Results from a first-in-human phase I safety trial to evaluate the use of a vascularized pericranial/temporoparietal fascial flap to line the resection cavity following resection of newly diagnosed glioblastoma.

PURPOSE: The efficacy of systemic therapies for glioblastoma (GBM) remains limited due to the constraints of systemic toxicity and blood-brain barrier (BBB) permeability. Temporoparietal fascial flaps (TPFFs) and vascularized peri cranial flaps (PCF) are not restricted by the blood-brain barrier (BBB), as they derive their vascular supply from branches of the external carotid artery. Transposition of a vascularized TPFF or PCF along a GBM resection cavity may bring autologous tissue not restricted by the BBB in close vicinity to the tumor bed microenvironment, permit ingrowth of vascular channels fed by the external circulation, and offer a mechanism of bypassing the BBB. In addition, circulating immune cells in the vascularized flap may have better access to tumor-associated antigens (TAA) within the tumor microenvironment. We conducted a first-in-human Phase I trial assessing the safety of lining the resection cavity with autologous TPFF/PCF of newly diagnosed patients with GBM. METHODS: 12 patients underwent safe, maximal surgical resection of newly diagnosed GBMs, followed by lining of the resection cavity with a pedicled, autologous TPFF or PCF. Safety was assessed by monitoring adverse events. Secondary analysis of efficacy was examined as the proportion of patients experiencing progression-free disease (PFS) as indicated by response assessment in neuro-oncology (RANO) criteria and overall survival (OS). The study was powered to determine whether a Phase II study was warranted based on these early results. For this analysis, subjects who were alive and had not progressed as of the date of the last follow-up were considered censored and all living patients who were alive as of the date of last follow-up were considered censored for overall survival. For simplicity, we assumed that a 70% PFS rate at 6 months would be considered an encouraging response and would make an argument for further investigation of the procedure. RESULTS: Median age of included patients was 57 years (range 46-69 years). All patients were Isocitrate dehydrogenase (IDH) wildtype. Average tumor volume was 56.6 cm3 (range 14-145 cm3). Resection was qualified as gross total resection (GTR) of all of the enhancing diseases in all patients. Grade III or above adverse events were encountered in 3 patients. No Grade IV or V serious adverse events occurred in the immediate post-operative period including seizure, infection, stroke, or tumor growing along the flap. Disease progression at the site of the original tumor was identified in only 4 (33%) patients (median 23 months, range 8-25 months), 3 of whom underwent re-operation. Histopathological analyses of those implanted flaps and tumor bed biopsy at repeat surgery demonstrated robust immune infiltrates within the transplanted flap. Importantly, no patient demonstrated evidence of tumor infiltration into the implanted flap. At the time of this manuscript preparation, only 4/12 (33%) of patients have died. Based on the statistical considerations above and including all 12 patients 10/12 (83.3%) had 6-month PFS. The median PFS was 9.10 months, and the OS was 17.6 months. 4/12 (33%) of patients have been alive for more than two years and our longest surviving patient currently is alive at 60 months. CONCLUSIONS: This pilot study suggests that insertion of pedicled autologous TPFF/PCF along a GBM resection cavity is safe and feasible. Based on the encouraging response rate in 6-month PFS and OS, larger phase II studies are warranted to assess and reproduce safety, feasibility, and efficacy. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION FOR PROSPECTIVELY REGISTERED TRIALS: ClinicalTrials.gov ID NCT03630289, dated: 08/02/2018.

Short and long-term prognostic value of intraoperative motor evoked potentials in brain tumor patients: a case series of 121 brain tumor patients.

PURPOSE: Iatrogenic neurologic deficits adversely affect patient outcomes following brain tumor resection. Motor evoked potential (MEP) monitoring allows surgeons to assess the integrity of motor-eloquent areas in real-time during tumor resection to lessen the risk of iatrogenic insult. We retrospectively associate intraoperative transcranial and direct cortical MEPs (TC-MEPs, DC-MEPs) to early and late post-operative motor function to prognosticate short- and long-term motor recovery in brain tumor patients undergoing surgical resection in peri-eloquent regions. METHODS: We reviewed 121 brain tumor patients undergoing craniotomies with DC-MEP and/or TC-MEP monitoring. Motor function scores were recorded at multiple time-points up to 1 year postoperatively. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were calculated at each time point. RESULTS: The sensitivity, specificity, PPV, and NPV of TC-MEP in the immediate postoperative period was 17.5%, 100%, 100%, and 69.4%, respectively. For DC-MEP monitoring, the respective values were 25.0%, 100%, 100%, and 68.8%. By discharge, sensitivity had increased for both TC-MEP and DC MEPs to 43.8%, and 50.0% respectively. Subset analysis on patients without tumor recurrence/progression at long term follow-up (n = 62 pts, 51.2%) found that all patients with stable monitoring maintained or improved from preoperative status. One patient with transient intraoperative TC-MEP loss and permanent DC-MEP loss suffered a permanent deficit. CONCLUSION: Brain tumor patients who undergo surgery with intact MEP monitoring and experience new postoperative deficits likely suffer transient deficits that will improve over the postoperative course in the absence of disease progression.

Improvement in visual outcomes of patients with base of skull meningioma as a result of evolution in the treatment techniques in the last three decades: a systematic review.

PURPOSE: We systematically reviewed visual outcomes over the last three decades in patients undergoing treatment for base of skull (BOS) meningiomas and provide recommendations to preserve vision. METHODS: In accordance with the PRISMA guidelines for systematic reviews, a search was conducted from 6/1/2022-9/1/2022 using PubMed and Web of Science. Inclusion criteria included (1) patients treated for BOS meningiomas (2) treatment modality specified (3) specifics of surgical techniques and/or dose/fractions of radiotherapy (4) individual patient outcomes of treatment. Each study was assessed for bias based on study design and heterogeneity of results. RESULTS: A total of 50 studies were included (N = 2911). When comparing improved vision versus unchanged or worsened vision, studies investigating surgery alone published from 2006 and onward had significantly better visual outcomes compared to pre-2006 studies (p = 0.02). When comparing improved vision versus unchanged or worsened vision, studies investigating combined therapy with surgery and radiation published from 2008 and onward had significantly better visual outcomes compared to pre-2008 studies (p < 0.01). Combined modality therapy was less likely to worsen vision compared to either surgery or radiation monotherapy (p < 0.01). However, surgery and radiation monotherapy were more likely to actually improve outcomes compared to combination therapy (p < 0.01). CONCLUSION: For over a decade we have observed improvement in visual outcomes in patients managed for meningioma of BOS, likely attributing the innovation in microsurgical and more targeted and conformal radiation techniques. Combination therapy may be the safest option for preventing worsening of vision, but the highest rates of improving visual function are achieved through monotherapy when indicated.

Dolichoectatic vertebrobasilar aneurysms: a systematic review and meta-analysis of management strategies and outcomes.

OBJECTIVE: The aim of this study was to describe the efficacy, clinical outcomes, and complications of open cerebrovascular surgery, endovascular surgery, and conservative management of dolichoectatic vertebrobasilar aneurysms (DVBAs). METHODS: Relevant articles were retrieved from PubMed, Scopus, Web of Science, and Cochrane databases according to PRISMA guidelines. A meta-analysis was conducted for clinical presentation, treatment protocols, and clinical outcomes-good (improved or stable clinical status) or poor (deteriorated clinical status or death)-and mortality rates. RESULTS: The 9 identified articles described 41 cases (27.5%) of open cerebrovascular surgery, 61 endovascular procedures (40.9%), and 47 cases (31.5%) of conservative management for DVBAs. The total cohort had a good outcome rate of 51.9% (95% CI 28.3%-74.6%), a poor outcome rate of 45.5% (95% CI 23.0%-70.1%), and a mortality rate of 22.3% (95% CI 11.8%-38.0%). The treatment groups had comparable good clinical outcome rates (open cerebrovascular surgery group: 24.7% [95% CI 2.9%-78.2%]; endovascular surgery group: 69.0% [95% CI 28.7%-92.5%]; conservative management group: 57.7% [95% CI 13.0%-92.5%]; p = 0.19) and poor outcome rates (open vascular surgery group: 75.3% [95% CI 21.8%-97.1%]; endovascular surgery group: 27.2% [95% CI 5.6%-0.70.2%]; conservative management group: 39.9% [95% CI 9.1%-81.6%]; p = 0.15). The treatment groups also had comparable mortality rates (open vascular surgery group: 39.5% [95% CI 11.4%-76.8%]; endovascular surgery group: 15.8% [95% CI 4.4%-43.0%]; conservative management group: 19.2% [95% CI 6.8%-43.5%]; p = 0.23). CONCLUSIONS: The current study of DVBAs illustrated poor outcomes and high mortality rates regardless of the treatment modality. The subgroup analysis showed heterogeneity among the subgroups and advice for personalized management.

Stroke mechanisms in adult moyamoya disease: The association between infarction patterns and quantitative magnetic resonance angiography flow state.

INTRODUCTION: Flow augmentation is the mainstay treatment for moyamoya disease as hemodynamic failure is believed to be the dominant mechanism. We aimed to investigate the mechanisms of stroke in moyamoya disease by assessing the relationship between infarction patterns and quantitative magnetic resonance angiography flow state. METHODS: A retrospective study of adult patients with suspected MMD who presented with MRI confirmed acute ischemic stroke predating or following QMRA by a maximum of six months between 2009 and 2021 was conducted. Of the 177 consecutive patients with MMD who received QMRA, 35 patients, consisting of 41 hemispheres, met inclusion criteria. Flow-status was dichotomized into low-flow and normal-flow state based on previously established criteria. RESULTS: Mixed infarction pattern was the most frequent finding (70.7 %), followed by embolic (17.1 %), perforator (7.3 %), and internal borderzone (IBZ) (4.9 %). Infarction patterns were further dichotomized into IBZ+ (internal borderzone alone or mixed) and IBZ- (no internal borderzone constituent). Low-flow states were not significantly more frequent in the IBZ+ compared to IBZ- population (48.4 % vs. 20.0 %, p = 0.14). Ipsilateral posterior cerebral artery fractional flow was significantly higher with IBZ+ compared to IBZ- (345.0 % vs. 214.7 %, p = 0.04). CONCLUSION: Mixed infarction pattern was the most common pattern of infarction in patients with moyamoya disease, implying hypoperfusion and thromboembolism are codominant stroke mechanisms. An association between ICA flow status and infarction pattern was not found, although QMRA evidence of more robust posterior cerebral artery leptomeningeal collaterals was found in patients with a hypoperfusion contribution to their stroke mechanism.

Stimulated Raman histology facilitates accurate diagnosis in neurosurgical patients: a one-to-one noninferiority study.

OBJECTIVE: Stimulated Raman histology (SRH) offers efficient and accurate intraoperative neuropathological tissue analysis without procedural alteration to the diagnostic specimen. However, there are limited data demonstrating one-to-one tissue comparisons between SRH and traditional frozen sectioning. This study explores the non-inferiority of SRH as compared to frozen section on the same piece of tissue in neurosurgical patients. METHODS: Tissue was collected over a 1-month period from 18 patients who underwent resection of central nervous system lesions. SRH and frozen section analyses were compared for diagnostic capabilities as well as assessed for quality and condition of tissue via a survey completed by pathologists. RESULTS: SRH was sufficient for diagnosis in 78% of specimens as compared to 94% of specimens by frozen section of the same specimen. A Fisher's exact test determined there was no significant difference in diagnostic capability between the two groups. Additionally, both quality of SRH and condition of tissue after SRH were deemed to be non-inferior to frozen section. CONCLUSIONS: This study provides further evidence for the non-inferiority of SRH techniques. It is also the first study to demonstrate SRH accuracy using one-to-one tissue analysis in neuropathological specimens.

Cranial transposition and revascularization of autologous omentum: a novel surgical technique for resection of recurrent glioblastoma multiforme.

Glioblastoma multiforme (GBM) patients continue to suffer a poor prognosis. The blood brain barrier (BBB) comprises one of the obstacles for therapy, creating a barrier that decreases the bioavailability of chemotherapeutic agents in the central nervous system. Previously, a vascularized temporoparietal fascial scalp flap (TPFF) lining the resection cavity was introduced in a trial conducted in our institution, in newly-diagnosed GBM patients in an attempt to bypass the BBB after initial resection. In this paper, we report on a new technique to bypass the BBB after re-resection and potentially to allow tumor antigens to be surveilled by the immune system. The study aims to assess the feasibility of performing a cranial transposition and revascularization of autologous omentum after re-resection of GBM. Laparoscopically harvested omental free flap was transposed to the resection cavity by a team consisting of neurosurgeons, otolaryngologists, and general surgeons. This was done as part of a single center, single arm, open-label, phase I study. Autologous abdominal omental tissue was harvested laparoscopically on its vascularized pedicle in 2 patients, transposed as a free flap, revascularized using external carotid artery, and carefully laid into the tumor resection cavity. Patients did well postoperatively returning to baseline activities. Graft viability was confirmed by cerebral angiogram. Omental cranial transposition of a laparoscopically harvested, vascularized flap, into the cavity of re-resected GBM patients is feasible and safe in the short term. Further studies are needed to ascertain whether such technique can improve progression free survival and overall survival in these patients.

Repeated superselective intraarterial bevacizumab after blood brain barrier disruption for newly diagnosed glioblastoma: a phase I/II clinical trial.

PURPOSE: Pre-clinical evidence suggests bevacizumab (BV) depletes the GBM peri-vascular cancer-stem cell niche. This phase I/II study assesses the safety and efficacy of repeated doses of superselective intra-arterial cerebral infusion (SIACI) of BV after blood-brain barrier disruption (BBBD). METHODS: Date of surgery was day 0. Evaluated patients received repeated SIACI bevacizumab (15 mg/kg) with BBBD at days 30 ± 7, 120 ± 7, and 210 ± 7 along with 6 weeks of standard chemoradiation. Response assessment in neuro-oncology criteria and the Kaplan-Meier product-limit method was used to evaluate progression free and overall survival (PFS and OS, respectively). RESULTS: Twenty-three patients with a median age of 60.5 years (SD = 12.6; 24.7-78.3) were included. Isocitrate dehydrogenase mutation was found in 1/23 (4%) patients. MGMT status was available for 11/23 patients (7 unmethylated; 3 methylated; 1 inconclusive). Median tumor volume was 24.0 cm3 (SD = 31.1, 1.7-48.3 cm3). Median PFS was 11.5 months (95% CI 7.7-25.9) with 6, 12, 24 and 60 month PFS estimated to be 91.3% (95% CI 69.5-97.8), 47.4% (26.3-65.9), 32.5% (14.4-52.2) and 5.4% (0.4-21.8), respectively. Median OS was 23.1 months (95% CI 12.2-36.9) with 12, 24, and 36 month OS as 77.3% (95% CI 53.6-89.9), 45.0% (22.3-65.3) and 32.1% (12.5-53.8), respectively. CONCLUSIONS: Repeated dosing of IA BV after BBBD offers an encouraging outcome in terms of PFS and OS. Phase III trials are warranted to determine whether repeated IA BV combined with Stupp protocol is superior to Stupp protocol alone for newly diagnosed GBM.

Technical aspects and operative nuances using a high-definition 4K-3-dimensional exoscope for carotid endarterectomy surgery.

PURPOSE: Carotid endarterectomy (CEA) is effective in treating carotid artery stenosis to prevent stroke. Historically, this operation has been performed utilizing loupe magnification with or without the operating microscope (OM). However, there remains a need for continued improvement in operative visualization and surgical ergonomics. Recently, newly developed digital 'exoscope' has provided the surgeon with unique lighting and magnification as well as improvements in surgical ergonomics and working angle. We sought to review our cumulative experience using a novel 4K high-definition (4K-HD) 3-dimensional (3D) exoscope (EX) for CEA surgery. METHODS: All CEA surgery cases at our institution between 2013 and 2019 using the 4K-HD 3D EX were reviewed. Operative parameters, patient outcome and operator's assessment of the EX compared to OM-assisted cases was conducted. RESULTS: 28 patients were treated, 10 of which were operated using the EX. All procedures were performed without perioperative complications, or significant differences in operative parameters (blood loss <20 cm3 and 164 ± 49.5 minutes) compared to OM-assisted cases. Operators reported improved level of comfort performing 'high' bifurcation surgery and improved visualization and posture during inspection of the distal ICA lumen as primary advantages of EX-assisted CEA over OM-assisted CEA. CONCLUSIONS: The ORBEYE EX, albeit a learning curve necessitating a short period of the OR team, provided safety and outcome comparable to OM-assisted surgery. Potential advantages noted were improved visualization and ergonomics specifically for when extreme working angles were required. Our experience suggests that the exoscope may become a valuable alternative to standard magnification tools in CEA surgery.

Correction to: Super selective intra­arterial cerebral infusion of modern chemotherapeutics after blood-brain barrier disruption: where are we now, and where we are going.

The name of author Jason A. Ellis was missing in the intial online publication, and there was a typo in the sixth author's first name. The original article has been corrected.

Super selective intra-arterial cerebral infusion of modern chemotherapeutics after blood-brain barrier disruption: where are we now, and where we are going.

INTRODUCTION: Intra-arterial (IA) delivery of therapeutic agents across the blood-brain barrier (BBB) is an evolving strategy which enables the distribution of high concentration therapeutics through a targeted vascular territory, while potentially limiting systemic toxicity. Studies have demonstrated IA methods to be safe and efficacious for a variety of therapeutics. However, further characterization of the clinical efficacy of IA therapy for the treatment of brain tumors and refinement of its potential applications are necessary. METHODS: We have reviewed the preclinical and clinical evidence supporting superselective intraarterial cerebral infusion (SSIACI) with BBB disruption for the treatment of brain tumors. In addition, we review ongoing clinical trials expanding the applicability and investigating the efficacy of IA therapy for the treatment of brain tumors. RESULTS: Trends in recent studies have embraced the use of SSIACI and less neurotoxic chemotherapies. The majority of trials continue to use mannitol as the preferred method of hyperosmolar BBB disruption. Recent preclinical and preliminary human investigations into the IA delivery of Bevacizumab have demonstrated its safety and efficacy as an anti-tumor agent both alone and in combination with chemotherapy. CONCLUSION: IA drug delivery may significantly affect the way treatments are delivered to patients with brain tumors, and in particular GBM. With refinement and standardization of the techniques of IA drug delivery, improved drug selection and formulations, and the development of methods to minimize treatment-related neurological injury, IA therapy may offer significant benefits for the treatment of brain tumors.

Cerebral revascularization after the Carotid Occlusion Surgery Study: what candidates remain, and can we do better?

OBJECTIVECerebral revascularization for carotid occlusion was previously a mainstay procedure for the cerebrovascular neurosurgeon. However, the 1985 extracranial-intracranial bypass trial and subsequently the Carotid Occlusion Surgery Study (COSS) provided level 1 evidence via randomized controlled trials against bypass for symptomatic atherosclerotic carotid occlusion disease. However, in a small number of patients optimal medical therapy fails, and some patients with flow-limiting stenosis develop a perfusion-dependent neurological examination. Therefore it is necessary to further stratify patients by risk to determine who may most benefit from this intervention as well as to determine perioperative morbidity in this high-risk patient population.METHODSA retrospective review was performed of all revascularization procedures done for symptomatic atherosclerotic cerebrovascular steno-occlusive disease. All patients undergoing revascularization after the publication of the COSS in 2011 were included. Perioperative morbidity and mortality were assessed as the primary outcome to determine safety of revascularization in this high-risk population. All patients had documented hypoperfusion on hemodynamic imaging.RESULTSAt total of 35 revascularization procedures were included in this review. The most common indication was for patients with recurrent strokes, who were receiving optimal medical therapy and who suffered from cerebrovascular steno-occlusion. At 30 days only 3 perioperative ischemic events were observed, 2 of which led to no long-term neurological deficit. Immediate graft patency was good, at 94%. Long term, no further strokes or ischemic events were observed, and graft patency remained high at 95%. There were no factors associated with perioperative ischemic events in the variables that were recorded.CONCLUSIONSCerebral revascularization may be done safely at high-volume cerebrovascular centers in high-risk patients in whom optimal medical therapy has failed. Further research must be done to develop an improved methodology of risk stratification for patients with symptomatic atherosclerotic cerebrovascular steno-occlusive disease to determine which patients may benefit from intervention. Given the high risk of recurrent stroke in certain patients, and the fact that patients fail medical therapy, surgical revascularization may provide the best method to ensure good long-term outcomes with manageable up-front risks.

Superselective intraarterial cerebral infusion of cetuximab with blood brain barrier disruption combined with Stupp Protocol for newly diagnosed glioblastoma.

OBJECTIVE: We describe the first case of a novel treatment for a newly diagnosed glioblastoma (GBM) using superselective intraarterial cerebral infusion (SIACI) of cetuximab after osmotic disruption of the blood-brain barrier (BBB) with mannitol. A 51year-old female underwent craniotomy for removal of a right frontal GBM. Pathology confirmed EGFR amplification, and she underwent three treatments of SIACI of cetuximab to the tumor site. The first treatment was given within a week of starting standard of care chemoradiation (Stupp protocol), which is a combination of radiation treatment (2 Gy per/ day x 30 days, total of 60 Gy) and oral temozolomide (75 mg/m2). The second and third SIACI of cetuximab were administered 3 and 6 months later, while the patient continued on maintenance temozolomide. Post-radiation changes on MRI were stable, and there were no signs of recurrence at 4 and 6 months post-resection. Herein, we detail the technical aspects of this novel treatment paradigm and suggest that SIACI of cetuximab after BBB disruption using mannitol, combined with the standard of care chemoradiation therapy, may be an effective treatment method for newly diagnosed EGFR amplified glioblastoma.

Durability of single dose intra-arterial bevacizumab after blood/brain barrier disruption for recurrent glioblastoma.

BACKGROUND: Bevacizumab (BV) has been used to treat recurrent glioblastoma with a progression free survival of approximately 3-3.5 months. Typically, it is administered intravenously every 2-3 weeks at dosages ranging from 5-15 mg/kg. Serious side effects include GI tract perforations, hematologic disorders, intracranial hemorrhage, and malignant hypertension. We hypothesized that selective intracranial intra-arterial infusion (SIACI) of BV following blood/brain barrier disruption (BBBD) with mannitol may allow for reduced dosage, lower toxicity, and equivalent or superior progression free survival (PFS). METHODS: Sixteen patients (8 males & 8 females) with a mean age of 55 years (range 27-68), KPS>70, and recurrent glioblastoma were enrolled. All patients underwent super-selective catheterization and were given a single intra-arterial dose of 15 mg/kg BV following osmotic blood/brain barrier disruption with mannitol to the arteries supplying the tumor. The patients had no additional treatment following that initial SIACI mannitol and BV until they met criteria for progression. PFS was assessed using modified Response Assessment in Neuro-Oncology (RANO) criteria. RESULTS: Median progression free survival from only one dose of SIACI mannitol and BV was 3.9 months. Side effects included seizure in 2 patients, and headache in 1 patient. Seizures were well controlled with medications, and there were no serious toxicities. There were no endovascular-related complications. CONCLUSION: SIACI of mannitol and BV at 15mg/kg allows for similar or better PFS compared to biweekly treatments of IV BV at 10mg/kg. The dosage required is lower and side effects were minimal and well tolerated. Future larger trials are warranted to assess whether repeated less frequent IA mannitol and BV may be superior to biweekly IV administration as a monotherapy.

Intra-arterial cetuximab for the treatment of recurrent unresectable head and neck squamous cell carcinoma†.

IMPORTANCE: Management of recurrent head and neck squamous cell carcinoma is a common and challenging clinical problem in head and neck oncology. OBJECTIVE: Here we present the first reported case of super-selective intra-arterial (SSIA) microcatheter based local delivery of cetuximab for head and neck cancer. This technical report describes the techniques used to deliver the SSIA dose of cetuximab, as well as the patient outcome. DESIGN: This technical report is part of an ongoing Phase I Clinical Trial. SETTING: The New York Head and Neck Institute (NYHNI) is a full-service otolaryngology and neurosurgery department at Lenox Hill Hospital, part of the Northwell Health System. The NYHNI serves a diverse patient population with a wide range of head and neck diseases in a tertiary hospital setting. INTERVENTION: SSIA Cetuximab. PARTICIPANT: A patient presents to our clinic with recurrent unresectable squamous cell carcinoma of the nasopharynx. He is recruited into the first cohort of a phase I clinical trial to assess the safety of SSIA cetuximab, dose starting at 100mg/m2. Adjuvant chemo-radiation therapy is also given. MEASURES: Safety, as measured by toxicity of SSIA cetuximab. RESULTS: SSIA Cetuximab has been demonstrated to be a safe and feasible procedure in this technical report. CONCLUSIONS: This case illustrates technical feasibility and a very preliminary assessment of the safety of a novel delivery of a biologic agent for squamous cell carcinoma of the head and neck, which is part of an ongoing phase I clinical trial. TRIAL REGISTRATION: NCT02438995.

Neuro-oncology biotech industry progress report.

The Brain Tumor Biotech Center at the Feinstein Institute for Medical Research, in collaboration with Voices Against Brain Cancer hosted The Brain Tumor Biotech Summit at in New York City in June 2015. The focus was once again on fostering collaboration between neuro-oncologist, neurosurgeons, scientists, leaders from biotechnology and pharmaceutical industries, and members of the financial community. The summit highlighted the recent advances in the treatment of brain tumor, and specifically focused on targeting of stem cells and EGFR, use of prophage and immunostimulatory vaccines, retroviral vectors for drug delivery, biologic prodrug, Cesium brachytherapy, and use of electric field to disrupt tumor cell proliferation. This article summarizes the current progress in brain tumor research as presented at 2015 The Brain Tumor Biotech Summit.

Superselective intraarterial cerebral infusion of cetuximab after osmotic blood/brain barrier disruption for recurrent malignant glioma: phase I study.

Objective To establish a maximum tolerated dose of superselective intraarterial cerebral infusion (SIACI) of Cetuximab after osmotic disruption of the blood-brain barrier (BBB) with mannitol, and examine safety of the procedure in patients with recurrent malignant glioma. Methods A total of 15 patients with recurrent malignant glioma were included in the current study. The starting dose of Cetuximab was 100 mg/m(2) and dose escalation was done to 250 mg/m(2). All patients were observed for 28 days post-infusion for any side effects. Results There was no dose-limiting toxicity from a single dose of SIACI of Cetuximab up to 250 mg/m(2) after osmotic BBB disruption with mannitol. A tolerable rash was seen in 2 patients, anaphylaxis in 1 patient, isolated seizure in 1 patient, and seizure and cerebral edema in 1 patient. Discussion SIACI of mannitol followed by Cetuximab (up to 250 mg/m(2)) for recurrent malignant glioma is safe and well tolerated. A Phase I/II trial is currently underway to determine the efficacy of SIACI of cetuximab in patients with high-grade glioma.

Analysis of superiorly projecting anterior communicating artery aneurysms: anatomy, techniques, and outcome. A proposed classification system.

Superiorly projecting (SP) anterior communicating artery (AComA) aneurysms are typically described as a homogenous group. Clinically and microsurgically, these aneurysms vary in multiple important characteristics. We propose a microsurgical classification system for these complex aneurysms and review its implications regarding presentation, microsurgical techniques, and outcome. This retrospective analysis reviews patients undergoing clipping of SP AComA aneurysms (2005-2013). The classification system is based on the virtual plane created by the A2 segments and its relationship to the aneurysm. Aneurysm type was assessed by intraoperative images and videos. Type 1 is defined by bisection of the dome by the virtual plane. Type 2 is defined by dome projection posterior to this plane. Sagittal rotation of the plane defines type 3. We analyzed clinical presentation, morphology, angiographic characteristics, operative technique, and outcome relative to the classification types. There were 44 SP AComA aneurysms. 3D angiographic images predicted classification type in 83%. Type 1 presented more often with SAH (95.5%, p = 0.0046). There was no statistically significant difference between the types regarding patient demographics or aneurysm characteristics. In type 2, fenestrated clips were used frequently (87.5% p= 0.0016), and there was higher rate of intraoperative rupture (37.5%). Although there was no statistically significant difference between the types in respect to HH grade upon presentation, patients with type 2 aneurysms experienced higher rates of poor GOS (50%). The proposed classification system for SP AComA aneurysms has implications regarding surgical planning, micro-dissection, clipping, and outcome. Type 2 aneurysms carry significant surgical risk.

How I do it: combined direct (STA-MCA) and indirect (EDAS) EC-IC bypass.

BACKGROUND: EC-IC bypass for the treatment of a hypoperfused hemisphere is currently the treatment of choice for symptomatic moyamoya patients. Use of the combination of direct (STA-MCA) and indirect (an STA branch lay-on bypass and flipped dural flaps; EDAS) EC-IC bypass is advocated as the optimal treatment option as it allows immediate augmentation of flow in the postoperative period while allowing the brain to acquire additional indirect flow in the long term. METHODS: We describe the technical nuances of a combined direct and indirect bypass in a 41-year-old woman with moyamoya syndrome diagnosed with transient ischemic attacks (TIAs) and cognitive decline. CONCLUSION: Combined direct and indirect bypass option should become a familiar treatment modality among vascular neurosurgeons. KEY POINTS: (1) Pay critical attention to not injuring the Superficial Temporal Artery, Parietal branch (STApb) while turning the skin incision anteriorly. Use the operating microscope to dissect the STApb. (2) Always mark the origin of the Superficial Temporal Artery, Frontal branch (STAfb) on the skin so that its location can be anticipated during STApb dissection. (3) When no frontal branch is available or if the frontal branch is of poor quality, the STApb can be used as a direct or indirect graft. (4) A craniotomy should be done 2-3 cm posterior to the course of the STApb to allow for adequate exposure for an indirect graft. (5) Manipulation of the donor vessels should be done with extreme care as spasm of the artery or intraluminal thrombosis may occur. Low cut flow in the direct graft should be interpreted with caution as vasospasm can result in significant temporary reduction of flow. (6) Aggressive distal dissection of the direct donor is a must. The distal 1-2 cm of the vessel should be cleaned of any loose tissue and be fishmouthed prior to anastomosis. (7) A blood-free field is mandatory. Perforators on the backside of the recipient should be sacrificed and cut to avoid backbleeding into the anastomotic segment during temporary occlusion. (8) When recirculating after the anastomosis has been completed, open the temporary clips on the recipient first. Backflow into the donor segment confirms a patent anastomosis. (9) Utilization of intraoperative angiography is not necessary as long as one utilizes flow measurements and ICG angiography. (10) Take great care with the bone flap reconstruction and the skin closure as the grafts can easily be compressed or sutured. Create a generous craniectomy in the bone flap to avoid any graft compression.