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.

Multifocal lumbar myxopapillary ependymoma presenting with drop metastasis: a case report and review of the literature.

INTRODUCTION: Spinal myxopapillary ependymomas (SME) are rare WHO grade II neoplasms of the spinal cord. Despite their good prognosis, they have a high propensity for metastasis and recurrence, although the presentation of SME as multifocal is uncommon. CASE PRESENTATION: Here we describe a rare case of a 34-year-old man who presented with painful bilateral radiculopathy with sexual dysfunction and altered sensation with defecation. The patient also reported worsening weakness of bilateral lower extremities when climbing stairs. Biopsy results revealed multifocal SME in the lumbar and sacral spine that was treated with staged surgical resection and post-operative focal radiation therapy. DISCUSSION: We discuss and evaluate surgical resection and the role of postoperative radiotherapy for SME. We also review the literature surrounding multifocal SME presenting in adults.

Calcifying Pseudoneoplasm of the Neuraxis in the Posterior Fossa: A Case Report and Literature Review.

Calcifying pseudoneoplasm of the neuraxis are rare fibro-osseous lesions that can occur throughout the central nervous system. This paper reports one case of this lesion within the posterior fossa and contains a literature review of all cases documented within the posterior fossa to date. A 53-year-old female patient with a history of epiphora, facial irritation, and headaches was found to have a mass centered in the posterior fossa. The patient underwent surgical resection for removal of the mass. Upon review by pathology, the final diagnosis was consistent with calcifying pseudoneoplasm of the neuraxis.

Sarcomatous Change of Cerebellopontine Angle Ependymoma Following Radiosurgery: A Case Report.

Sarcomatous change in ependymal tumors is rare and has been poorly described. We report on a cerebellopontine angle lesion that demonstrated rapid progression two years after radiosurgery in a 73-year-old female patient. Histopathological diagnosis at clinical progression showed an ependymoma with sarcomatous change ("ependymosarcoma") that was believed to be due to radiation. The patient underwent a complex tumor resection without complications using an exhaustive multi-modal neuromonitoring paradigm throughout the dissection and resection of the tumor. Given the limited available data on these rare tumors, we review their presentation, imaging, and histopathology in the context of the previous literature, and also discuss the management of these lesions in the cerebellopontine angle.

Erosion of the sella turcica and pituitary expansion secondary to polymicrobial brain abscesses: a case report.

INTRODUCTION: Brain abscesses can lead to a diverse array of complications, especially when they are polymicrobial in nature. Multiple underlying pathogens may present with a unique set of clinical symptoms which require an early identification and treatment. Skull base osteomyelitis with sellar floor erosion and pituitary involvement with SIADH are such rare complications of brain abscesses which have never been reported previously in the literature. CASE PRESENTATION: We report the case of an immunocompetent 38-year-old male with altered mental sensorium and left hemiparesis due to polymicrobial brain abscess which required surgical evacuation. The post-operative recovery was complicated by severe hyponatremia secondary to SIADH which was treated uneventfully. Radiological imaging demonstrated pituitary enlargement with herniation through an eroded sella turcica without active CSF leak. Patient responded well to the antibiotic therapy based on microbiological susceptibility testing with a complete resolution of the pituitary enlargement on radiological follow-up. CONCLUSION: Conservative treatment with targeted antibiotics can lead to the resolution of pituitary enlargement secondary to a brain abscess. However, a close clinical follow-up is required to look for a CSF leak considering the sellar floor erosion due to osteomyelitis.

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.

Doing Great With DOTATATE: Update on GA-68 DOTATATE Positron Emission Tomography/Computed Tomography and Magnetic Resonance Imaging for Evaluation of Sinonasal Tumors.

ABSTRACT: Sinonasal tumors are relatively rare and radiographically challenging to evaluate due to their wide variety of pathologies and imaging features. However, sinonasal tumors possessing somatostatin receptor overexpression have the benefit of utilizing a multimodality anatomic and functional imaging for a more comprehensive evaluation. This is particularly evident with esthesioneuroblastoma, with computed tomography and magnetic resonance imaging defining the anatomic extent of the tumor, whereas somatostatin receptor imaging, particularly with gallium-68 DOTATATE positron emission tomography/computed tomography, is used to assess the presence of metastatic disease for staging purposes as well as in the surveillance for tumor recurrence. In addition, areas which accumulate gallium-68 DOTATATE are potentially amenable to treatment with peptide receptor radionuclide therapy. In this manner, a combined approach of anatomic and functional imaging is critical for optimal imaging evaluation and treatment strategy of patients with sinonasal tumors.

Multiple Brain Abscesses Due to Nocardia otitidiscaviarum: Case Report and Treatment Implications.

Nocardia infections typically present in immunocompromised hosts. Brain abscesses caused by species such as Nocardia  asteroides, farcinica, and abscessus are well-documented in the literature. We present a rare case of an immunocompetent patient with multiple brain abscesses due to Nocardia otitidiscaviarum requiring a decompressive fronto-temporoparietal craniectomy due to symptomatic intracranial hypertension. The patient was treated with intrathecal amikacin in addition to standard antibiotics with the resolution of the disease and good neurologic outcome. This is one of few case reports overall involving this species within the brain, and the second to report favorable outcomes. This case describes implications for treatment and adds to sparse literature regarding this particular pathogen.

Updates on Deep Learning and Glioma: Use of Convolutional Neural Networks to Image Glioma Heterogeneity.

Deep learning represents end-to-end machine learning in which feature selection from images and classification happen concurrently. This articles provides updates on how deep learning is being applied to the study of glioma and its genetic heterogeneity. Deep learning algorithms can detect patterns in routine and advanced MR imaging that elude the eyes of neuroradiologists and make predictions about glioma genetics, which impact diagnosis, treatment response, patient management, and long-term survival. The success of these deep learning initiatives may enhance the performance of neuroradiologists and add greater value to patient care by expediting treatment.

Deep Learning AI Applications in the Imaging of Glioma.

This manuscript will review emerging applications of artificial intelligence, specifically deep learning, and its application to glioblastoma multiforme (GBM), the most common primary malignant brain tumor. Current deep learning approaches, commonly convolutional neural networks (CNNs), that take input data from MR images to grade gliomas (high grade from low grade) and predict overall survival will be shown. There will be more in-depth review of recent articles that have applied different CNNs to predict the genetics of glioma on pre-operative MR images, specifically 1p19q codeletion, MGMT promoter, and IDH mutations, which are important criteria for the diagnosis, treatment management, and prognostication of patients with GBM. Finally, there will be a brief mention of current challenges with DL techniques and their application to image analysis in GBM.