Citations

Abstract In-stent stenosis has a reported prevalence of 14% to 19% at 1-yr follow-up after carotid stenting and is associated with an increased risk of acute ischemic stroke. 1,2 Risk factors include female sex, diabetes, and dyslipidemia. Cutting balloon angioplasty is a safe and effective treatment modality for the treatment of carotid in-stent stenosis, and alternative treatment options include observation with medical management and placement of another stent. 3,4 The authors present the case of a 61-yr-old man with carotid in-stent restenosis and progressive worsening on serial imaging with ultrasound. The patient had a history of carotid stenting for symptomatic stenosis 6 mo prior and was maintained on aspirin and clopidogrel. In light of the progressive worsening, the in-stent stenosis was confirmed on computed tomography (CT) angiogram. The options were discussed with the patient and he consented for treatment with cutting balloon angioplasty. Final angiogram showed improvement of the luminal diameter with a residual stenosis of 15%. The patient tolerated the procedure well and was discharged home on postoperative day 1. Follow-up ultrasound demonstrated moderate improvement in peak systolic velocities, and the plan is to continue observation with a clinical follow-up and repeat carotid Dopplers at 3 mo.

2014 Background: The cyclin D-CDK4/6-Rb pathway is activated in most glioblastomas. Abemaciclib is a potent CDK4/6 inhibitor with good brain penetration approved for HR+/HER2- breast cancer. In order to efficiently evaluate the potential impact of abemaciclib on overall survival (OS) in newly diagnosed glioblastoma and to simultaneously develop information regarding potential genomic biomarker associations, abemaciclib was included as an arm on the Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT) trial. INSIGhT is a phase II platform trial using response adaptive randomization and deep genomic profiling to more efficiently test experimental agents in MGMT unmethylated glioblastoma and potentially accelerate identification of novel therapies for phase III testing. Initial randomization was equal between abemaciclib, control, and two other experimental arms but subsequent randomization was adapted based on efficacy as determined by progression-free survival (PFS). Ineffective arms were discontinued and new arms added by protocol amendment. We report preliminary results for the abemaciclib arm which has completed accrual. Methods: Patients with newly diagnosed MGMT-unmethylated glioblastoma were randomized to receive either radiotherapy with concomitant and adjuvant temozolomide at standard doses or standard radiochemotherapy followed by adjuvant abemaciclib (150-200 mg orally BID). Treatment continued until progression or development of unacceptable toxicities. The primary endpoint was OS which was assessed using the log-rank test estimated via the Kaplan Meier method using a type I error of 5%. The hazard ratio (HR) was estimated using a cox proportional hazards model. Association between abemaciclib efficacy and cyclin D-CDK4/6-Rb pathway genomic alterations was also investigated. Results: There were 142 patients (69 control; 73 treated with abemaciclib). Abemaciclib was generally well-tolerated with no new toxicity signals identified. PFS was significantly longer (HR 0.67; p = 0.03, logrank test) with abemaciclib (median 6.54 months) compared to the control arm (median 5.88 months). For patients with activation of the CDK4 pathway the PFS HR was 0.64 (p-value = 0.04). However, there was no significant improvement in overall survival (HR 0.9; p-value > 0.05) between abemaciclib (median 15.5) compared to the control arm (median 15.5). Conclusions: Abemaciclib was well-tolerated and prolonged PFS but there is no evidence of an overall survival improvement compared to standard radiochemotherapy. Clinical trial information: NCT02977780.

2006 Background: Adaptive randomization adjusts enrollment rates based upon early trial results, which can allow for decreased enrollment for therapies less likely to meet the primary endpoint of a trial. CC-115, a CNS-penetrant, oral inhibitor of mammalian target of rapamycin kinase (mTOR) and deoxyribonucleic acid-dependent protein kinase (DNA-PK), was evaluated in the Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT) trial. As CC-115 was discontinued due to concerns about toxicity and unfavorable risk-to-benefit ratio, we sought to investigate the impact of adaptive randomization in its testing. Methods: In INSIGhT, adults with newly diagnosed MGMT-unmethylated glioblastoma and available genomic data are adaptively randomized to an experimental arm or the control arm of standard radiotherapy with concurrent and adjuvant temozolomide. Patients randomized to CC-115 received it (10mg po BID) with radiotherapy and as adjuvant monotherapy, and a safety lead-in 3+3 design was used for this arm. By simulating the INSIGhT trial with standard uniform randomization, we estimated the reduction of enrollment rate and sample size of the CC-115 arm that was attributable to adaptive randomization. Results: Twelve patients were randomized to CC-115; 58% (n = 7) patients had possible treatment-related CTCAE grade > 3 toxicity. Compared to the control arm, there was no significant difference in progression-free survival (PFS, HR 0.66, 95% CI 0.32-1.36, p = 0.3) or overall survival (OS, HR 0.93, 95% CI 0.43-2.03, p = 0.8). Based on early PFS results, randomization probability to CC-115 decreased from 25% to 16%. At the time of the CC-115 arm closure, 14% of enrolled INSIGhT patients had been randomized to this arm. Compared to average expected enrollment by standard randomization, the use of adaptive randomization decreased the number of patients randomized to CC-115 by 50% (12 patients vs. 18 patients [95% CI 11-25 patients]). Conclusions: The INSIGhT trial, designed with adaptive randomization, facilitated more efficient testing of CC-115 and decreased the number of patients allocated to the CC-115 arm relative to a standard randomization design. Clinical trial information: NCT02977780.

Abstract Embolic protection devices (EPDs) have become a standard of care during internal carotid artery revascularization. 1,2 This video is about a 57-yr-old-male who presented with a wake-up stroke with a left hemispheric syndrome. Head computed tomography angiography (CTA) revealed tandem occlusions of the proximal left internal carotid artery (ICA) and of the distal left middle cerebral artery (MCA) with an ASPECT (Alberta Stroke Program Early CT Score) score of 6. The patient underwent a cerebral angiogram and was treated with balloon angioplasty with a distal EPD and mechanical thrombectomy. The EPD became occluded with thrombus from the ICA and was retrieved through a 6-Fr Sofia (MicroVention) under continuous aspiration. Successful revascularization of the proximal ICA and distal MCA was achieved. No procedure-related complications occurred, and the patient's neurological exam improved. Tandem occlusions can occur in up to 15% of strokes. The optimal treatment can be controversial, but mechanical thrombectomy and ICA revascularization with a distal EPD appear to be safe and effective in selected patients. 3 Consent was obtained for the procedure and for the video production.

Abstract Intracranial atherosclerotic disease (ICAD) is a common cause of stroke. Antiplatelet therapy is the mainstay for symptomatic ICAD treatment. Endovascular management with submaximal angioplasty and/or intracranial stenting is reserved for patients with repeated ischemic events despite optimal medical therapy. We demonstrate intracranial angioplasty and stenting technique, technique indications, and sizing of stent and target vessel diameter. Stenting and angioplasty have been described in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis and Wingspan Stent System Post Market Surveillance trials. 1,2 Submaximal angioplasty has also been described. 3 This patient, who had been on dual antiplatelet therapy for several months, initially presented with occlusion of the left middle cerebral artery M2 inferior division and underwent mechanical thrombectomy with successful reperfusion. Postoperatively, the patient's symptoms did not improve. Medical management was optimized with heparin infusion. However, repeat stroke study demonstrated M2 inferior division reocclusion. A decision was made to proceed with intracranial angioplasty and stenting. P2Y12 levels were therapeutic. Under moderate conscious sedation, submaximal angioplasty of up to 80% of the normal M2 caliber was attempted. However, we observed persistent high-grade stenosis of the M2 inferior division. The major risk of crossing the lesion for angioplasty is vessel perforation. To safely perform this maneuver, we used a J-configured Synchro-2 microwire (Stryker). Because of the patient's recent thrombectomy, we also had prior tactile feedback about how much resistance was encountered while crossing the occlusion. We then deployed a balloon-mounted intracranial stent for optimal radial force across the stenotic area to restore perfusion. Postoperative computed tomography perfusion showed resolution of the previously noticed perfusion deficit. The patient gave informed consent for the procedures and video recording. Institutional review board approval was deemed unnecessary. Video. ©University at Buffalo Neurosurgery, September 2020. With permission.

Abstract Vascular access for cerebral angiography has traditionally been performed via the common femoral artery. It is crucial to obtain safe access to prevent complications that could lead to limb ischemia, groin hematoma, or retroperitoneal hematoma. This is especially true in neurointervention as many patients are anticoagulated or have received intravenous thrombolytics prior to their intervention. Special attention to anatomic landmarks, both grossly and radiographically, can help to assure safe access. The patient consented for this procedure. This video details rapid but safe femoral artery access in a patient undergoing emergent thrombectomy.

Abstract Management options for carotid stenosis include medical management, carotid endarterectomy, carotid stenting with distal filter protection, or stenting with either flow arrest or flow reversal techniques. 1 Flow reversal with transcarotid artery revascularization (TCAR) technique represents a hybrid approach with surgical access to the common carotid for endovascular placement of a stent in the internal carotid artery. This direct access to the carotid artery avoids navigating the challenging anatomy of the aortic arch with endovascular devices. 2 Compared to transfemoral stenting, TCAR possesses lower risk of transient ischemic attack and stroke, and compared to carotid endarterectomy, there is less risk of cranial neuropathy. 3,4 We present the case of an 87-yr-old man with recurrent severe stenosis (85%) of the right internal carotid artery. The patient had a remote history of bilateral endarterectomies for asymptomatic stenosis and was found with recurrence and progression of right internal carotid artery stenosis. Options were discussed and decision was made to proceed with TCAR after he consented for the procedure. The patient tolerated the procedure well with satisfactory revascularization. Exam remained unremarkable prior to discharge on postoperative day 1 and during follow-up at 1 mo. Patient consented to the publication of their image.

Abstract Cerebral venous sinus stenting has gained popularity in recent years as a safe and efficacious treatment of selected patients with idiopathic intracranial hypertension (IIH) and focal venous sinus stenosis.1–3 - 3 The main goal of treatment is to prevent visual loss, and often patients report resolution of headache and visual symptoms within 21 mo of mean follow-up.4–8 - 8 We present the case of a 57-yr-old woman with medically refractory IIH, bilateral sinus stenosis, and a mass lesion causing stenosis on the left. Venous angiogram with pressure monitoring was completed with the patient awake, which showed a significant pressure gradient on the right (19 mm Hg) and borderline gradient on the left (8 mm Hg). Options were reviewed and decision was made to proceed with the treatment of the right-sided stenosis with stenting and continue with the observation of the lesion on the left to prevent further visual deterioration. The patient consented for the procedure, and she tolerated the procedure well. Neurological exam remained at baseline, and she was discharged home on post-operative day #1. At 2 mo’s follow-up, the patient reported improvement in headaches and remained intact neurologically.

Abstract Purpose: Small-bowel adenocarcinoma (SBA) is rare, and no standard of care exists for metastatic disease beyond first-line FOLFOX/CAPOX. SBA has higher rates of microsatellite instability (MSI-H) and T-lymphocyte infiltration than other gastrointestinal cancers. We hypothesize that pembrolizumab, a PD-1 inhibitor, will induce antitumor response. Patients and Methods: Patients with previously treated advanced SBA received pembrolizumab 200 mg i.v. every 3 weeks until disease progression (PD), toxicity, or 35 doses maximum. Primary endpoint was confirmed overall response rate (ORR) with secondary progression-free survival (PFS), overall survival (OS), and toxicity assessment endpoints. Outcomes were stratified by tumor location, microsatellite stability (MSS) or instability (MSI-H), and PD-L1 level. Results: Forty patients were treated for a median duration of four cycles (range, 1–35). All patients are off study treatment due to PD (75%), death (10%), 35 cycles completed (8%), refusal (3%), and adverse effects (AEs, 5%). Three confirmed partial responses [PRs; 8%; 95% confidence interval (CI), 2–20] did not meet predefined success criteria of ORR 30%. Median OS (7.1 months; 95% CI, 5.1–17.1) and median PFS (2.8 months; 95% CI, 2.7–4.2) were similar across primary tumor sites. One confirmed PR (3%) was seen in patients with low MSS/MSI tumors and correlated with high tumor mutation burden (TMB). Fifty percent of patients with MSI-H tumors achieved PR and remain alive without progression. Twenty-five patients (63%) had grade ≥3 AEs and 11 patients (28%) had grade 4/5 AEs. Conclusions: In the largest study of SBA to date, pembrolizumab did not induce the hypothesized response rate; however, we did identify responses in key biomarker-selected cohorts.

Abstract Wide-necked bifurcation aneurysms pose technical and anatomical challenges to endovascular treatment, which make the simpler assisted (balloon or single stent) coiling techniques less effective. 1 Consequently, unique endovascular solutions to treat such aneurysms have been devised. 2,3 One such device is PulseRider (Cerenovus, New Brunswick, New Jersey), which is designed to provide neck support for a coil mass while protecting the bifurcation. 3 The device comprises a body or stem that is deployed in the parent artery and a saddle component that sits at the aneurysm neck to keep the coil mass away from the bifurcation. There are several technical nuances involved in successful use of the device during positioning, deployment, and detachment. 3 We present a surgical video detailing the steps of PulseRider-assisted coiling of unruptured basilar bifurcation (or basilar apex) aneurysms. The first case highlights index treatment at diagnosis and the second showcases treatment of a recurrent basilar apex aneurysm. Both patients provided informed consent to the procedure. We also briefly discuss the rationale for treating basilar apex aneurysms. 4,5