livers were subjected to oxygenated normothermic machine perfusion at three HA flow rates (0.02, 0.15, and 0.22 mL/min/g liver tissue; n = 3 per condition). Five fractions of 250 mg nonradioactive 165Ho-loaded microspheres were administered to n = 9 livers, and four additional fractions of 1,000 mg to n = 6 livers. Dynamic contrast-enhanced and Ho-sensitive T2*-weighed MR scans were acquired to extract perfusion rates, fictive dose maps, and homogeneity indices (HI). Microsphere distribution correlated moderately with perfusion rate at low HA flow rate (r = 0.611), and very strongly at higher HA flow rates (r = 0.977 and 0.951 for 0.15 and 0.22 mL/min/g, respectively). Homogeneity increased with increasing flow rates, with HIs ranging from 3.68-4.72 at low, to 2.01-2.66 at medium, and 1.60-2.36 at high HA flow rate. HI decreased with higher microsphere concentrations, though distribution patterns remained unchanged. In our ex vivo model, higher HA flow rates resulted in more homogeneous microsphere distributions. The impact on tumourous tissue needs further investigation to determine whether pre-TARE HA blood flow measurements could improve microsphere distribution predictions. Mapping of the hepatic arterial blood flow rate before transarterial radioembolisation and adjusting the treatment accordingly may help to improve outcomes for patients with liver cancer. Parameters influencing microsphere distribution were studied in MRI-perfused healthy porcine livers. Higher hepatic arterial blood flow rates led to more homogeneous microsphere distributions. Administering large numbers of microspheres did not alter microsphere distribution patterns. Impact on tumour tissue should be further investigated.

BackgroundUsing data collected in the prospective observational study CIRSE Registry for SIR-Spheres Therapy, the present study aimed at identifying predictors of adverse events (AEs) following transarterial radioembolization (TARE) with Yttrium-90 resin microspheres for liver tumours.MethodsWe analysed 1027 patients enrolled between January 2015 and December 2017 and followed up for 24 months. Four hundred and twenty-two patients with hepatocellular carcinoma (HCC), 120 with intrahepatic carcinoma (ICC), 237 with colorectal liver metastases and 248 with liver metastases from other primaries were included. Prognostic factors were calculated with a univariable analysis by using the overall AEs burden score (AEBS).ResultsAll-cause AEs were reported in 401/1027 (39.1%) patients, with AEs associated with TARE, such as abdominal pain (16.6%), fatigue (17%), and nausea (11.7%) reported most frequently. Grade 3 or higher AEs were reported in 92/1027 (9%) patients. Reports on grade ≥ 3 gastrointestinal ulcerations (0.4%), gastritis (0.3%), radiation cholecystitis (0.2%) or radioembolization-induced liver disease (0.5%) were uncommon. Univariable analysis showed that in HCC, AEBS increased for Eastern Cooperative Oncology Group (ECOG) 0 (p = 0.0045), 1 tumour nodule (0.0081), > 1 TARE treatment (p = 0.0224), no prophylactic embolization (p = 0.0211), partition model dosimetry (p = 0.0007) and unilobar treatment target (0.0032). For ICC, > 1 TARE treatment was associated with an increase in AEBS (p = 0.0224), and for colorectal liver metastases, ECOG 0 (p = 0.0188), > 2 prior systemic treatments (p = 0.0127), and 1 tumour nodule (p = 0.0155) were associated with an increased AEBS.ConclusionOur study confirms that TARE is a safe treatment with low toxicity and a minimal impact on quality of life.

PurposeTo address the lack of prospective data on the real-life clinical application of trans-arterial radioembolization (TARE) in Europe, the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) initiated the prospective observational study CIRSE Registry for SIR-Spheres® Therapy (CIRT).Materials and MethodsPatients were enrolled from 1 January 2015 till 31 December 2017. Eligible patients were adult patients treated with TARE with Y90 resin microspheres for primary or metastatic liver tumours. Patients were followed up for 24 months after treatment, whereas data on the clinical context of TARE, overall survival (OS) and safety were collected.ResultsTotally, 1027 patients were analysed. 68.2% of the intention of treatment was palliative. Up to half of the patients received systemic therapy and/or locoregional treatments prior to TARE (53.1%; 38.3%). Median overall survival (OS) was reported per cohort and was 16.5 months (95% confidence interval (CI) 14.2–19.3) for hepatocellular carcinoma, 14.6 months (95% CI 10.9–17.9) for intrahepatic cholangiocarcinoma. For liver metastases, median OS for colorectal cancer was 9.8 months (95% CI 8.3–12.9), 5.6 months for pancreatic cancer (95% CI 4.1–6.6), 10.6 months (95% CI 7.3–14.4) for breast cancer, 14.6 months (95% CI 7.3–21.4) for melanoma and 33.1 months (95% CI 22.1–nr) for neuroendocrine tumours. Statistically significant prognostic factors in terms of OS include the presence of ascites, cirrhosis, extra-hepatic disease, patient performance status (Eastern Cooperative Oncology Group), number of chemotherapy lines prior to TARE and tumour burden. Thirty-day mortality rate was 1.0%. 2.5% experienced adverse events grade 3 or 4 within 30 days after TARE.ConclusionIn the real-life clinical setting, TARE is largely considered to be a part of a palliative treatment strategy across indications and provides an excellent safety profile.Level of evidenceLevel 3.Trial registrationClinicalTrials.gov NCT02305459.

Continuous education in gastroenterology: the present and the future.

P-130 Real-world outcomes of patients with colorectal liver metastases treated with transarterial radioembolization: Results from CIRT, a large European, prospective multi-centre, observational study

2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease: Executive Summary

The indications and results of preoperative localization, surgical strategy, indication for thymectomy, the application of intraoperative parathyroid hormone (PTH) monitoring, cryopreservation, and replantation of cryopreserved parathyroid tissue are not well documented in renal hyperparathyroidism (RHPT). The current trends in surgery for RHPT are to be evaluated in an international online survey. Thirty-three questions regarding preoperative localization, surgical management of RHPT, intraoperative PTH monitoring, immediate/delayed autotransplantation (AT), and parathyroid cryopreservation were sent to members of various societies of endocrine surgeons. The data from 86 responses were analyzed, 61.6 % reported more than 50 parathyroid surgeries per year, and 62.7 % operated on less than 16 patients with RHPT per year. Subtotal or total parathyroidectomy (with/without AT) was the standard procedure in 98.8 % of the cases. Immediate AT was performed in 40.7 % (72.7 % in the forearm). In most patients, the onset of graft function was documented later than 1 week after AT. Cryopreservation was routinely performed in 27.4 %. In 10.7 %, replantation was performed in more than five patients (hypo- or aparathyroidism: n = 41; fresh graft failure: n = 13; reoperations: n = 9). Intraoperative PTH monitoring (in RHPT) was routinely used in 46.2 %. Its influence on surgical strategy was confirmed in 40 %. The survey reflects the divergent strategies applied for AT, cryopreservation, and PTH monitoring in RHPT.