Lomustine overdose in a patient with diffuse glioma: symptoms, management and outcome.

A male patient started PCV chemotherapy (a combination of procarbazine, lomustine and vincristine) for a recurrent oligodendroglioma grade 2. Unfortunately, our patient took an unintended overdose of lomustine during the first PCV course: instead of 160 mg absolute dose of lomustine on day 1 only, he consumed 160 mg absolute dose of lomustine for seven consecutive days to a total dose of 1120 mg. Pancytopenia became evident after 24 days, and several months of severe myelosuppression, infections, reduced general condition, and nutrition difficulties followed. Fortunately, our patient with time recovered his bone marrow function. However, the patient's quality of life was reduced for a long time and several lessons were learnt: oral and written information on chemotherapy is essential, but not always sufficient to ensure the correct dosing of patient-administered chemotherapy. Oral chemotherapeutics should be delivered as a single-dose supply or be administered by experienced health personnel.

Oligodendroglioma: a neurological perspective in Sub-saharan Africa.

Gliomas are a kind of brain cancer that develops from glial cells. Glial cells provide nourishment and energy to nerve cells, and they also preserve the blood-brain barrier. A primary cancer of the central nervous system (CNS) is oligodendroglioma. This suggests that it originates in the brain or spinal cord. While oligodendrogliomas can strike anyone at any age, the age range of 35 to 44 is when they most commonly occur. Oligodendrogliomas are rare in young people and more common in men than women. Based on anecdotal data, patients with oligodendroglioma may present management challenges in Africa. There are delays in diagnosis and referrals due to the scarcity of neuroimaging facilities. A wide range of strategies have been put forth to improve pathology services in low- and middle-income nations. Adequate mentorship, short-term visitor programs, overcoming supply chain constraints, establishing training standards, and establishing the role of pathologists in cancer screening and early diagnosis have all been proposed as solutions to this problem. To sum up, oligodendroglioma is one of the low-grade gliomas this study looked at. Brain cancer is a serious public health concern in Africa. Improved options for screening and therapy are required to better address this problem.

Extracranial metastatic oligodendroglioma with molecular progression, case presentation.

BACKGROUND: Extraneural metastasis of central nervous system tumors is generally rare and most often reported in glioblastomas and medulloblastomas, whereas oligodendrogliomas seem to have the lowest risk of extracranial metastasis. Given its infrequent occurrence, both the diagnosis and therapy of metastatic oligodendroglioma is often challenging. CASE PRESENTATION: This case study presents an oligodendroglioma, the isocitrate dehydrogenase 1 (IDH1) mutant, 1p/19q-codeleted tumor with bone marrow metastasis. The significance of this case lies in the comprehensive molecular analysis conducted for both the primary tumor and the metastasis. Chromosome 7 trisomy and chromosome 10 monosomy (+ 7/-10) were detected in the metastasis indicating molecular progression, which, to the best of our knowledge, has not been previously documented in metastatic oligodendroglioma. CONCLUSIONS: This case study serves additional information for better understanding of the metastatic capabilities of CNS tumors.

A systematic review and meta-analysis informing the role of adjuvant radiotherapy (RT) in Grade 2 and 3 oligodendroglioma.

BACKGROUND AND PURPOSE: Evidence and clinical guidelines support the use of adjuvant RT in high-risk low-grade gliomas. However, patients with oligodendroglioma have a more indolent disease course and delaying or avoiding RT is often considered to reduce treatment-related toxicities. As the optimal adjuvant management for oligodendroglioma is unclear, we aimed to assess the effect of adjuvant RT on overall survival (OS) and progression-free survival (PFS). METHODS: MEDLINE, EMBASE, CENTRAL and CINAHL were searched from January 1990 to February 2023 for studies comparing adjuvant RT versus no adjuvant RT for patients with oligodendroglioma. RESULTS: This review found 17 eligible studies including 14 comparative retrospective studies and 3 randomized controlled trials. Using random-effects model, the results suggested that adjuvant RT improved OS by 28 % (HR 0.72, 95 % CI (0.56-0.93), I2 = 86 %), and PFS by 48 % (HR 0.52, (95 % CI 0.40-0.66), I2 = 48 %) compared to patients without adjuvant RT. Subgroup analysis showed that upfront adjuvant RT improved OS and PFS compared to salvage RT. There were no significant differences in OS and PFS between adjuvant RT versus adjuvant chemotherapy. There was improvement in PFS but not OS for adjuvant chemoradiotherapy versus adjuvant chemotherapy alone. Adjuvant RT improved OS in WHO Grade 3 but not WHO Grade 2 oligodendroglioma. CONCLUSION: Overall, adjuvant RT improved OS and PFS in patients with oligodendroglioma. In patients with low-risk features (e.g. Grade 2, gross total resection), alternative approaches and individualization of management such as adjuvant chemotherapy alone may be reasonable considering the lack of survival benefit. Future efforts should prospectively investigate these treatment regimens on molecularly-classified oligodendroglioma patients (defined by presence of IDH mutation and 1p/19q co-deletion), balancing between maximizing survival outcomes and reducing RT-related toxicities.

Revisiting oligodendroglioma grading in the 2021 WHO classification: calcification and larger contrast-enhancing tumor volume may predict higher oligodendroglioma grade.

PURPOSE: To investigate whether qualitative and quantitative imaging phenotypes can predict the grade of oligodendroglioma. METHODS: Retrospective chart and imaging reviews were conducted on 180 adults with oligodendroglioma (IDH-mutant and 1p/19q codeleted) between 2005 and 2021. Qualitative imaging characteristics including tumor location, calcification, gliomatosis cerebri, cystic change, necrosis, and infiltrative pattern were analyzed. Quantitative imaging assessment was performed from the tumor mask via automatic segmentation to calculate total, contrast-enhancing (CE), non-enhancing (NE), and necrotic tumor volumes. Logistic analyses were conducted to determine predictors of oligodendroglioma grade. RESULTS: This study included 180 patients (84 [46.7%] with grade 2 and 96 [53.3%] with grade 3 oligodendrogliomas), with a median age of 42 years (range 23-76 years), comprising 91 females and 89 males. On univariable analysis, calcification (odds ratio [OR] = 6.00, P < 0.001), necrosis (OR = 21.84, P = 0.003), presence of CE tumor (OR = 7.86, P < 0.001), larger total (OR = 1.01, P < 0.001), larger CE (OR = 2.22, P = 0.010), and larger NE (OR = 1.01, P < 0.001) tumor volumes were predictors of grade 3 oligodendroglioma. On multivariable analysis, calcification (OR = 3.79, P < 0.001) and larger CE tumor volume (OR = 2.70, P = 0.043) remained as independent predictors of grade 3 oligodendroglioma. The multivariable model exhibited an AUC, accuracy, sensitivity, specificity of 0.78 (95% confidence interval 0.72-0.84), 72.8%, 79.2%, 69.1%, respectively. CONCLUSION: Presence of calcification and larger CE tumor volume may serve as useful imaging biomarkers for prediction of oligodendroglioma grade. CLINICAL RELEVANCE STATEMENT: Assessment of intratumoral calcification and CE tumor volume may facilitate accurate preoperative estimation of oligodendroglioma grade. Presence of intratumoral calcification and larger contrast-enhancing tumor volume were the significant predictors of higher grade oligodendroglioma based on the 2021 WHO classification.

Clinical applicability of signal heterogeneity and tumor border assessment on T2-weighted MR images to distinguish astrocytic from oligodendroglial origin of gliomas.

BACKGROUND AND PURPOSE: Radiological features on magnetic resonance imaging (MRI) were attributed to oligodendroglioma, although the diagnostic accuracy in a real-world clinical setting remains partially elusive. This study investigated the accuracy and robustness of tumor heterogeneity and tumor border delineation on T2-weighted MRI to distinguish oligodendroglioma from astrocytoma. MATERIALS AND METHODS: Eight readers from three different specialties (radiology, neurology, neurosurgery) with varying levels of experience blindly rated 79 T2-weighted MR images of patients with either oligodendroglioma or astrocytoma. After the first reading session, all readers were re-invited for a second reading session within three weeks. Diagnostic accuracy, including area under the receiver operator characteristics curve (AUC), and intra-observer variability and inter-observer variability were used as outcome measures. RESULTS: Pooled sensitivity and specificity to distinguish oligodendroglioma from astrocytoma for the use of tumor heterogeneity were 59.9 % respectively 74.5 %, and 85.7 % respectively 40.1 % for tumor border. A second reading session did not result in a significant change in sensitivity or specificity for tumor heterogeneity (P = 0.752 and P = 0.733, respectively) or tumor border (P = 0.309 and P = 0.271, respectively). An AUC of 0.825 was achieved with regard to predicting oligodendroglial origin of gliomas. Intra-observer agreement ranged from moderate to very good for tumor heterogeneity (kappa-value 0.43-0.87) and tumor border (0.40-0.84). A moderate inter-oberserver agreement was achieved for tumor heterogeneity and tumor border (kappa-value of 0.50 and 0.45, respectively). CONCLUSION: This study demonstrates that tumor heterogeneity and tumor borders on T2-weighted MRI could be used with moderate Finter-observer agreement to non-invasively distinguish oligodendroglioma from astrocytoma.

Higher YAP1 Levels Are Associated With Shorter Survival of Patients With Low Grade Astrocytoma.

BACKGROUND/AIM: Glioblastoma multiforme (GBM) is one of the most lethal types of brain cancer with a median survival of only 12 months due to its aggressiveness and lack of effective treatment options. Astrocytomas and oligodendrogliomas are classified as low-grade gliomas (LGG) and have the potential to progress into secondary GBM. YAP1 and TAZ are transcriptional co-activators of the hippo pathway and play an important role in tumorigenesis by controlling cell proliferation and differentiation. The aim of this study was to analyze whether YAP1 and TAZ influence the survival in patients with astrocytoma and oligodendroglioma. PATIENTS AND METHODS: A total of 22 patient samples of astrocytoma and 11 samples of oligodendroglioma were analyzed using real-time PCR. We utilized open-access data from The Cancer Genome Atlas (TCGA) focusing on "brain lower grade glioma". mRNA expression rates were used to validate our findings on survival analysis. RESULTS: Expression of YAP1 was twice as high in astrocytoma than in oligodendroglioma, whereas there was no difference in TAZ. In oligodendrogliomas, the expression of TAZ was higher in relapsed than in primary tumors. Patients with astrocytoma having a high YAP1 expression had a significantly shorter overall survival than patients with lower expression (median survival 161 vs. 86 months, p=0.0248). These findings were validated with survival analysis of TCGA data. CONCLUSION: High YAP1 expression shows a high correlation with poorer overall survival in LGG. YAP1 has higher levels of expression in astrocytomas than in oligodendrogliomas.

Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC), new name and new problems: an illustration of one case with atypical morphology and biology.

A novel histomolecular tumor of the central nervous system (CNS), the "diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC)," has recently been identified, based on a distinct DNA methylation profile and has been added to the 2021 World Health Organization Classification of CNS Tumors. This glioneuronal tumor mainly affects the supratentorial area in children and recurrently presents with a monosomy of chromosome 14. Herein, we report the case of a DNA-methylation based diagnosis of DGONC having atypical features, such as pseudo-rosettes and the absence of a chromosome 14 monosomy, thus rendering its diagnosis very challenging. Because of the wide variety of morphologies harbored by DGONC, a large range of differential diagnoses may be hypothesized from benign to malignant. Interestingly, the current case, like one previously reported, exhibited a co-expression of OLIG2, synaptophysin and SOX10, without GFAP immunopositivity. This particular immunophenotype seems to be a good indicator for a DGONC diagnosis. The classification of DGONC amongst glioneuronal or embryonal tumors is still debated. The clinical (a pediatric supratentorial tumor), morphological (from a benign oligodendroglioma-like tumor with microcalcifications and possible neuropil-like islands to a malignant embryonal tumor with a possible spongioblastic pattern), and immunohistochemical (co-expression of OLIG2 and synaptophsyin) profiles resemble CNS, neuroblastoma, FOXR2-activated and may potentially bring them together in a future classification. Further comprehensive studies are needed to conclude the cellular origin of DGONC and its prognosis.

Differential tractography and whole brain connectometry in primary motor area gliomas resection: A feasibility study.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Association of Clinical, Tumor, and Treatment Characteristics With Seizure Control in Patients With IDH1/2-Mutant Lower-Grade Glioma.

BACKGROUND AND OBJECTIVES: Patients with IDH1/2-mutant lower-grade glioma have a high frequency of seizures. We aimed to investigate the correlations between seizures and tumor/patient characteristics and the impact of surgery and adjuvant treatments (AT) on seizure control along the disease trajectory. METHODS: We retrospectively included patients with IDH1/2-mutant lower-grade glioma who underwent surgery at the neurosurgery divisions of the University of Turin and Milan and were treated at the Division of Neuro-Oncology of Turin. Inclusion criteria were a diagnosis according to the 2021 WHO Classification and presentation with seizures; exclusion criteria were presence of CDKN2A/B homozygous deletion, intense/ring contrast enhancement on MRI at presentation, and small tissue biopsy. We evaluated seizure freedom for 2 months after surgery, 6 months from starting observation or AT, at recurrence, and for 6 months after treatments of recurrence. RESULTS: We included 150 patients. There were 77 (51%) and 31 (21%) patients with IDH-mutant/1p19q-codeleted grade 2 and 3 oligodendroglioma and 30 (20%) and 12 (8%) with IDH-mutant grade 2 and 3 astrocytoma, respectively. Total resection was accomplished in 68 (45%). Seventy-five patients (50%) received AT while the remaining 75 were observed with MRI. After 6 months after AT, 28 of 29 patients (96.5%) displayed seizure reduction, 5 of 28 (18%) being seizure-free. 66 of 124 patients (53%) had seizures at recurrence. After 6 months after second-line treatments, 60 of 66 patients (91%) had seizure reduction, 11 (17%) being seizure-free. In multivariable analyses, grade 3 histology positively correlated with seizure freedom at 2 months after surgery (OR 3.5, 1.4-8.9, p = 0.008), 6 months after AT (OR 9.0, 1.5-54.9, p = 0.017), and 6 months after treatment of recurrence (OR 4.9, 1.5-16.5, p = 0.009). Adjuvant radiotherapy reduced seizures at recurrence in a univariate analysis (OR 0.14, 0.03-0.7, p = 0.020). Patients with seizure freedom after surgery and AT displayed longer progression-free survival (PFS) (65, 24.5-105, vs 48 months, 32-63.5, p = 0.037). DISCUSSION: This study analyzed seizure control in patients with IDH1/2-mutant lower-grade glioma across multiple time points. Grade 3 correlated with better seizure control throughout the entire disease trajectory, and seizure freedom after surgery and AT correlated with a longer PFS regardless of tumor grade. These results could serve as an external control arm in clinical trials evaluating the efficacy on seizures of antitumor agents in patients with IDH-mutant lower-grade glioma.

Oligodendroglioma, IDH-mutant and 1p/19q-codeleted-prognostic factors, standard of care and chemotherapy, and future perspectives with neoadjuvant strategy.

Oligodendroglioma, IDH-mutant and 1p/19q-codeleted is known for their relative chemosensitivity and indolent clinical course among diffuse gliomas of adult type. Based on the data from phase 3 clinical trials, the standard of post-surgical care for those tumors is considered to be initial chemoradiotherapy regardless of histopathological grade, particularly with PCV. However, partly due to its renewed definition in late years, prognostic factors in patients with those tumors are not well established. Moreover, the survival rate declines over 15 years, with only a 37% OS rate at 20 years for grade 3 tumors, even with the current standard of care. Given that most of this disease occurs in young or middle-aged adults, further improvements in treatment and management are necessary. Here, we discuss prognostic factors, standard of care and chemotherapy, and future perspectives with neoadjuvant strategy in those tumors.

Mutant IDH inhibitors induce lineage differentiation in IDH-mutant oligodendroglioma.

A subset of patients with IDH-mutant glioma respond to inhibitors of mutant IDH (IDHi), yet the molecular underpinnings of such responses are not understood. Here, we profiled by single-cell or single-nucleus RNA-sequencing three IDH-mutant oligodendrogliomas from patients who derived clinical benefit from IDHi. Importantly, the tissues were sampled on-drug, four weeks from treatment initiation. We further integrate our findings with analysis of single-cell and bulk transcriptomes from independent cohorts and experimental models. We find that IDHi treatment induces a robust differentiation toward the astrocytic lineage, accompanied by a depletion of stem-like cells and a reduction of cell proliferation. Furthermore, mutations in NOTCH1 are associated with decreased astrocytic differentiation and may limit the response to IDHi. Our study highlights the differentiating potential of IDHi on the cellular hierarchies that drive oligodendrogliomas and suggests a genetic modifier that may improve patient stratification.

Construction and Validation of Nomograms for Predicting Overall Survival and Cancer-Specific Survival in Patients with Primary Anaplastic Oligodendroglioma.

OBJECTIVE: Anaplastic oligodendroglioma (AOD) is a rare high-grade central nervous system tumor. The current research on prognostic prediction of AOD remains limited. This study aimed to identify prognostic factors and establish the nomograms to predict overall survival (OS) and cancer-specific survival (CSS) for patients with AOD. METHODS: Patients diagnosed with AOD between 1992 and 2020 were extracted from the Surveillance, Epidemiology, and End Result database. We performed univariate and multivariate Cox regression analyses to identify independent prognostic factors based on the training group. Kaplan-Meier survival curves were used to compare the impact of various independent factors on patient prognosis. For OS and CSS, the nomograms were constructed and verified by the validation group. Harrell''s concordance index, receiver operating characteristic curves, calibration curves, and decision curve analyses were used to assess the discrimination, consistency, and clinical value of the nomograms. RESULTS: A total of 1202 AOD patients were enrolled, being randomly divided into training (n = 841) and validation (n = 361) groups (7:3 ratio). Univariate and multivariate Cox analysis identified 4 significant independent factors (tumor site, age, surgery, and chemotherapy). For OS and CSS, Harrell''s concordance index were 0.731 (0.705-0.757) and 0.728 (0.701-0.754) in the training group, 0.688 (0.646-0.731) and 0.684 (0.639-0.729) in the validation group, respectively. Receiver operating characteristic curves and Calibration curves showed good discrimination and consistency, respectively. In addition, the decision curve analyses curves showed the nomograms have good clinical benefits. CONCLUSIONS: We successfully established the nomograms to predict the OS and CSS for AOD patients. The nomograms showed good performance in prognostic prediction, assisting clinicians in evaluating patient prognosis and personalizing treatment plans.

Genetically Distinct Oligosarcoma Arising from Oligodendroglioma: Systematic Review & Illustrative Case Example.

BACKGROUND: Oligosarcoma is a rare central nervous system (CNS) neoplasm that may arise following oligodendroglioma resection, which demonstrates a unique genetic profile and aggressive clinical phenotype. We present a systematic review and illustrative case example emphasizing the clinical and prognostic features of this unusual and unfavorable neuro-oncologic disease. METHODS: Systematic literature review and illustrative case report. RESULTS: A 41-year-old man who had undergone 2 neurosurgical resections for a World Health Organization grade II oligodendroglioma (Ki-67 = 5-10%, 1p/19q codeleted, IDH2 mutated), without adjuvant chemoradiation, presented with seizures seven years after resection. An extra-axial mass was identified adjacent to the resection cavity, in which gross total resection was achieved. Pathology confirmed World Health Organization grade IV oligosarcoma (Ki-67 = 20%). Adjuvant chemoradiation was initiated, with disease control observed over 6 months of follow-up. Seven publications met inclusion criteria. Oligosarcoma has been confirmed in 36 lesions, arising in 35 patients; 5 were primary oligosarcoma, while 31 occurred in the setting of prior resected oligodendroglioma or oligoastrocytoma. Features shared by these lesions include regain of H3K27me3 expression, 1p/19q codeletion, homozygous deletion of CDKN2A/B, loss of 6q, loss of NF1 and YAP1, and attenuation of CpG island methylator. Median survival after oligosarcoma diagnosis was 1.3 years (range, 0-5.2; n = 35). CONCLUSIONS: Oligosarcoma is a prognostically unfavorable CNS neoplasm with characteristic imaging and pathologic features, and a strong association with previously resected oligodendroglioma. Aggressive treatment is recommended, including gross total resection and adjuvant chemoradiation. Further study is required to define optimal treatment protocol for this CNS malignancy.

From molecular signatures to radiomics: tailoring neurooncological strategies through forecasting of glioma growth.

OBJECTIVE: Contemporary oncological paradigms for adjuvant treatment of low- and intermediate-grade gliomas are often guided by a limited array of parameters, overlooking the dynamic nature of the disease. The authors' aim was to develop a comprehensive multivariate glioma growth model based on multicentric data, to facilitate more individualized therapeutic strategies. METHODS: Random slope models with subject-specific random intercepts were fitted to a retrospective cohort of grade II and III gliomas from the database at Kepler University Hospital (n = 191) to predict future mean tumor diameters. Deep learning-based radiomics was used together with a comprehensive clinical dataset and evaluated on an external prospectively collected validation cohort from University Hospital Zurich (n = 9). Prediction quality was assessed via mean squared prediction error. RESULTS: A mean squared prediction error of 0.58 cm for the external validation cohort was achieved, indicating very good prognostic value. The mean ± SD time to adjuvant therapy was 28.7 ± 43.3 months and 16.1 ± 14.6 months for the training and validation cohort, respectively, with a mean of 6.2 ± 5 and 3.6 ± 0.7, respectively, for number of observations. The observed mean tumor diameter per year was 0.38 cm (95% CI 0.25-0.51) for the training cohort, and 1.02 cm (95% CI 0.78-2.82) for the validation cohort. Glioma of the superior frontal gyrus showed a higher rate of tumor growth than insular glioma. Oligodendroglioma showed less pronounced growth, anaplastic astrocytoma-unlike anaplastic oligodendroglioma-was associated with faster tumor growth. Unlike the impact of extent of resection, isocitrate dehydrogenase (IDH) had negligible influence on tumor growth. Inclusion of radiomics variables significantly enhanced the prediction performance of the random slope model used. CONCLUSIONS: The authors developed an advanced statistical model to predict tumor volumes both pre- and postoperatively, using comprehensive data prior to the initiation of adjuvant therapy. Using radiomics enhanced the precision of the prediction models. Whereas tumor extent of resection and topology emerged as influential factors in tumor growth, the IDH status did not. This study emphasizes the imperative of advanced computational methods in refining personalized low-grade glioma treatment, advocating a move beyond traditional paradigms.

Distant recurrence in the cerebellar dentate nucleus through the dentato-rubro-thalamo-cortical pathway in supratentorial glioma cases.

BACKGROUND: Distant recurrence can occur by infiltration along white matter tracts or dissemination through the cerebrospinal fluid (CSF). This study aimed to clarify the clinical features and mechanisms of recurrence in the dentate nucleus (DN) in patients with supratentorial gliomas. Based on the review of our patients, we verified the hypothesis that distant DN recurrence from a supratentorial lesion occurs through the dentato-rubro-thalamo-cortical (DRTC) pathway. METHODS: A total of 380 patients with supratentorial astrocytoma, isocitrate dehydrogenase (IDH)-mutant (astrocytoma), oligodendroglioma, IDH mutant and 1p/19q-codeleted (oligodendroglioma), glioblastoma, IDH-wild type (GB), and thalamic diffuse midline glioma, H3 K27-altered (DMG), who underwent tumor resection at our department from 2009 to 2022 were included in this study. Recurrence patterns were reviewed. Additionally, clinical features and magnetic resonance imaging findings before treatment, at the appearance of an abnormal signal, and at further progression due to delayed diagnosis or after salvage treatment of cases with recurrence in the DN were reviewed. RESULTS: Of the 380 patients, 8 (2.1%) had first recurrence in the DN, 3 were asymptomatic when abnormal signals appeared, and 5 were diagnosed within one month after the onset of symptoms. Recurrence in the DN developed in 8 (7.4%) of 108 cases of astrocytoma, GB, or DMG at the frontal lobe or thalamus, whereas no other histological types or sites showed recurrence in the DN. At the time of the appearance of abnormal signals, a diffuse lesion developed at the hilus of the DN. The patterns of further progression showed that the lesions extended to the superior cerebellar peduncle, tectum, tegmentum, red nucleus, thalamus, and internal capsule along the DRTC pathway. CONCLUSION: Distant recurrence along the DRTC pathway is not rare in astrocytomas, GB, or DMG at the frontal lobe or thalamus. Recurrence in the DN developed as a result of the infiltration of tumor cells through the DRTC pathway, not dissemination through the CSF.

Patterns of T2-FLAIR discordance across a cohort of adult-type diffuse gliomas and deviations from the classic T2-FLAIR mismatch sign.

PURPOSE: T2-FLAIR mismatch serves as a highly specific but insensitive marker for IDH-mutant (IDHm) astrocytoma with potential limitations in real-world application. We aimed to assess the utility of a broader definition of T2-FLAIR discordance across a cohort of adult-type diffuse lower-grade gliomas (LrGG) to see if specific patterns emerge and additionally examine factors determining deviation from the classic T2-FLAIR mismatch sign. METHODS: Preoperative MRIs of non-enhancing adult-type diffuse LrGGs were reviewed. Relevant demographic, molecular, and MRI data were compared across tumor subgroups. RESULTS: Eighty cases satisfied the inclusion criteria. Highest discordance prevalence and > 50% T2-FLAIR discordance volume were noted with IDHm astrocytomas (P < 0.001), while < 25% discordance volume was associated with oligodendrogliomas (P = 0.03) and IDH-wildtype (IDHw) LrGG (P = 0.004). "T2-FLAIR matched pattern" was associated with IDHw LrGG (P < 0.001) and small or minimal areas of discordance with oligodendrogliomas (P = 0.03). Sensitivity and specificity of classic mismatch sign for IDHm astrocytoma were 25.7% and 100%, respectively (P = 0.06). Retained ATRX expression and/or non-canonical IDH mutation (n = 10) emerged as a significant factor associated with absence of classic T2-FLAIR mismatch sign in IDHm astrocytomas (100%, P = 0.02) and instead had minimal discordance or matched pattern (40%, P = 0.04). CONCLUSION: T2-FLAIR discordance patterns in adult-type diffuse LrGGs exist on a diverging but distinct spectrum of classic mismatch to T2-FLAIR matched patterns. Specific molecular markers may play a role in deviations from classic mismatch sign.

The development of a custom RNA-sequencing panel for the identification of predictive and diagnostic biomarkers in glioma.

PURPOSE: Various molecular profiles are needed to classify malignant brain tumors, including gliomas, based on the latest classification criteria of the World Health Organization, and their poor prognosis necessitates new therapeutic targets. The Todai OncoPanel 2 RNA Panel (TOP2-RNA) is a custom-target RNA-sequencing (RNA-seq) using the junction capture method to maximize the sensitivity of detecting 455 fusion gene transcripts and analyze the expression profiles of 1,390 genes. This study aimed to classify gliomas and identify their molecular targets using TOP2-RNA. METHODS: A total of 124 frozen samples of malignant gliomas were subjected to TOP2-RNA for classification based on their molecular profiles and the identification of molecular targets. RESULTS: Among 55 glioblastoma cases, gene fusions were detected in 11 cases (20%), including novel MET fusions. Seven tyrosine kinase genes were found to be overexpressed in 15 cases (27.3%). In contrast to isocitrate dehydrogenase (IDH) wild-type glioblastoma, IDH-mutant tumors, including astrocytomas and oligodendrogliomas, barely harbor fusion genes or gene overexpression. Of the 34 overexpressed tyrosine kinase genes, MDM2 and CDK4 in glioblastoma, 22 copy number amplifications (64.7%) were observed. When comparing astrocytomas and oligodendrogliomas in gene set enrichment analysis, the gene sets related to 1p36 and 19q were highly enriched in astrocytomas, suggesting that regional genomic DNA copy number alterations can be evaluated by gene expression analysis. CONCLUSIONS: TOP2-RNA is a highly sensitive assay for detecting fusion genes, exon skipping, and aberrant gene expression. Alterations in targetable driver genes were identified in more than 50% of glioblastoma. Molecular profiling by TOP2-RNA provides ample predictive, prognostic, and diagnostic biomarkers that may not be identified by conventional assays and, therefore, is expected to increase treatment options for individual patients with glioma.

Comparison of diagnostic performance of radiologist- and AI-based assessments of T2-FLAIR mismatch sign and quantitative assessment using synthetic MRI in the differential diagnosis between astrocytoma, IDH-mutant and oligodendroglioma, IDH-mutant and 1p/19q-codeleted.

PURPOSE: This study aimed to compare assessments by radiologists, artificial intelligence (AI), and quantitative measurement using synthetic MRI (SyMRI) for differential diagnosis between astrocytoma, IDH-mutant and oligodendroglioma, and IDH-mutant and 1p/19q-codeleted and to identify the superior method. METHODS: Thirty-three cases (men, 14; women, 19) comprising 19 astrocytomas and 14 oligodendrogliomas were evaluated. Four radiologists independently evaluated the presence of the T2-FLAIR mismatch sign. A 3D convolutional neural network (CNN) model was trained using 50 patients outside the test group (28 astrocytomas and 22 oligodendrogliomas) and transferred to evaluate the T2-FLAIR mismatch lesions in the test group. If the CNN labeled more than 50% of the T2-prolonged lesion area, the result was considered positive. The T1/T2-relaxation times and proton density (PD) derived from SyMRI were measured in both gliomas. Each quantitative parameter (T1, T2, and PD) was compared between gliomas using the Mann-Whitney U-test. Receiver-operating characteristic analysis was used to evaluate the diagnostic performance. RESULTS: The mean sensitivity, specificity, and area under the curve (AUC) of radiologists vs. AI were 76.3% vs. 94.7%; 100% vs. 92.9%; and 0.880 vs. 0.938, respectively. The two types of diffuse gliomas could be differentiated using a cutoff value of 2290/128 ms for a combined 90th percentile of T1 and 10th percentile of T2 relaxation times with 94.4/100% sensitivity/specificity with an AUC of 0.981. CONCLUSION: Compared to the radiologists' assessment using the T2-FLAIR mismatch sign, the AI and the SyMRI assessments increased both sensitivity and objectivity, resulting in improved diagnostic performance in differentiating gliomas.