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Brain tumors represent the second most frequent etiology in patients with focal seizure onset before 18 years of age and submitted to epilepsy surgery. Hence, this category of brain tumors, herein defined as low-grade, developmental, epilepsy-associated brain tumors (LEAT) is different from those frequently encountered in adults as (A): 77% of LEAT occur in the temporal lobe; (B): the vast majority of LEAT are of low malignancy and classified as WHO I°; (C): LEAT are often composed of mixed glial and neuronal cell components and present with variable growth patterns including small cysts or nodules; (D): LEAT do not share common gene driving mutations, such as IDH1 or 1p/19q co-deletions. Characteristic entities comprise the ganglioglioma (GG), the dysembryoplastic neuroepithelial tumor (DNT), the angiocentric glioma (AG), the isomorphic diffuse glioma (IDG) and the papillary glio-neuronal tumor (PGNT), representing 73.2% of 1680 tumors collected in a large German series of 6747 patients submitted to epilepsy surgery. In the realm of exciting discoveries of genetic drivers of brain tumors new genes have been also reported for LEAT. BRAF V600E mutations were linked to GG with CD34 expression, FGFR1 mutations to DNT, MYB alterations to AG and also IDG and PRKCA fusions to PGNT, suggesting the possibility to also develop a genetically driven tumor classification scheme for LEAT. Rare availability of LEAT in a single center is a challenging obstacle, however, to systematically unravel the neurobiological nature and clinical behavior of LEAT. Other challenges in need of clarification include malignant tumor progression of LEAT entities, seizure relapse in patients following bulk tumor resection and the controversial issue of associated focal cortical dysplasia as additional pathomechanism. In order to advance our understanding and promote reliable diagnostic work-up of LEAT, we recommend, therefore, international collaboration to achieve our goals.

The main goal of brain tumor surgery is to maximize tumor resection while preserving brain function. However, existing imaging and surgical techniques do not offer the molecular information needed to delineate tumor boundaries. We have developed a system to rapidly analyze and classify brain tumors based on lipid information acquired by desorption electrospray ionization mass spectrometry (DESI-MS). In this study, a classifier was built to discriminate gliomas and meningiomas based on 36 glioma and 19 meningioma samples. The classifier was tested and results were validated for intraoperative use by analyzing and diagnosing tissue sections from 32 surgical specimens obtained from five research subjects who underwent brain tumor resection. The samples analyzed included oligodendroglioma, astrocytoma, and meningioma tumors of different histological grades and tumor cell concentrations. The molecular diagnosis derived from mass-spectrometry imaging corresponded to histopathology diagnosis with very few exceptions. Our work demonstrates that DESI-MS technology has the potential to identify the histology type of brain tumors. It provides information on glioma grade and, most importantly, may help define tumor margins by measuring the tumor cell concentration in a specimen. Results for stereotactically registered samples were correlated to preoperative MRI through neuronavigation, and visualized over segmented 3D MRI tumor volume reconstruction. Our findings demonstrate the potential of ambient mass spectrometry to guide brain tumor surgery by providing rapid diagnosis, and tumor margin assessment in near–real time.

Background National guidelines recommend maximal safe resection of low-grade and high-grade oligodendrogliomas. However, there is no level 1 evidence to support these guidelines, and recent retrospective studies on the topic have yielded mixed results. Objective To assess the association between extent of resection (EOR) and survival for oligodendrogliomas in the general U.S. population. Methods Cases diagnosed between 2004 and 2013 were selected from the Surveillance, Epidemiology, and End-Results (SEER) Program and retrospectively analyzed for treatment, prognostic factors, and survival times. Cases that did not undergo tumor de-bulking surgery (e.g. no surgery or biopsy alone) were compared to subtotal resection (resection) and gross-total resection (GTR). The primary end-points were overall survival (OS) and cause-specific survival (CSS). An external validation cohort with 1p/19q-codeleted tumors was creating using the TCGA and GSE16011 datasets. Results 3135 Cases were included in the final analysis. The 75% survival time (75ST) and 5-year survival rates were 47 months and 70.8%, respectively. Subtotal resection (STR, 75ST = 50 months) and GTR (75ST = 61 months) were associated with improved survival times compared to cases that did not undergo surgical debulking (75ST = 20 months, P  < 0.001 for both), with reduced hazard ratios (HRs) after controlling for other factors (HR 0.81 [0.68–0.97] and HR 0.65 [0.54–0.79], respectively). GTR was associated with improved OS in both low-grade and anaplastic oligodendroglioma subgroups (HR 0.74 [0.58–0.95], HR 0.60 [0.44–0.82], respectively) while STR fell short of significance in the subgroup analysis. All findings were corroborated by multivariable analysis of CSS and externally validated in a cohort of patients with 1p19q-codeleted tumors. Conclusion Greater EOR is associated with improved survival in oligodendrogliomas. Our findings in this U.S. population-based cohort support national guidelines.

We evaluated prognostic factors of adult low-grade glioma (LGG) according to the new 2016 WHO classification. Records of 153 patients diagnosed with WHO grade II LGG between 2003 and 2015 were retrospectively reviewed. Based on the 2016 WHO classification, 80 patients (52.3%) had diffuse astrocytoma, IDH -mutant; 45 (29.4%) had oligodendroglioma, IDH -mutant and 1p/19q-codeleted (ODG); and 28 (18.3%) had diffuse astrocytoma, IDH -wildtype. Gross total resection (GTR) was performed in 71 patients (46.4%), subtotal resection in 31 (20.3%), partial resection in 43 (28.1%), and biopsy in 8 (5.2%). One hundred two patients (66.7%) received postoperative radiotherapy. The 5- and 10-year progression-free survival (PFS) rates were 72.7% and 51.5%, respectively, and the 5- and 10-year overall survival (OS) rates were 82.5% and 63.5%, respectively. GTR and IDH -mutant and/or 1p/19q codeletion were favorable prognostic factors for PFS and OS. Patients with IDH -wildtype had significantly decreased OS. Among patients with ODG who underwent GTR, no recurrence was observed after radiotherapy. Patients who underwent non-GTR frequently experienced recurrence after radiotherapy ( IDH -mutant: 47.6%, IDH -wildtype: 57.9%). In conclusion, molecular classification of LGG was of prognostic relevance, with IDH -wildtype patients having a particularly poor outcome, regardless of the treatment. Favorable results were observed in patients who underwent GTR.

PurposeMaximal surgical resection is associated with survival benefit in the majority of studies in adult diffuse glioma. This study aims to characterize the prognostic value of surgical resection in molecular subgroups of diffuse glioma.Methods1178 patients with diffuse glioma from our centers and 422 from TCGA dataset were collected. The Kaplan–Meier analysis and multivariable Cox regression models were conducted to identify the prognostic value of surgical resection through different histological and molecular stratifications.ResultsFirstly, we confirmed progression-free survival (PFS) benefit associated with gross total resection (GTR) over sub-total resection (STR) in lower-grade glioma (HR 1.49; 95% CI 1.17–1.90; P = 0.001). Intriguingly however, we were unable to detect a significant PFS or overall survival (OS) benefit in oligodendroglioma (N = 397; HR 1.36; 95% CI 0.86–2.14; P = 0.19 and HR 1.05; 95% CI 0.55–1.99; P = 0.89, respectively). Secondly, when analyzed in molecular subgroups, we were similarly unable to detect a significant PFS or OS benefit in IDH MT/codel subgroup (N = 269; HR 1.47; 95% CI 0.92–2.34; P = 0.11 and HR 1.54; 95% CI 0.78–3.05; P = 0.21, respectively), oligodendroglioma with IDH MT/codel subgroup (N = 233; HR 1.33; 95% CI 0.79–2.21; P = 0.28 and HR 1.16; 95% CI 0.53–2.54; P = 0.70, respectively) or other relevant subgroups. TCGA validation also showed a significant survival benefit in astrocytoma rather than oligodendroglioma. Exploratory RNAseq analysis displayed that fewer cell proliferation-related gene expression features were specific to oligodendroglioma.ConclusionThese results suggest that the benefit of maximal surgery may be attenuated in patients within oligodendroglioma relevant subgroups because of the chemosensitive and indolent nature. The aggressive surgery accompanying with risk of neurologic morbidity may be unnecessary for these patients given the lack of survival benefit with gross total resection.

The pathological diagnosis of intracranial germinoma (IG), oligodendroglioma, and low‐grade astrocytoma on intraoperative frozen section (IFS) and hematoxylin–eosin (HE)‐staining section directly determines patients' treatment options, but it is a difficult task for pathologists. We aimed to investigate whether whole‐slide imaging (WSI)‐based deep learning can contribute new precision to the diagnosis of IG, oligodendroglioma, and low‐grade astrocytoma. Two types of WSIs (500 IFSs and 832 HE‐staining sections) were collected from 379 patients at multiple medical centers. Patients at Center 1 were split into the training, testing, and internal validation sets (3:1:1), while the other centers were the external validation sets. First, we subdivided WSIs into small tiles and selected tissue tiles using a tissue tile selection model. Then a tile‐level classification model was established, and the majority voting method was used to determine the final diagnoses. Color jitter was applied to the tiles so that the deep learning (DL) models could adapt to the variations in the staining. Last, we investigated the effectiveness of model assistance. The internal validation accuracies of the IFS and HE models were 93.9% and 95.3%, respectively. The external validation accuracies of the IFS and HE models were 82.0% and 76.9%, respectively. Furthermore, the IFS and HE models can predict Ki‐67 positive cell areas with R2 of 0.81 and 0.86, respectively. With model assistance, the IFS and HE diagnosis accuracy of pathologists improved from 54.6%–69.7% and 53.5%–83.7% to 87.9%–93.9% and 86.0%–90.7%, respectively. Both the IFS model and the HE model can differentiate the three tumors, predict the expression of Ki‐67, and improve the diagnostic accuracy of pathologists. The use of our model can assist clinicians in providing patients with optimal and timely treatment options. The whole slide imaging‐based deep learning can contribute new precision to the diagnosis of IG, oligodendroglioma, and lower‐grade astrocytoma on intraoperative frozen sections (IFS) and postoperative hematoxylin‐eosin (HE)‐staining sections. The proposed model can help pathologists immediately discriminate tumor types during operations, while our HE model can assist pathologists with early postoperative treatment regimens.

ABSTRACT OBJECTIVE It remains unknown whether the extent of surgical resection affects survival or disease progression in patients with supratentorial low-grade gliomas. METHODS We conducted a retrospective cohort study (n = 170) between 1996 and 2007 at a single institution to determine whether increasing extent of surgical resection was associated with improved progression-free survival (PFS) and overall survival (OS). Surgical resection of gliomas defined as gross total resection (GTR) (complete resection of the preoperative fluid-attenuated inversion recovery signal abnormality), near total resection (NTR) (<3-mm thin residual fluid-attenuated inversion recovery signal abnormality around the rim of the resection cavity only), or subtotal resection (STR) (residual nodular fluid-attenuated inversion recovery signal abnormality) based on magnetic resonance imaging performed less than 48 hours after surgery. Our main outcome measures were OS, PFS, and malignant degeneration-free survival (conversion to high-grade glioma). RESULTS One hundred thirty-two primary and 38 revision resections were performed for low-grade astrocytomas (n = 93) or oligodendrogliomas (n = 77). GTR, NTR, and STR were achieved in 65 (38%), 39 (23%), and 66 (39%) cases, respectively. GTR versus STR was independently associated with increased OS (hazard ratio, 0.36; 95% confidence interval, 0.16–0.84; P = 0.017) and PFS (HR, 0.56; 95% confidence interval, 0.32–0.98; P = 0.043) and a trend of increased malignant degeneration-free survival (hazard ratio, 0.46; 95% confidence interval, 0.20–1.03; P = 0.060). NTR versus STR was not independently associated with improved OS, PFS, or malignant degeneration-free survival. Five-year OS after GTR, NTR, and STR was 95, 80, 70%, respectively, and 10-year OS was 76, 57, and 49%, respectively. After GTR, NTR, and STR, median time to tumor progression was 7.0, 4.0, and 3.5 years, respectively. Median time to malignant degeneration after GTR, NTR, and STR was 12.5, 5.8, and 7 years, respectively. CONCLUSION GTR was associated with a delay in tumor progression and malignant degeneration as well as improved OS independent of age, degree of disability, histological subtype, or revision versus primary resection. GTR should be safely attempted when not limited by eloquent cortex.

Purpose To retrospectively evaluate preoperative clinical factors for their ability to preoperatively differentiate malignancy grades in patients with incipient supratentorial grade II/III diffuse gliomas. Methods This retrospective study included 206 adult patients with incipient supratentorial grade II/III diffuse gliomas according to the 2016 World Health Organization classification of tumors of the central nervous system. The cohort included 136 men and 70 women, with a median age of 41 years. Preoperative factors included age, sex, presence of calcifications on computed tomography scans, and preoperative tumor volume measured using preoperative magnetic resonance imaging. Results In patients with oligodendrogliomas ( IDH -mutant and 1p/19q-codeleted), calcifications were significantly more frequent (p = 0.0034) and tumor volume was significantly larger (p < 0.001) in patients with grade III tumors than in those with grade II tumors. Moreover, in patients with IDH -mutant astrocytomas, preoperative tumor volume was significantly larger (p = 0.0042) in patients with grade III tumors than in those with grade II tumors. In contrast, none of the evaluated preoperative clinical factors were significantly different between the patients with grade II and III IDH -wildtype astrocytomas. Conclusion In adult patients with suspicison incipient supratentorial grade II/III diffuse gliomas, presence of calcifications and larger preoperative tumor volume might be used as preoperative indices to differentiate between malignancy grades II and III in oligodendrogliomas ( IDH -mutant and 1p/19q-codeleted) and larger preoperative tumor volume might have similar utility in IDH -mutant astrocytomas.

Anaplastic oligodendroglioma is a rare disease with an inadequately understood prognosis. The aim of this study was to investigate factors associated with survival outcome in anaplastic oligodendroglioma patients. A population-based cohort study was conducted based on the Surveillance, Epidemiology, and End Results program. In total, 1899 patients with a histological diagnosis of anaplastic oligodendroglioma from 1973 to 2015 were included. Mean age at diagnosis was 49.2 years, and 56.19% were male. In our study, 62.40% of patients were married, and 87.05% were white. Most patients (90.42%) were diagnosed with anaplastic oligodendroglioma as their first malignant primary tumor, but 9.58% had a diagnosis of at least one other primary malignancy; 87.89% of patients had received cancer-directed surgery. Patients receiving surgery had a better prognosis for overall survival compared to those not receiving surgery after propensity score matching analysis (p<0.05). The overall 1-, 3-, 5-, and 10-year survival of anaplastic oligodendroglioma was 78.7%, 60%, 50.2%, and 36.2%, respectively. Kaplan-Meier analysis indicated that age, marital status, presence of multiple primary malignancies, and surgical treatment were associated with overall survival, whereas sex and race were not. Moreover, age at diagnosis of 52 years was calculated as an optimal cutoff value to distinguish better and worse overall survival. Multivariate Cox proportional hazard analysis indicated that older age (OR 1.040, 95%CI1.035-1.045), single patients (OR 1.293, 95%CI 1.103-1.515), and presence of multiple primary malignancies (OR 1.501, 95%CI 1.238-1.820) were significantly associated with worse overall survival, whereas surgery (OR 0.584, 95%CI 0.494-0.689) was associated with better overall survival. A nomogram predicting 5-, and 10-year survival probability for anaplastic oligodendroglioma was constructed based on these variables. In conclusion, age, marital status, presence of multiple primary malignancies, and surgical treatment were associated with survival of anaplastic oligodendroglioma.

Establish the evolution of the connectome before and after resection of motor area glioma using a comparison of connectome maps and high-definition differential tractography (DifT). DifT was done using normalized quantitative anisotropy (NQA) with DSI Studio. The quantitative analysis involved obtaining mean NQA and fractional anisotropy (FA) values for the disrupted pathways tracing the corticospinal tract (CST), and white fiber network changes over time. We described the baseline tractography, DifT, and white matter network changes from two patients who underwent resection of an oligodendroglioma (Case 1) and an IDH mutant astrocytoma, grade 4 (Case 2). Case 1. There was a slight decrease in the diffusion signal of the compromised CST in the immediate postop. The NQA and FA values increased at the 1-year follow-up (0.18 vs. 0.32 and 0.35 vs. 0.44, respectively). Case 2. There was an important decrease in the immediate postop, followed by an increase in the follow-up. In the 1-year follow-up, the patient presented with radiation necrosis and tumor recurrence, increasing NQA from 0.18 in the preop to 0.29. Fiber network analysis: whole-brain connectome comparison demonstrated no significant changes in the immediate postop. However, in the 1-year follow up there was a notorious reorganization of the fibers in both cases, showing the decreased density of connections. Connectome studies and DifT constitute new potential tools to predict early reorganization changes in a patient’s networks, showing the brain plasticity capacity, and helping to establish timelines for the progression of the tumor and treatment-induced changes. •Differential NQA and FA values are subjective measurements of the preservation of function postoperatively.•Our study sheds light on how the connectome undergoes sequential reorganization in an evolving manner, varying on a case-by-case basis.•The reorganization of the fibers and changes in the values may not necessarily correlate with clinical outcomes, particularly in high-grade gliomas.•DfT directly reflects brain plasticity; however, functionality prediction requires more sophisticated methods, such as predictability models.