Citations

Abstract Wide-necked aneurysms often pose challenges for distal access to the distal vasculature. This 64-yr-old woman without neurological deficits presented with atypical headaches of gradual onset. MRI revealed a large, symptomatic, unruptured carotid terminus aneurysm incorporating the origin of both the middle (MCA) and anterior cerebral arteries (ACA). Its wide neck created significant risks to coil prolapse and parent vessel compromise, risking stroke. With other options of higher risks, we recommended an around-the-world technique. Standard transfemoral access was used to the right internal carotid artery (ICA) with a 6F-Shuttle sheath and intracranial carotid with a 6F-Sofia distal access catheter. With dual-microcatheter access, 1 catheter was placed in the aneurysm dome, a second in the MCA for stent placement. Advancing the wire around the aneurysm first formed a loop from the lateral to medial wall for access to the MCA. The microcatheter was then advanced around the wire into the MCA, keeping the loop within the dome. With the loop's distal tip anchored, the distal end of the stent was deployed and anchored into the MCA. Both pitfalls (ie, lack of sufficient distal access, collapse of stent device during deployment) were resolved using a balloon catheter. With the balloon positioned and inflated as the anchor, the wire and catheter were pulled together. The loop in the aneurysm's dome straightened out across the neck, the stent was advanced into the MCA, and coiling proceeded. A large neck remnant had partially closed on 6-mo follow-up angiogram. Patient consented to undergo the procedure. Illustrations in video published/printed with permission from Mayfield Clinic.

Abstract Sidewall aneurysm treatment often requires complex management strategies. These can include advanced clipping techniques or stent-assisted coiling techniques. Endovascular coiling alone has been associated with high recurrence rates and is often not feasible. 1-4 Flow-diversion embolization has recently become a standard of care for many aneurysms, demonstrating high occlusion rates. 4,5 However, the third generation of coil-assist stents can be delivered with 0.0165” microcatheters, being an ideal adjunct to manage this group of aneurysms in more distal locations. In this video, a 16-yr-old teenager with Parry-Romberg syndrome and congenital adrenal hyperplasia had an incidental finding of a 6.5-mm sidewall aneurysm arising off the angular branch of the left middle cerebral artery, found during the work-up of complex partial seizures. The patient consented to the procedure. Due to his young age and aneurysm size, a decision was made to treat the aneurysm through an endovascular approach. Under general anesthesia, a transfemoral approach was carried out using a 6-French short sheath. A 6-French guiding catheter was left in the distal cervical left internal carotid artery; a 0.0165” microcatheter was used to first deploy a 3.0 × 15 mm Neuroform Atlas stent, completely covering the length of the aneurysm. Then, the stent was traversed with the microcatheter to coil the aneurysm. Follow-up cerebral angiogram confirmed complete occlusion of the aneurysm.

Abstract BACKGROUND CC-115 is an oral, CNS-penetrant, selective inhibitor of mammalian target of rapamycin kinase (mTOR) and deoxyribonucleic acid-dependent protein kinase (DNA-PK). Both targets are important in glioblastoma; PI3K/Akt/mTOR signaling is hyperactive in most glioblastomas, and DNA-PK is integral to repair of radiotherapy-mediated DNA damage. To investigate CC-115 in newly diagnosed glioblastoma and explore potential genomic biomarker associations, CC-115 was evaluated in the Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT) trial, an adaptive platform trial designed to efficiently test experimental agents. METHODS Adults with newly diagnosed MGMT-unmethylated glioblastoma, with genomic data available, are eligible for this ongoing trial. Patients are adaptively randomized to one of several experimental arms or the control arm: standard radiotherapy with concurrent and adjuvant temozolomide. The primary endpoint is overall survival (OS). Patients randomized to CC-115 (10mg po BID) received it concurrently with radiotherapy and as adjuvant monotherapy. As the first in-human use of CC-115 with radiation, a safety lead-in 3 + 3 design was used. RESULTS Twelve patients were randomized to CC-115; seven patients had possible treatment-related CTCAE grade > 3 toxicity, including four pre-specified dose-limiting toxicities: liver function abnormality (n=1), hyperlipidemia (n=1), lipase elevation (n=1) and cerebral edema (n=1). There was no significant difference in progression-free survival (PFS, median 4.2 months [CC-115] vs. 5.2 months, p=0.9) or OS (median 10.1 months [CC-115] vs. 14.5 months, p=0.9) compared to the 50 patients randomized to the control arm. Based on early PFS results, randomization probability to CC-115 decreased from 25% to < 10% at time of the trial arm closure. CONCLUSION Concurrent and adjuvant CC-115 was associated with toxicity and failed to improve PFS or OS. The INSIGhT trial design allowed for more efficient testing of CC-115, decreasing patients and resources allocated to a therapy that was discontinued due to concerns about toxicity and unfavorable risk-to-benefit ratio.

Abstract 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 ER/PR/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) without temozolomide. Treatment continued until progression or development of unacceptable toxicities. The primary endpoint was OS. Association between abemaciclib efficacy and cyclin D-CDK4/6-Rb pathway genomic alterations was also investigated. RESULTS There were 123 patients (50 control; 73 treated with abemaciclib). Abemaciclib was generally well-tolerated with no new toxicity signals identified. PFS was significantly longer (p=0.03, logrank test) with abemaciclib (median 6.31 months 95% CI [5.29, 8.18]) compared to the control arm (5.16 months 95% CI [4.37, 6.28]). 28/50 control and 36/73 abemaciclib patients remain alive. CONCLUSION Preliminary analysis suggests that abemaciclib increases PFS compared to control. Updated toxicity, PFS and survival data and potential genomic biomarker associations will be presented.

I. Executive Summary Background The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS.

The coronavirus disease 2019 (COVID-19) global pandemic has resulted in diversion of healthcare resources to the management of patients infected with SARS-CoV-2 virus. Elective interventions and surgical procedures in most countries have been postponed and operating room resources have been diverted to manage the pandemic. The Venous and Lymphatic Triage and Acuity Scale was developed to provide an international standard to rationalise and harmonise the management of patients with venous and lymphatic disorders or vascular anomalies. Triage urgency was determined based on clinical assessment of urgency with which a patient would require medical treatment or surgical intervention. Clinical conditions were classified into six categories of: (1) venous thromboembolism (VTE), (2) chronic venous disease, (3) vascular anomalies, (4) venous trauma, (5) venous compression and (6) lymphatic disease. Triage urgency was categorised into four groups and individual conditions were allocated to each class of triage. These included (1) medical emergencies (requiring immediate attendance), example massive pulmonary embolism; (2) urgent (to be seen as soon as possible), example deep vein thrombosis; (3) semi-urgent (to be attended to within 30–90 days), example highly symptomatic chronic venous disease, and (4) discretionary/non-urgent- (to be seen within 6–12 months), example chronic lymphoedema. Venous and Lymphatic Triage and Acuity Scale aims to standardise the triage of patients with venous and lymphatic disease or vascular anomalies by providing an international consensus-based classification of clinical categories and triage urgency. The scale may be used during pandemics such as the current COVID-19 crisis but may also be used as a general framework to classify urgency of the listed conditions.

Abstract This is a protocol for a co‐registered Cochrane and Campbell Review (Methodology). The objectives are as follows: To identify, describe and assess methods for: when to replicate a systematic review; how to replicate a systematic review.

5517 Background: Anti-angiogenic therapy is active in OC; the combination of VEGF and mTOR inhibitors is hypothesized to further improve activity. This report is the OC cohort of a multi-histology phase II study assessing the activity and toxicity of B/T. Methods: Patients (Pts) with recurrent epithelial OC who had received ≤ 2 chemotherapy regimens and no prior treatment with a VEGF or mTOR inhibitor were eligible. A two-stage design was used with second stage accrual if >6 pts had objective responses (OR) or >10 pts of the first 25 remained progression-free (PF) at six months (mo). Pre-defined end-points for a recommendation for further clinical trial evaluation included at least 15/50 with OR or 26/50 PF at six mo. Treatment included T 25 mg IV wkly and B 10 mg/kg IV q14 days on 28 day cycles. Results: 58 pts were enrolled (the first 50 pts are used to determine a final recommendation). Median age=62 (range 35-82). A median of 4 (range 1-23) cycles were administered. 24 were platinum-sensitive, 34 resistant. Off-study reasons included 13 adverse events and disease progression in 38. 3 refused further therapy due to toxicity. 14 of the first 50 pts had partial response (PR) (9 platinum-resistant); 25/50 remained PF (8 PR, 15 SD, 2 non-progressing) at 6 mo. Grade (gr) 3/4 toxicities occurring >2 events include: fatigue (4), stomatitis (7), hypertension (5), neutropenia (4), thrombocytopenia (4), hypokalemia (3). One rectal and one vaginal fistula, and two colonic perforations (one gr 2 and one gr 3 during cycles 3 and 1 respectively) were observed. Episodes of gr 1/2 oral, nasal, pulmonary, vaginal and gastrointestinal hemorrhage were also observed. Conclusions: Although the OR and PFS did not reach pre-defined standards, the numbers of OR and 6 mo PFS suggest potential enhanced activity with a combination of mTOR inhibitor with anti-angiogenic therapy. Other combinations of these targeted agents may result in more satisfactory activity with less toxicity. N01-CM-62203 (PMH) N01-CM-62208 (Southeast Phase 2) N01 CM-62209 (CCCP) N01-CM-62204 (NYCC) N01-CM-2011-0071C (Chicago) N01-CM62205 (Mayo) Clinical trial information: NCT01010126.