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Background: Second and third surgeries were demonstrated as safe and efficient in recurrent diffuse low-grade glioma (LGG). Here, the feasibility of more than 3 resections is investigated. Methods: Patients who underwent 4 or 5 operations for recurrent initially WHO grade 2 IDH-mutated gliomas were consecutively selected. Results: Twenty-three operations were performed in five patients (all males, mean age 27.2 ± 4 years). Three patients underwent 5 surgeries and two patients underwent 4 surgeries. Twelve procedures (52%) were achieved with awake mapping, including all 4th and 5th operations but one. Repeat electrical mapping detected changes of the cortical maps between at least two awake surgeries in 4 patients. No patients experienced permanent neurological impairment (KPS score ≥ 80 in all cases). The patients returned to work after 22 surgeries among 23 (95.6%). There were 3 oligodendrogliomas and 2 astrocytomas (4 gliomas became malignant at fourth or fifth operation). Although the preoperative tumor volume significantly increased before the fourth (p = 0.026) and fifth operation (p = 0.003) compared with the first operation, there was no significant difference between the residual tumor volume after the fourth or fifth resection versus the first one. The mean delay was 10.6 ± 3.9 years before chemotherapy and 15.4 ± 3.4 years before radiotherapy (one patient never received adjuvant treatment after 21.5 years). The mean follow-up duration was 18.3 ± 3.1 years since the first surgery (2.3 ± 1.8 years since the last surgery). Three patients were still alive at last follow-up. Conclusions: This is the first series showing that to reoperate beyond three times is feasible with a low functional risk and a long survival in multiple LGG recurrences, with the use of awake mapping in 87.5% of 4th and 5th surgeries. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinicopathologic and other molecular markers features of oligodendrogliomas in adults with non-codeletion of 1p/19q. Methods 326 cases of oligodendrogliomas, anaplastic oligodendrogliomas, oligoastrocytomas, and anaplastic oligoastrocytomas diagnosed by histopathology after surgical resection were collected. The polymorphism of chromosome 1p and 19q were analyzed by fluorescence in situ hybridization ( FISH) . Isocitrate dehydrogenase ( IDH) 1/2 mutation, TP53 and promoter of telomerase reverse transcriptase (TERTp) were detected by Sanger sequencing. The expression levels of ATRX, PDGFRA, EGFR, CIC, FUBP1, INA, and PTEN were detected by immunohistochemical staining, and methylation specific PCR (MSP) was used to detect the methylation of MGMT promotor. Results The 1p/19q status of 326 adult oligodendrogliomas showed that 37.6% of the tumors were 1p/19q non-codeletion, and more than half of the 1p/19q non-codeleted oligodendrogliomas showed lack of expression of p53 and ATRX, the defining astrocytic markers. In the cohort of 1p/19q non-codeleted "oligodendrogliomas", patients with younger age ( <45 years), WHO grade 2, and typical oligodendroglioma histomorphology had a better prognosis (P < 0.01), and the typical histomorphology of oligodendrogliomas was associated with TERTp mutation status, p53 expression, EFGR expression, PDGFRA expression ( P < 0.05) . The expression of FUBP1, TERT, MGMT, PDGFRA, EGFR, PTEN, INA, and CIC was not found to have significant prognostic value (P > 0.05) . Conclusion According to the 5th edition of the 2021 WHO Classification of Tumors of the Central Nervous System, astrocytomas do not account for all 1p/19q non-codeleted oligodendrogliomas, and 1p/19q non-codeleted oligodendrogliomas may represent a distinct subgroup of diffuse gliomas. [ABSTRACT FROM AUTHOR]

Objective: Presurgical differentiation between astrocytomas and oligodendrogliomas remains an unresolved challenge in neuro-oncology. This research aims to provide a comprehensive understanding of each tumor's DSC-PWI signatures, evaluate the discriminative capacity of cerebral blood volume (CBV) and percentage of signal recovery (PSR) percentile values, and explore the synergy of CBV and PSR combination for pre-surgical differentiation. Methods: Patients diagnosed with grade 2 and 3 IDH-mutant astrocytomas and IDH-mutant 1p19q-codeleted oligodendrogliomas were retrospectively retrieved (2010–2022). 3D segmentations of each tumor were conducted, and voxel-level CBV and PSR were extracted to compute mean, minimum, maximum, and percentile values. Statistical comparisons were performed using the Mann-Whitney U test and the area under the receiver operating characteristic curve (AUC-ROC). Lastly, the five most discriminative variables were combined for classification with internal cross-validation. Results: The study enrolled 52 patients (mean age 45-year-old, 28 men): 28 astrocytomas and 24 oligodendrogliomas. Oligodendrogliomas exhibited higher CBV and lower PSR than astrocytomas across all metrics (e.g., mean CBV = 2.05 and 1.55, PSR = 0.68 and 0.81 respectively). The highest AUC-ROCs and the smallest p values originated from CBV and PSR percentiles (e.g., PSRp70 AUC-ROC = 0.84 and p value = 0.0005, CBVp75 AUC-ROC = 0.8 and p value = 0.0006). The mean, minimum, and maximum values yielded lower results. Combining the best five variables (PSRp65, CBVp70, PSRp60, CBVp75, and PSRp40) achieved a mean AUC-ROC of 0.87 for differentiation. Conclusions: Oligodendrogliomas exhibit higher CBV and lower PSR than astrocytomas, traits that are emphasized when considering percentiles rather than mean or extreme values. The combination of CBV and PSR percentiles results in promising classification outcomes. Clinical relevance statement: The combination of histogram-derived percentile values of cerebral blood volume and percentage of signal recovery from DSC-PWI enhances the presurgical differentiation between astrocytomas and oligodendrogliomas, suggesting that incorporating these metrics into clinical practice could be beneficial. Key Points: • The unsupervised selection of percentile values for cerebral blood volume and percentage of signal recovery enhances presurgical differentiation of astrocytomas and oligodendrogliomas. • Oligodendrogliomas exhibit higher cerebral blood volume and lower percentage of signal recovery than astrocytomas. • Cerebral blood volume and percentage of signal recovery combined provide a broader perspective on tumor vasculature and yield promising results for this preoperative classification. [ABSTRACT FROM AUTHOR]

BACKGROUND: Telomere maintenance by telomerase reverse transcriptase (TERT) is essential for immortality in most cancers, including oligodendrogliomas. Agents that disrupt telomere maintenance such as the telomere uncapping agent 6-thio-2-deoxyguanosine (6-thio-dG) are in clinical trials. We previously showed that TERT expression in oligodendrogliomas is associated with upregulation of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway (PPP). We also showed that hyperpolarized δ-[1-13C]-gluconolactone metabolism to 6-phosphogluconate (6-PG) can be used to probe the PPP in glioblastomas. The goal of this study was to determine whether hyperpolarized 13C imaging using δ-[1-13C]-gluconolactone can monitor TERT expression and response to 6-thio-dG in oligodendrogliomas. METHODS: We examined patient-derived oligodendroglioma cells and orthotopic tumors to assess the link between TERT and hyperpolarized δ-[1-13C]-gluconolactone metabolism. We performed in vivo imaging to assess the ability of hyperpolarized δ-[1-13C]-gluconolactone to report on TERT and response to 6-thio-dG in rats bearing orthotopic oligodendrogliomas in vivo. RESULTS: Doxycycline-inducible TERT silencing abrogated 6-PG production from hyperpolarized δ-[1-13C]-gluconolactone in oligodendroglioma cells, consistent with the loss of G6PD activity. Rescuing TERT expression by doxycycline removal restored G6PD activity and, concomitantly, 6-PG production. 6-PG production from hyperpolarized δ-[1-13C]-gluconolactone demarcated TERT-expressing tumor from surrounding TERT-negative normal brain in vivo. Importantly, 6-thio-dG abrogated 6-PG production at an early timepoint preceding MRI-detectable alterations in rats bearing orthotopic oligodendrogliomas in vivo. CONCLUSIONS: These results indicate that hyperpolarized δ-[1-13C]-gluconolactone reports on TERT expression and early response to therapy in oligodendrogliomas. Our studies identify a novel agent for imaging tumor proliferation and treatment response in oligodendroglioma patients.

Objective: Calcification is a hallmark characteristic of oligodendroglioma (ODG) that may be used as a diagnostic factor, but its prognostic implications remain unclear. This study aimed to investigate the features of calcified ODGs and to evaluate the differences in survival between patients with calcified and noncalcified ODGs. Methods: We retrospectively reviewed the records of 305 consecutive patients who were diagnosed with IDH-mutant, 1p/19q codeleted ODG at our institution from July 2009 to August 2020. Patients with intratumoral calcification were identified. The clinical, radiologic, and molecular features of the patients in the calcified group and noncalcified group were recorded. Univariate and multivariate analyses were performed to identify prognostic factors. Results: Of the 305 patients, 112 (36.7%) were confirmed to have intratumoral calcification. Compared to ODGs without calcification, ODGs with calcifications had a larger tumor diameter; lower degree of resection; higher tumor grade; higher MGMT methylation level; higher Ki-67 index; and higher rates of midline crossing, enhancement, cyst, and 1q/19p copolysomy, and patients with calcification were more likely to receive chemoradiotherapy. ODGs with T2 hypointense calcification had a higher Hounsfield unit (HU) value on CT scans, and a lower degree of resection. Patients with T2 hypointense calcification ODGs had a shorter survival than those with non-hypointense calcification ODGs. ODGs with calcification and cysts showed a higher Ki-67 index, tumor grade, and enhanced rate, and the patients had an unfavorable overall survival (OS). Calcification was found to be a negative prognostic factor for both progression-free survival (PFS) and OS by univariate analysis, which was confirmed by the Cox proportional hazard model. Conclusions: Calcification is a useful negative prognostic factor for PFS and OS in patients with ODGs and could therefore be helpful in guiding personalized treatment and predicting patient prognosis. Clinical relevance statement: Calcification can serve as an independent prognostic factor for patients with oligodendroglioma and shows a vital role in guiding individualized treatment. Key Points: • Intratumoral calcification is an independent negative prognostic risk factor for progression-free survival and overall survival in oligodendroglioma patients. • Calcifications in oligodendroglioma can be divided into hypointense and non-hypointense subtypes based on T2-weighted imaging, and patients with T2-hypointense calcification oligodendrogliomas have worse prognosis. • Calcification concurrent with cysts indicates a more aggressive phenotype of oligodendrogliomas and a significantly reduced survival rate. [ABSTRACT FROM AUTHOR]

Diffuse gliomas are the most common type of adult primary brain tumors, and they have been recently classified into three types: astrocytoma IDH-mutant, oligodendroglioma, and glioblastoma IDH-wildtype. Molecular testing is now used to diagnose these tumors, but imaging still plays a role in providing diagnostic and prognostic information. A study published in European Radiology evaluated the use of two imaging metrics, normalized relative cerebral blood volume (nrCBV) and percentage signal recovery (PSR), to differentiate between astrocytoma and oligodendroglioma. The results showed that PSR performed better than nrCBV, and combining the two metrics improved their performance. However, further research is needed to validate these findings and determine the optimal imaging parameters for clinical use. [Extracted from the article]

In IDH-mutant (mt) lower grade gliomas, homozygous deletion in CDKN2A/B (CDK-del) is an adverse prognostic marker. For astrocytomas, in recognition of a worse prognosis, tumors with CDK-del are upgraded to grade 4 in WHO 2021. Similarly, IDH-mt 1p/19q co-deleted oligodendrogliomas with CDK-del or chromosome 9p aberrations, where the CDKN2A/B locus resides, have a worse prognosis than their wildtype counterpart. However, given the rarity of this subtype, no consensus exists on how to classify and treat this subtype of oligodendrogliomas. In this preliminary analysis of an ongoing multi-institutional retrospective database of oligodendrogliomas, we hypothesize that CDK-del and associated chromosomal aberrations are adverse prognostic markers. This multi-institutional retrospective analysis comprises of over 5 major cancer institutes with ongoing accrual. Clinical information from molecularly confirmed oligodendrogliomas (IDH-mt 1p/19q co-del) are being collected. This includes histologic, pathologic, and molecular details, comprehensive course of treatment(s), patient outcomes, and follow-up data. For this preliminary analysis, median follow up and survival times were calculated using a reverse and regular Kaplan-Meier method, respectively. Currently, we have identified 20 patients with oligodendroglioma, 17 with CDK-del and 3 with chromosome 9p hemizygous loss. 50%, 39%, and 11% were histologic grade II, III, and IV, respectively. However, WHO grading system varied (2007, 2016, 2021), depending on time of diagnosis. Detailed treatment courses were available for 18 patients. 17 had upfront surgical resection, 65% with subtotal resection. Initial management was observation in 35%, chemotherapy alone in 12%, sequential chemoradiation in 18%, and concurrent chemoradiation in 35%. Of those treated with radiotherapy, 85% received 60 Gy. Chemotherapy regimens were PCV in 25%, TMZ in 67%, and Ivosidenib (IDH inhibitor) in 8%. Outcome data were available for all 20 patients, with a median follow-up of 95 months (IQR 21, 200) and a median survival of 71 months (IQR 46, 214). Preliminary analyses suggest CDKN2A/B homozygous deletion and associated chromosomal aberrations are adverse prognostic markers for oligodendrogliomas with a median survival approximately 40% of what is expected from historical comparisons of patients with predominantly wild-type CDK (e.g. median survival of 14.7 years in RTOG 9402). CDK-del was previously reported to be mutually exclusive with WHO grade II oligodendroglioma; this was not observed in our data. Further data collection are ongoing, with the goal of improving the classification and possibly, treatment recommendations for this subset of oligodendrogliomas (IRB 69688). [ABSTRACT FROM AUTHOR]

Background: Pseudoprogression in gliomas has been extensively described after radiotherapy with or without chemotherapy, but not after chemotherapy alone. Here we describe the occurrence of pseudoprogression in patients with anaplastic oligodendrogliomas treated with postoperative procarbazine, lomustine and vincristine (PCV) chemotherapy alone. Methods: We retrospectively reviewed the medical and radiological files of patients with 1p/19q codeleted, IDH‐mutant anaplastic oligodendrogliomas treated with PCV chemotherapy alone who presented magnetic resonance imaging (MRI) modifications suggestive of tumour progression and in whom the final diagnosis was a pseudoprogression. Results: We identified six patients. All patients underwent a surgical resection and were treated with PCV chemotherapy without radiotherapy. After a median of 11 months following the initiation of chemotherapy (range: 3–49 months), the patients developed asymptomatic white matter MRI modifications around the surgical cavity leading to the suspicion of a tumour progression. These modifications appeared as hyperintense on T2‐fluid‐attenuated inversion recovery (FLAIR) sequence, hypointense on T1 sequence, and lacked mass effect (0/6), contrast enhancement (0/6), restriction on diffusion‐weighted imaging (0/4), relative cerebral blood volume (rCBV) increase on perfusion MRI (0/4), and hypermetabolism on 18F‐fluoro‐L‐dopa positron emission tomography (18F‐DOPA PET) scan (0/3). One patient underwent a surgical resection demonstrating no tumour recurrence; the five other patients were considered as having post‐therapeutic modifications based on imaging characteristics. After a median follow‐up of 4 years all patients were progression‐free. Conclusions: Anaplastic oligodendroglioma patients treated with postoperative PCV chemotherapy alone occasionally develop T2/FLAIR hyperintensities around the surgical cavity that can wrongly suggest tumour progression. Multimodal imaging and close follow‐up should be considered in this situation. [ABSTRACT FROM AUTHOR]

The classification of diffuse gliomas into the adult type and the pediatric type is the new basis for the diagnosis and clinical evaluation. The knowledge for the neuroradiologist should not remain limited to radiological aspects but should be based additionally on the current edition of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS). This classification defines the 11 entities of diffuse gliomas, which are included in the 3 large groups of adult-type diffuse gliomas, pediatric-type diffuse low-grade gliomas, and pediatric-type diffuse high-grade gliomas. This article provides a detailed overview of important molecular, morphological, and clinical aspects for all 11 entities, such as typical genetic alterations, age distribution, variability of the tumor localization, variability of histopathological and radiological findings within each entity, as well as currently available statistical information on prognosis and outcome. Important differential diagnoses are also discussed. [ABSTRACT FROM AUTHOR]

Background: Oligodendroglioma is known for its relatively better prognosis and responsiveness to radiotherapy and chemotherapy. However, little is known about the evolution of genetic changes as oligodendroglioma progresses. Methods: In this study, we evaluated gene evolution invivo during tumor progression based on deep whole‐genome sequencing data (ctDNA). We analyzed longitudinal genomic data from six patients during tumor evolution, of which five patients developed distant recurrence. Results: Whole‐exome sequencing demonstrated that the rate of shared mutations between the primary and recurrent samples was relatively low. In two cases, even well‐known major driver mutations in CIC and FUBP1 that were detected in primary tumors were not detected in the relapse samples. Among these cases, two patients had a conversion from the IDH mutation in the originating state to the IDH1 wild state during the process of gene evolution under chemotherapy treatment, indicating that the cell phenotype and genetic characteristics of oligodendroglioma may change during tumor evolution. Two patients received long‐term temozolomide (TMZ) treatment before the operation, and we found that recurrence tumors harbored mutations in the PI3K/AKT and Sonic hedgehog (SHh) signaling pathways. Hypermutation occurred with mutations in MMR genes in one patient, contributing to the rapid progression of the tumor. Conclusion: Oligodendroglioma displayed great spatial and temporal heterogeneity during tumor evolution. The PI3K/AKT and SHh signaling pathways may play an important role in promoting treatment resistance and distant relapse during oligodendroglioma evolution. In addition, there was a tendency to increase the degree of tumor malignancy during evolution. Distant recurrence may be a later event duringoligodendroglioma progression. ClinicalTrials.gov, Identifier: NCT05512325. [ABSTRACT FROM AUTHOR]

Purpose: Since the introduction of the molecular definition of oligodendrogliomas based on isocitrate dehydrogenase (IDH)-status and the 1p19q-codeletion, it has become increasingly evident how this glioma entity differs much from other diffuse lower grade gliomas and stands out with longer survival and often better responsiveness to adjuvant therapy. Therefore, apart from using a molecular oligodendroglioma definition, an extended follow-up time is necessary to understand the nature of this slow growing, yet malignant condition. The aim of this study was to describe the long-term course of the oligodendroglioma disease in a population-based setting and to determine which factors affect outcome in terms of survival. Methods: All adults with WHO-grade 2 oligodendrogliomas with known 1p19q-codeletion from five Scandinavian neurosurgical centers and with a follow-up time exceeding 5 years, were analyzed regarding survival and factors potentially affecting survival. Results: 126 patients diagnosed between 1998 and 2016 were identified. The median follow-up was 12.0 years, and the median survival was 17.8 years (95% CI 16.0–19.6). Factors associated with shorter survival in multivariable analysis were age (HR 1.05 per year; CI 1.02–1.08, p < 0.001), tumor diameter (HR 1.05 per millimeter; CI 1.02–1.08, p < 0.001) and poor preoperative functional status (KPS < 80) (HR 4.47; CI 1.70–11.78, p = 0.002). In our material, surgical strategy was not associated with survival. Conclusion: Individuals with molecularly defined oligodendrogliomas demonstrate long survival, also in a population-based setting. This is important to consider for optimal timing of therapies that may cause long-term side effects. Advanced age, large tumors and poor function before surgery are predictors of shorter survival. [ABSTRACT FROM AUTHOR]

Glioma is one of the most aggressive tumors that develop in the glial cells of the brain. It has subtypes such as astrocytomas, oligodendrogliomas and ependymomas. Gliomas comprise about 30% of all brain tumors and are mostly malignant. Gliomas are classified into four grades and the severity of the disease increases with the grade. Like many cancer types, development of gliomas is under the control of genetic, epigenetic and environmental factors. Epigenetics is the area that examines the expression changes in genes that do not change the structure of DNA, but cause behavioral changes in uncontrolled proliferation, growth, migration, death and many other processes in the cell by affecting the gene. Methylation, acetylation, micro RNAs (miRNAs), histone modifications are among the well-known epigenetic factors. This review aims to describe the most common and wellidentified epigenetic changes that can result in glioma formation. [ABSTRACT FROM AUTHOR]

Background: In humans, the T2‐weighted (T2W)—fluid‐attenuated inversion recovery (FLAIR) mismatch sign (T2FMM) is a specific imaging biomarker for the isocitrate dehydrogenase 1 (IDH1)‐mutated, 1p/19q non‐codeleted low‐grade astrocytomas (LGA). The T2FMM is characterized by a homogeneous hyperintense T2W signal and a hypointense signal with a hyperintense peripheral rim on FLAIR sequences. In gliomas in dogs, the T2FMM has not been described. Hypotheses/Objectives: In dogs with focal intra‐axial brain lesions, T2FMM will discriminate gliomas from other lesions. The T2FMM will be associated with the LGA phenotype and presence of microcysts on histopathology. Interobserver agreement for T2FMM magnetic resonance imaging (MRI) features will be high. Animals: One hundred eighty‐six dogs with histopathologically diagnosed focal intra‐axial lesions on brain MRI including oligodendrogliomas (n = 90), astrocytomas (n = 47), undefined gliomas (n = 9), cerebrovascular accidents (n = 33), and inflammatory lesions (n = 7). Methods: Two blinded raters evaluated the 186 MRI studies and identified cases with the T2FMM. Histopathologic and immunohistochemical slides of T2FMM cases were evaluated for morphologic features and IDH1‐mutations and compared to cases without the T2FMM. Gene expression analyses were performed on a subset of oligodendrogliomas (n = 10) with and without T2FMM. Results: The T2FMM was identified in 14/186 (8%) of MRI studies, and all dogs with T2FMM had oligodendrogliomas (n = 12 low‐grade [LGO], n = 2 high‐grade [HGO]; P <.001). Microcystic change was significantly associated with the T2FMM (P <.00001). In oligodendrogliomas with T2FMM, IDH1‐mutations or specific differentially expressed genes were not identified. Conclusion and Clinical Importance: The T2FMM can be readily identified on routinely obtained MRI sequences. It is a specific biomarker for oligodendroglioma in dogs, and was significantly associated with non‐enhancing LGO. [ABSTRACT FROM AUTHOR]

Astrocytoma and oligodendroglioma are primary brain tumors classified as gliomas. Because there is difference in the prognostic significance of the extent of resection between IDH-mutant astrocytoma and oligodendroglioma, intraoperative differential diagnosis between them provides important information for optimal extent of resection. Although the characteristics of genetic mutations and chromosomal aberrations in both tumors have been reported, there is no molecular diagnostic methods that is able to be used quickly and simply for differentiate the two tumors. Therefore, we aimed to search for biomarker candidates for differentiating them with metabolome analysis using liquid chromatography/tandem mass spectrometry and develop a molecular diagnostic method based on quantitative analysis. We searched for peaks that differed in two types of gliomas using global metabolomics. Next, we identified five biomarker candidates as hypoxanthine, inosine, cystine, proline and uric acid, respectively. Next, we developed an LC/MS/MS analytical method for five biomarker candidates and quantified them in brain tumors. Cystine had significantly lower amounts in astrocytomas than in oligodendrogliomas. We developed two prediction models for differentiation of the two gliomas and validated them using the separated two dataset. The logistic regression model with only cystine provided the best prediction performance. It was suggested that mass spectrometric analysis of cystine in surgery might be useful for differentiating astrocytoma and oligodendroglioma with 91.7% positive prediction value and 80.0% specificity whereas negative predictive value and sensitivity was lesser than 70%, so that further exploration for unknown metabolite is mandatory.

Pyruvate carboxylase (PC) is an enzyme catalyzing the carboxylation of pyruvate to oxaloacetate. The enzymatic generation of oxaloacetate, an intermediate of the Krebs cycle, could provide the cancer cells with the additional anaplerotic capacity and promote their anabolic metabolism. Recent studies revealed that several types of cancer cells express PC. The gained anaplerotic capability of cells mediated by PC correlates with their expedited growth, higher aggressiveness, and increased metastatic potential. By immunohistochemical staining and immunoblotting analysis, we investigated PC expression among samples of different types of human brain tumors. Our results show that PC is expressed by the cells in glioblastoma, astrocytoma, oligodendroglioma, and meningioma tumors. The presence of PC in these tumors suppose that PC could support the anabolic metabolism of their cellular constituents by its anaplerotic capability. [ABSTRACT FROM AUTHOR]

Introduction: Gliomas, being the most common Central Nervous System (CNS) neoplasms, are broadly divided into astrocytomas, oligodendrogliomas and ependymomas. World Health Organisation (WHO) 2016 criteria incorporated Immunohistochemistry (IHC), molecular diagnostic techniques and histological tumour grading into its diagnostic criteria. Isocitrate Dehydrogenase (IDH1) mutations are commonly seen in young people with good prognostic implications. The detection of Tumor Protein53 (p53) mutations in gliomas and its association with the grade of the tumour can be used as a diagnostic, prognostic and therapeutic tool for better survival in affected individuals. IHC can be used as surrogate markers in detecting the mutational status of IDH1 and p53. Aim: To study the expression of IDH1 and p53 mutations in gliomas and to evaluate its association with known clinicopathological variables. Materials and Methods: This cross-sectional, retrospective, analytical study was conducted in the Department of Pathology at JSSAHER, Mysuru, Karnataka, India. The duration of the study was three years and 11 months, from October 2018 to September 2022. All histopathologically diagnosed glioma cases, who underwent surgery, were appropriately reviewed and graded. IHC was performed for the detection of IDH1mutational status and p53 expression. The tumour was labelled as, IDH1 positive with cytoplasmic staining and p53 positive when nuclear staining was observed in more than 5% of tumour cells. The p53 expression was further quantified in scores as low =8 and high >8 score. The associations of clinicopathological variables and the comparison of the scores of p53 mutation across various categories of gliomas were analysed statistically. The data was analysed using Statistical package for Social Sciences (SPSS) version 26.0. Results: The mean age of the study participants was 42.6 years with the standard deviation of 12.8 years. A total of 35 cases (20 males and 15 females) were analysed. The maximum number of cases was in the age group of 31-40 years (n=13) followed by 41-50 years of age group (n=11). Three of them were seen in age less than 20 years. The male: female ratio was 1.33:1. Out of total cases, 20 cases showed IDH1 positivity, 11 cases showed high p53 expression and five cases demonstrated both IDH1 positivity and high expression of p53. A statistically significant association (p-value=0.014) was seen between the grade of the tumour and p53 immunoreaction. Conclusion: The present study of the detection of IDH1 and p53 mutations, could provide reliable information for improved tailoring of patient therapy as study revealed that, there was a significant association of p53 expression with the grade of the tumour with low expression in low grade gliomas and high p53 expression in high grade gliomas. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to investigate the clinical utility of the sinuous, wave-like intratumoral-wall (SWITW) sign on T2WI in diagnosing isocitrate dehydrogenase (IDH) mutant and 1p/19q codeleted (IDHmut-Codel) oligodendrogliomas, for which a relatively conservative resection strategy might be sufficient due to a better response to chemoradiotherapy and favorable prognosis. Methods: Imaging data from consecutive adult patients with diffuse lower-grade gliomas (LGGs, histological grades 2–3) in Beijing Tiantan Hospital (December 1, 2013, to October 31, 2021, BTH set, n = 711) and the Cancer Imaging Archive (TCIA) LGGs set (n = 117) were used to develop and validate our findings. Two independent observers assessed the SWITW sign and some well-reported discriminative radiological features to establish a practical diagnostic strategy. Results: The SWITW sign showed satisfying sensitivity (0.684 and 0.722 for BTH and TCIA sets) and specificity (0.938 and 0.914 for BTH and TCIA sets) in defining IDHmut-Codels, and the interobserver agreement was substantial (κ 0.718 and 0.756 for BTH and TCIA sets). Compared to calcification, the SWITW sign improved the sensitivity by 0.28 (0.404 to 0.684) in the BTH set, and 81.0% (277/342) of IDHmut-Codel cases demonstrated SWITW and/ or calcification positivity. Combining the SWITW sign, calcification, low ADC values, and other discriminative features, we established a concise and reliable diagnostic protocol for IDHmut-Codels. Conclusions: The SWITW sign was a sensitive and specific imaging biomarker for IDHmut-Codels. The integrated protocol provided an explicable, efficient, and reproducible method for precise preoperative diagnosis, which was essential to guide individualized surgical plan-making. Key Points: • The SWITW sign was a sensitive and specific imaging biomarker for IDHmut-Codel oligodendrogliomas. • The SWITW sign was more sensitive than calcification and an integrated strategy could improve diagnostic sensitivity for IDHmut-Codel oligodendrogliomas. • Combining SWITW, calcification, low ADC values, and other discriminative features could make a precise preoperative diagnosis for IDHmut-Codel oligodendrogliomas. [ABSTRACT FROM AUTHOR]

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Introduction: Gliomas, being the most common Central Nervous System (CNS) neoplasms, are broadly divided into astrocytomas, oligodendrogliomas and ependymomas. World Health Organisation (WHO) 2016 criteria incorporated Immunohistochemistry (IHC), molecular diagnostic techniques and histological tumour grading into its diagnostic criteria. Isocitrate Dehydrogenase (IDH1) mutations are commonly seen in young people with good prognostic implications. The detection of Tumor Protein53 (p53) mutations in gliomas and its association with the grade of the tumour can be used as a diagnostic, prognostic and therapeutic tool for better survival in affected individuals. IHC can be used as surrogate markers in detecting the mutational status of IDH1 and p53. Aim: To study the expression of IDH1 and p53 mutations in gliomas and to evaluate its association with known clinicopathological variables. Materials and Methods: This cross-sectional, retrospective, analytical study was conducted in the Department of Pathology at JSSAHER, Mysuru, Karnataka, India. The duration of the study was three years and 11 months, from October 2018 to September 2022. All histopathologically diagnosed glioma cases, who underwent surgery, were appropriately reviewed and graded. IHC was performed for the detection of IDH1mutational status and p53 expression. The tumour was labelled as, IDH1 positive with cytoplasmic staining and p53 positive when nuclear staining was observed in more than 5% of tumour cells. The p53 expression was further quantified in scores as low ≤8 and high >8 score. The associations of clinicopathological variables and the comparison of the scores of p53 mutation across various categories of gliomas were analysed statistically. The data was analysed using Statistical package for Social Sciences (SPSS) version 26.0. Results: The mean age of the study participants was 15.3 years. A total of 35 cases (20 males and 15 females) were analysed. The maximum number of cases was in the age group of 31-40 years (n=13) followed by 41-50 years of age group (n=11). Three of them were seen in age less than 20 years. The male: female ratio was 1.33:1. Out of total cases, 20 cases showed IDH1 positivity, 12 cases showed high p53 expression and six cases demonstrated both, IDH1 positivity and high expression of p53. A statistically significant association (p-value=0.014) was seen between the grade of the tumour and p53 immunoreaction. Conclusion: The present study of the detection of IDH1 and p53 mutations, could provide reliable information for improved tailoring of patient therapy as study revealed that, there was a significant association of p53 expression with the grade of the tumour with low expression in low grade gliomas and high p53 expression in high grade gliomas.

Molecular profiling of gliomas helps ensure diagnostic accuracy, inform prognosis, and identify treatment options. This review aims to show that with next generation sequencing (NGS) the diagnosis of patients with oligodendrogliomas can be more accurate. In addition, with an in vitro diagnostic device, based on NSG (F1CDx), in which glioma paraffin blocks are used to analyze up to 395 cancer-related genes (including IDH 1 and 2), it is also possible to report the loss of the entire short arm of chromosome 1 and the long arm of chromosome 19 (1p/19q codeletion), unlike fluorescence in situ hybridization (FISH) that detects even the slightest deletion, making them sensitive but not specific, as FISH is unable to distinguish between the loss of the entire arm of the chromosome and a focal deletion. This distinction is important since survival is lower in tumors with partial deletion compared to oligodendrogliomas, which by definition have the total loss of both chromosomes. Reference is also made to other genomic platforms such as GlioSeq and GLIO-DNA panel, which can fulfill the same function. In conclusion, the F1CDx can accurately determine 1p/19q with a concordance of 96.7% against FISH. The cases in which the FISH was positive and did not agree with F1CDx, it was because they were not oligodendrogliomas. F1CDx also analyzes all the genes that allow the most accurate approach to the diagnosis of oligodendroglioma. [ABSTRACT FROM AUTHOR]

Astrocytoma and oligodendroglioma are primary brain tumors classified as gliomas. Because there is difference in the prognostic significance of the extent of resection between IDH-mutant astrocytoma and oligodendroglioma, intraoperative differential diagnosis between them provides important information for optimal extent of resection. Although the characteristics of genetic mutations and chromosomal aberrations in both tumors have been reported, there is no molecular diagnostic methods that is able to be used quickly and simply for differentiate the two tumors. Therefore, we aimed to search for biomarker candidates for differentiating them with metabolome analysis using liquid chromatography/tandem mass spectrometry and develop a molecular diagnostic method based on quantitative analysis. We searched for peaks that differed in two types of gliomas using global metabolomics. Next, we identified five biomarker candidates as hypoxanthine, inosine, cystine, proline and uric acid, respectively. Next, we developed an LC/MS/MS analytical method for five biomarker candidates and quantified them in brain tumors. Cystine had significantly lower amounts in astrocytomas than in oligodendrogliomas. We developed two prediction models for differentiation of the two gliomas and validated them using the separated two dataset. The logistic regression model with only cystine provided the best prediction performance. It was suggested that mass spectrometric analysis of cystine in surgery might be useful for differentiating astrocytoma and oligodendroglioma with 91.7% positive prediction value and 80.0% specificity whereas negative predictive value and sensitivity was lesser than 70%, so that further exploration for unknown metabolite is mandatory. [ABSTRACT FROM AUTHOR]

Oligodendrogliomas (ODGs) are neuroepithelial tumors that need personalized treatment plans because of their unique molecular and histological features. Non-coding RNAs form an epigenetic class of molecules that act as the first steps in gene regulation. They consist of microRNAs, long non-coding RNAs, and circular RNAs. These molecules significantly participate in ODG pathogenesis by regulating ODG initiation, progression, and treatment response. This review is designated to analyze the literature and describe the genomic profile of ODGs, the complex actions of ncRNAs in ODGs pathogenesis and treatment, and their roles as appropriate biomarkers and as one of the precision mechanisms action targets, such as antisense oligonucleotides, small interfering RNAs, gene therapy vectors, peptide nucleic acids, and small molecule inhibitors. Overall, ncRNAs considerably alter the pathological spectrum of ODGs by influencing fundamental processes in tumor biology. Applying ncRNAs in a clinical context exhibits promise for enhanced diagnosis and individualized therapeutic interventions. Nevertheless, the delivery efficacy and potential adverse "off-target" sequels retain the main obstacles undermining clinical potential. Continuous research and technological advancements in ncRNAs offer new insights and promising prospects for revolutionizing oligodendroglioma care, leading to better, personalized treatment outcomes. [ABSTRACT FROM AUTHOR]

Summary: Background: Human oligodendroglioma presents as a heterogeneous disease, primarily characterized by the isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion. Therapy development for this tumor is hindered by incomplete knowledge of somatic driving alterations and suboptimal disease classification. We herein aim to identify intrinsic molecular subtypes through integrated analysis of transcriptome, genome and methylome. Methods: 137 oligodendroglioma patients from the Cancer Genome Atlas (TCGA) dataset were collected for unsupervised clustering analysis of immune gene expression profiles and comparative analysis of genome and methylome. Two independent datasets containing 218 patients were used for validation. Findings: We identified and independently validated two reproducible subtypes associated with distinct molecular characteristics and clinical outcomes. The proliferative subtype, named Oligo1, was characterized by more tumors of CNS WHO grade 3, as well as worse prognosis compared to the Oligo2 subtype. Besides the clinicopathologic features, Oligo1 exhibited enrichment of cell proliferation, regulation of cell cycle and Wnt signaling pathways, and significantly altered genes, such as EGFR, NOTCH1 and MET. In contrast, Oligo2, with favorable outcome, presented increased activation of immune response and metabolic process. Higher T cell/APC co-inhibition and inhibitory checkpoint levels were observed in Oligo2 tumors. Finally, multivariable analysis revealed our classification was an independent prognostic factor in oligodendrogliomas, and the robustness of these molecular subgroups was verified in the validation cohorts. Interpretation: This study provides further insights into patient stratification as well as presents opportunities for therapeutic development in human oligodendrogliomas. Funding: The funders are listed in the Acknowledgement.

Oligodendrogliomas are typically associated with the most favorable prognosis among diffuse gliomas. However, many of the tumors progress, eventually leading to patient death. To characterize the changes associated with oligodendroglioma recurrence and progression, we analyzed two recurrent oligodendroglioma tumors upon diagnosis and after tumor relapse based on whole-genome and RNA sequencing. Relapsed tumors were diagnosed as glioblastomas with an oligodendroglioma component before the World Health Organization classification update in 2016. Both patients died within 12 months after relapse. One patient carried an inactivating POLE mutation leading to a clearly hypermutated progressed tumor. Strikingly, both relapsed tumors carried focal chromosomal rearrangements in PTPRD and CNTNAP2 genes with associated decreased gene expression. TP53 mutation was also detected in both patients after tumor relapse. In The Cancer Genome Atlas (TCGA) diffuse glioma cohort, PTPRD and CNTNAP2 expression decreased by tumor grade in oligodendrogliomas and PTPRD expression also in IDH-mutant astrocytomas. Low expression of the genes was associated with poor overall survival. Our analysis provides information about aggressive oligodendrogliomas with worse prognosis and suggests that PTPRD and CNTNAP2 expression could represent an informative marker for their stratification. [ABSTRACT FROM AUTHOR]

The majority of oligodendrogliomas exhibit an intrinsic tendency to develop into malignant high-grade tumors. Angiogenesis is a major factor contributing to the malignant transformation of oligodendroglioma, and its molecular regulatory mechanism needs further study. We provide a case report of an oligodendroglioma patient with two recurrences whose disease progressed from WHO grade II to grade III. We showed that the expression of insulin gene enhancer protein (ISL2) and its angiogenic ability were positively correlated with the progression of oligodendroglioma. In Low-grade glioma (LGG) patients, including oligodendroglioma patients, overexpression of ISL2 was correlated with poor prognosis, and this correlation was not affected by gender or isocitrate dehydrogenase 1(IDH1) mutation status. ISL2 expression and ISL2-mediated angiogenic pathway activity are ideal biomarkers for the malignant transformation of oligodendroglioma. Anti-ISL2 therapy is also a potential treatment option for malignantly transformed oligodendroglioma. [ABSTRACT FROM AUTHOR]

Pilocytic astrocytoma with a predominant oligodendrocyte-like component can be difficult to distinguish from oligodendroglioma, dysembryoplastic neuroepithelial tumors (DNTs), central neurocytoma, and ependymoma (clear cell phenotype). The utility of GFAP immunostaining in this context is not well discussed. All cases with a diagnosis of pilocytic astrocytoma were retrieved from the pathological archives along with the following information: age, sex, and pathological description. The GFAP immunostaining was scored as score 1 (<25%), score 2 (25–50%), score 3 (50–75%), and score 4 (>75%). The comparison group included oligodendrogliomas, DNTs, ependymomas, and central neurocytomas. All 26 cases (16 males and 10 females) of pilocytic astrocytoma showed strong and diffuse (score 4) GFAP immunostaining in the neoplastic cells of both the solid fibrillary and oligodendrocyte-like components. The staining pattern in the neoplastic round cells in the oligodendrocyte-like areas was perinuclear cytoplasmic with no processes. In the comparison group, GFAP immunostaining was mostly restricted to the reactive astrocytes in the background. Focal areas of the neoplastic cells showed scores of 1–3 in the neoplastic cells, but the staining pattern was different from those in pilocytic astrocytoma. In the setting of tumors with predominant oligodendrocyte-like areas, the GFAP immunostaining score and pattern help distinguish pilocytic astrocytoma from its mimickers. [ABSTRACT FROM AUTHOR]

Doublecortin (DCX) and neuronal nuclear protein (NeuN) can be used as immunomarkers of neuronal progenitor cells and mature neurons, respectively. Increased DCX immunolabeling has been associated with tumor invasion in human gliomas and anaplastic canine meningiomas. These immunomarkers have not been assessed in feline gliomas. Here we characterized the DCX and NeuN immunohistochemistry (IHC) profile in 11 feline gliomas (7 oligodendrogliomas, 4 astrocytomas). Immunolabeling was classified according to intensity (weak, moderate, strong), distribution of neoplastic cell immunolabeling (1 = <30%, 2 = 30–70%, 3 = >70%), and predominant location within the neoplasm (random or at tumor margins). DCX immunolabeling was strong in 6 cases, weak in 4 cases, and moderate in 1 case. The distribution of DCX immunolabeling was characterized as 1 (4 cases), 2 (4 cases), and 3 (3 cases). DCX immunolabeling occurred predominantly in astrocytomas, which had stronger immunostaining at the tumor margins. NeuN immunolabeling was absent in all cases. Our IHC findings are similar to those reported for DCX and NeuN IHC in canine gliomas. The increased DCX immunolabeling at tumor margins is similar to labeling in invasive human gliomas and anaplastic canine meningiomas. [ABSTRACT FROM AUTHOR]

Background: Diffuse gliomas are the most frequent primary central nervous system (CNS) neoplasms, originating from the parenchyma itself, oligodendrogliomas accounting for approximately 10% of cerebral gliomas. For the past 20 years, the study of genetic/molecular mechanisms of glioma genesis and progression has gradually come into focus. However, the biological and clinical significance of these mutations are still to be completely characterized. The purpose of this article is to describe our clinical experience with oligodendrogliomas and to review the current literature, in order to better describe the characteristics of the molecular/genetic oligodendroglioma subgroups. Methods: We performed a single-institution retrospective study that included 66 patients with oligodendrogliomas operated in our department between January 2011 and December 2018. Results: Our study included 26 female patients (39%) and 40 male patients (59%). The mean age at presentation was 39.9year-old (range 26-59year-old). The tumours were located predominantly in the right hemisphere (53%), the majority being situated in the frontal lobe (59%). 64% of the patients had signs of mass effect on the imaging studies, 13% presented with brain herniation syndromes, and 16 % of the surgically treated patients had a relapse with regrowth and malignant transformation of the tumour. The most common complaint that the patients had at admission was a headache. Seizures were the second most common symptom that determined the patients to seek medical attention. Conclusion: The expanding knowledge regarding the genetic alterations of oligodendroglial tumours could lead to significant changes in treatment strategies. However, the utility of each particular marker in planning the treatment has yet to be established. Emerging data will, most likely, improve outcome prediction and adjuvant therapy strategies by identifying the patients most likely to benefit from a particular treatment. [ABSTRACT FROM AUTHOR]

Oligodendrogliomas (ODGs) are rare brain tumors in adults, mostly presenting as a supratentorial solid mass, while less than 10% occur infratentorially. Infratentorial cystic ODGs are extremely rare. We reported a large partially cystic cerebellar ODG in a 31‐week pregnant patient with an unusual presentation and discussed the challenging management. [ABSTRACT FROM AUTHOR]

Introduction: Isocitrate dehydrogenase (IDH) mutations are disease-defining mutations in IDH-mutant astrocytomas and IDH-mutant and 1p/19q-codeleted oligodendrogliomas. In more than 80% of these tumors, point mutations in IDH type 1 (IDH1) lead to expression of the tumor-specific protein IDH1R132H. IDH1R132H harbors a major histocompatibility complex class II (MHCII)-restricted neoantigen that was safely and successfully targeted in a first-in human clinical phase 1 trial evaluating an IDH1R132H 20-mer peptide vaccine (IDH1-vac) in newly diagnosed astrocytomas concomitant to standard of care (SOC). Methods: AMPLIFY-NEOVAC is a randomized, 3-arm, window-of-opportunity, multicenter national phase 1 trial to assess safety, tolerability and immunogenicity of IDH1-vac combined with avelumab (AVE), an immune checkpoint inhibitor (ICI) targeting programmed death-ligand 1 (PD-L1). The target population includes patients with resectable IDH1R132H-mutant recurrent astrocytoma or oligodendroglioma after SOC. Neoadjuvant and adjuvant immunotherapy will be administered to 48 evaluable patients. In arm 1, 12 patients will receive IDH1-vac; in arm 2, 12 patients will receive the combination of IDH1-vac and AVE, and in arm 3, 24 patients will receive AVE only. Until disease progression according to immunotherapy response assessment for neuro-oncology (iRANO) criteria, treatment will be administered over a period of maximum 43 weeks (primary treatment phase) followed by facultative maintenance treatment. Perspective: IDH1R132H 20-mer peptide is a shared clonal driver mutation-derived neoepitope in diffuse gliomas. IDH1-vac safely targets IDH1R132H in newly diagnosed astrocytomas. AMPLIFY-NEOVAC aims at (1) demonstrating safety of enhanced peripheral IDH1-vac-induced T cell responses by combined therapy with AVE compared to IDH1-vac only and (2) investigating intra-glioma abundance and phenotypes of IDH1-vac induced T cells in exploratory post-treatment tissue analyses. In an exploratory analysis, both will be correlated with clinical outcome. Trial registration: NCT03893903. [ABSTRACT FROM AUTHOR]

Background The optimal chemotherapy regimen between temozolomide and procarbazine, lomustine, and vincristine (PCV) remains uncertain for WHO grade 3 oligodendroglioma (Olig3) patients. We therefore investigated this question using national data. Methods Patients diagnosed with radiotherapy-treated 1p/19q-codeleted Olig3 between 2010 and 2018 were identified from the National Cancer Database. The overall survival (OS) associated with first-line single-agent temozolomide vs multi-agent PCV was estimated by Kaplan-Meier techniques and evaluated by multivariable Cox regression. Results One thousand five hundred ninety-six radiotherapy-treated 1p/19q-codeleted Olig3 patients were identified: 88.6% (n = 1414) treated with temozolomide and 11.4% (n = 182) with PCV (from 5.4% in 2010 to 12.0% in 2018) in the first-line setting. The median follow-up was 35.5 months (interquartile range [IQR] 20.7-60.6 months) with 63.3% of patients alive at the time of analysis. There was a significant difference in unadjusted OS between temozolomide (5-year OS 58.9%, 95%CI: 55.6-62.0) and PCV (5-year OS 65.1%, 95%CI: 54.8-73.5; P  = .04). However, a significant OS difference between temozolomide and PCV was not observed in the Cox regression analysis adjusted by age and extent of resection (PCV vs temozolomide HR 0.81, 95%CI: 0.59-1.11, P  = .18). PCV was more frequently used for younger Olig3s but otherwise was not associated with patient's insurance status or care setting. Conclusions In a national analysis of Olig3s, first-line PCV chemotherapy was associated with a slightly improved unadjusted short-term OS compared to temozolomide; but not following adjustment by patient age and extent of resection. There has been an increase in PCV utilization since 2010. These findings provide preliminary data while we await the definitive results from the CODEL trial. [ABSTRACT FROM AUTHOR]

Gliomas are the most frequent primary tumors of the brain. They can be divided into grade II-IV astrocytomas and grade II-III oligodendrogliomas, based on their histomolecular profile. The prognosis and treatment is highly dependent on grade and well-identified prognostic and/or predictive molecular markers. Multi-parametric MRI, including diffusion weighted imaging, perfusion, and MR spectroscopy, showed increasing value in the non-invasive characterization of specific molecular subsets of gliomas. Radiolabeled amino-acid analogues, such as 18F-FET, have also been proven valuable in glioma imaging. These tracers not only contribute in the diagnostic process by detecting areas of dedifferentiation in diffuse gliomas, but this technique is also valuable in the follow-up of gliomas, as it can differentiate pseudo-progression from real tumor progression. Since multi-parametric MRI and 18F-FET PET are complementary imaging techniques, there may be a synergistic role for PET-MRI imaging in the neuro-oncological imaging of primary brain tumors. This could be of value for both primary staging, as well as during treatment and follow-up. [ABSTRACT FROM AUTHOR]

Medical image processing and its quantitative analysis plays a vital role in several clinical scenarios, such as diagnosis as well as treatment. The results of this study show that there are 478 mRNAs differentially expressed in low grade as compared to anaplastic oligodendroglial tumor (2 Fold greater, p

Background: Diffuse gliomas are the most frequent primary central nervous system (CNS) neoplasms, originating from the parenchyma itself, oligodendrogliomas accounting for approximately 10% of cerebral gliomas. For the past 20 years, the study of genetic/molecular mechanisms of glioma genesis and progression has gradually come into focus. However, the biological and clinical significance of these mutations are still to be completely characterized. The purpose of this article is to describe our clinical experience with oligodendrogliomas and to review the current literature, in order to better describe the characteristics of the molecular/genetic oligodendroglioma subgroups. Methods: We performed a single-institution retrospective study that included 66 patients with oligodendrogliomas operated in our department between January 2011 and December 2018. Results: Our study included 26 female patients (39%) and 40 male patients (59%). The mean age at presentation was 39.9year-old (range 26-59year-old). The tumours were located predominantly in the right hemisphere (53%), the majority being situated in the frontal lobe (59%). 64% of the patients had signs of mass effect on the imaging studies, 13% presented with brain herniation syndromes, and 16 % of the surgically treated patients had a relapse with regrowth and malignant transformation of the tumour. The most common complaint that the patients had at admission was a headache. Seizures were the second most common symptom that determined the patients to seek medical attention. Conclusion: The expanding knowledge regarding the genetic alterations of oligodendroglial tumours could lead to significant changes in treatment strategies. However, the utility of each particular marker in planning the treatment has yet to be established. Emerging data will, most likely, improve outcome prediction and adjuvant therapy strategies by identifying the patients most likely to benefit from a particular treatment.

Oligodendrogliomas are defined at the molecular level by the presence of an IDH mutation and codeletion of chromosomal arms 1p and 19q. In the past, case reports and small studies described gliomas with sarcomatous features arising from oligodendrogliomas, so called oligosarcomas. Here, we report a series of 24 IDH-mutant oligosarcomas from 23 patients forming a distinct methylation class. The tumors were recurrences from prior oligodendrogliomas or developed de novo. Precursor tumors of 12 oligosarcomas were histologically and molecularly indistinguishable from conventional oligodendrogliomas. Oligosarcoma tumor cells were embedded in a dense network of reticulin fibers, frequently showing p53 accumulation, positivity for SMA and CALD1, loss of OLIG2 and gain of H3K27 trimethylation (H3K27me3) as compared to primary lesions. In 5 oligosarcomas no 1p/19q codeletion was detectable, although it was present in the primary lesions. Copy number neutral LOH was determined as underlying mechanism. Oligosarcomas harbored an increased chromosomal copy number variation load with frequent CDKN2A/B deletions. Proteomic profiling demonstrated oligosarcomas to be highly distinct from conventional CNS WHO grade 3 oligodendrogliomas with consistent evidence for a smooth muscle differentiation. Expression of several tumor suppressors was reduced with NF1 being lost frequently. In contrast, oncogenic YAP1 was aberrantly overexpressed in oligosarcomas. Panel sequencing revealed mutations in NF1 and TP53 along with IDH1/2 and TERT promoter mutations. Survival of patients was significantly poorer for oligosarcomas as first recurrence than for grade 3 oligodendrogliomas as first recurrence. These results establish oligosarcomas as a distinct group of IDH-mutant gliomas differing from conventional oligodendrogliomas on the histologic, epigenetic, proteomic, molecular and clinical level. The diagnosis can be based on the combined presence of (a) sarcomatous histology, (b) IDH-mutation and (c) TERT promoter mutation and/or 1p/19q codeletion, or, in unresolved cases, on its characteristic DNA methylation profile. [ABSTRACT FROM AUTHOR]

Background Population-based analyses of patterns of care and survival of older patients diagnosed with grade II-III oligodendroglioma (OLI) or astrocytoma (AST) can aid clinicians in their understanding and care of these patients. Methods We identified patients diagnosed between 2006 and 2015 with primary glioma diagnoses (OLI or AST) who were older than 65 years using the latest release of the Surveillance, Epidemiology, and End Results-Medicare–linked database. Medicare claims were used to identify cancer treatments (surgery, chemotherapy, and radiation therapy) from 2006 to 2016. Kaplan-Meier methodology was used to describe overall survival (OS). Cox proportional hazards regression was used to associate variables of interest, including treatments in a time-dependent manner, with OS. Hazard ratios (HRs) and 95% confidence intervals (CIs) from multivariable, cause-specific competing risk models identified associations with treatments. All statistical tests were 2-sided. Results We identified 1291 patients comprising 158 with OLI, 1043 with AST, and 90 with mixed histologies. Median OS was 6.5 (95% CI = 6.1 to 7.3) months for the overall cohort, 22.6 (95% CI = 13.9 to 33.1) months for OLI, and 5.8 (95% CI = 5.3 to 6.4) months for AST. Patients who received surgery and patients who received both chemotherapy and radiation therapy in combination experienced better OS (HR = 0.87, 95% CI = 0.79 to 0.96, and HR = 0.58, 95% CI = 0.35 to 0.96, respectively). Over the time frame studied, there was a 4.0% increase per year in prescription of chemotherapy (P  = .03) and a 2.0% improvement in OS for each calendar year (P  = .003). Conclusions We provide population-based evidence that patients older than 65 years with grade II-III glioma have experienced increased chemotherapy use as well as improvement in survival over time. [ABSTRACT FROM AUTHOR]

Background: Oligodendrogliomas are generally low-grade glial neoplasms commonly occurring in a cortical or subcortical location and frequently contain coarse calcifications. Tumors with 1p and 19q codeletions behave atypically and are more likely to have ill-defined margins and tend to have calcification. Very rarely, diffuse pattern and gliomatosis type of infiltrative nature of oligodendrogliomas have been described in sporadic case reports. Case Description: In this article, we present a case of a 31-year-old male who had diffuse multifocal oligodendroglioma with rare features of extensive callosal and brainstem involvement on imaging. Conclusion: Rare cases of oligodendrocytic gliomatosis cerebri or oligodendrogliomatosis with diffuse white matter spread of these tumors usually lead to a detrimental course of neurological status and a poor prognosis in these patients. [ABSTRACT FROM AUTHOR]

Abstract Background Low‐grade gliomas (LGGs) are primary diffuse slow‐growing brain tumors derived from glial cells. The management of these tumors is dependent on their location, which often harbors eloquent areas. We retrospectively recorded the location of diffuse gliomas to identify whether specific differences exist between the histological types. Methods We analyzed 102 patients with previous histological diagnosis of WHO‐II astrocytomas (62) and WHO‐II oligodendrogliomas (40) according to WHO‐2016 classification. MRI sequences (T2‐FLAIR) were used for tumor volume segmentation and to create a frequency map of their locations within the Montreal Neurological Institute (MNI) space. The Brain‐Grid (BG) system (standardized radiological tool of intersected lines according to anatomical landmarks) was created and merged with a tractography atlas for infiltration analysis. Results Astrocytomas frequently infiltrated association and projection white matter pathways within fronto‐temporo‐insular regions on the left side. Oligodendrogliomas infiltrated larger white matter networks (association‐commissural‐projection) of the frontal lobe bilaterally. A critical number of infiltrated BG voxels (7 for astrocytomas, 10 for oligodendrogliomas) significantly predicted shorter overall survival (OS) in both groups. Bilateral tumor extension in astrocytomas and preoperative tumor volume in oligodendrogliomas were independent prognostic factors for shorter OS. Conclusions Astrocytomas and oligodendrogliomas differ in preferential location, and this has an impact on the type and the extent of white matter involvement. The number of BG voxels infiltrated reflected different tumor invasiveness and its impact on OS in both groups. All this new information may be valuable in neurosurgical oncology to classify and plan treatment for patients with diffuse gliomas.

Objective: To stratify diffuse gliomas into subtypes including diffuse astrocytomas, oligodendrogliomas and glioblastomas based on recent molecular updates and assess their frequencies in our local subpopulation. Study Design: Cross-sectional study. Place and Duration of Study: Department of Histopathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, from Jun 2015 to Jul 2017 Methodology: Two hundred and fourteen (n=214) cases of adult diffuse gliomas were evaluated. Clinical and morphological features like age, gender and type of tumor were quantified. Molecular studies including IDH 1 by antibody and PCR, ATRX by antibody and 1p/19q co-deletion by FISH were tested. Gliomas were subcategorised based on WHO 2016 guidelines. Results: Mean age of presentation was 39 years. Overall n=146/214 (68.2%) of the cases were completely classifiable including Diffuse Astrocytomas, Oligodendrogliomas and Glioblastomas. Out of the glioblastomas (n=81), 67/81(n=82.7%) were IDH Wild type and 14/81 (17.3%) were IDH Mutant. Conclusion: In this study, glioblastomas are the most frequent gliomas as categorized by current WHO molecular guidelines followed by diffuse astrocytomas. Oligodendrogliomas are the least common.

Abstract Background The medical imaging to differentiate World Health Organization (WHO) grade II (ODG2) from III (ODG3) oligodendrogliomas still remains a challenge. We investigated whether combination of machine leaning with radiomics from conventional T1 contrast-enhanced (T1 CE) and fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) offered superior efficacy. Methods Thirty-six patients with histologically confirmed ODGs underwent T1 CE and 33 of them underwent FLAIR MR examination before any intervention from January 2015 to July 2017 were retrospectively recruited in the current study. The volume of interest (VOI) covering the whole tumor enhancement were manually drawn on the T1 CE and FLAIR slice by slice using ITK-SNAP and a total of 1072 features were extracted from the VOI using 3-D slicer software. Random forest (RF) algorithm was applied to differentiate ODG2 from ODG3 and the efficacy was tested with 5-fold cross validation. The diagnostic efficacy of radiomics-based machine learning and radiologist’s assessment were also compared. Results Nineteen ODG2 and 17 ODG3 were included in this study and ODG3 tended to present with prominent necrosis and nodular/ring-like enhancement (P

Background: Genetic subsets of oligodendrogliomas (OD) have distinct chromosomal and biophysical profiles. Pretherapeutic tumor grade and genotype analysis is a challenging aspect of management, with 1p/19q codeletion status and grade of oligodendroglioma among the most important considerations for clinical decision making. Methodology: Seventy-three patients with histopathological diagnosis of oligodendroglioma were selected, and their preoperative 1.5T magnetic resonance imaging (MRI) scans were reviewed through parameters including diffusion weighted image, susceptibility-weighted imaging, and apparent diffusion coefficient (ADC). These images were correlated with patients' histopathological and chromosomal testing. Tumor border irregularity, homogeneity, contrast enhancement, and other MRI characteristics were also studied. For analysis, descriptive statistics were generated, and normality was evaluated for ADC value, age, and Ki-67 tumor proliferation index. Objectives: The study aimed to determine the correlation of ADC with Ki-67, grade, and 1p/19q co-deletion in oligodendroglioma at a tertiary care hospital within a low-middle income country. Results: Ki-67 tumor proliferation index was high in 33 tumors. It was found to be statistically significant (P = 0.048) with respect to ADC, showing that 1p/19q co-deleted tumors have a difference in their Ki-67 index. Ki-67 also showed a significant relationship (P < 0.05) with grade of OD. However, there was no statistically significant relationship between 1p19q chromosomal co-deletion and ADC. Linear regression was carried out as the data set was continuous. Univariate analysis showed no significant result with all P values above 0.10. Conclusion: Mean ADC is a viable tool to predict Ki-67 and assist prognostic clinical decisions. However, mean ADC alone cannot predict 1p/19q codeletion and tumor grades in OD. Further supplementation with other radiological modalities may provide greater yield and positive results. [ABSTRACT FROM AUTHOR]

Pineal region glioma histologies are fibrillary astrocytoma, pilocytic astrocytoma, anaplastic astrocytoma, glioblastoma, oligodendroglioma, ependymoma, and choroid plexus papilloma. Malignant tumors of the pineal region are difficult to manage. Glioblastomas are rare aggressive tumors that can cause acute hydrocephalus and life-threatening complications in this area. We present a case of pineal region glioblastoma, who diagnosed and treated with neuroendoscopy as well as radiotherapy and chemotherapy. We also provided a literature review specifically focused on neuroendoscopic treatment of the disease with a comparison between those with and without surgical resection. [ABSTRACT FROM AUTHOR]

Infratentorial oligodendrogliomas, a rare pathological entity, are generally considered metastatic lesions from supratentorial primary tumors. Here, we report the case of a 23-year-old man presenting with a histopathologically confirmed right precentral gyrus grade 2 oligodendroglioma and a concurrent pontine grade 3 oligodendroglioma. The pontine lesion was biopsied approximately a year after the biopsy of the precentral lesion due to disease progression despite 4 cycles of procarbazine-CCNU-vincristine (PCV) chemotherapy and stable supratentorial disease. Histology and genetic analysis of the pontine biopsy were consistent with grade 3 oligodendroglioma, and comparison of the two lesions demonstrated common 1p/19q co-deletions and TERT promoter mutations but distinct IDH1 mutations, with a non-canonical IDH1 R132G mutation identified in the infratentorial lesion and a R132H mutation identified in the cortical lesion. Initiation of Temozolomide led to complete response of the supratentorial lesion and durable disease control, while Temozolomide with subsequent radiation therapy of 54 Gy in 30 fractions resulted in partial response of the pontine lesion. This case report supports possible distinct molecular pathogenesis in supratentorial and infratentorial oligodendrogliomas and raises questions about the role of different IDH1 mutant isoforms in explaining treatment resistance to different chemotherapy regimens. Importantly, this case suggests that biopsies of all radiographic lesions, when feasible and safe, should be considered in order to adequately guide management in multicentric oligodendrogliomas. [ABSTRACT FROM AUTHOR]

Objective: Scalp defects may occur following trauma, radiotherapy, oncologic resection, and recurrent surgeries. The hair-bearing scalp has a dual role, which consists of protecting the calvarium and contributing to aesthetic appearance. While the "reconstructive ladder" approach may be used to close small and medium-sized scalp defects, it is not the case for larger ones involving the calvarium or with a radiation therapy history. The aim of this study is to present cases operated due to complex scalp defects, analyze complications, and discuss the choice of reconstruction. Material and Methods: The study consists of 14 patients who were operated between December 2017 and August 2019 due to a complex scalp defect. Patient were evaluated according to age, gender, etiology, radiation therapy history, defect size and location, reconstruction steps, cranioplasty and duraplasty options, type of free flap, recipient artery, vein graft requirement, and complications. Results: The mean age of patients, which consists of 11 men and three women, was 56.7 years. The etiology for scalp defects included basosquamous carcinoma, squamous cell carcinoma, giant basal cell carcinoma, atypical meningioma, glioblastoma multiforme, angiosarcoma, and anaplastic oligodendroglioma. The defect involved the full thickness of calvarium in nine cases and pericranium in five cases. Cranioplasties were made with rib graft (n=1), bone graft (n=1), and titanium mesh (n=7). Free flaps used for reconstruction were musculocutaneous latissimus dorsi (LD) (n=4), LD muscle (n=3), anterolateral thigh (ALT) (n=4), musculocutaneous ALT (n=1), vastus lateralis muscle (1), and rectus abdominis muscle (n=1). Flap loss was not observed. Complications occurred in four of the patients; include a partial graft loss, a wound dehiscence, seroma, and an unsatisfactory esthetic result. Conclusion: Free tissue transfers rather than local flaps should be opted to reconstruct complex scalp defects, as failure of the latter, could create much greater defects, and worse consequences. There are many options for proper reconstruction, and it is essential to select the appropriate one, taking into account the comorbid conditions of each case. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • Single-cell analysis of on-treatment gliomas reveals cellular basis of drug responses • In responders, mutant IDH inhibitors induce lineage differentiation • The differentiation favors astrocytic-like over stem/progenitor-like states • NOTCH1 mutations modify the response and may serve to stratify patients The molecular response of IDH-mutant glioma to mutant IDH inhibitors is poorly understood. Spitzer et al. show that, in patients with clinical response, mutant IDH inhibitors induce lineage differentiation of cancer cells and deplete cells in a stem/progenitor-like state. They further highlight potential modifiers of such differentiation response in glioma. [ABSTRACT FROM AUTHOR]

To evaluate the surgical effect on survival in patients with incidental low-grade glioma (LGG) through comparison between asymptomatic and symptomatic patients. The medical records of surgically treated adult cerebral incidental LGG (iLGG) patients in our department between January 2008 and December 2015 were retrospectively reviewed. The survival of patients was calculated starting from the initial imaging diagnosis. Factors related to progression-free survival (PFS), overall survival (OS) and malignant progression-free survival (MPFS) were statistically analyzed. Seventy-five iLGG patients underwent surgery: 49 in the asymptomatic group, who underwent surgery in the asymptomatic period, and 26 in the symptomatic group, who underwent surgery after the tumor had grown and the patients had developed tumor-related symptoms. Significantly more tumors were initially located adjacent to the functional area in the symptomatic group than in the asymptomatic group (P < 0.05), but there was no significant difference in the total resection rate between the two groups. The incidence of postoperative complications (15.4%) and postoperative epilepsy (23.1%) was higher in the symptomatic group than in the asymptomatic group (4.1% and 10.2%, respectively). Multivariate analysis showed that surgical timing, namely, surgery performed before or after symptom occurrence, had no significant effect on PFS, OS or MPFS, while total resection significantly prolonged PFS, OS and MPFS, and the pathology of oligodendroglioma was positively correlated with PFS and OS (P < 0.05). Surgical timing for iLGGs should facilitate total resection. If total resection can be achieved, even after symptom occurrence, patients can achieve comparable survival benefits to those treated with surgery in the asymptomatic phase. [ABSTRACT FROM AUTHOR]

Purpose: Magnetic resonance image (MRI) guided radiation therapy has the potential to improve outcomes for glioblastoma by adapting to tumor changes during radiation therapy. This study quantifies interfraction dynamics (tumor size, position, and geometry) based on sequential magnetic resonance imaging scans obtained during standard 6-week chemoradiation.Methods and Materials: Sixty-one patients were prospectively imaged with gadolinium-enhanced T1 (T1c) and T2/FLAIR axial sequences at planning (Fx0), fraction 10 (Fx10), fraction 20 (Fx20), and 1 month after the final fraction of chemoradiation therapy (P1M). Gross tumor volumes (GTVs) and clinical target volumes (CTVs) were contoured at all time points. Target dynamics were quantified by absolute volume (V), volume relative to Fx0 (Vrel), and the migration distance (dmigrate; the linear displacement of the GTV or CTV relative to Fx0). Temporal changes were assessed using a linear mixed-effects model.Results: Median volumes at Fx0, Fx10, Fx20, and P1M for the GTV were 18.4 cm3 (range, 1.1-110.5 cm3), 14.7 cm3 (range, 0.9-115.1 cm3), 13.7 cm3 (range, 0.6-174.2 cm3), and 13.0 cm3 (range, 0.9-76.3 cm3), respectively, with corresponding median Vrel of 0.88 at Fx10, 0.77 at Fx20, and 0.71 at P1M relative to Fx0 (P < .001 for all). The GTV (CTV) migration distances were greater than 5 mm in 46% (54%) of patients at Fx10, 50% (58%) of patients at Fx20, and 52% (57%) of patients at P1M. Dynamic tumor morphologic changes were observed, with 40% of patients exhibiting a decreased GTV (Vrel ≤1) with a dmigrate >5 mm during chemoradiation therapy.Conclusions: Clinically meaningful tumor dynamics were observed during chemoradiation therapy for glioblastoma, supporting evaluation of daily MRI guided radiation therapy and treatment plan adaptation. [ABSTRACT FROM AUTHOR]