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Idiopathic intracranial hypertension (IIH) can cause debilitating symptoms and optic nerve ischemia if untreated. Cerebrospinal fluid diversion is often necessary to reduce intracranial pressure; however, current ventriculoperitoneal and lumboperitoneal shunting techniques have high failure rates in patients with IIH.To describe our experience treating IIH with a novel stereotactic-guided transcerebellar cisternoperitoneal shunt (SGTC-CPS) technique that places the proximal shunt catheter in the posterior cisterna magnum.Retrospective perioperative and postoperative data from all patients who underwent SGTC-CPS placement for IIH from March 1, 2015, to December 31, 2020, were analyzed. Patients were positioned as for ventriculoperitoneal shunt placement but with the head turned farther laterally to adequately expose the retrosigmoid space. Using neuronavigation, an opening was made near the transverse-sigmoid junction, and the proximal catheter was inserted transcerebellarly into the posterior foramen magnum.Thirty-two patients underwent SGTC-CPS placement (29 female; mean body mass index, 36.0 ± 7.5; 14 with prior shunt failures). The mean procedure time for shunt placement was 145 minutes. No intraoperative complications occurred, and all patients were discharged uneventfully. At the 6-month follow-up, 81% of patients (21 of 26) had relief of their presenting symptoms. Shunt survival without revision was 86% (25 of 29) at 1 year and 67% (10 of 15) at 3 years, with no infections.The SGTC-CPS offers an alternative solution for cerebrospinal fluid diversion in patients with IIH and demonstrates a lower failure rate and more durable symptom relief compared with ventriculoperitoneal or lumboperitoneal shunt placement. Using proper techniques and equipment promotes safe and facile placement of the proximal catheter.

Objective Surgical techniques to achieve complete resection of mesial–basal temporal tumors should be pursued by neurosurgical oncologists. We describe the anatomical subpial amygdalohippocampectomy (SpAH) technique for tumor resection. Methods The key anatomical landmarks and critical steps of the SpAH technique were outlined and emphasized with medical illustrations and intraoperative photographs. The senior author's 90-day surgical outcomes with this approach were reviewed. Results Twenty-five patients (men, 17 [68%]; women, 8 [32%]; median [range] age, 59 [23–80] years) with temporal tumors involving the amygdalohippocampal region were included. SpAH was performed selectively in 8 [32%] patients, whereas 17 [68%] patients underwent SpAH in conjunction with an anterior temporal lobectomy due to tumor involvement of the anterolateral temporal cortex. The subpial resection of the amygdala protected the critical structures of the suprasellar cistern and sylvian fissure. Identifying the choroidal fissure as the superior-most aspect of hippocampal resection protected the optic tract and the thalamus. Subpial resection of the parahippocampal gyrus inferiorly protected the brainstem and critical structures of the ambient cistern. Tumors in the amygdalohippocampal region were anatomically and completely resected in all 25 patients. Of the 15 patients who presented with seizures, 13 (87%) were seizure-free at the 90-day postsurgical follow-up. Permanent neurologic deficits occurred in 3 patients (12%). Conclusions The SpAH technique permits complete resection of mesial–basal temporal tumors with an acceptable morbidity profile. An in-depth understanding of temporal lobe anatomy combined with a refined microsurgical technique allows for reproducible resection of tumor in the amygdalohippocampal region while protecting critical neurovascular structures.

This study describes a retrospective case series of patients with glioma who received ketogenic metabolic therapy through dietary adherence and intermittent fasting.A retrospective chart review of a single surgeon's clinic records was performed to identify patients who maintained nutritional ketosis for at least four months between January 2015 and October 2020.Sixteen patients who met the inclusion criteria constituted a heterogeneous population of patients with diagnoses including eight World Health Organization (WHO) grade IV gliomas (seven glioblastoma, one gliosarcoma), seven WHO grade III gliomas (three oligodendroglioma, four astrocytoma), and one WHO grade II oligodendroglioma.Ketogenic metabolic therapy appears to convey a survival advantage within this patient series, which highlights the possibility that this therapy, when strictly applied, can augment the standard of care. Further exploration of this modality in a prospective series is warranted to formally explore this therapy.

High grade gliomas (HGG) are aggressive primary brain malignancies typified by diffuse invasion, genetic heterogeneity, and a universally fatal outcome. MRI-defined contrast-enhancing (CE) tumor burden serves as the clinical standard that guides maximal surgical resection and post-therapy response assessment. However, HGGs also comprise an invasive non-enhancing (NE) tumor margin that extends beyond the CE core and harbors the cells that contribute to recurrence. Sampling restrictions have hindered the comprehensive study of these NE HGG cell populations driving tumor progression. Herein, we present an integrated multi-omic analysis of 313 spatially matched multi-regional CE and NE tumor biopsies from 68 HGG patients, performing whole exome and RNA sequencing of both IDH wild-type and IDH mutant HGGs. We report spatially restricted molecular profiles in IDH-mutant HGG, highlighting a concern for sampling bias given the importance of molecular diagnosis and prognostication in IDH-mutant HGG. Regardless of IDH status, we found that NE tumor regions harbored the highest proportion of private mutations, which reflects an increased development of regional genomic complexity in infiltrative tumor. The multiregional genomic profiling of our IDH wild-type HGG cohort reveals that EGFR and NF1 somatic alterations occur as mutually exclusive events in 98.7% of tumors. However, we resolved rare low allele frequency co-alterations of EGFR and NF1 within the NE region. We find this co-occurrence enriched in recurrent tumors, pointing to the early emergence of NF1 inactivation in the NE regions. We constructed genomic models predictive of recurrent disease from both NE and CE regions, which highlight the occurrence of clonal EGFR copy number alterations and NF1 loss as clonal or subclonal events, respectively, emphasizing the regional and temporal complexity of well-studied canonical driver alterations. We detailed the spatially unique acquisition of multiple distinct EGFR alterations giving rise to intra-tumoral EGFR mosaicism, a challenge in the implementation of EGFR directed therapies. Our study also identified two transcriptomic clusters delineated by the significant overrepresentation of neuronal (NEU) and glycolytic/plurimetabolic (GPM) pathway-based functional states in the NE region. NE regions of the NEU subtype harbor the greatest proportion of private mutations, suggesting these infiltrative tumor cells accumulate alterations without clonal expansion. GPM populations conversely displayed a less branched phylogeny and were transcriptionally enriched in immune cell signatures. This phenotypic dichotomy between GPM and NEU populations supports the growing body of evidence that invasive GBM cells either take on a neuronal phenotype for active invasion or a more metabolic phenotype involving interaction with astrocytes, other glial cells, and infiltrating immune cells. Citation Format: Mylan R. Blomquist, Leland S. Hu, Fulvio D'Angelo, Taylor M. Weiskittel, Francesca P. Caruso, Shannon P. Fortin Ensign, Christopher Sereduk, Gustavo De Leon, Lee Curtin, Javier Urcuyo, Ashlynn Gonzalez, Ashley Nespodzany, Teresa Noviello, Jennifer M. Eschbacher, Kris A. Smith, Peter Nakaji, Bernard R. Bendok, Richard S. Zimmerman, Chandan Krishna, Devi Patra, Naresh Patel, Mark Lyons, Kliment Donev, Maciej Mrugala, Alyx Porter, Anna Lasorella, Kristin R. Swanson, Michele Ceccarelli, Antonio Iavarone, Nhan L. Tran. Multiregional sampling of high grade glioma identifies regional biologic signatures [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1507.

Objective Epilepsy with periventricular nodular heterotopia (PVNH) lacks a conclusive surgical treatment strategy as eloquent cortex and important white matter tracts frequently overlay the deep periventricular nodules. Our goal was to evaluate the safety and efficacy of laser interstitial thermal therapy (LITT) for the treatment of epilepsy in PVNH. Methods Data on demographic characteristics, complications, visual outcomes, Engel classification at last follow-up, antiepileptic drug use, morbidity, and mortality among patients who underwent this procedure were retrospectively reviewed. Results Between May 2015 and January 2019, 5 patients underwent 6 LITT procedures for epilepsy with PVNH. One patient had residual nodules after their first procedure and underwent a second ablation. The average follow-up time was 12 months. Three patients were Engel class Ia, 1 patient was Engel class II, and 1 patient was Engel class III at last follow-up. Two patients were able to reduce their antiepileptic drugs postoperatively. Three patients had no changes in vision, 1 patient experienced a quadrantanopsia, and 1 patient had subjective blurry vision after their procedures. No patients experienced motor deficits, dysphasia, infection, or mortality. Conclusions LITT appears to be a safe and promising option to provide seizure relief for patients with refractory epilepsy and PVNH that otherwise may not be surgical candidates. Some appropriately determined patients with refractory epilepsy may benefit from LITT before proceeding with an invasive intracranial evaluation. A larger sample size and long-term follow-up is necessary to further elucidate safety and efficacy.

BACKGROUND Laser Ablation of Abnormal Neurological Tissue using Robotic NeuroBlate System (LAANTERN) is an ongoing multicenter prospective NeuroBlate (Monteris Medical) LITT (laser interstitial thermal therapy) registry collecting real-world outcomes and quality-of-life (QoL) data. OBJECTIVE To compare 12-mo outcomes from all subjects undergoing LITT for intracranial tumors/neoplasms. METHODS Demographics, intraprocedural data, adverse events, QoL, hospitalizations, health economics, and survival data are collected; standard data management and monitoring occur. RESULTS A total of 14 centers enrolled 223 subjects; the median follow-up was 223 d. There were 119 (53.4%) females and 104 (46.6%) males. The median age was 54.3 yr (range 3-86) and 72.6% had at least 1 baseline comorbidity. The median baseline Karnofsky Performance Score (KPS) was 90. Of the ablated tumors, 131 were primary and 92 were metastatic. Most patients with primary tumors had high-grade gliomas (80.9%). Patients with metastatic cancer had recurrence (50.6%) or radiation necrosis (40%). The median postprocedure hospital stay was 33.4 h (12.7-733.4). The 1-yr estimated survival rate was 73%, and this was not impacted by disease etiology. Patient-reported QoL as assessed by the Functional Assessment of Cancer Therapy-Brain was stabilized postprocedure. KPS declined by an average of 5.7 to 10.5 points postprocedure; however, 50.5% had stabilized/improved KPS at 6 mo. There were no significant differences in KPS or QoL between patients with metastatic vs primary tumors. CONCLUSION Results from the ongoing LAANTERN registry demonstrate that LITT stabilizes and improves QoL from baseline levels in a malignant brain tumor patient population with high rates of comorbidities. Overall survival was better than anticipated for a real-world registry and comparative to published literature., Graphical Abstract Graphical Abstract

BACKGROUND AND PURPOSE: Perfusion MR imaging measures of relative CBV can distinguish recurrent tumor from posttreatment radiation effects in high-grade gliomas. Currently, relative CBV measurement requires normalization based on user-defined reference tissues. A recently proposed method of relative CBV standardization eliminates the need for user input. This study compares the predictive performance of relative CBV standardization against relative CBV normalization for quantifying recurrent tumor burden in high-grade gliomas relative to posttreatment radiation effects. MATERIALS AND METHODS: We recruited 38 previously treated patients with high-grade gliomas (World Health Organization grades III or IV) undergoing surgical re-resection for new contrast-enhancing lesions concerning for recurrent tumor versus posttreatment radiation effects. We recovered 112 image-localized biopsies and quantified the percentage of histologic tumor content versus posttreatment radiation effects for each sample. We measured spatially matched normalized and standardized relative CBV metrics (mean, median) and fractional tumor burden for each biopsy. We compared relative CBV performance to predict tumor content, including the Pearson correlation (r), against histologic tumor content (0%–100%) and the receiver operating characteristic area under the curve for predicting high-versus-low tumor content using binary histologic cutoffs (≥50%; ≥80% tumor). RESULTS: Across relative CBV metrics, fractional tumor burden showed the highest correlations with tumor content (0%–100%) for normalized (r = 0.63, P

Objective In ventriculoperitoneal shunt (VPS) placement, distal placement of the peritoneal catheter will typically be performed by a neurosurgeon. More recently, laparoscopic-assisted (LA) placement of the distal peritoneal catheter by general surgeons has become common. The present study examined whether LA placement of a VPS (LAVPS) is associated with a reduced operative time, lower hospital costs, and fewer distal revisions. Methods A retrospective review was performed of the data from all patients who had received a new VPS at our institution from 2013 to 2016. Age, sex, diagnosis, previous abdominal surgery, operative time, anesthesia grade, incidence of 30-day shunt failure, and total hospital charges were analyzed. Results A total of 680 patients had undergone first-time VPS placement, including 199 with LAVPS and 481 with non–LAVPS placement (non-LAVPS). The mean age of the LAVPS patients was significantly older than that of the non-LAVPS patients (64.1 vs. 59.3 years; P = 0.002). The mean operative time was shorter in the LAVPS group than in the non-LAVPS group (55 vs. 75 minutes; P Conclusions Compared with non-LAVPS, LAVPS was associated with significantly shorter operative times and fewer distal shunt revisions within 30 days. The findings from a subset analysis supported a decrease in total hospital charges. Additional studies are needed; however, these data suggest that LAVPS is a safer, less-expensive alternative to non-LAVPS.

Background Stereoelectroencephalography (SEEG) is a commonly used technique for mapping the epileptogenic zone before epilepsy surgery. Many SEEG depth electrode implantation techniques involve the use of extensive technological equipment and shaving of the patient's entire head before electrode implantation. Our goal was to evaluate an SEEG depth electrode implantation technique that used readily available cost-effective neurosurgical equipment, was minimally invasive in nature, and required negligible hair shaving. Methods Data on demographic characteristics, operative time, hemorrhagic complications, implantation complications, infection, morbidity, and mortality among patients who underwent this procedure were reviewed retrospectively. Results Between April 2016 and March 2018, 23 patients underwent implantation of 213 depth electrodes with use of this technique. Mean (SD) operative time was 123 (32) minutes (range, 66–181 minutes). A mean (SD) of 9.3 (1.4) electrodes were placed for each patient (range, 8–13 electrodes). Two of the 213 electrodes (0.9%) were associated with postimplantation asymptomatic hemorrhage. One of the 213 electrodes (0.5%) was placed extradurally or incorrectly. None of the 213 electrodes was associated with symptomatic complications. No patients experienced infectious complications at any point in the preoperative, perioperative, or postoperative stages. Conclusions This minimally invasive, cost-effective technique for SEEG depth electrode implantation is a safe, efficient method that uses readily available basic neurosurgical equipment. This technique may be useful in neurosurgery centers with more limited resources. This study suggests that leaving the patient's hair largely intact throughout the procedure does not pose an additional infection risk.

OBJECTIVE Communication between neurosurgeons and pathologists is mandatory for intraoperative decision-making and optimization of resection, especially for invasive masses. Handheld confocal laser endomicroscopy (CLE) technology provides in vivo intraoperative visualization of tissue histoarchitecture at cellular resolution. The authors evaluated the feasibility of using an innovative surgical telepathology software platform (TSP) to establish real-time, on-the-fly remote communication between the neurosurgeon using CLE and the pathologist. METHODS CLE and a TSP were integrated into the surgical workflow for 11 patients with brain masses (6 patients with gliomas, 3 with other primary tumors, 1 with metastasis, and 1 with reactive brain tissue). Neurosurgeons used CLE to generate video-flow images of the operative field that were displayed on monitors in the operating room. The pathologist simultaneously viewed video-flow CLE imaging using a digital tablet and communicated with the surgeon while physically located outside the operating room (1 pathologist was in another state, 4 were at home, and 6 were elsewhere in the hospital). Interpretations of the still CLE images and video-flow CLE imaging were compared with the findings on the corresponding frozen and permanent H&E histology sections. RESULTS Overall, 24 optical biopsies were acquired with mean ± SD 2 ± 1 optical biopsies per case. The mean duration of CLE system use was 1 ± 0.3 minutes/case and 0.25 ± 0.23 seconds/optical biopsy. The first image with identifiable histopathological features was acquired within 6 ± 0.1 seconds. Frozen sections were processed within 23 ± 2.8 minutes, which was significantly longer than CLE usage (p < 0.001). Video-flow CLE was used to correctly interpret tissue histoarchitecture in 96% of optical biopsies, which was substantially higher than the accuracy of using still CLE images (63%) (p = 0.005). CONCLUSIONS When CLE is employed in tandem with a TSP, neurosurgeons and pathologists can view and interpret CLE images remotely and in real time without the need to biopsy tissue. A TSP allowed neurosurgeons to receive real-time feedback on the optically interrogated tissue microstructure, thereby improving cross-functional communication and intraoperative decision-making and resulting in significant workflow advantages over the use of frozen section analysis.

Background: Laser interstitial thermal therapy (LITT) has emerged as a minimally invasive treatment modality for ablation of low-grade glioma (LGG) and radiation necrosis (RN). Objective: To evaluate the efficacy, safety, and survival outcomes of patients with radiographically presumed recurrent or newly diagnosed LGG and RN treated with LITT. Methods: The neuro-oncological database of a quaternary center was reviewed for all patients who underwent LITT for management of LGG between 1 January 2013 and 31 December 2020. Clinical data including demographics, lesion characteristics, and clinical and radiographic outcomes were collected. Kaplan-Meier analyses comprised overall survival (OS) and progression-free survival (PFS). Results: Nine patients (7 men, 2 women; mean [SD] age 50 [16] years) were included. Patients underwent LITT at a mean (SD) of 11.6 (8.5) years after diagnosis. Two (22%) patients had new lesions on radiographic imaging without prior treatment. In the other 7 patients, all (78%) had surgical resection, 6 (67%) had intensity-modulated radiation therapy and chemotherapy, respectively, and 4 (44%) had stereotactic radiosurgery. Two (22%) patients had lesions that were wild-type IDH1 status. Volumetric assessment of preoperative T1-weighted contrast-enhancing and T2-weighted fluid-attenuated inversion recovery (FLAIR) sequences yielded mean (SD) lesion volumes of 4.1 (6.5) cm(3) and 26.7 (27.9) cm(3), respectively. Three (33%) patients had evidence of radiographic progression after LITT. The pooled median (IQR) PFS for the cohort was 52 (56) months, median (IQR) OS after diagnosis was 183 (72) months, and median (IQR) OS after LITT was 52 (60) months. At the time of the study, 2 (22%) patients were deceased. Conclusions: LITT is a safe and effective treatment option for management of LGG and RN, however, there may be increased risk of permanent complications with treatment of deep-seated subcortical lesions.

OBJECTIVEEffective treatments for recurrent, previously irradiated intracranial meningiomas are limited, and resection alone is not usually curative. Thus, the authors studied the combination of maximum safe resection and adjuvant radiation using permanent intracranial brachytherapy (R+BT) in patients with recurrent, previously irradiated aggressive meningiomas.METHODSPatients with recurrent, previously irradiated meningiomas were treated between June 2013 and October 2016 in a prospective single-arm trial of R+BT. Cesium-131 (Cs-131) radiation sources were embedded in modular collagen carriers positioned in the operative bed on completion of resection. The Cox proportional hazards model with this treatment as a predictive term was used to model its effect on time to local tumor progression.RESULTSNineteen patients (median age 64.5 years, range 50–78 years) with 20 recurrent, previously irradiated tumors were treated. The WHO grade at R+BT was I in 4 (20%), II in 14 (70%), and III in 2 (10%) cases. The median number of prior same-site radiation courses and same-site surgeries were 1 (range 1–3) and 2 (range 1–4), respectively; the median preoperative tumor volume was 11.3 cm3 (range 0.9–92.0 cm3). The median radiation dose from BT was 63 Gy (range 54–80 Gy). At a median radiographic follow-up of 15.4 months (range 0.03–47.5 months), local failure (within 1.5 cm of the implant bed) occurred in 2 cases (10%). The median treatment-site time to progression after R+BT has not been reached; that after the most recent prior therapy was 18.3 months (range 3.9–321.9 months; HR 0.17, p = 0.02, log-rank test). The median overall survival after R+BT was 26 months, with 9 patient deaths (47% of patients). Treatment was well tolerated; 2 patients required surgery for complications, and 2 experienced radiation necrosis, which was managed medically.CONCLUSIONSR+BT utilizing Cs-131 sources in modular carriers represents a potentially safe and effective treatment option for recurrent, previously irradiated aggressive meningiomas.

Precise communication between neurosurgeons and pathologists is crucial for optimizing patient care, especially for intraoperative diagnoses. Confocal laser endomicroscopy (CLE) combined with a telepathology software platform (TSP) provides a novel venue for neurosurgeons and pathologists to review CLE images and converse intraoperatively in real-time.To describe the feasibility of integrating CLE and a TSP in the surgical workflow for real-time review of in vivo digital fluorescence tissue imaging in 3 patients with intracranial tumors.Although the neurosurgeon used the CLE probe to generate fluorescence images of histoarchitecture within the operative field that were displayed on monitors in the operating room, the pathologist simultaneously remotely viewed the CLE images. The neurosurgeon and pathologist discussed in real-time the histological structures of intraoperative imaging locations.The neurosurgeon placed the CLE probe at various locations on and around the tumor, in the surgical resection bed, and on surrounding brain tissue with communication through the TSP. The neurosurgeon oriented the pathologist to the location of the CLE, and the pathologist and neurosurgeon discussed the CLE images in real-time. The TSP and CLE were integrated successfully and rapidly in the operating room in all 3 cases. No patient had perioperative complications.Two novel digital neurosurgical cellular imaging technologies were combined with intraoperative neurosurgeon-pathologist communication to guide the identification of abnormal histoarchitectural tissue features in real-time. CLE with the TSP may allow rapid decision-making during tumor resection that may hold significant advantages over the frozen section process and surgical workflow in general.

OBJECTIVEThe objective of this study was to assess long-term outcomes of facial pain and numbness after radiosurgery for multiple sclerosis (MS)–related trigeminal neuralgia (MS-TN).METHODSThe authors conducted a retrospective review of their Gamma Knife radiosurgeries (GKRSs) to identify all patients treated for MS-TN (1998–2014) with at least 3 years of follow-up. Treatment and clinical data were obtained via chart review and mailed or telephone surveys. Pain control was defined as a facial pain score of I–IIIb on the Barrow Neurological Institute (BNI) Facial Pain Intensity Scale. Kaplan-Meier analysis was performed to determine the rates of pain control after index and first salvage GKRS procedures. Patients could have had more than 1 salvage procedure. Pain control rates were based on the number of patients at risk during follow-up.RESULTSOf the 50 living patients who underwent GKRS, 42 responded to surveys (31 women [74%], median age 59 years, range 32–76 years). During the initial GKRS, the trigeminal nerve root entry zone was targeted with a single isocenter, using a 4-mm collimator with the 90% isodose line completely covering the trigeminal nerve and the 50% isodose line abutting the surface of the brainstem. The median maximum radiation dose was 85 Gy (range 50–85 Gy). The median follow-up period was 78 months (range 36–226 months). The rate of pain control after the index GKRS (n = 42) was 62%, 29%, 22%, and 13% at 1, 3, 5, and 7 years, respectively. Twenty-eight patients (67%) underwent salvage treatment, including 25 (60%) whose first salvage treatment was GKRS. The rate of pain control after the first salvage GKRS (n = 25) was 84%, 50%, 44%, and 17% at 1, 3, 5, and 7 years, respectively. The rate of pain control after the index GKRS with or without 1 salvage GKRS (n = 33) was 92%, 72%, 52%, 46%, and 17% at 1, 3, 5, 7, and 10 years, respectively. At last follow-up, 9 (21%) of the 42 patients had BNI grade I facial pain, 35 (83%) had achieved pain control, and 4 (10%) had BNI grade IV facial numbness (very bothersome in daily life).CONCLUSIONSIndex GKRS offers good short-term pain control for MS-TN, but long-term pain control is uncommon. If the index GKRS fails, salvage GKRS appears to offer beneficial pain control with low rates of bothersome facial numbness.

This article proposes a new topology of double-sided linear Vernier permanent magnet (LVPM) machine with segmented translator structure. A combination of a typical Halbach array consists of two horizontally magnetised permanent magnets (PMs) sandwiched between a salient iron tooth and adjacent vertically magnetised PM pole with the aim of improving its electromagnetic performance. The coreless partitioned translator contributes to a significant reduction in mass and the associated cost. With the aid of finite element analysis (FEA), two LVPM machines with the same PM, and stator volume have been investigated, analysed, and compared. The results imply that the proposed LVPM is capable of producing higher force density, while it exhibits lower cogging force and force ripple compared to its counterpart.

PURPOSE/OBJECTIVE(S) Recurrent GBM (rGBM) is a diffuse disease, and local treatment alone does not provide durable local control (LC) or prolong overall survival (OS). Hypothesizing resection (R) plus immediate-onset radiation therapy (RT) may achieve durable LC and secondarily improve OS by permitting time for subsequent potentially effective but biologically slower treatments to have an impact, we analyzed R plus surgically targeted radiation therapy (STaRT) using a collagen tile brachytherapy (CTBT) device without or with additional systemic (Sys) therapies. MATERIALS/METHODS From 2/13-2/18 patients (pts) with locally recurrent GBM were treated on a prospective single arm, single institution trial (NCT03088579) of maximum safe resection and a permanently implanted CTBT device (GammaTile, GT Medical Technologies, Tempe AZ USA). At resection completion at-risk areas of the surgical bed were lined with bioresorbable collagen squares containing four 3.5U Cs 131 seed sources designed to deliver 60-80 Gy at 5 mm deep to the operative bed. Follow up treatments were not specified; no pt. underwent additional local therapy without progression, and no pt. was lost to follow up. We present here the study-specified endpoints of local control (LC), overall survival (OS), and adverse events (AE), and a post hoc, hypothesis-generating analysis of LC and OS by receipt of Sys therapy. RESULTS 28 locally recurrent GBM were treated, 20 at first progression (range 1-3). Median age was 58 years (yrs.) (range 21-80), KPS 80 (60-100), female: male ratio 10:18 (36/64%). MGMT was methylated in 11%, unmethylated in 18%, and unknown in 71%. For all pts., median OS was 10.7 months (mo.) (range .1-42.3), and radiographic LC was 8.8 mo. (range 0.01-34.5). LC (defined as ≤ 15 mm from surgical bed) was maintained in 50% of pts., and no first failure was local. 12 mo. OS was 75% for pts. < 50 yrs. vs. 43% for ≥ 50 yrs. (HR .46, P = 0.009). MGMT, KPS, and sex were non-predictive. After R+GT, 17 pts. received ≥ 1 cycle of Sys therapy, alone or in combination. Sys was bevacizumab (BEV) in 15 pts., temozolomide (TMZ) in 12, and lomustine (CCNU) in 8. Post hoc analysis disclosed a 15.1 mo. OS for pts. receiving ≥ 1 cycle of Sys (Sys+, N = 17) vs. 6.5 mo. for no Sys (Sys-, N = 11) (hazard ratio (HR) .38, P = 0.017). LC was 11.4 mo. for Sys+ and 2.1 mo. for Sys- (HR .44; P = .16). Median OS (mo.) for BEV+ vs. BEV- was 16.7/4.5 (HR .38, P = 0.017), for TMZ+ vs. TMZ- 17.5/6.7 (HR .40, P = 0.025) and for CCNU+ vs. CCNU- 17.5/7.9 (HR .61, P = .25), respectively. Three AE occurred, 1 dehiscence requiring surgery and 2 radiation brain effects treated medically. CONCLUSION In this study local treatment alone was insufficient to achieve prolonged OS. Post hoc analysis suggests R+ CTBT + Sys may have potential to impact OS in rGBM. A phase 4 study enrolling rGBM pts opened in 2020 (NCT04427384). The device is FDA cleared for newly diagnosed malignant and all recurrent intracranial neoplasms. AUTHOR DISCLOSURE P. Nakaji: Stock; GT Medical Technology. D. Brachman: Stock; GT Medical Technology. Uncompensated member; GT Medical Technology. K. Smith: Stock; GT Medical Technology. T. Thomas: Stock; GT Medical Technology. C. Dardis: None. D. Pinnaduwage: None. G. Wallstrom: None. C. Rogers: Research Grant; NCI - ActNOW. Stock; GT Medical Technology. E.F. Youssef: Stock; GT Medical Technology.

Introduction Achieving durable local control (LC) for larger (e.g., >2-3 cm) brain metastasis whether newly diagnosed or recurrent remains problematic. Resection (R) alone is typically insufficient and adding radiation therapy (RT) still results in a 12-month recurrence rate of 20% or more in many series. Hypothesizing that R plus immediate radiation utilizing brachytherapy may improve outcomes for this cohort of patients, we designed and prospectively evaluated a permanently implanted surgically targeted radiation therapy (STaRT) device consisting of cesium-131 (Cs-131) seeds positioned within a collagen carrier (GammaTile, GT Medical Technologies, Tempe, AZ). The device was designed to prevent direct source-to-brain contact and maintain inter-source spacing after closure. Methods This was a subgroup analysis of a cohort of patients with either recurrent or previously untreated brain metastases enrolled in a prospective, multi-histology single-arm trial (ClinicalTrials.gov, NCT#03088579), conducted between February 2013 and February 2018, of resection and tumor bed brachytherapy with Cs-131 containing permanently implanted collagen tiles to deliver 60 Gray (Gy) at .5 cm depth. No additional local therapy was given without progression. Results A total of 16 metastases in 11 patients were treated; 12 tumors were recurrent and four were previously untreated. The median preoperative maximum diameter was 3.2 cm (range: 1.9-5.1 cm). Histology was seven breasts, six lungs, and three sarcomas. The median age was 60 years (range: 41-80 years); the Karnofsky Performance Status (KPS) was 70 (range: 70-90). The cohort consisted of seven females and four males. The mean time for implantation completion was five minutes. The median overall survival (OS) was 9.3 months. At a median radiographic follow-up of 9.5 months' treatment, site progression was found in 1/16 (6%) at 10.9 months, and the median treatment site time-to-progression (TTP) has not been reached [95% confidence interval (CI): >10.9 months]. At 12 months, the Kaplan-Meier (K-M) estimates for LC after R+STaRT for all tumors was 83%; for previously untreated tumors, LC at 12 months was 100% and for recurrent tumors, it was 80%. Two tumor beds (12.5%) experienced radiation brain changes: one had grade two and the other grade three. No surgical adverse events occurred. Conclusion In this single-arm precommercial study, R+STaRT demonstrated excellent safety and LC in this cohort. The device has recently received FDA clearance for use in newly diagnosed and recurrent brain metastasis, and randomized clinical trials vs. standard of care treatments in both settings are scheduled to open in 2020.

INTRODUCTION Achieving durable local control (LC) for aggressive or recurrent meningiomas remains problematic. Resection (R) alone is insufficient and even with the addition of radiation therapy (RT), outcomes are suboptimal in many series. OBJECTIVE Hypothesizing R plus Surgically Targeted Radiation Therapy (STaRT) may improve LC, we evaluated a permanently implanted brachytherapy device consisting of Cs-131 seeds positioned within modular resorbable collagen carrier/spacer tiles (GammaTile, GT Medical Technologies, Tempe AZ). METHODS From 2/2013-2/2018 recurrent and newly diagnosed aggressive meningiomas were treated on a prospective single-arm study (NCT#03088579). At completion of maximum safe resection the tumor bed was lined with collagen tiles imbedded with Cs-131, delivering 60–80 Gy at 5 mm depth. No additional local therapy was given absent progression. RESULTS 35 meningiomas in 28 patients were treated; 29 recurrent (22 prior R+RT, 6 R only, and 1 RT only) and 6 without prior therapy. WHO grade was I in 2 patients, II in 28, and III in 5. Median age was 66 years (range 37–82), KPS 80 (70–100), female: male ratio 15:13. Mean time for implantation was 5 minutes. At a median radiographic follow-up of 25.5 months (range 0.1–71) LC was 80% (28/35) and median time to progression had not been reached (95% CI > 35.6 months). LC at 12/24/36/48 months was 100/89/72/72% for all tumors, 100/93/79/79% for Grade II, and 100/50/0/0% for Grade III, respectively. No patient receiving STaRT as their initial RT failed. Median overall survival was 50 months. Four symptomatic adverse events occurred, 2 wound breakdowns requiring surgery and 2 radiation-related brain changes, medically treated. CONCLUSION R+STaRT demonstrates favorable safety and LC outcomes in this single-arm prospective trial that includes heavily pre-treated patients. A commercial version of the device recently received FDA clearance for use in newly diagnosed malignant or recurrent intracranial neoplasms including meningiomas.

Glioblastomas (GBMs) are the most aggressive primary brain tumours and have no known cure. Each individual tumour comprises multiple sub-populations of genetically-distinct cells that may respond differently to targeted therapies and may contribute to disappointing clinical trial results. Image-localized biopsy techniques allow multiple biopsies to be taken during surgery and provide information that identifies regions where particular sub-populations occur within an individual GBM, thus providing insight into their regional genetic variability. These sub-populations may also interact with one another through a competitive or cooperative nature; it is important to ascertain the nature of these interactions, as they may have implications for responses to targeted therapies. We combine genetic information from biopsies with a mechanistic model of interacting GBM sub-populations to characterise the nature of interactions between two commonly occurring GBM sub-populations, those with EGFR and PDGFRA genes amplified. We study population levels found across image-localized biopsy data from a cohort of 25 patients and compare this to model outputs under competitive, cooperative and neutral interaction assumptions. We explore other factors affecting the observed simulated sub-populations, such as selection advantages and phylogenetic ordering of mutations, which may also contribute to the levels of EGFR and PDGFRA amplified populations observed in biopsy data.

BACKGROUNDRadiogenomics uses machine-learning (ML) to directly connect the morphologic and physiological appearance of tumors on clinical imaging with underlying genomic features. Despite extensive growth in the area of radiogenomics across many cancers, and its potential role in advancing clinical decision making, no published studies have directly addressed uncertainty in these model predictions.METHODSWe developed a radiogenomics ML model to quantify uncertainty using transductive Gaussian Processes (GP) and a unique dataset of 95 image-localized biopsies with spatially matched MRI from 25 untreated Glioblastoma (GBM) patients. The model generated predictions for regional EGFR amplification status (a common and important target in GBM) to resolve the intratumoral genetic heterogeneity across each individual tumor - a key factor for future personalized therapeutic paradigms. The model used probability distributions for each sample prediction to quantify uncertainty, and used transductive learning to reduce the overall uncertainty. We compared predictive accuracy and uncertainty of the transductive learning GP model against a standard GP model using leave-one-patient-out cross validation.RESULTSPredictive uncertainty informed the likelihood of achieving an accurate sample prediction. When stratifying predictions based on uncertainty, we observed substantially higher performance in the group cohort (75% accuracy, n=95) and amongst sample predictions with the lowest uncertainty (83% accuracy, n=72) compared to predictions with higher uncertainty (48% accuracy, n=23), due largely to data interpolation (rather than extrapolation).CONCLUSIONWe present a novel approach to quantify radiogenomics uncertainty to enhance model performance and clinical interpretability. This should help integrate more reliable radiogenomics models for improved medical decision-making.

INTRODUCTION: We examined patient outcomes after Gamma Knife stereotactic radiosurgery (GKSRS) salvage therapy for recurrent high-grade gliomas (HGGs) to determine whether tumor grade or lesion size affected overall survival (OS) and progression-free survival (PFS). METHODS: This single-center retrospective study assessed radiographic response and clinical outcomes following GKSRS salvage treatment of recurrent malignant gliomas (January 2005–March 2014). RESULTS: A total of 121 patients (67 female) with 132 tumors were treated. Median (range) PFS was 4.7 (3.9-5.4) months for the cohort, 6.8 (4.6-8.9) months for initial grade 2 tumors, 4.2 (1.9-6.5) months for initial grade 3 tumors, and 4.3 (3.7-4.9) months for initial grade 4 tumors. Patients with small lesions (≤6.7 cm(3); n = 53) had significantly longer median (range) PFS (6.8 [4.8-8.8], P=0.02). CONCLUSIONS: GKSRS offers meaningful salvage therapy with minimal morbidity in appropriately selected patients with focally recurrent HGGs.

Objective The Barrow Innovation Center consists of an educational program that promotes interdisciplinary collaboration among neurosurgery, legal, and engineering professionals to foster the development of new medical devices. This report describes a common issue faced during the placement of ventricular shunts for the treatment of hydrocephalus and the solution to this problem that was developed through the Barrow Innovation Center. Methods Neurosurgery residents involved in the Barrow Innovation Center presented the problem of ferromagnetic retractors interfering with pinless image-guidance systems at a monthly meeting. Potential solutions were openly discussed by an interdisciplinary committee of neurosurgeons, patent lawyers, and biomedical engineers. The committee decided to pursue development of a novel self-retaining retractor made of nonferromagnetic material as a solution to the problem. Results Each retractor design was tested in the cadaver laboratory for size and functionality. A final design was chosen and used in a surgical case requiring ventriculoperitoneal shunt placement. The new retractor successfully retracted the scalp without interfering with the electromagnetic image-guidance system. Conclusions Through the interdisciplinary Barrow Innovation Center program, a newly designed, 3-dimensional–printed skin and soft-tissue retractor was created, along with an innovative universal shunt retainer. Through this integrated program dedicated to surgical innovation (i.e., the Barrow Innovation Center), the process of developing and implementing new technology at our institution has been streamlined, creating a culture of innovation within the neurosurgery training program.

INTRODUCTION Recurrent GBM is a diffuse disease and resection (R) alone does not routinely provide durable local control (LC) or prolonged overall survival (OS). We hypothesized R plus immediate radiation (RT) utilizing a novel brachytherapy device might achieve more durable LC and thereby secondarily improve OS. METHODS From 2/2013-2/2018, locally recurrent GBM were treated in a single arm trial (ClinicalTrials.gov, NCT#03088579) of R plus immediate implantation of a surgically targeted radiation therapy (STaRT) device utilizing Cs-131 in bioresorbable collagen tiles (GammaTile, GT Medical Technologies, Tempe AZ USA). RESULTS 28 patients (pts) were treated, 20 at first recurrence (range 1-3). Median age 58 (range 21-80), KPS 80 (60-100), female:male ratio 10:18. Median OS was 10.7 mo., radiographic LC 8.8 mo., and no first failure was local. MGMT, KPS, and sex were non-predictive. Post hoc analysis disclosed after R+STaRT, 17 pts (54%) received > 1 cycle of Sys (“Sys+”) and 13 (46%) did not (“Sys- “). Sys was given as adjuvant, salvage, or both, either alone or in combination. 15 pts received bevacizumab (BEV), 12 temozolomide (TMZ) and 8 lomustine (CCNU). Median OS (mo.) for Sys+ vs. Sys- was 15.1/6.5 (hazard ratio (HR) .38, p=.017); OS for BEV+ vs. BEV- was 16.7/4.5 (HR .38, p=.017), TMZ+ vs. TMZ- 17.5/6.7 (HR .40, p=.025) and for CCNU+ vs. CCNU- 17.5/7.9 (HR .61, p=.25), respectively. LC was 11.4 mo. for Sys+ vs. 2.1 mo. for Sys- (HR .44; p=.16). Three attributed AE occurred, 1 wound infection requiring surgery and 2 radiation brain effects, managed medically. CONCLUSION Post hoc analysis suggests R+STaRT+Sys may have the potential to impact OS in locally recurrent GBM, possibly by allowing sufficient time for effective but biologically slower treatments to have an impact. FDA clearance was received in 2018 for recurrent intracranial neoplasms and in 2020 for newly-diagnosed malignant brain tumors.

Background The diagnosis and management of patients with idiopathic intracranial hypertension (IIH) frequently relies on lumbar puncture to ascertain intracranial pressure (ICP). However, ICP values derived this way may be spurious owing to patient body habitus and behavior. We recently incorporated direct continuous ICP monitoring into the work-up for IIH. Methods Through billing records, we identified all patients during a 3-year period who had a diagnosis of IIH and who underwent ICP monitoring before shunt placement or revision. Patient demographics and clinical data were reviewed. Results Of 30 patients who underwent ICP monitoring with an intraparenchymal wire, 17 had undergone lumbar puncture within the previous 6 months. Results from lumbar punctures showed an elevated opening pressure in all 17 patients, whereas only 2 patients (12%) were found to have consistently elevated ICP with direct ICP monitoring. Of 15 patients being evaluated for shunting, 4 (27%) were found to have elevated ICP. Of the 15 patients with existing shunts, 2 patients (13%) were found to have malfunctioning shunts after pressure monitoring, and 3 patients (20%) had shunts that were found to be unnecessary and were removed. No patient experienced any complication from invasive monitoring. Conclusions Direct ICP monitoring is the gold standard for determining ICP and can be safely and effectively applied to the work-up and treatment of patients with IIH to reduce the occurrence of misdiagnosis and unnecessary surgery.

OBJECTIVE Cerebral venous pressure gradient (CVPG) from dural venous sinus stenosis is implicated in headache syndromes such as idiopathic intracranial hypertension (IIH). The incidence of CVPG in headache patients has not been reported. METHODS The authors reviewed all cerebral venograms with manometry performed for headache between January 2008 and May 2015. Patient demographics, headache etiology, intracranial pressure (ICP) measurements, and radiographic and manometric results were recorded. CVPG was defined as a difference ≥ 8 mm Hg by venographic manometry. RESULTS One hundred sixty-four venograms were performed in 155 patients. There were no procedural complications. Ninety-six procedures (58.5%) were for patients with IIH. The overall incidence of CVPG was 25.6% (42 of 164 procedures): 35.4% (34 of 96 procedures) in IIH patients and 11.8% (8 of 68 procedures) in non-IIH patients. Sixty procedures (36.6%) were performed in patients with preexisting shunts. Seventy-seven patients (49.7%) had procedures preceded by an ICP measurement within 4 weeks of venography, and in 66 (85.7%) of these patients, the ICP had been found to be elevated. CVPG was seen in 8.3% (n = 5) of the procedures in the 60 patients with a preexisting shunt and in 0% (n = 0) of the 11 procedures in the 77 patients with normal ICP (p < 0.001 for both). Noninvasive imaging (MR venography, CT venography) was assessed prior to venography in 112 (68.3%) of 164 cases, and dural venous sinus abnormalities were demonstrated in 73 (65.2%) of these cases; there was a trend toward CVPG (p = 0.07). Multivariate analysis demonstrated an increased likelihood of CVPG in patients with IIH (OR 4.97, 95% CI 1.71–14.47) and a decreased likelihood in patients with a preexisting shunt (OR 0.09, 95% CI 0.02–0.44). CONCLUSIONS CVPG is uncommon in IIH patients, rare in those with preexisting shunts, and absent in those with normal ICP.

OBJECTIVE Debate continues over proper surgical treatment for mesial temporal lobe epilepsy (MTLE). Few large comprehensive studies exist that have examined outcomes for the subtemporal selective amygdalohippocampectomy (sSAH) approach. This study describes a minimally invasive technique for sSAH and examines seizure and neuropsychological outcomes in a large series of patients who underwent sSAH for MTLE. METHODS Data for 152 patients (94 women, 61.8%; 58 men, 38.2%) who underwent sSAH performed by a single surgeon were retrospectively reviewed. The sSAH technique involves a small, minimally invasive opening and preserves the anterolateral temporal lobe and the temporal stem. RESULTS All patients in the study had at least 1 year of follow-up (mean [SD] 4.52 [2.57] years), of whom 57.9% (88/152) had Engel class I seizure outcomes. Of the patients with at least 2 years of follow-up (mean [SD] 5.2 [2.36] years), 56.5% (70/124) had Engel class I seizure outcomes. Preoperative and postoperative neuropsychological test results indicated no significant change in intelligence, verbal comprehension, perceptual reasoning, attention and processing, cognitive flexibility, visuospatial memory, or mood. There was a significant change in word retrieval regardless of the side of surgery and a significant change in verbal memory in patients who underwent dominant-side resection (p < 0.05). Complication rates were low, with a 1.3% (2/152) permanent morbidity rate and 0.0% mortality rate. CONCLUSIONS This study reports a large series of patients who have undergone sSAH, with a comprehensive presentation of a minimally invasive technique. The sSAH approach described in this study appears to be a safe, effective, minimally invasive technique for the treatment of MTLE.

Glioblastoma (GBM) is a heterogeneous and lethal brain cancer. These tumors are followed using magnetic resonance imaging (MRI), which is unable to precisely identify tumor cell invasion, impairing effective surgery and radiation planning. We present a novel hybrid model, based on multiparametric intensities, which combines machine learning (ML) with a mechanistic model of tumor growth to provide spatially resolved tumor cell density predictions. The ML component is an imaging data-driven graph-based semi-supervised learning model and we use the Proliferation-Invasion (PI) mechanistic tumor growth model. We thus refer to the hybrid model as the ML-PI model. The hybrid model was trained using 82 image-localized biopsies from 18 primary GBM patients with pre-operative MRI using a leave-one-patient-out cross validation framework. A Relief algorithm was developed to quantify relative contributions from the data sources. The ML-PI model statistically significantly outperformed (p

Background Choroid plexus papillomas (CPPs) are benign World Health Organization grade I tumors that comprise 2%–4% of all brain tumors among children and less than 1% of brain tumors in adults. Most adult cases occur in the fourth ventricle, with only 1 previous report describing an adult patient with a temporal horn CPP. Case Description We report a rare case of a temporal horn CPP presenting in an adult with seizures. We performed a minimally invasive subtemporal approach for gross total resection of the lesion. Conclusions CPP presenting in the temporal horn is rare among adults. We discuss the surgical nuances of the subtemporal approach for resection and review the literature regarding adult presentation of CPP and the treatment strategies for adult CPP.

BackgroundThe selective posterior cerebral artery (PCA) amobarbital test, or PCA Wada test, is used to predict memory impairment after epilepsy surgery in patients who have previously had a failed internal carotid artery (ICA) amobarbital test.MethodsMedical records from 2012 to 2018 were retrospectively reviewed for all patients with seizures who underwent a selective PCA Wada test at our institution following a failed or inconclusive ICA Wada test. Standardized neuropsychological testing was performed before and during the Wada procedure and postoperatively in patients who underwent resection.ResultsThirty-three patients underwent a selective PCA Wada test, with no complications. Twenty-six patients with medically refractory epilepsy had a seizure focus amenable to selective amygdalohippocampectomy (AHE). Six patients (23%, n=26) had a failed PCA Wada test and did not undergo selective AHE, seven (27%) declined surgical resection, leaving 13 patients who underwent subtemporal selective AHE. Hippocampal sclerosis was found in all 13 patients (100%). Twelve patients (92%) subsequently underwent formal neuropsychological testing and all were found to have stable memory. Ten patients (77%) were seizure-free (Engel Class I), with average follow-up of 13 months.ConclusionThe selective PCA Wada test is predictive of memory outcomes after subtemporal selective AHE in patients with a failed or inconclusive ICA Wada test. Furthermore, given the low risk of complications and potential benefit of seizure freedom, a selective PCA Wada test may be warranted in patients with medically intractable epilepsy who are candidates for a selective AHE and who have a prior failed or inconclusive ICA Wada test.

BACKGROUND: MRI-based modeling of tumor cell density (TCD) can significantly improve targeted treatment of Glioblastoma (GBM). Unfortunately, interpatient variability limits the predictive ability of many modeling approaches. We present a Transfer Learning (TL) method that generates individualized patient models, grounded in the wealth of population data, while also detecting and adjusting for interpatient variabilities based on each patient’s own histologic data. METHODS: We recruited primary GBM patients undergoing image-guided biopsies and preoperative imaging including contrast-enhanced MRI (CE-MRI), Dynamic-Susceptibility-Contrast (DSC)-MRI, and Diffusion Tensor Imaging (DTI). We calculated relative cerebral blood volume (rCBV) from DSC-MRI and mean diffusivity (MD) and fractional anisotropy (FA) from DTI. Following image coregistration, we assessed TCD for each biopsy and identified corresponding localized MRI measurements. We then explored a range of univariate and multivariate predictive models of TCD based on MRI measurements in a generalized one-model-fits-all (OMFA) approach. We then implemented both univariate and multivariate individualized TL predictive models, which harness the available population level data but allow for individual variability in their predictions. Finally, we compared Pearson correlation coefficients and mean absolute error between the individualized TL versus generalized OMFA models. RESULTS: TCD significantly correlated with rCBV (r=0.33,p

2054 Background: Recurrent GBM (rGBM) is a diffuse disease, and resection (R) alone does not provide durable local control (LC) or prolong overall survival (OS). Hypothesizing R plus immediate radiation (RT) may achieve durable LC and secondarily improve OS by permitting time for subsequent potentially effective but biologically slower treatments to have an impact, we prospectively evaluated R combined with a novel surgically targeted radiation therapy (STaRT) device utilizing Cs-131 embedded in bioresorbable collagen tiles. Methods: From 2/13-2/18 patients (pts) with locally recurrent GBM were treated on a prospective single arm trial (ClinicalTrials.gov, NCT#03088579) of maximum safe resection and immediate RT (GammaTile, GT Medical Technologies, Tempe AZ). Upon resection the at-risk areas of the surgical bed were lined with the GammaTile (GT) device, delivering 60-80 Gy at 5 mm. Follow up treatments were not specified but captured; no pt. underwent additional local therapy without progression, and no pt. was lost to follow up. We present study specified endpoints of local control (LC), overall survival (OS), and adverse events (AE), and a post hoc, hypothesis-generating analysis of outcomes by receipt of systemic (Sys) therapy. Results: 28 locally recurrent GBM were treated, 20 at first progression (range 1-3). Median age was 58 years (yrs.) (range 21-80), KPS 80 (60-100), female: male ratio 10:18 (36/64%). MGMT was methylated in 11%, unmethylated in 18%, and unknown in 71%. For all pts., median OS was 10.7 months (mo.) (range.1-42.3), and radiographic LC was 8.8 mo. (range.01-34.5). LC (defined as < 15 mm from surgical bed) was maintained in 50% of pts., and no first failure was local. 12 mo. OS was 75% for pts. < 50 yrs. vs. 43% for > 50 yrs. (HR.46, p =.009). MGMT, KPS, and sex were non-predictive. After R+GT, 17 pts. received > 1 cycle of systemic therapy (Sys), either as adjuvant or salvage, alone or in combination . Sys was bevacizumab (BEV) in 15 pts., temozolomide (TMZ) in 12, and lomustine (CCNU) in 8 (N > 17 as some pts. received > 1 Sys). Post hoc analysis disclosed a 15.1 mo. OS for pts. receiving > 1 cycle of Sys (Sys+, N = 17) vs. 6.5 mo. for no Sys (Sys-, N = 11) (hazard ratio (HR).38, p =.017)). LC was 11.4 mo. for Sys+ and 2.1 mo. for Sys- (HR.44; p =.16)). Median OS (mo.) for BEV+ vs. BEV- was 16.7/4.5 (HR.38, p =.017), for TMZ+ vs. TMZ- 17.5/6.7 (HR.40, p =.025) and for CCNU+ vs. CCNU- 17.5/7.9 (HR.61, p =.25), respectively. Three attributed AE occurred, 1 dehiscence requiring surgery and 2 radiation brain effects, medically treated. 4 unrelated deaths occurred < 60 days post-op, all in the Sys- cohort, impacting their opportunity for subsequent treatment. Conclusions: In this study local treatment alone was insufficient to achieve prolonged OS. Post hoc analysis suggests R+GT coupled with Sys may have potential to impact OS in rGBM patients. GT was FDA cleared in 2020 for use in newly diagnosed malignant and all recurrent intracranial neoplasms. Clinical trial information: NCT#03088579.

Background Glioblastoma (GBM) exhibits profound intratumoral genetic heterogeneity. Each tumor comprises multiple genetically distinct clonal populations with different therapeutic sensitivities. This has implications for targeted therapy and genetically informed paradigms. Contrast-enhanced (CE)-MRI and conventional sampling techniques have failed to resolve this heterogeneity, particularly for nonenhancing tumor populations. This study explores the feasibility of using multiparametric MRI and texture analysis to characterize regional genetic heterogeneity throughout MRI-enhancing and nonenhancing tumor segments. Methods We collected multiple image-guided biopsies from primary GBM patients throughout regions of enhancement (ENH) and nonenhancing parenchyma (so called brain-around-tumor, [BAT]). For each biopsy, we analyzed DNA copy number variants for core GBM driver genes reported by The Cancer Genome Atlas. We co-registered biopsy locations with MRI and texture maps to correlate regional genetic status with spatially matched imaging measurements. We also built multivariate predictive decision-tree models for each GBM driver gene and validated accuracies using leave-one-out-cross-validation (LOOCV). Results We collected 48 biopsies (13 tumors) and identified significant imaging correlations (univariate analysis) for 6 driver genes: EGFR, PDGFRA, PTEN, CDKN2A, RB1, and TP53. Predictive model accuracies (on LOOCV) varied by driver gene of interest. Highest accuracies were observed for PDGFRA (77.1%), EGFR (75%), CDKN2A (87.5%), and RB1 (87.5%), while lowest accuracy was observed in TP53 (37.5%). Models for 4 driver genes (EGFR, RB1, CDKN2A, and PTEN) showed higher accuracy in BAT samples (n = 16) compared with those from ENH segments (n = 32). Conclusion MRI and texture analysis can help characterize regional genetic heterogeneity, which offers potential diagnostic value under the paradigm of individualized oncology.

Mesial temporal lobe epilepsy is a common condition that is frequently drug resistant. Anterior temporal lobectomy has been shown to be effective in controlling seizures but entails resecting anterior and lateral temporal lobe regions that are not necessarily included in the epileptogenic zone. Selective amygdalohippocampectomy spares uninvolved structures while providing the same benefit as anterior temporal lobectomy. This article describes the 3 most common surgical approaches for performing selective amygdalohippocampectomy and discusses their relative merits and risks.

INTRODUCTION Achieving durable local control for larger brain metastases remains problematic. Resection (R) alone is typically insufficient. Even with the addition of stereotactic radiation the 12-month recurrence rate for larger lesions (i.e., >2.5–3 cm) is 20% or more in many series. To improve outcomes we designed and prospectively evaluated a permanently implanted radiation device consisting of Cs-131 seeds positioned within a collagen tile (GammaTile, GT Medical Technologies, Tempe AZ). We combined maximum safe resection and collagen tile brachytherapy (CTBT) with the hypothesis that immediate radiation initiation and/or dose intensification could improve outcomes. MATERIALS/METHODS From 2013–2018 patients undergoing resection with either previously untreated or recurrent brain metastasis were enrolled on a single arm, multi-histology study (ClinicalTrials.gov, NCT#03088579). At resection completion the tumor bed was lined with collagen tiles imbedded with Cs-131, delivering 60–80 Gy at 5 mm depth. The device was designed to prevent direct source-to-brain contact and to maintain inter-source spacing after closure. No additional local therapy was given unless progression occurred. RESULTS 16 metastases (12 recurrent/4 previously untreated) in 11 patients were treated. Median diameter 3.1 cm, range 1.9–5.1. Histology was 7 breast, 6 lung, and 3 sarcoma. Median age 60 years; 7 females/4 males. Average time for implantation was 5 minutes. At median radiographic follow-up of 9.5 months (range 0.1–25.2) treatment site progression occurred 1/16 (6%) at 10.9 months. Median treatment site time-to-progression (TTP) has not been reached (95% CI, >10.9 months). Median overall survival (OS) 9.3 months. No surgical adverse events occurred. One patient (6.2%) experienced radiation brain changes and was treated medically. CONCLUSION R+CTBT demonstrated excellent safety and local control outcomes in this single-arm pre-commercial study. The device recently received FDA clearance for use in newly diagnosed and recurrent brain metastasis. Randomized clinical trials vs standard of care treatments are expected to open in 2020.

The posterior interhemispheric approach can be useful in accessing a wide range of lesions in the falcotentorial region. We demonstrate the case of a 59-year-old woman with a long history of headache who was found to have a large falcotentorial meningioma on imaging workup. The deep venous structures of the Galenic complex were displaced inferiorly by the tumor, thus indicating a supratentorial approach. Risks and alternatives to the approach demonstrated in this video were discussed with the patient, and she wished to proceed. The patient was positioned in a three-quarters prone (“park bench”) position in order to allow gravity retraction of the right hemisphere, which facilitated tumor visualization. The tumor was removed completely, and the patient tolerated the procedure well without complication. Patient consent was obtained for the use of the operative video. Used with permission from Barrow Neurological Institute, Phoenix, Arizona. Keywords: Falcotentorial, Meningioma, Posterior interhemispheric