Classification of tumors in neuro-oncology today relies on molecular patterns (mostly DNA methylation) and their machine learning-supported interpretation. Understanding the process of algorithmic interpretation is essential for safe application in clinical routine. This is paradigmatically true for the most common primary intracranial tumor in adults, meningioma. Here, by applying multiomic profiling and multiple lines of orthogonal computational evaluation in multiple independent datasets, we found that not only tumor cell characteristics but also incremental changes in the tumor microenvironment (TME) have impact on epigenetic meningioma classification and clinical outcome. Besides revealing the decisive role of non-neoplastic cells in the CNS methylation classifier, this challenges the model of distinct meningioma subgroups toward a TME-determined risk continuum. This refines current controversies in molecular meningioma subtyping. In addition, we apply these learnings to devise and validate a simple diagnostic approach for increased clinical prediction accuracy based on immunohistochemistry, which is also applicable in resource-limited settings.

Background:Tumor-treating fields (TTFields) have demonstrated efficacy in newly diagnosed glioblastoma (ndGBM) when combined with adjuvant temozolomide (TMZ). Preclinical studies suggest that  TTFields enhance the therapeutic effect of radiotherapy (RT), providing a rationale for concurrent administration with radiotherapy (RT). This phase 2 randomized trial evaluated the addition of TTFields to standard RT and TMZ, followed by adjuvant  TMZ with  TTFields, in patients with ndGBM. Methods:Patients were randomized prior to chemoradiation to receive RT and TMZ with or without concurrent TTFields, followed by maintenance  TMZ with  TTFields in both groups. The evaluable cohort, defined as an exploratory analysis, included patients who completed at least 4-weeks of RT (≥40Gy) and  TTFields in the experimental arm the primary endpoint, based on the intention-to-treat (ITT) population, was 1-year progression-free survival (PFS12). Secondary endpoints included PFS, overall survival (OS) and safety. Results:Sixty-six patients were randomized (experimental n = 32; control n = 34). In the ITT population, PFS12 favored the experimental group (28.7% vs 17.3%) but did not reach statistical significance (P = .146). Median PFS was 5.4 vs 4.13 months (P = .14) and median OS was 18.5 vs 16.5 months (P = .95) respectively. In the evaluable cohort (n = 54), PFS12 favored experimental group (37.5% vs 17.3%, P = .06), with a significantly longer median PFS (9.9 vs 4.1 months, P = .016). Median OS favored the experimental group (25.9 vs 16.6 months, P = .308). Treatment was well tolerated, with adverse events similar between groups. Conclusions:Early integration of  TTFields with chemoradiation in ndGBM is safe, feasible. Although the primary endpoint was not met, observed survival trends support further evaluation in larger multicenter trials to confirm the potential benefit of concurrent  TTFields with chemoradiation.

OBJECTIVE:Intraoperative identification of language white matter tracts (WMTs) is challenging, as these tracts are visually imperceptible. This study aimed to assess whether proximity to the language WMTs can be determined intraoperatively by correlating direct electrical stimulation (DES) intensity with the distance to language tracts as defined by preoperative diffusion tensor imaging (DTI)-based tractography. METHODS:Twenty-eight patients undergoing awake craniotomy for diffuse glioma resection participated in the study. All patients received preoperative language assessments and DTI-based language tract reconstruction. Subcortical DES was applied along the tumor cavity border using bipolar or monopolar stimulation, with DES locations registered for offline analysis. RESULTS:A positive linear correlation was found between the distance from the stimulated point to the closest language WMT and the subcortical DES electrical threshold (r = 0.57). Stimulation that evoked interference had a significantly lower intensity (mean 6.93, SD 3.82; n = 21) than noninterfering cases [mean 15.06, SD 7.4; n = 11; t(30) = 3.2, p < 0.001]. Tumor pathology, volume, and associated edema did not significantly affect the distance-intensity correlation or likelihood of language interference. Only the bipolar stimulation correlation remained significant following separate analysis of the bipolar and monopolar methods. CONCLUSIONS:These findings suggest that intraoperative threshold-based electrical mapping can feasibly assess language tract proximity, supporting maximal tumor resection while minimizing language deficits.

Machine learning-based molecular classifications, particularly those using DNA methylation data, have greatly advanced diagnostics for meningioma, the most common type of primary intracranial tumor. Meningiomas have historically been classified into NF2-mutant and NF2-wild-type groups, while additional mutations and copy-number variations associated with progression risk have been incorporated into WHO grading. Several genome-wide methylation-based classification systems have been proposed. The systems, such as the random forest Brain Tumour Classifier, have been incorporated into diagnostic guidelines. However, while a number of core archetypes are shared among the different classifications, discrepancies on the definition and granularity of subtypes remain an obstacle to their clinical application. Understanding the underlying heterogeneity driving these classifications is therefore crucial. Through an integrated analysis of single-nuclei and spatially resolved transcriptomic data, as well as DNA methylation array data from multiple meningioma cohorts, we identified cell types and epigenetic signatures that are associated with increased aggressiveness in meningiomas. The results demonstrated that incremental changes in the tumor microenvironment (TME), particularly shifts in compositions and epigenetic-transcriptomic signatures in tumor-associated monocytes/macrophages and microglia-like cells, have a decisive impact on epigenetic classifications alongside tumor cells, and significantly affect clinical outcome. Therefore, we refine the previously proposed distinct molecular subtypes with a TME-determined risk continuum model for NF2-mutant meningiomas. Based on these discoveries, we additionally designed an immunohistochemistry-based diagnostic approach, which also captures intra-tumoral heterogeneities.

The relationship between tumor-to-corticospinal tract (CST) distance and the subcortical motor evoked potential (scMEP) threshold remains unclear. This study examines how contrast-enhancement charecteristics influence this correlation. We retrospectively analyzed preoperative imaging and intraoperative electrophysiological data from 323 patients who underwent resection of intra-axial tumors adjacent to the CST. We recorded the shortest distance from the tumor margin to the CST (as defined by DTI-based tractography) and the lowest stimulation current required to elicit an scMEP. To ensure the lowest threshold corresponded the minimal tumor-to-CST distance, only patient underwent gross total resection were included. Correlation between tumor-to-CST distance and scMEP threshold were analyzed, stratified by contrast enhancement status. Of the 203 patients meeting inclusion criteria, 158 had contrast-enhancing tumors. The mean preoperative tumor-to-CST distance was 9 ± 7.4 mm (range: 0–20 mm) for enhancing tumors and 7.2 ± 5.4 mm (range: 0.9–20 mm) for non-enhancing tumors. The mean lowest scMEP threshold was 7.9 ± 4.7 mA (range: 1–25 mA) for enhancing tumors and 6.5 ± 4.5 mA (range: 1–20 mA) for non-enhancing tumors. A strong correlation was observed between tumor-to-CST distance and scMEP threshold in non-enhancing tumors (r = 0.73; 95% CI: 0.54–0.85; P <.0001), whereas the correlation was weaker in enhancing tumors (r = 0.37; 95% CI: 0.21–0.51; P <.0001). In non-enhancing tumors, preoperative tumor-to-CST distance reliably predicts the minimal current required to elicit an scMEP. However, in contrast-enhancing tumors, intraoperative scMEP mapping offers superior functional guidance, underscoring its critical role in surgical planning and decision-making.

Cushing’s disease (CD) is a rare condition with variable surgical outcomes. This study aimed to assess remission and recurrence rates in CD patients undergoing transsphenoidal surgery (TSS) at a major Israeli referral center, and to identify predictive factors for these outcomes. We hypothesized that microadenomas would have higher remission rates than macroadenomas. This retrospective analysis included 97 CD patients who underwent TSS at Tel Aviv Sourasky Medical Center (2002–2022). Remission was defined by biochemical criteria and clinical improvement. Suspected recurrence was confirmed by pathological dexamethasone suppression and/or elevated urinary free cortisol. Univariate and multivariate analyses identified predictors of remission, while Kaplan-Meier survival analysis and Cox proportional hazard modeling determined factors associated with recurrence. The overall remission rate was 63.9

It has been five years since the last version of the clinical practice guidelines for the management of adult diffuse gliomas was published by the Asian Glioma Genome Atlas (AGGA). Significant progress and revisions have occurred in the diagnosis and treatment of adult diffuse gliomas in recent years. In response to these updates, the joint guideline committee of the Chinese Glioma Cooperative Group (CGCG), the Society for Neuro-Oncology of China (SNO-China), and the Chinese Brain Cancer Association (CBCA) has revised the clinical practice guidelines. This updated guideline emphasizes molecular and pathological diagnostics, as well as the primary treatment modalities of surgery, radiotherapy, chemotherapy, and targeted therapy. Additionally, we have incorporated findings from recent clinical trials of new therapies to align with cutting-edge treatment strategies. This guideline is designed to serve as a practical resource for all professionals involved in managing adult diffuse glioma patients, while also providing valuable information for insurance companies and other institutions responsible for regulating cancer care costs in China and beyond.

Abstract Glioblastoma (GB) is an aggressive type of brain cancer with a high mortality rate. It is a highly angiogenic tumor exhibiting an extremely invasive nature. As such, its brain microenvironment plays a crucial role in its progression. Microglia are the brain resident immune cells that have been shown to facilitate GB cell invasion and immune suppression. The mechanism by which GB cells alter microglia behavior is yet to be fully understood. One proposed mechanism involves adhesion molecules such as the Selectins family of proteins which are expressed on the surface of endothelial and immune cells and are involved in immune modulation and cancer immunity. We have previously shown that one member of the Selectin family, P-Selectin (SELP), is expressed by GB cells. Here, we investigated the functional role of SELP in GB-microglia interactions. First, we found that microglia cells facilitate the expression and secretion of SELP by GB cells, and that GB cells facilitate the expression of P-Selectin ligand-1 (PSGL-1) by Glioma-associated microglia/macrophages (GAMs). We then showed that SELP mediates GAMs-enhanced GB invasion and proliferation in our unique 3D-bioprinted ex vitro models and has a role in GAMs activation state. These findings were validated in vivo, showing that inhibition or downregulation of SELP leads to reduced tumor growth, increased overall survival, and improved immune response. Single-cell RNA-seq analysis of the tumors revealed an increase in pro-inflammatory GAMs signature, reduction in cancer cell tumorigenesis potential, and improved T cell activation. Thus, combining SELP inhibition with other immune checkpoint inhibitors, such as anti-PD-1, may have a synergistic effect by harnessing both the innate and the adaptive immune systems against the tumor. Furthermore, we found SELP/PSGL-1 axis to be involved in the progression of brain metastasis originating from melanoma, and breast, and lung cancer. Thus, we have begun an investigator-initiated clinical trial, testing the efficacy of the anti-SELP antibody, Crizanlizumab, alone or in combination with anti-PD-1 antibody, Nivolumab, for GB and melanoma brain metastasis patients (NCT05909618). Crizanlizumab, approved by the FDA and EMA for sickle cell pain crisis (VOC, Vaso-Occlusive Crisis) of sickle-cell anemia patients, was proven to be safe for human use, and efficient in inhibiting SELP function. As such, it has the potential to reduce tumor burden and improve patient outcomes. This work can improve our understanding of GAMs function, which may pave the way for new and effective treatments for primary and secondary brain tumors. Citation Format: Eilam Yeini, Ronnie Frommer-Shapira, Alisa Talianski, Paula Ofek, Sabina Pozzi, Nitzan Albeck, Dikla Ben-Shushan, Galia Tiram, Sapir Golan, Ron Kleiner, Ron Sheinin, Shlomit Reich-Zeliger, Rachel Grossman, Zvi Ram, Henry Brem, Thomas M. Hyde, Prerna Magod, Dinorah Friedmann-Morvinski, Asaf Madi, Ronit Satchi-Fainaro. P-selectin as an emerging target for the treatment of primary and secondary brain tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4031.

BACKGROUND:GBM is an aggressive grade 4 primary brain tumor (BT), with a 5%-13% 5-year survival. Most human GBMs manifest as immunologically "cold" tumors or "immune deserts," yet the promoting or suppressive roles of specific lymphocytes within the GBM tumor microenvironment (TME) is of considerable debate. METHODS:We used meticulous multiparametric flow cytometry (FC) to determine the lymphocytic frequencies in 102 GBMs, lower-grade gliomas, brain metastases, and nontumorous brain specimen. FC-attained frequencies were compared with frequencies estimated by "digital cytometry." The FC-derived data were combined with the patients' demographic, clinical, molecular, histopathological, radiological, and survival data. RESULTS:Comparison of FC-derived data to CIBERSORT-estimated data revealed the poor capacity of digital cytometry to estimate cell frequencies below 0.2%, the frequency range of most immune cells in BTs. Isocitrate dehydrogenase (IDH) mutation status was found to affect TME composition more than the gliomas' pathological grade. Combining FC and survival data disclosed that unlike other cancer types, the frequency of helper T cells (Th) and cytotoxic T lymphocytes (CTL) correlated negatively with glioma survival. In contrast, the frequencies of γδ-T cells and CD56bright natural killer cells correlated positively with survival. A composite parameter combining the frequencies of these 4 tumoral lymphocytes separated the survival curves of GBM patients with a median difference of 10 months (FC-derived data; P < .0001, discovery cohort), or 4.1 months (CIBERSORT-estimated data; P = .01, validation cohort). CONCLUSIONS:The frequencies of 4 TME lymphocytes strongly correlate with the survival of patients with GBM, a tumor considered an immune desert.

Background: In the surgical management of glioblastoma, a highly aggressive and incurable type of brain cancer, identification and treatment of residual tissue is the most common site of disease recurrence. Monitoring and localized treatment are achieved with engineered microbubbles (MBs) by combining ultrasound and fluorescence imaging with actively targeted temozolomide (TMZ) delivery.Methods: The MBs were conjugated with a near-infrared fluorescence probe CF790, cyclic pentapeptide bearing the RGD sequence and a carboxyl-temozolomide, TMZA. The efficiency of adhesion to HUVEC cells was assessed in vitro in realistic physiological conditions of shear rate and vascular dimensions. Cytotoxicity of TMZA-loaded MBs on U87 MG cells and IC50 were assessed by MTT tests.Results: We report on the design of injectable poly(vinyl alcohol) echogenic MBs designed as a platform with active targeting ability to tumor tissues, by tethering on the surface a ligand having the tripeptide sequence, RGD. The biorecognition of RGD-MBs onto HUVEC cells is quantitatively proved. Efficient NIR emission from the CF790-decorated MBs was successfully detected. The conjugation on the MBs surface of a specific drug as TMZ is achieved. The pharmacological activity of the coupled-to-surface drug is preserved by controlling the reaction conditions.Conclusions: We present an improved formulation of PVA-MBs to achieve a multifunctional device with adhesion ability, cytotoxicity on glioblastoma cells and supporting imaging.& COPY; 2023 Elsevier Inc. All rights reserved.

Glioblastoma (GB) is the most aggressive neoplasm of the brain. Poor prognosis is mainly attributed to tumor heterogeneity, invasiveness and drug resistance. Only a small fraction of GB patients survives longer than 24 months from the time of diagnosis (ie, long-term survivors [LTS]). In our study, we aimed to identify molecular markers associated with favorable GB prognosis as a basis to develop therapeutic applications to improve patients' outcome. We have recently assembled a proteogenomic dataset of 87 GB clinical samples of varying survival rates. Following RNA-seq and mass spectrometry (MS)-based proteomics analysis, we identified several differentially expressed genes and proteins, including some known cancer-related pathways and some less established that showed higher expression in short-term (<6 months) survivors (STS) compared to LTS. One such target found was deoxyhypusine hydroxylase (DOHH), which is known to be involved in the biosynthesis of hypusine, an unusual amino acid essential for the function of the eukaryotic translation initiation factor 5A (eIF5A), which promotes tumor growth. We consequently validated DOHH overexpression in STS samples by quantitative polymerase chain reaction (qPCR) and immunohistochemistry. We further showed robust inhibition of proliferation, migration and invasion of GB cells following silencing of DOHH with short hairpin RNA (shRNA) or inhibition of its activity with small molecules, ciclopirox and deferiprone. Moreover, DOHH silencing led to significant inhibition of tumor progression and prolonged survival in GB mouse models. Searching for a potential mechanism by which DOHH promotes tumor aggressiveness, we found that it supports the transition of GB cells to a more invasive phenotype via epithelial-mesenchymal transition (EMT)-related pathways.

Personalized vaccines against patient-unique tumor-associated antigens represent a promising new approach for cancer immunotherapy. Vaccine efficacy is assessed by quantification of changes in the frequency and/or the activity of antigen-specific T cells. Enzyme-linked immunosorbent spot (ELISpot) and flow cytometry (FCM) are methodologies frequently used for assessing vaccine efficacy. We tested these methodologies and found that both ELISpot and standard FCM [monitoring CD3/CD4/CD8/IFNγ/Viability+CD14+CD19 (dump)] demonstrate background IFNγ secretion, which, in many cases, was higher than the antigen-specific signal measured by the respective methodology (frequently ranging around 0.05–0.2%). To detect such weak T-cell responses, we developed an FCM panel that included two early activation markers, 4-1BB (CD137) and CD40L (CD154), in addition to the above-cited markers. These two activation markers have a close to zero background expression and are rapidly upregulated following antigen-specific activation. They enabled the quantification of rare T cells responding to antigens within the assay well. Background IFNγ-positive CD4 T cell frequencies decreased to 0.019% ± 0.028% and CD8 T cells to 0.009% ± 0.013%, which are 19 and 13 times lower, respectively, than without the use of these markers. The presented methodology enables highly sensitive monitoring of T-cell responses to tumor-associated antigens in the very low, but clinically relevant, frequencies.

This Phase 1 study evaluates the intra- and peritumoral administration by convection enhanced delivery (CED) of human recombinant Bone Morphogenetic Protein 4 (hrBMP4) – an inhibitory regulator of cancer stem cells (CSCs) – in recurrent glioblastoma. In a 3 + 3 dose escalation design, over four to six days, fifteen recurrent glioblastoma patients received, by CED, one of five doses of hrBMP4 ranging from 0·5 to 18 mg. Patients were followed by periodic physical, neurological, blood testing, magnetic resonance imaging (MRI) and quality of life evaluations. The primary objective of this first-in-human study was to determine the safety, dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of hrBMP4. Secondary objectives were to assess potential efficacy and systemic exposure to hrBMP4 upon intracerebral infusion. Intra- and peritumoral infusion of hrBMP4 was safe and well-tolerated. We observed no serious adverse events related to this drug. Neither MTD nor DLT were reached. Three patients had increased hrBMP4 serum levels at the end of infusion, which normalized within 4 weeks, without sign of toxicity. One patient showed partial response and two patients a complete (local) tumor response, which was maintained until the most recent follow-up, 57 and 30 months post-hrBMP4. Tumor growth was inhibited in areas permeated by hrBMP4. Local delivery of hrBMP4 in and around recurring glioblastoma is safe and well-tolerated. Three patients responded to the treatment. A complete response and long-term survival occurred in two of them. This warrants further clinical studies on this novel treatment targeting glioblastoma CSCs. : ClinicaTrials.gov identifier: NCT02869243.

Gliadel occasionally induces edema following its implantation. We aimed to correlate such post-surgical radiological changes to its efficacy and subsequent survival. Fifty-six patients with recurrent high grade glioma were treated between 2005 and 2016 with Gliadel implantation. Volumetric measurements of MRI features, including FLAIR abnormalities, tumor bulk (volume of gadolinium enhancement on T1) and resection cavity volumes over time were conducted. To assess dynamics over time, linear regression trendlines for each of these were calculated and examined to correlate with survival. Median follow-up after resection was 21.5 months. Median survival post-Gliadel implantation and overall survival since diagnosis were 12 months and 22 months, respectively. A subgroup of patients (n = 6) with a transient increase in FLAIR changes volume over time survived significantly longer post-Gliadel compared to those who did not demonstrate such change (36 vs 12 months, p = .03). Positive trends, representing overall growth in volume over time, of tumor bulk and resection cavity predicted survival in multivariate analyses (hazard ratios 7.9 and 84, p = .003 and .002, respectively). Increase in tumor bulk and resection cavity over time were associated with decreased survival, while transient FLAIR increase was a favorable prognostic factor. This may represent a transient inflammatory process in the tumor, possibly stemming from a presumed immune-mediated anti-tumor response.

Purpose: Tumor-treating fields (TTFields) are an antimitotic treatment modality that interfere with glioblastoma (GBM) cell division and organelle assembly by delivering low-intensity, alternating electric fields to the tumor. A previous analysis from the pivotal EF-14 trial demonstrated a clear correlation between TTFields dose density at the tumor bed and survival in patients treated with TTFields. This study tests the hypothesis that the antimitotic effects of TTFields result in measurable changes in the location and patterns of progression of newly diagnosed GBM. Methods and Materials: Magnetic resonance images of 428 newly diagnosed GBM patients who participated in the pivotal EF-14 trial were reviewed, and the rates at which distant progression occurred in the TTFields treatment and control arm were compared. Realistic head models of 252 TTFields-treated patients were created, and TTFields intensity distributions were calculated using a finite element method. The TTFields dose was calculated within regions of the tumor bed and normal brain, and its relationship with progression was determined. Results: Distant progression was frequently observed in the TTFields-treated arm, and distant lesions in the TTFields-treated arm appeared at greater distances from the primary lesion than in the control arm. Distant progression correlated with improved clinical outcome in the TTFields patients, with no such correlation observed in the controls. Areas of normal brain that remained normal were exposed to higher TTFields doses compared with normal brain that subsequently exhibited neoplastic progression. Additionally, the average dose to areas of the enhancing tumor that returned to normal was significantly higher than in the areas of the normal brain that progressed to enhancing tumor. Conclusions: There was a direct correlation between TTFields dose distribution and tumor response, confirming the therapeutic activity of TTFields and the rationale for optimizing array placement to maximize the TTFields dose in areas at highest risk of progression, as well as array layout adaptation after progression. (C) 2021 The Authors. Published by Elsevier Inc.

Surgery-related strokes are an important cause of morbidity following resection of high-grade glioma (HGG). We explored the incidence, risk factors and clinical consequences of intra-operative ischemic strokes in surgeries for resection of HGG. We retrospectively followed a cohort of 239 patients who underwent surgical resection of HGG between 2013 and 2017. Tumor types included both isocitrate dehydrogenase (IDH) wildtype glioblastoma and IDH-mutant WHO grade 4 astrocytoma. We analyzed pre- and post-operative demographic, clinical, radiological, anesthesiology and intraoperative neurophysiology data, including overall survival and functional outcomes. Acute ischemic strokes were seen on postoperative diffusion-weighted imaging (DWI) in 30 patients (12.5%), 13 of whom (43%) developed new neurological deficits. Infarcts were more common in insular (23%, p = 0.019) and temporal surgeries (57%, p = 0.01). Immediately after surgery, 35% of patients without infarcts and 57% of those with infarcts experienced motor deficits (p = 0.022). Six months later, rates of motor deficits decreased to 25% in the non-infarcts group and 37% in the infarcts group (p = 0.023 and 0.105, respectively) with a significantly lower Karnofsky-Performance Score (KPS, p = 0.001). Intra-operative language decline in awake procedures was a significant indicator of the occurrence of intra-operative stroke (p = 0.029). In conclusion, intraoperative ischemic events are more common in insular and temporal surgeries for resection of HGG and their intra-operative detection is limited. These strokes can impair motor and speech functions as well as patients’ performance status.

Introduction Endoscopic endonasal surgery (EES) has become the preferred approach for pituitary tumor resection. Nevertheless, research on quality of life related to pituitary adenoma surgery is scarce. Objective The aim of the study is to evaluate short-term quality of life in patients after endoscopic endonasal resection of pituitary tumors and to find predictors for poor quality of life (QOL) outcome. Materials and Methods A prospective cohort study was conducted, including all patients who underwent EES for pituitary tumors in a tertiary medical referral center. Recruited patients completed the Anterior Skull Base Disease-Specific QOL (ASBS-Q) questionnaire and the Sinonasal Outcome Test 22 (SNOT-22) questionnaire before surgery, 2 and 4 to 6 months after surgery. Demographic and clinical data was collected. Results Our study included 49 patients. The overall ASBS-Q scores significantly improved 4 to 6 months after surgery (4.46 vs. 4.2, p < 0.05). We found a significant improvement in QOL related to emotional state 2 months post surgery (4.41 vs. 3.87, p < 0.05), which became borderline significant 4 to 6 months post surgery. There was a significant improvement in pain (4.5 vs. 4.08, p < 0.05) and vitality (4.43 vs. 4.16, p < 0.05) domains 4 to 6 months post surgery. SNOT-22 scores did not change significantly postoperatively. Factors such as secreting and non-secreting tumors, tumor size, intraoperative cerebrospinal fluid leak, gross tumor resection, endocrine remission, and the use of nasoseptal flap reconstruction did not have a significant effect on QOL. Conclusion We found that patients after EES reported improved QOL 4 to 6 months post surgery. Specific improvement was noted in the QOL related to pain and vitality.

PURPOSE:Non-small cell lung cancer (NSCLC) tends to metastasize to the brain. Between 10 and 60% of NSCLCs harbor an activating mutation in the epidermal growth-factor receptor (EGFR), which may be targeted with selective EGFR inhibitors. However, due to a high discordance rate between the molecular profile of the primary tumor and the brain metastases (BMs), identifying an individual patient's EGFR status of the BMs necessitates tissue diagnosis via an invasive surgical procedure. We employed a deep learning (DL) method with the aim of noninvasive detection of the EGFR mutation status in NSCLC BM.METHODS:We retrospectively collected clinical, radiological, and pathological-molecular data of all the NSCLC patients who had been diagnosed with BMs and underwent resection of their BM during 2009-2019. The study population was then divided into two groups based upon EGFR mutational status. We further employed a DL technique to classify the two groups according to their preoperative magnetic resonance imaging features. Augmentation techniques, transfer learning approach, and post-processing of the predicted results were applied to overcome the relatively small cohort. Finally, we established the accuracy of our model in predicting EGFR mutation status of BM of NSCLC.RESULTS:Fifty-nine patients were included in the study, 16 patients harbored EGFR mutations. Our model predicted mutational status with mean accuracy of 89.8%, sensitivity of 68.7%, specificity of 97.7%, and a receiver operating characteristic curve value of 0.91 across the 5 validation datasets.CONCLUSION:DL-based noninvasive molecular characterization is feasible, has high accuracy and should be further validated in large prospective cohorts.