EMBIO trial study protocol: left gastric artery embolisation for weight loss in patients living with obesity with a BMI 35-50 kg/m2.

INTRODUCTION: Left gastric artery embolisation (LGAE) is a well-established treatment for major upper gastrointestinal (GI) bleeding when control is not established via upper GI endoscopy and recently has shown promising results for weight loss in small single arm studies. LGAE could be a treatment option in between our current tier-3 and tier-4 services for obesity. EMBIO is a National Institute for Health Research funded trial, a multicentre double-blinded randomised controlled trial between Imperial College National Health Service Trust and University College London Hospital, comparing LGAE versus Placebo procedure. The key aims of the trial is to evaluate LGAE efficacy on weight loss, its mechanism of action, safety profile and obesity-related comorbidities. METHODS AND ANALYSIS: 76 participants will be recruited from the existing tier-3 database after providing informed consent. Key inclusion criteria include adults aged 18-70 with a body mass index 35-50 kg/m2 and appropriate anatomy of the left gastric artery and coeliac plexus on CT Angiogram. Key exclusion criteria included previous major abdominal and bariatric surgery, weight >150 kg, type 2 diabetes on any medications other than metformin and the use of weight modifying medications. Participants will undergo mechanistic visits 1 week prior to the intervention and 3, 6 and 12 months postintervention. Informed consent will be received from each participant and they will be randomised in a 1:1 ratio to left gastric artery embolisation and placebo treatment. Blinding strategies include the use of moderate doses of sedation, visual and auditory isolation. All participants will enter a tier-3 weight management programme postintervention. The primary analysis will estimate the difference between the groups in the mean per cent weight loss at 12 months. ETHICS AND DISSEMINATION: This trial shall be conducted in full conformity with the 1964 Declaration of Helsinki and all subsequent revisions. Local research ethics approval was granted by London-Central Research Ethics Committee, (Reference 19/LO/0509) on 11 October 2019. The Medicines and Healthcare products Regulatory Agency (MHRA) issued the Letter of No Objection on 8 April 2022 (Reference CI/2022/0008/GB). The trial's development and progress are monitored by an independent trial steering committee and data monitoring and ethics committee. The researchers plan to disseminate results at conferences, in peer- reviewed journals as well as lay media and to patient organisations. TRIAL REGISTRATION NUMBER: ISRCTN16158402.

Phase 0 Study of Vandetanib-Eluting Radiopaque Embolics as a Preoperative Embolization Treatment in Patients with Resectable Liver Malignancies.

PURPOSE: To assess the safety and tolerability of a vandetanib-eluting radiopaque embolic (BTG-002814) for transarterial chemoembolization (TACE) in patients with resectable liver malignancies. MATERIALS AND METHODS: The VEROnA clinical trial was a first-in-human, phase 0, single-arm, window-of-opportunity study. Eligible patients were aged ≥18 years and had resectable hepatocellular carcinoma (HCC) (Child-Pugh A) or metastatic colorectal cancer (mCRC). Patients received 1 mL of BTG-002814 transarterially (containing 100 mg of vandetanib) 7-21 days prior to surgery. The primary objectives were to establish the safety and tolerability of BTG-002814 and determine the concentrations of vandetanib and the N-desmethyl vandetanib metabolite in the plasma and resected liver after treatment. Biomarker studies included circulating proangiogenic factors, perfusion computed tomography, and dynamic contrast-enhanced magnetic resonance imaging. RESULTS: Eight patients were enrolled: 2 with HCC and 6 with mCRC. There was 1 grade 3 adverse event (AE) before surgery and 18 after surgery; 6 AEs were deemed to be related to BTG-002814. Surgical resection was not delayed. Vandetanib was present in the plasma of all patients 12 days after treatment, with a mean maximum concentration of 24.3 ng/mL (standard deviation ± 13.94 ng/mL), and in resected liver tissue up to 32 days after treatment (441-404,000 ng/g). The median percentage of tumor necrosis was 92.5% (range, 5%-100%). There were no significant changes in perfusion imaging parameters after TACE. CONCLUSIONS: BTG-002814 has an acceptable safety profile in patients before surgery. The presence of vandetanib in the tumor specimens up to 32 days after treatment suggests sustained anticancer activity, while the low vandetanib levels in the plasma suggest minimal release into the systemic circulation. Further evaluation of this TACE combination is warranted in dose-finding and efficacy studies.

VEROnA Protocol: A Pilot, Open-Label, Single-Arm, Phase 0, Window-of-Opportunity Study of Vandetanib-Eluting Radiopaque Embolic Beads (BTG-002814) in Patients With Resectable Liver Malignancies.

BACKGROUND: Transarterial chemoembolization (TACE) is the current standard of care for patients with intermediate-stage hepatocellular carcinoma (HCC) and is also a treatment option for patients with liver metastases from colorectal cancer. However, TACE is not a curative treatment, and tumor progression occurs in more than half of the patients treated. Despite advances and technical refinements of TACE, including the introduction of drug-eluting beads-TACE, the clinical efficacy of TACE has not been optimized, and improved arterial therapies are required. OBJECTIVE: The primary objectives of the VEROnA study are to evaluate the safety and tolerability of vandetanib-eluting radiopaque embolic beads (BTG-002814) in patients with resectable liver malignancies and to determine concentrations of vandetanib and the N-desmethyl metabolite in plasma and resected liver following treatment with BTG-002814. METHODS: The VEROnA study is a first-in-human, open-label, single-arm, phase 0, window-of-opportunity study of BTG-002814 (containing 100 mg vandetanib) delivered transarterially, 7 to 21 days before surgery in patients with resectable liver malignancies. Eligible patients have a diagnosis of colorectal liver metastases, or HCC (Childs Pugh A), diagnosed histologically or radiologically, and are candidates for liver surgery. All patients are followed up for 28 days following surgery. Secondary objectives of this study are to evaluate the anatomical distribution of BTG-002814 on noncontrast-enhanced imaging, to evaluate histopathological features in the surgical specimen, and to assess changes in blood flow on dynamic contrast-enhanced magnetic resonance imaging following treatment with BTG-002814. Exploratory objectives of this study are to study blood biomarkers with the potential to identify patients likely to respond to treatment and to correlate the distribution of BTG-002814 on imaging with pathology by 3-dimensional modeling. RESULTS: Enrollment for the study was completed in February 2019. Results of a planned interim analysis were reviewed by a safety committee after the first 3 patients completed follow-up. The recommendation of the committee was to continue the study without any changes to the dose or trial design, as there were no significant unexpected toxicities related to BTG-002814. CONCLUSIONS: The VEROnA study is studying the feasibility of administering BTG-002814 to optimize the use of this novel technology as liver-directed therapy for patients with primary and secondary liver cancer. TRIAL REGISTRATION: ClinicalTrial.gov NCT03291379; https://clinicaltrials.gov/ct2/show/NCT03291379. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13696.

Transarterial Chemoembolisation of Colorectal Liver Metastases with Irinotecan-Loaded Beads: A Bi-institutional Analysis of 125 Treatments in 53 Patients.

PURPOSE: To retrospectively review outcomes in patients treated for colorectal liver metastases with DEBIRI. MATERIALS AND METHODS: A retrospective analysis of patients with CRLM treated with DEBIRI was performed between 2008 and 2017 between two tertiary centres. Outcome parameters were overall survival and hepatic progression-free survival, as well as safety. Subgroup analyses were performed to assess the impact on outcomes of hepatic tumour burden at time of treatment, the presence of extrahepatic disease, prior systemic chemotherapy and the prior administration of systemic irinotecan-containing chemotherapy. RESULTS: Fifty-three patients received 125 treatments with DEBIRI over the study period. Median age of patients was 71 (range 41-88). Patients previously received a median of 1 line of chemotherapy (range 1-5). Median number of DEBIRI treatments was 2 (range 1-6). The median survival from first treatment was 14.5 months (range 1-107). Median hepatic progression-free survival was 5 months (0-86.5 months). The presence of extrahepatic disease (seen in 45% of patients) correlated with lower OS. Prolonged OS was seen in patients who received previous ablation and systemic chemotherapy. Technical success rate was found to be 99%. Post-procedural complication rate was 6%. CONCLUSION: Our findings add to the growing body of literature to support the safety profile of DEBIRI in the treatment of CRLM. Further studies will be necessary to help establish the optimum berth of DEBIRI in the treatment algorithm for colorectal liver metastases.

Pharmacomechanical thrombolysis in the management of paget-schroetter syndrome.

Paget-Schroetter syndrome (PSS) is a rare form of thoracic outlet syndrome caused by axillosubclavian vein thrombosis which typically presents in healthy young adults. Prompt therapy, traditionally by means of catheter-directed thrombolysis (CDT) prior to definitive surgery, can prevent the subsequent onset of postthrombotic syndrome (PTS) and considerable disability. As CDT is associated with major haemorrhage and high overall treatment cost, pharmacomechanical thrombectomy (PMT) seems to be an attractive alternative which combines pharmacological thrombolysis with mechanical clot disruption. The Trellis-8 peripheral infusion catheter is an example of such a treatment which provides topical thrombolysis in an isolated zone. We describe the use of the Trellis-8 PMT system in the successful management of three patients with PSS.

Placement of a branched stent graft into the false lumen of a chronic type B aortic dissection.

The treatment of chronic type B aortic dissections remains challenging and controversial. Currently most centers advocate open or endovascular intervention for patients with evidence of malperfusion, rupture or impending rupture, continued pain, or aneurysm formation. Regardless of the type of intervention, the incidence of complications or death remains high, even when undertaken in an elective setting. The standard endovascular treatment usually involves placement of a stent graft into the true lumen of the dissection in an effort to exclude the false lumen. This case report describes the placement of a branched stent graft into the false lumen of a patient with chronic type B dissection to encourage exclusion and thrombosis of the true lumen whilst maintaining flow to all visceral vessels.