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.

Symptomatic infratentorial ependymal cyst arising from the medulla: a case report with review of literature.

BACKGROUND: Ependymal cysts (EC) typically present supra-tentorially near the lateral ventricle, juxta ventricular, or temporoparietal regions. Previous cases have also identified infratentorial EC of the brainstem, cerebellum, and subarachnoid spaces. They are mostly asymptomatic. In this paper, we present the first-ever case of a symptomatic medullary ependymal cyst treated with surgery, along with a comprehensive review of the literature on EC of other parts of the brain stem. CASE DESCRIPTION: This 51-year-old female presented with hearing loss, dizziness, diplopia, and ataxia. Radiographic imaging indicated the presence of a non-enhancing lesion in the medulla with a mass effect on the brainstem. Pathological examination confirmed its characterization as an ependymal cyst. The patient underwent a suboccipital craniotomy for the fenestration of the medullary ependymal cyst under neuro-navigation, Intra-op ultrasound and intra-operative neuro-monitoring. Histopathological examination confirmed the diagnosis of an ependymal cyst. At one month follow-up, her KPS is 90, ECOG PS 1, and her ataxia has improved with complete resolution of diplopia. CONCLUSION: Due to their rarity and potential similarity to other cystic structures, EC may be overlooked or incorrectly diagnosed resulting in mismanagement and surgical disaster. Therefore, a comprehensive understanding and awareness of their distinct characteristics are essential for accurate diagnosis and appropriate management.

Autologous cell immunotherapy (IGV-001) with IGF-1R antisense oligonucleotide in newly diagnosed glioblastoma patients.

Standard-of-care first-line therapy for patients with newly diagnosed glioblastoma (ndGBM) is maximal safe surgical resection, then concurrent radiotherapy and temozolomide, followed by maintenance temozolomide. IGV-001, the first product of the Goldspire™ platform, is a first-in-class autologous immunotherapeutic product that combines personalized whole tumor-derived cells with an antisense oligonucleotide (IMV-001) in implantable biodiffusion chambers, with the intent to induce a tumor-specific immune response in patients with ndGBM. Here, we describe the design and rationale of a randomized, double-blind, phase IIb trial evaluating IGV-001 compared with placebo, both followed by standard-of-care treatment in patients with ndGBM. The primary end point is progression-free survival, and key secondary end points include overall survival and safety.

Glioblastoma (GBM) is a fast-growing brain tumor that happens in about half of all gliomas. Surgery is the first treatment for patients with newly diagnosed GBM, followed by the usual radiation and chemotherapy pills named temozolomide. Temozolomide pills are then given as a long-term treatment. The outcome for the patient with newly diagnosed GBM remains poor. IGV-001 is specially made for each patient. The tumor cells are removed during surgery and mixed in the laboratory with a small DNA, IMV-001. This mix is the IGV-001 therapy that is designed to give antitumor immunity against GBM. IGV-001 is put into small biodiffusion chambers that are irradiated to stop the growth of any tumor cells in the chambers. In the phase IIb study, patients with newly diagnosed GBM are chosen and assigned to either the IGV-001 or the placebo group. A placebo does not contain any active ingredients. The small biodiffusion chambers containing either IGV-001 or placebo are surgically placed into the belly for 48 to 52 h and then removed. Patients then receive the usual radiation and chemotherapy treatment. Patients must be adults aged between 18 and 70 years. Patients also should be able to care for themselves overall, but may be unable to work or have lower ability to function. Patients with tumors on both sides of the brain are not eligible. The main point of this study is to see if IGV-001 helps patients live longer without making the illness worse compared with placebo. Clinical Trial Registration: NCT04485949 (ClinicalTrials.gov).

An algorithm for the treatment of concurrent pituitary adenoma and cavernous sinus aneurysm: A systematic review & case report.

BACKGROUND: Rarely, Pituitary adenomas (PA) can co-occur with intrasellar or intracavernous aneurysms. There is currently no clear guidance for the management of this dual pathology. We attempt to provide an algorithm to help guide clinical decision making for treatment of PAs co-occurring with adjacent cerebral aneurysms. METHODS: A comprehensive literature search was conducted following PRISMA guidelines using various databases. Search terms included "(Pituitary Adenoma OR Prolactinoma OR Macroadenoma OR Adenoma) AND (ICA OR Internal Carotid Artery OR paracliniod OR clinoid) Aneurysm AND (Intra-cavernous OR intracavernous OR intrasellar OR Cavernous)." RESULTS: A total of 24 studies with 24 patients were included. Twelve (50%) patients experienced visual symptoms. Ten patients (42%) had an aneurysm embedded within the adenoma. Fourteen patients (58%) had an aneurysm adjacent to the adenoma. Embedded aneurysms were significantly associated with rupture events. CONCLUSION: Vision loss is the most pressing determinant of treatment. In the absence of visual symptoms, the aneurysm should be treated first by coil embolization. If not amenable to coiling, place flow diverting stent followed by six months of anticoagulation and antiplatelet therapy. If visual loss is apparent, the adenoma-aneurysm spatial relationship becomes critical. In cases of an adjacent aneurysm, the adenoma should be removed transsphenoidally with extreme care and aneurysm rupture protocols in place. If the aneurysm is embedded within the adenoma, then a BTO is favored with permanent ICA occlusion followed by transsphenoidal resection if adequate collateral supply is demonstrated. If there is inadequate collateral supply, then an open-approach for amenable aneurysms with transcranial adenoma debulking should be performed.

First in-human intrathecal delivery of bevacizumab for leptomeningeal spread from recurrent glioblastoma: rationale for a dose escalation trial.

PURPOSE: To outline the dose rationale for the first in-human intrathecal delivery of bevacizumab for LMS of GBM. METHODS: A 19-year-old female patient presented to Lenox Hill Hospital following thalamic GBM recurrence. She subsequently underwent two infusions of intra-arterial BEV (NCT01269853) and experienced a period of relative disease stability until progression in 2022. One month later, MRI disclosed diffuse enhancement representative of LMS of GBM. The patient subsequently underwent five cycles of IT BEV in mid-2022 (IND 162119). Doses of 25 mg, 37.5 mg, 50 mg, 50 mg, and 37.8 mg were delivered at two-week intervals between doses 1-4. The final 37.8 mg dose was given one day following her fourth dose, given that the patient was to be discharged, traveled several hours to our center, and was tolerating therapy well. Dosage was decreased due to the short interval between the final two treatments. Shortly after IT BEV completion, she received a third dose of IA BEV. RESULTS: Our patient did not show any signs of serious adverse effects or dose limiting toxicities following any of the treatments. It is difficult to determine PFS due to the rapid progression associated with LMS of GBM and rapid timeframe of treatment. CONCLUSION: LMS continues to be a devastating progression in many types of cancer, including GBM, and novel ways to deliver therapeutics may offer patients symptomatic and therapeutic benefits.

Hippocampal avoidance in whole brain radiotherapy and prophylactic cranial irradiation: a systematic review and meta-analysis.

PURPOSE: We systematically reviewed the current landscape of hippocampal-avoidance radiotherapy, focusing specifically on rates of hippocampal tumor recurrence and changes in neurocognitive function. METHODS: PubMed was queried for studies involving hippocampal-avoidance radiation therapy and results were screened using PRISMA guidelines. Results were analyzed for median overall survival, progression-free survival, hippocampal relapse rates, and neurocognitive function testing. RESULTS: Of 3709 search results, 19 articles were included and a total of 1611 patients analyzed. Of these studies, 7 were randomized controlled trials, 4 prospective cohort studies, and 8 retrospective cohort studies. All studies evaluated hippocampal-avoidance whole brain radiation treatment (WBRT) and/or prophylactic cranial irradiation (PCI) in patients with brain metastases. Hippocampal relapse rates were low (overall effect size = 0.04; 95% confidence interval [0.03, 0.05]) and there was no significant difference in risk of relapse between the five studies that compared HA-WBRT/HA-PCI and WBRT/PCI groups (risk difference = 0.01; 95% confidence interval [- 0.02, 0.03]; p = 0.63). 11 out of 19 studies included neurocognitive function testing. Significant differences were reported in overall cognitive function and memory and verbal learning 3-24 months post-RT. Differences in executive function were reported by one study, Brown et al., at 4 months. No studies reported differences in verbal fluency, visual learning, concentration, processing speed, and psychomotor speed at any timepoint. CONCLUSION: Current studies in HA-WBRT/HA-PCI showed low hippocampal relapse or metastasis rates. Significant differences in neurocognitive testing were most prominent in overall cognitive function, memory, and verbal learning. Studies were hampered by loss to follow-up.

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.

Optimization of novel exoscopic blue light filter during fluorescence-guided resection of Glioblastoma.

PURPOSE: Operative guidelines and use optimization for new surgical exoscopes are not well described in the literature. In this study, we evaluated use of the ORBEYE (Olympus) surgical exoscope system during 5-ALA fluorescence-guided resection of GBMs to optimize workflow and exoscope settings. METHODS: The ORBEYE exoscope system was fitted with a blue light filter for 5-ALA mediated fluorescence-guided surgery (FGS). Intraoperative images were obtained during 5-ALA FGS in 9 patients with primary or recurrent GBM. The exoscope was set up at constant, increasing focal distances from the target tissue, and light source intensity varied. High-resolution 4 K images were captured and analyzed. Comparisons of fluorescence to background were then generated for use optimization. RESULTS: Light intensity did not significantly influence tumor fluorescence (P = 0.878). However, focal distance significantly impacted relative fluorescent intensity (P = 0.007). Maximum average fluorescence was seen consistently at a focal length of 220 mm and a light intensity of approximately 75% maximum. Decreasing focal distance from 400 mm to 220 mm significantly increased visualized fluorescence (P = 0.0038). CONCLUSIONS: The ORBEYE surgical exoscope system with blue light filter is a powerful imaging tool for 5-ALA FGS in GBM. The ORBEYE blue filter performs optimally at shorter focal distance with moderate light intensity. Similar to microscope systems, decreasing focal distance significantly influences visualized fluorescence.

Childhood Brain Tumors: A Review of Strategies to Translate CNS Drug Delivery to Clinical Trials.

Brain and spinal tumors affect 1 in 1000 people by 25 years of age, and have diverse histological, biological, anatomical and dissemination characteristics. A mortality of 30-40% means the majority are cured, although two-thirds have life-long disability, linked to accumulated brain injury that is acquired prior to diagnosis, and after surgery or chemo-radiotherapy. Only four drugs have been licensed globally for brain tumors in 40 years and only one for children. Most new cancer drugs in clinical trials do not cross the blood-brain barrier (BBB). Techniques to enhance brain tumor drug delivery are explored in this review, and cover those that augment penetration of the BBB, and those that bypass the BBB. Developing appropriate delivery techniques could improve patient outcomes by ensuring efficacious drug exposure to tumors (including those that are drug-resistant), reducing systemic toxicities and targeting leptomeningeal metastases. Together, this drug delivery strategy seeks to enhance the efficacy of new drugs and enable re-evaluation of existing drugs that might have previously failed because of inadequate delivery. A literature review of repurposed drugs is reported, and a range of preclinical brain tumor models available for translational development are explored.

Cesium-131 brachytherapy for the treatment of brain metastases: Current status and future perspectives.

Adjuvant radiotherapy is often necessary following surgical resection of brain metastases to improve local tumor control and survival. Brachytherapy using cesium-131 offers a novel method for loco-regional radiotherapy. We reviewed the current literature reporting the use of cesium-131 brachytherapy for the treatment of brain metastases. Published studies and ongoing trials were reviewed to identify treatment protocols and clinical outcomes of cesium-131 brachytherapy for brain metastases. Cesium-131 brachytherapy was further compared to current outcomes for iodine-125 brachytherapy and stereotactic radiosurgery. Intraoperative brachytherapy allows patients to receive two treatment modalities in one setting while minimizing tumor cell repopulation. After initial interest, the use of iodine-125 brachytherapy has declined due to unfavorable rates of radiation necrosis without survival improvement. Recent data on intracavitary cesium-131 brachytherapy in brain metastases have demonstrated improved locoregional tumor control with low risks of radiation necrosis, with associated improvements in patients compliance and satisfaction. Cesium-131 isotope has a short half-life, delivers 90% of its dose within a month, shortens the time to initiation of systemic therapy compared to iodine-125 or external radiotherapy, and has an excellent radiation safety profile. Further analyses have demonstrated superior cost-effectiveness and quality-of-life improvement ratios of cesium-131 brachytherapy than adjuvant stereotactic radiosurgery. Cesium-131 brachytherapy is a safe and effective post-surgical treatment option for brain metastases with associated clinical and cost-effectiveness benefits in appropriately selected patients.

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.

Evolution of flash visual evoked potentials to monitor visual pathway integrity during tumor resection: illustrative cases and literature review.

Flash visual evoked potentials (fVEPs) provide a means to interrogate visual system functioning intraoperatively during tumor resection in which the optic pathway is at risk for injury. Due to technical limitations, fVEPs have remained underutilized in the armamentarium of intraoperative neurophysiological monitoring (IONM) techniques. Here we review the evolution of fVEPs as an IONM technique with emphasis on the enabling technological and intraoperative improvements. A combined approach with electroretinography (ERG) has enhanced feasibility of fVEP neuromonitoring as a practical application to increase safety and reduce error during tumor resection near the prechiasmal optic pathway. The major advance has been towards differentiating true cases of damage from false findings. We use two illustrative neurosurgical cases in which fVEPs were monitored with and without ERG to discuss limitations and demonstrate how ERG data can clarify false-positive findings in the operating room. Standardization measures have focused on uniformity of photostimulation parameters for fVEP recordings between neurosurgical groups.

#Neurosurgery: A Cross-Sectional Analysis of Neurosurgical Content on TikTok.

Objectives: TikTok is a social media platform that has gained popularity and become a powerful engine to disseminate public health and medical information. To date, no study has characterized the qualities of popular TikTok videos related to neurosurgery, or assessed biases in the content of these videos. Methods: The TikTok web browser application was queried using "#neurosurgery" to identify neurosurgery-related videos. The top 100 videos meeting inclusion criteria were analyzed and video characteristics determined. Bias was assessed by the DISCERN scoring system using 3 independent reviewers. A Kruskal-Wallis H test was used to correlate video popularity with video characteristics and to correlate bias with creator and video type. Results: The 100 videos evaluated totaled 8.8 million likes, 104,718 comments, and 100,856 shares. The oldest video was posted February 2020 and the most recent March 2022. Videos were most commonly entertaining (n = 64, 64%), and educational (n = 46, 46%). Video popularity was associated with videos that aimed to entertain, and least associated with videos depicting neurosurgery lifestyle. Low DISCERN scores, indicating more biased content, were seen across the neurosurgical content with the entertaining video category demonstrating the highest bias. Conclusions: Neurosurgical content on TikTok contains a high degree of bias across all creator and video types. Entertaining videos are associated with the highest numbers of likes but also the greatest bias. These data may be used to guide institutions and neurosurgeons to grow interest in the field of neurosurgery and disseminate unbiased information while expanding their social media presence.

Reconstruction of the Anterior Skull Base Using the Nasoseptal Flap: A Review.

The nasoseptal flap is a workhorse reconstructive option for anterior skull base defects during endonasal surgery. This paper highlights the versatility of the nasoseptal flap. After providing a brief historical perspective, this review will focus on the relevant primary literature published in the last ten years. We will touch upon new applications of the flap, how the flap has been modified to expand its reach and robustness, and some of the current limitations. We will conclude by discussing what the future holds for improving upon the design and use of the nasoseptal flap in anterior skull base reconstruction.

BRAINterns 2.0: Durability of Webinar-Based Education and Social Media Beyond the Coronavirus Disease 2019 Pandemic.

BACKGROUND: Webinars offer novel educational opportunities beyond those of traditional, in-person experiences. BRAINterns is an open-access webinar-based education platform created to replace opportunities lost during the coronavirus disease 2019 pandemic. This program previously showed the efficacy of webinars to expand access to careers in medicine, and in particular, neurosurgery. BRAINterns 2.0 was established to assess the durability of Web-based learning. METHODS: A modified 4-week webinar series was held during July 2021. A retrospective exit survey was distributed to participants and responses analyzed. RESULTS: A total of 16,045 people registered for BRAINterns 2.0, representing 103 countries. Survey responses were received from 3765 participants (23% response rate). New, first-time registrants comprised 66% of participants, with the rest being returning participants. A total of 342 students participated in a dedicated module delivered entirely in Spanish. Females represented 81% of respondents. Participants identified that desirable elements of the program were opportunities to hear from women (53%) and people of color (44%) in health care. Participants heard about the series through TikTok (n = 1251; 33%), Instagram (n = 1109; 29%), Facebook (n = 637; 17%), and word of mouth (n = 708; 19%) with assistance from an ambassador program. CONCLUSIONS: Webinar-based education programs continue to be of interest to students in an increasingly digital world. Social media, and specifically the use of educational ambassadors, are effective to improve visibility of educational programs across a diverse population of students. Understanding the desires of participants is critical to building a successful online education platform.

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.

Microsurgical Management of Complex Hypothalamic Hamartomas in the Era of Minimally Invasive Therapy: A Case Series and Narrative Review.

BACKGROUND: There has been a paradigm shift in the management of hypothalamic hamartoma (HH) from traditional microsurgical techniques to less invasive alternatives. However, large and extensive HH may fail to respond to these therapies, necessitating craniotomies. METHODS: All patients who underwent microsurgical resection of a complex HH by the 2 senior authors from 2011 to 2021 were included. Charts were retrospectively reviewed and demographic, clinical, imaging, and outcome data were recorded. RESULTS: Eight patients (mean age, 7 years) were included. Two had failed previous treatments. All 7 presented with gelastic seizures and cognitive dysfunction, 6 showed central precocious puberty, and 3 had behavioral problems. The mean lesion size was 21.6 mm and all had interpeduncular extension, 5 had intraventricular extension (Delalande type I, 3; type III, 4; type IV, 1). A frontotemporal orbitozygomatic approach with optic nerve decompression was used in all patients, supplemented by another approach in 3 (endoscopic transventricular, 3; transcallosal, 1). Gross total resection was achieved in 6 patients and subtotal resection in 2. Transient complications occurred in 3 patients (37.5%): self-limited sodium imbalance (n = 3), subdural hygroma (n = 2). Permanent complications occurred in 2 patients (25%): perforator infarct (n = 1) and short-term memory loss (n = 1). All patients experienced seizure resolution with preserved hypothalamic-pituitary axis function. After a mean follow-up of 41 months (range, 2-66 months), 7 patients remained seizure free, and 1 had rare seizures. Cognitive and behavioral symptoms improved in all patients. CONCLUSIONS: For large HH with interpeduncular extension, microsurgery via the frontotemporal orbitozygomatic approach is a safe and highly effective treatment modality.

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.