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Purpose: Multidisciplinary tumor boards (MTBs) integrate clinical, molecular, and radiological information and facilitate coordination of neuro-oncology care. During the COVID-19 pandemic, our MTB transitioned to a virtual and multi-institutional format. We hypothesized that this expansion would allow expert review of challenging neuro-oncology cases and contribute to the care of patients with limited access to specialized centers., Methods: We retrospectively reviewed records from virtual MTBs held between 04/2020-03/2021. Data collected included measures of potential clinical impact, including referrals to observational or therapeutic studies, referrals for specialized neuropathology analysis, and whether molecular findings led to a change in diagnosis and/or guided management suggestions., Results: During 25 meetings, 32 presenters discussed 44 cases. Approximately half (n = 20; 48%) involved a rare central nervous system (CNS) tumor. In 21% (n = 9) the diagnosis was changed or refined based on molecular profiling obtained at the NIH and in 36% (n = 15) molecular findings guided management. Clinical trial suggestions were offered to 31% (n = 13), enrollment in the observational NCI Natural History Study to 21% (n = 9), neuropathology review and molecular testing at the NIH to 17% (n = 7), and all received management suggestions., Conclusion: Virtual multi-institutional MTBs enable remote expert review of CNS tumors. We propose them as a strategy to facilitate expert opinions from specialized centers, especially for rare CNS tumors, helping mitigate geographic barriers to patient care and serving as a pre-screening tool for studies. Advanced molecular testing is key to obtaining a precise diagnosis, discovering potentially actionable targets, and guiding management., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for glioblastoma by releasing our consensus model, and 3) demonstrate the FL effectiveness at such scale and task-complexity as a paradigm shift for multi-site collaborations, alleviating the need for data-sharing., (© 2022. The Author(s).)

Background: Meningiomas are the most common intracranial neoplasms. Although genomic analysis has helped elucidate differences in survival, there is evidence that racial disparities may influence outcomes. African Americans have a higher incidence of meningiomas and poorer survival outcomes. The etiology of these disparities remains unclear, but may include a combination of pathophysiology and other factors., Objective: To determine factors that contribute to different clinical outcomes in racial populations., Methods: We retrospectively reviewed 305 patients who underwent resection for meningiomas at a single tertiary care facility. We used descriptive statistics and univariate, multivariable, and Kaplan-Meier analyses to study clinical, radiographical, and histopathological differences., Results: Minority patients were more likely to present through the emergency department than an outpatient clinic (P < .0001). They were more likely to present with more advanced clinical symptoms with lower Karnofsky Performance scores, more frequently had peritumoral edema (P = .0031), and experienced longer postoperative stays in the hospital (P = .0053), and African-American patients had higher hospitalization costs (P = .046) and were more likely to be publicly insured. Extent of resection was an independent predictor of recurrence freedom (P = .039). Presentation in clinic setting trended toward an association with recurrence-free survival (P = .055). We observed no significant difference in gross total resection rates, postoperative recurrence, or recurrence-free survival., Conclusion: Minority patients are more likely to present with severe symptoms, require longer perioperative hospitalization, and generate higher hospitalization costs. This may be due to socioeconomic factors that affect access to health care. Targeting barriers to access, especially to subspecialty care, may facilitate more appropriate and timely diagnosis, thereby improving patient care and outcomes., (Copyright © Congress of Neurological Surgeons 2021. All rights reserved.)

Background: Gliomas manifest in a variety of histological phenotypes with varying aggressiveness. The etiology of glioma remains largely unknown. Taller stature in adulthood has been linked with glioma risk. The aim of this study was to discern whether this association can be detected in adolescence., Methods: The cohort included 2 223 168 adolescents between the ages of 16 and 19 years. Anthropometric measurements were collected at baseline. Incident cases of glioma were extracted from the Israel National Cancer Registry over a follow-up period spanning 47 635 745 person-years. Cox proportional hazard models were used to estimate the hazard ratio (HR) for glioma and glioma subtypes according to height, body mass index (BMI), and sex., Results: A total of 1195 patients were diagnosed with glioma during the study period. Mean (SD) age at diagnosis was 38.1 (11.7) years. Taller adolescent height (per 10-cm increase) was positively associated with the risk for glioma of any type (HR: 1.15; P = .002). The association was retained in subgroup analyses for low-grade glioma (HR: 1.17; P = .031), high-grade glioma (HR: 1.15; P = .025), oligodendroglioma (HR: 1.31; P = .015), astrocytoma (HR: 1.12; P = .049), and a category of presumed IDH-mutated glioma (HR: 1.17; P = .013). There was a trend toward a positive association between height and glioblastoma, however this had borderline statistical significance (HR: 1.15; P = .07). After stratification of the cohort by sex, height remained a risk factor for men but not for women., Conclusions: The previously established association between taller stature in adulthood and glioma risk can be traced back to adolescence. The magnitude of association differs by glioma subtype., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Intracranial solitary fibrous tumors (ISFTs) are rare neoplasms of mesenchymal origin that originate from the meninges. ISFTs of the skull base can be challenging to treat, as resection can be complicated by skull base anatomy. We present 2 cases of ISFT, the first manifesting with compressive cranial neuropathy from Meckel cave involvement and the second a posterior fossa lesion causing symptomatic hydrocephalus., Methods: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PubMed database was queried with title/abstract keywords "intracranial," "solitary fibrous tumor," "hemangiopericytoma," "SFT," and "HPC." Search results were reviewed to exclude cases not involving the skull base. References from all selected articles were reviewed for potential additional cases. Patient demographic and clinical data from 58 identified skull base cases were collected for qualitative synthesis., Results: Visual disturbances were the most common presenting symptom (30 cases, 52%) followed by headache (22 cases, 38%). The most common site of involvement was the sellar/parasellar region (18 cases, 31%) followed by middle fossa/temporal bone (14 cases, 24%). Resection was performed in 55 cases; gross total resection was reported in 26 cases (45%) and subtotal resection was reported in 21 cases (36%). Tumor recurrence was documented in 15 cases (26%) with median and mean follow-up periods of 16 and 29.9 months, respectively., Conclusions: We discuss presentation, imaging, histopathology, and management considerations for ISFTs while highlighting the potentially complex nature of skull base lesions and need for multidisciplinary approach to treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Glioblastoma (GBM) typically presents as a single lesion. Multicentric GBM are defined as well separated lesions on MRI (enhancing and non-enhancing). Multicentric GBM with non-enhancing lesions (MNE-GBM) are rarely described in literature. We aimed at describing the radiologic characteristics, treatment, and clinical course of those patients. The institutional neuropathological database was searched for GBM patients diagnosed between 1/1/2015 and 31/05/2018. All pre-operative MRI brain scans were reviewed to identify patients with MNE-GBM. Electronic medical records and follow-up MRI scans were reviewed to assess progression-free survival (PFS) and overall survival (OS). Out of 149 adult patients with newly diagnosed GBM, 12 met the inclusion criteria of MNE-GBM, all of them presented at least one enhancing lesion. Median follow-up for the MNE-GBM patients was 16.1 months. At last follow-up, all patients had recurrence (median PFS 7.6 months) and eleven patients had deceased. Median OS was 16.2 months (95% CI, 4.1-27.5). Eleven patients received radiotherapy concomitant with temozolomide as initial treatment. Radiation field included all the disease foci (enhancing and non-enhancing lesions) in 8 patients, five of them progressed within the non-enhancing lesion. Three patients did not receive radiation for the entire non-enhancing lesions, and two of them progressed within the non-irradiated areas. In conclusion, MNE-GBM is not rare, and has high risk of aggressive progression within the separate non-enhancing lesion., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Paraneoplastic syndromes can commonly occur due to lung cancer, especially small cell lung cancer. Frequently paraneoplastic syndromes can precede the diagnosis of the neoplasm or present with limited stage disease. However, these syndromes can also occur at the time of recurrence or metastasis of disease. This review focuses on the epidemiology, pathogenesis, clinical features, and current management of the most common paraneoplastic syndromes encountered in patients with small cell lung cancer. Manifestations of paraneoplastic syndromes in small cell lung cancer include endocrine syndromes with secretion of excess hormones, and neurologic syndromes due to the production of antibodies causing an autoimmune condition. Recent advances have allowed for greater understanding of these syndromes and for the development of improved diagnostic as well as therapeutic tools. Awareness of paraneoplastic syndromes in small cell lung cancer can lead to an earlier diagnosis and recognition of both the condition and in some cases the disease potentially improving the overall survival and prognosis for patients. Further research examining effective methods to improve recovery from neurologic deficits in patients with a paraneoplastic neurologic illness is warranted., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd.2020.03.88). The series “Small Cell Lung Cancer” was commissioned by the editorial office without any funding or sponsorship. JM reports other from Bayer Pharmaceuticals, outside the submitted work. Other authors have no other conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Central nervous system (CNS) metastases occur frequently in oncogene-driven non-small cell lung cancer (NSCLC). Standard treatment approaches can potentially delay systemic treatment (surgical intervention) or result in neurocognitive impairment (radiotherapy). Recently, next-generation tyrosine kinase inhibitors (TKIs) have demonstrated remarkable intracranial activity. However, most clinical trials did not enroll patients suffering neurological symptoms. Our study aimed to assess the CNS activity of targeted therapies in this patient population. We present a case series of nine NSCLC patients with either EGFR mutation or ALK rearrangement and symptomatic CNS metastases that were treated with TKIs. Clinicopathological characteristics, treatment, and outcomes were analyzed. Most patients presented with symptomatic CNS metastases at time of metastatic disease presentation (6/9). Additionally, the majority of patients had leptomeningeal disease (6/9) and multiple parenchymal metastases. Patients presented with a variety of CNS symptoms with the most common being nausea, vomiting, headache, and confusion. Most patients (6/9) responded rapidly both clinically and radiographically to the targeted treatment, with a marked correlation between systemic and intracranial radiographic response. In conclusion, upfront use of next-generation TKIs in patients with oncogene-driven NSCLC with symptomatic CNS metastases is associated with reasonable intracranial activity and represents a valuable treatment option., Competing Interests: Elizabeth Dudnik reported grants from Boehringer Ingelheim and personal fees for consulting or advisory services from Boehringer Ingelheim, Roche, Astra Zeneca, Pfizer, MSD, BMS, Novartis, and Takeda. Alona Zer reported grants from BMS and personal fees for consulting or advisory services from Roche, MSD, BMS, and AstraZeneca. Jacob Mandel served on a medical advisory board for Bayer. Jair Bar reported grants from MSD, Roche, AstraZeneca, and Pfizer and reported personal fees for consulting or advisory services from MSD, Roche, Boehringer Ingelheim, AstraZeneca, Pfizer, BMS, Takeda, VBL, Bayer, Novartis, and AbbVie. Shlomit Yust reported grants from MSD and and personal fees from AbbVie. Other authors declare no conflicts of interest., (Copyright © 2020 Omer Gal et al.)

Background: Meningiomas are the most common primary central nervous system tumors. Potential risk factors include obesity, height, history of allergy/atopy, and autoimmune diseases, but findings are conflicting. This study sought to assess the role of the different risk factors in the development of meningioma in adolescents/young adults., Methods: The cohort included 2,035,915 Jewish men and women who had undergone compulsory physical examination between 1967 and 2011, at age 16 to 19 years, prior to and independent of actual military enlistment. To determine the incidence of meningioma, the military database was matched with the Israel National Cancer Registry. Cox proportional hazard models were used to estimate the hazard ratios for meningioma according to sex, body mass index (BMI), height, and history of allergic or autoimmune disease., Results: A total of 480 subjects (328 females) were diagnosed with meningioma during a follow-up of 40,304,078 person-years. Median age at diagnosis was 42.1 ± 9.4 years (range 17.4-62.6). On univariate analysis, female sex (p < 0.01) and height (p < 0.01) were associated with risk of meningioma. When the data were stratified by sex, height remained a significant factor only in men. Spline analysis of the male subjects showed that a height of 1.62 m was associated with a minimum disease risk and a height of 1.85+ meters, with a significant risk., Conclusions: This large population study showed that sex and adolescent height in males (> 1.85 m) were associated with an increased risk of meningioma in adulthood.

Competing Interests: Competing interests: None declared.

Background: We sought to ascertain the immune effector function of pembrolizumab within the glioblastoma (GBM) microenvironment during the therapeutic window., Methods: In an open-label, single-center, single-arm phase II "window-of-opportunity" trial in 15 patients with recurrent (operable) GBM receiving up to 2 pembrolizumab doses before surgery and every 3 weeks afterward until disease progression or unacceptable toxicities occurred, immune responses were evaluated within the tumor., Results: No treatment-related deaths occurred. Overall median follow-up time was 50 months. Of 14 patients monitored, 10 had progressive disease, 3 had a partial response, and 1 had stable disease. Median progression-free survival (PFS) was 4.5 months (95% CI: 2.27, 6.83), and the 6-month PFS rate was 40%. Median overall survival (OS) was 20 months, with an estimated 1-year OS rate of 63%. GBM patients' recurrent tumors contained few T cells that demonstrated a paucity of immune activation markers, but the tumor microenvironment was markedly enriched for CD68+ macrophages., Conclusions: Immune analyses indicated that pembrolizumab anti-programmed cell death 1 (PD-1) monotherapy alone can't induce effector immunologic response in most GBM patients, probably owing to a scarcity of T cells within the tumor microenvironment and a CD68+ macrophage preponderance., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Intracranial metastasis of Gastrointestinal Stromal Tumors (GISTs) is rare but presents unique treatment challenges. We present a case of intracranial metastasis of GIST with a systematic review of the literature. A literature search using key terms "'gastrointestinal stromal tumor' AND brain AND metastasis"" was conducted through May 2019 via Embase and Pubmed according to PRISMA guidelines. Only cases describing intradural metastases rather than calvarial or intraorbital metastases were included., Case Presentation: A 57-year-old woman with history of GIST metastatic to the liver presented with a six-week history of left facial weakness, left hearing loss, and left facial numbness, and a one-week history of headaches, gait disturbance, and dizziness. MRI revealed a contrast-enhancing dural-based left middle cranial fossa mass measuring 2.9 cm × 3.1 cm × 3.4 cm with extension into the internal auditory canal and cerebral edema. A left temporal craniotomy was performed to excise the lesion, and the patient was discharged to a rehabilitation facility at her preoperative baseline. Intraoperative pathology revealed a spindle cell neoplasm, postoperative MRI demonstrated gross total resection of the lesion, and microscopic analysis demonstrated sheets of spindled tumor cells with short ovoid, irregular, hyperchromatic nuclei and scattered large atypical nuclei without extensive necrosis. Immunohistochemical staining was positive for KIT proto-oncogene (CD117, c-KIT), and the patient was put on imatinib (400 mg/day)., Conclusions: Of the 18 cases analyzed and our present case, metastasis typically involved the cerebrum with only one in infratentorial elements. The tumors in seven of the cases involved the dura, and one case metastasized to the pituitary. Eight patients died following treatment. Surgery remains the mainstay of intracranial metastatic GIST, however there are many reports of good responses to radiation or chemotherapy alone. More investigation is required to determine the best treatment course for these patients.

Immune checkpoint inhibitors (ICPIs) have recently emerged as a novel treatment for cancer. These agents, transforming the field of oncology, are not devoid of toxicity and cause immune-related side effects which can involve any organ including the nervous system. In this study, we present 9 patients (7 men and 2 women) with neurologic complications secondary to ICPI treatment. These included meningoencephalitis, limbic encephalitis, polyradiculitis, cranial polyneuropathy, myasthenic syndrome and myositis. Four patients received dual ICPI therapy comprised of programmed cell death-1 and cytotoxic lymphocyte associated protein-4 blocking antibodies. Median time to onset of neurologic adverse event during immune checkpoint inhibitor treatment was 8 weeks (range 5 days-19 weeks). In all patients ICPIs were stopped and corticosteroids were initiated, resulting in a marked improvement in seven out of nine patients. Two patients, one with myositis and one with myasthenic syndrome, died. In two patients ICPI therapy was resumed after resolution of the neurological adverse event with no additional neurologic complications. This series highlights the very broad spectrum of neurological complications of ICPIs, emphasizes the need for expedited diagnosis and suggests that withholding treatment early, accompanied with steroid therapy, carries the potential of complete resolution of the neurological immune-mediated condition. Thus, a high level of suspicion and rapid initiation of corticosteroids are mandatory to prevent uncontrolled clinical deterioration, which might be fatal.

Bevacizumab (BEV) is commonly used for treating recurrent glioblastoma (GBM), and wound healing is a well-established adverse event. Retrospective analysis of GBM patients with and without wound healing complications while on BEV treatment is reported. 287 patients identified, majority were males (60 %) with median age of 52.5 years. 14 cases identified with wound healing problems, related to either craniotomy (n = 8) or other soft tissue wounds (n = 6). Median duration of BEV treatment to complication was 62 days (range 6-559). Majority received 10 mg/kg (n = 11) and nine (64.3 %) were on corticosteroids, with median daily dose of 6 mg (range 1-16 mg) for median of 473 days before starting BEV. For dehisced craniotomy wounds, median time for starting BEV from last surgery was 29 days (range 27-345). Median time from starting BEV to developing wound complication was 47 days (range 16-173). Seven (87.5 %) had infected wounds requiring antibiotics, hospitalization. Four (50 %) required plastic surgery. BEV stopped and safely resumed in 6 (75 %) patients; median delay was 70 days (range 34-346). Soft tissue wounds included decubitus ulcer, dehisced striae, herpes simplex, trauma to hand and back, and abscess. Median time from starting BEV to wound issues was 72 days (range 6-559). Five (83.3 %) were infected, requiring antibiotics. While three (50 %) required hospitalization, none required plastic surgery. Treatment stopped in five (83.3 %) and restarted in two (median delay 48 days, range 26-69). Wound healing complications are uncommon but associated with significant morbidity. Identifying those at risk and contributing factors warrants further investigation.