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Neurology May 2024Patients with -mutant lower-grade glioma have a high frequency of seizures. We aimed to investigate the correlations between seizures and tumor/patient characteristics...
BACKGROUND AND OBJECTIVES
Patients with -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 -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 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 -mutant/1p19q-codeleted grade 2 and 3 oligodendroglioma and 30 (20%) and 12 (8%) with -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, = 0.008), 6 months after AT (OR 9.0, 1.5-54.9, = 0.017), and 6 months after treatment of recurrence (OR 4.9, 1.5-16.5, = 0.009). Adjuvant radiotherapy reduced seizures at recurrence in a univariate analysis (OR 0.14, 0.03-0.7, = 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, = 0.037).
DISCUSSION
This study analyzed seizure control in patients with 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 -mutant lower-grade glioma.
Topics: Humans; Isocitrate Dehydrogenase; Male; Female; Brain Neoplasms; Middle Aged; Seizures; Glioma; Retrospective Studies; Adult; Mutation; Aged; Oligodendroglioma; Neoplasm Grading; Astrocytoma
PubMed: 38684041
DOI: 10.1212/WNL.0000000000209352 -
World Neurosurgery Apr 2024Anaplastic oligodendroglioma (AOD) is a rare high-grade central nervous system tumor. The current research on prognostic prediction of AOD remains limited. This study...
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.
PubMed: 38677647
DOI: 10.1016/j.wneu.2024.04.111 -
Biology Mar 2024Gliomas have displayed significant challenges in oncology due to their high degree of invasiveness, recurrence, and resistance to treatment strategies. In this work, the...
Gliomas have displayed significant challenges in oncology due to their high degree of invasiveness, recurrence, and resistance to treatment strategies. In this work, the key hub genes mainly associated with different grades of glioma, which were represented by pilocytic astrocytoma (PA), oligodendroglioma (OG), anaplastic astrocytoma (AA), and glioblastoma multiforme (GBM), were identified through weighted gene co-expression network analysis (WGCNA) of microarray datasets retrieved from the Gene Expression Omnibus (GEO) database. Through this, four highly correlated modules were observed to be present across the PA (GSE50161), OG (GSE4290), AA (GSE43378), and GBM (GSE36245) datasets. The functional annotation and pathway enrichment analysis done through the Database for Annotation, Visualization, and Integrated Discovery (DAVID) showed that the modules and hub genes identified were mainly involved in signal transduction, transcription regulation, and protein binding, which collectively deregulate several signaling pathways, mainly PI3K/Akt and metabolic pathways. The involvement of several hub genes primarily linked to other signaling pathways, including the cAMP, MAPK/ERK, Wnt/β-catenin, and calcium signaling pathways, indicates potential interconnectivity and influence on the PI3K/Akt pathway and, subsequently, glioma severity. The Drug Repurposing Encyclopedia (DRE) was used to screen for potential drugs based on the up- and downregulated hub genes, wherein the synthetic progestin hormones norgestimate and ethisterone were the top drug candidates. This shows the potential neuroprotective effect of progesterone against glioma due to its influence on EGFR expression and other signaling pathways. Aside from these, several experimental and approved drug candidates were also identified, which include an adrenergic receptor antagonist, a PPAR-γ receptor agonist, a CDK inhibitor, a sodium channel blocker, a bradykinin receptor antagonist, and a dopamine receptor agonist, which further highlights the gene network as a potential therapeutic avenue for glioma.
PubMed: 38666818
DOI: 10.3390/biology13040206 -
Clinical & Translational Oncology :... Apr 2024The 2021 World Health Organization (WHO) classification has updated the definition of grade 2 gliomas and the presence of isocitrate dehydrogenase (IDH) mutation has...
The 2021 World Health Organization (WHO) classification has updated the definition of grade 2 gliomas and the presence of isocitrate dehydrogenase (IDH) mutation has been deemed the cornerstone of diagnosis. Though slow-growing and having a low proliferative index, grade 2 gliomas are incurable by surgery and complementary treatments are vital to improving prognosis. This guideline provides recommendations on the multidisciplinary treatment of grade 2 astrocytomas and oligodendrogliomas based on the best evidence available.
PubMed: 38662171
DOI: 10.1007/s12094-024-03456-x -
Neuroradiology Jun 2024The rarity of IDH2 mutations in supratentorial gliomas has led to gaps in understanding their radiological characteristics, potentially resulting in misdiagnosis based...
PURPOSE
The rarity of IDH2 mutations in supratentorial gliomas has led to gaps in understanding their radiological characteristics, potentially resulting in misdiagnosis based solely on negative IDH1 immunohistochemical staining. We aimed to investigate the clinical and imaging characteristics of IDH2-mutant gliomas.
METHODS
We analyzed imaging data from adult patients with pathologically confirmed diffuse lower-grade gliomas and known IDH1/2 alteration and 1p/19q codeletion statuses obtained from the records of our institute (January 2011 to August 2022, Cohort 1) and The Cancer Imaging Archive (TCIA, Cohort 2). Two radiologists evaluated clinical information and radiological findings using standardized methods. Furthermore, we compared the data for IDH2-mutant and IDH-wildtype gliomas. Multivariate logistic regression was used to identify the predictors of IDH2 mutation status, and receiver operating characteristic curve analysis was employed to assess the predictive performance of the model.
RESULTS
Of the 20 IDH2-mutant supratentorial gliomas, 95% were in the frontal lobes, with 75% classified as oligodendrogliomas. Age and the T2-FLAIR discordance were independent predictors of IDH2 mutations. Receiver operating characteristic curve analysis for the model using age and T2-FLAIR discordance demonstrated a strong potential for discriminating between IDH2-mutant and IDH-wildtype gliomas, with an area under the curve of 0.96 (95% CI, 0.91-0.98, P = .02).
CONCLUSION
A high frequency of oligodendrogliomas with 1p/19q codeletion was observed in IDH2-mutated gliomas. Younger age and the presence of the T2-FLAIR discordance were associated with IDH2 mutations and these findings may help with precise diagnoses and treatment decisions in clinical practice.
Topics: Humans; Isocitrate Dehydrogenase; Male; Female; Glioma; Mutation; Middle Aged; Adult; Supratentorial Neoplasms; Magnetic Resonance Imaging; Aged; Retrospective Studies
PubMed: 38653782
DOI: 10.1007/s00234-024-03361-8 -
Frontiers in Oncology 2024The incidence of cerebral herniation caused by intratumoral hemorrhage (ITH) in cystic oligodendroglioma (COD) is exceedingly rare. This study presents a case of...
The incidence of cerebral herniation caused by intratumoral hemorrhage (ITH) in cystic oligodendroglioma (COD) is exceedingly rare. This study presents a case of cerebral herniation subsequent to cystic oligodendroglioma (COD) and sudden intratumoral hemorrhage. Following initial emergency treatment and evaluation, we successfully circumvented the solid component of the tumor and proceeded with cystic puncture and external drainage to prevent the incidence of brain herniation and mitigate the severity of associated symptoms. Based on preoperative examination results, the cystic glioma was successfully resected, and the patient experienced an uneventful recovery. According to the pathological findings, the oligodendroglioma was classified as World Health Organization (WHO) grade III. The treatment efficacy was comparable to cases of the same pathological grade, in which neither intratumoral hemorrhage nor cerebral hernia was observed.
PubMed: 38634059
DOI: 10.3389/fonc.2024.1295483 -
Frontiers in Oncology 2024Strong interactions between art and health are well-known. While advances in brain surgery resulted in an improved preservation of sensorimotor, visuospatial, language...
BACKGROUND
Strong interactions between art and health are well-known. While advances in brain surgery resulted in an improved preservation of sensorimotor, visuospatial, language and cognitive functions, creative abilities received less attention. However, creativity may represent a critical issue to resume an optimal quality of life, especially in artists. Here, a unique case of sudden change in creative style in a painter who underwent glioma resection is described. This prompts to explore further creative thinking and its clinical implications in routine practice.
METHODS
A 36-year-old right-handed woman experienced inaugural seizures, allowing the discovery of a right frontal lesion. The patient was a professional painter and did not complain about any decline in her creativity. The preoperative neurological examination was normal.
RESULTS
Surgery was achieved with a maximal tumor resection through a frontal lobectomy. A WHO grade II oligodendroglioma was diagnosed. A regular surveillance was performed without adjuvant oncological treatment. The patient did not exhibit postoperative functional deterioration and she returned to normal activities including painting during 15 years. Remarkably, even though her creative activity was judged by the patient herself to be rich and satisfying, her style drastically changed from surrealism and mysticism to cubism whereas she was not able to explain why.
CONCLUSION
This is the first report of acute modification of the painting style following frontal lobectomy for a low-grade glioma, supporting that brain resective surgery may impact creativity. While neglected for many decades, this complex human ability should be evaluated more regularly in neurosurgical practice, particularly in artists.
PubMed: 38606096
DOI: 10.3389/fonc.2024.1394609 -
Frontiers in Neuroscience 2024The 2021 World Health Organization Classification of Central Nervous System Tumors updates glioma subtyping and grading system, and incorporates amplification (Amp) as...
BACKGROUND
The 2021 World Health Organization Classification of Central Nervous System Tumors updates glioma subtyping and grading system, and incorporates amplification (Amp) as one of diagnostic markers for glioblastoma (GBM).
PURPOSE
This study aimed to describe the frequency, clinical value and molecular correlation of Amp in diffuse gliomas based on the latest classification.
METHODS
We reviewed glioma patients between 2011 and 2022 at our hospital, and included 187 adult glioma patients with available tumor tissue for detection of Amp and other 59 molecular markers of interest. Clinical, radiological and pathological data was analyzed based on the status of Amp in different glioma subtypes.
RESULTS
163 gliomas were classified as adult-type diffuse gliomas, and the number of astrocytoma, oligodendroglioma and GBM was 41, 46, and 76. Amp was more common in IDH-wildtype diffuse gliomas (66.0%) and GBM (85.5%) than IDH-mutant diffuse gliomas (32.2%) and its subtypes (astrocytoma, 29.3%; oligodendroglioma, 34.8%). Amp did not stratify overall survival (OS) in IDH-mutant diffuse gliomas and astrocytoma, while was significantly associated with poorer OS in IDH-wildtype diffuse gliomas, histologic grade 2 and 3 IDH-wildtype diffuse astrocytic gliomas and GBM.
CONCLUSION
Our study validated Amp as a diagnostic marker for GBM and still a useful predictor for shortened OS in this group.
PubMed: 38595969
DOI: 10.3389/fnins.2024.1308627 -
World Neurosurgery Jun 2024To clarify the relationships between C-methionine (MET) positron emission tomography (PET) metrics and the histology, genetics, and prognosis of adult-type diffuse...
Association Between Pretreatment C-Methionine Positron Emission Tomography Metrics, Histology, and Prognosis in 125 Newly Diagnosed Patients with Adult-Type Diffuse Glioma Based on the World Health Organization 2021Classification.
OBJECTIVE
To clarify the relationships between C-methionine (MET) positron emission tomography (PET) metrics and the histology, genetics, and prognosis of adult-type diffuse glioma (ADG) based on the World Health Organization (WHO) 2021 classification.
METHODS
A total of 125 newly diagnosed patients with ADG were enrolled. We compared the maximum standardized uptake value (SUVmax), tumor-to-normal background ratio (TNR), metabolic tumor volume (MTV), and total lesion methionine uptake (TLMU) to the histology and genetics of the patients with ADG. We also evaluated the prognoses of the 93 surgically treated patients.
RESULTS
The patients with isocitrate dehydrogenase wild ADG showed significantly higher MET-PET metrics (P < 0.05 for all parameters), significantly shorter overall survival and progression-free survival (P < 0.0001 for both) than those of the patients with isocitrate dehydrogenase mutant (IDHm) ADG. In the IDHm ADG group, the SUVmax, MTV, and TLMU values were significantly higher in patients with IDHm grade (G) 4 astrocytoma than patients with IDHm G2/3 astrocytoma (P < 0.05 for all), but not than patients with G2-3 oligodendroglioma. The progression-free survival was significantly shorter in the patients with G4 astrocytoma versus the patients with G2/3 astrocytoma and G3 oligodendroglioma (P < 0.05 for both). The SUVmax and TNR values were significantly higher in recurrent patients than nonrecurrent patients (P < 0.01 for both), but no significant differences were found in MTV or TLMU values.
CONCLUSIONS
MET-PET metrics well reflect the histological subtype, WHO grade and prognosis of ADG based on the 2021 WHO classification, with the exception of oligodendroglial tumors. Volumetric parameters were not significantly associated with recurrence, unlike the SUVmax and TNR.
Topics: Humans; Methionine; Male; Female; Middle Aged; Adult; Brain Neoplasms; Glioma; World Health Organization; Prognosis; Positron-Emission Tomography; Aged; Isocitrate Dehydrogenase; Young Adult; Carbon Radioisotopes; Retrospective Studies; Tumor Burden
PubMed: 38583563
DOI: 10.1016/j.wneu.2024.03.164 -
Neuropathology : Official Journal of... Apr 2024In 2016, the World Health Organization (WHO) eliminated "oligoastrocytoma" from the classification of central nervous system (CNS) tumors, in favor of an integrated...
In 2016, the World Health Organization (WHO) eliminated "oligoastrocytoma" from the classification of central nervous system (CNS) tumors, in favor of an integrated histologic and molecular diagnosis. Consistent with the 2016 classification, in the 2021 classification, oligodendrogliomas are defined by mutations in isocitrate dehydrogenase (IDH) with concurrent 1p19q codeletion, while astrocytomas are IDH mutant tumors, usually with ATRX loss. In 2007, a 24-year-old man presented with a brain tumor histologically described as astrocytoma, but with molecular studies consistent with an oligodendroglioma, IDH mutant and 1p19q-codeleted. Years later, at resection, pathology revealed an astrocytoma, with variable ATRX expression and mutations of IDH, ATRX, TP53, and TERT by DNA sequencing. Fluorescence in situ hybridization studies confirmed 1p19q codeletion in sections of the tumor shown to histologically retain ATRX expression. Separately, in 2017, a 36-year-old woman presented with a frontal brain tumor with pathology consistent with an oligodendroglioma, IDH mutant and 1p19q-codeleted. Two years later, pathology revealed an astrocytoma, IDH1 mutant, with ATRX loss. These two cases likely represent the rare occurrence of dual-genotype IDH mutant infiltrating glioma. Nine cases of dual-genotype IDH mutant glioma were previously reported in the literature. We present two cases in which this distinct molecular phenotype is present in a tumor in the same location with surgeries at two points in time, both with 1p19q codeletion and ATRX loss at the time of resection. Whether this represents a true "collision tumor" or genetic switching over time is not known, but the co-occurrence of these hybrid mutations supports a diagnosis of dual-genotype IDH mutant glioma.
PubMed: 38581197
DOI: 10.1111/neup.12975