Altered Motor Excitability in Patients With Diffuse Gliomas Involving Motor Eloquent Areas: The Impact of Tumor Grading

Neurosurgery ◽  
2021 ◽  
Vol 89 (Supplement_2) ◽  
pp. S72-S72
Author(s):  
José Pedro Lavrador ◽  
Ifigeneia Gioti ◽  
Szymon Hoppe ◽  
Josephine Jung ◽  
Sabina Patel ◽  
...  
Keyword(s):  
Tumor Grading ◽  
Eloquent Areas ◽  
Diffuse Gliomas ◽  
Motor Excitability ◽  
The Impact

scholarly journals Letter: Altered Motor Excitability in Patients With Diffuse Gliomas Involving Motor Eloquent Areas: The Impact of Tumor Grading

Neurosurgery ◽  
2020 ◽  
Author(s):  
Alexandra Gomes dos Santos ◽  
Cintya Yukie Hayashi ◽  
Cesar Cimonari de Almeida ◽  
Wellingson Silva Paiva ◽  
Daniel Ciampi de Andrade ◽  
...  
Keyword(s):  
Tumor Grading ◽  
Eloquent Areas ◽  
Diffuse Gliomas ◽  
Motor Excitability ◽  
The Impact

scholarly journals TERT promoter mutation confers favorable prognosis regardless of 1p/19q status in adult diffuse gliomas with IDH1/2 mutations

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Hideyuki Arita ◽  
Yuko Matsushita ◽  
Ryunosuke Machida ◽  
Kai Yamasaki ◽  
Nobuhiro Hata ◽  
...  
Keyword(s):  
Cox Regression ◽  
Hazard Ratio ◽  
Prognostic Impact ◽  
Promoter Mutation ◽  
Who Grade ◽  
Favorable Prognosis ◽  
Diffuse Gliomas ◽  
Grade Ii ◽  
Promoter Mutations ◽  
The Impact

AbstractTERT promoter mutations are commonly associated with 1p/19q codeletion in IDH-mutated gliomas. However, whether these mutations have an impact on patient survival independent of 1p/19q codeletion is unknown. In this study, we investigated the impact of TERT promoter mutations on survival in IDH-mutated glioma cases. Detailed clinical information and molecular status data were collected for a cohort of 560 adult patients with IDH-mutated gliomas. Among these patients, 279 had both TERT promoter mutation and 1p/19q codeletion, while 30 had either TERT promoter mutation (n = 24) or 1p/19q codeletion (n = 6) alone. A univariable Cox proportional hazard analysis for survival using clinical and genetic factors indicated that a Karnofsky performance status score (KPS) of 90 or 100, WHO grade II or III, TERT promoter mutation, 1p/19q codeletion, radiation therapy, and extent of resection (90–100%) were associated with favorable prognosis (p < 0.05). A multivariable Cox regression model revealed that TERT promoter mutation had a significantly favorable prognostic impact (hazard ratio = 0.421, p = 0.049), while 1p/19q codeletion did not have a significant impact (hazard ratio = 0.648, p = 0.349). Analyses incorporating patient clinical and genetic information were further conducted to identify subgroups showing the favorable prognostic impact of TERT promoter mutation. Among the grade II-III glioma patients with a KPS score of 90 or 100, those with IDH-TERT co-mutation and intact 1p/19q (n = 17) showed significantly longer survival than those with IDH mutation, wild-type TERT, and intact 1p/19q (n = 185) (5-year overall survival, 94% and 77%, respectively; p = 0.032). Our results demonstrate that TERT promoter mutation predicts favorable prognosis independent of 1p/19q codeletion in IDH-mutated gliomas. Combined with its adverse effect on survival among IDH-wild glioma cases, the bivalent prognostic impact of TERT promoter mutation may help further refine the molecular diagnosis and prognostication of diffuse gliomas.

scholarly journals Molecular Classification of Diffuse Gliomas

2020 ◽  
Vol 47 (4) ◽  
pp. 464-473
Author(s):  
Navya Kalidindi ◽  
Rosemarylin Or ◽  
Sam Babak ◽  
Warren Mason
Keyword(s):  
Dna Methylation ◽  
Molecular Markers ◽  
World Health ◽  
Low Grade ◽  
Diffuse Glioma ◽  
Isocitrate Dehydrogenase 1 ◽  
Anaplastic Gliomas ◽  
Diffuse Gliomas ◽  
The Impact

ABSTRACT:Technological advances in the field of molecular genetics have improved the ability to classify brain tumors into subgroups with distinct clinical features and important therapeutic implications. The World Health Organization’s newest update on classification of gliomas (2016) incorporated isocitrate dehydrogenase 1 and 2 mutations, ATRX loss, 1p/19q codeletion status, and TP53 mutations to allow for improved classification of glioblastomas, low-grade and anaplastic gliomas. This paper reviews current advances in the understanding of diffuse glioma classification and the impact of molecular markers and DNA methylation studies on survival of patients with these tumors. We also discuss whether the classification and grading of diffuse gliomas should be based on histological findings, molecular markers, or DNA methylation subgroups in future iterations of the classification system.

scholarly journals Clinical insights gained by refining the 2016 WHO classification of diffuse gliomas with: EGFR amplification, TERT mutations, PTEN deletion and MGMT methylation

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Cheila Brito ◽  
Ana Azevedo ◽  
Susana Esteves ◽  
Ana Rita Marques ◽  
Carmo Martins ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Promoter Methylation ◽  
Who Classification ◽  
Response To Therapy ◽  
World Health ◽  
Common Diagnosis ◽  
Diffuse Gliomas ◽  
Promoter Mutations ◽  
The Impact

Abstract Background Significant advances in the molecular profiling of gliomas, led the 2016 World Health Organization (WHO) Classification to include, for the first-time, molecular biomarkers in glioma diagnosis: IDH mutations and 1p/19q codeletion. Here, we evaluated the effect of this new classification in the stratification of gliomas previously diagnosed according to 2007 WHO classification. Then, we also analyzed the impact of TERT promoter mutations, PTEN deletion, EGFR amplification and MGMT promoter methylation in diagnosis, prognosis and response to therapy in glioma molecular subgroup. Methods A cohort of 444 adult gliomas was analyzed and reclassified according to the 2016 WHO. Mutational analysis of IDH1 and TERT promoter mutations was performed by Sanger sequencing. Statistical analysis was done using SPSS Statistics 21.0. Results The reclassification of this cohort using 2016 WHO criteria led to a decrease of the number of oligodendrogliomas (from 82 to 49) and an increase of astrocytomas (from 49 to 98), while glioblastomas (GBM) remained the same (n = 256). GBM was the most common diagnosis (57.7%), of which 55.2% were IDH-wildtype. 1p/19q codeleted gliomas were the subgroup associated with longer median overall survival (198 months), while GBM IDH-wildtype had the worst outcome (10 months). Interestingly, PTEN deletion had poor prognostic value in astrocytomas IDH-wildtype (p = 0.015), while in GBM IDH-wildtype was associated with better overall survival (p = 0.042) as well as MGMT promoter methylation (p = 0.009). EGFR amplification and TERT mutations had no impact in prognosis. Notably, EGFR amplification predicted a better response to radiotherapy (p = 0.011) and MGMT methylation to chemo-radiotherapy (p = 0.003). Conclusion In this study we observed that the 2016 WHO classification improved the accuracy of diagnosis and prognosis of diffuse gliomas, although the available biomarkers are not enough. Therefore, we suggest MGMT promoter methylation should be added to glioma classification. Moreover, we found two genetic/clinical correlations that must be evaluated to understand their impact in the clinical setting: i) how is PTEN deletion a favorable prognostic factor in GBM IDH wildtype and an unfavorable prognostic factor in astrocytoma IDH wildtype and ii) how EGFR amplification is an independent and strong factor of response to radiotherapy.

Altered Motor Excitability in Patients With Diffuse Gliomas Involving Motor Eloquent Areas: The Impact of Tumor Grading

Neurosurgery ◽  
2020 ◽  
Vol 88 (1) ◽  
pp. 183-192 ◽  
Author(s):  
José Pedro Lavrador ◽  
Ifigeneia Gioti ◽  
Szymon Hoppe ◽  
Josephine Jung ◽  
Sabina Patel ◽  
...  
Keyword(s):  
Lower Limb ◽  
World Health ◽  
Grading System ◽  
Low Grade ◽  
Wild Type ◽  
Who Grade ◽  
Adjusted Analysis ◽  
Eloquent Areas ◽  
Diffuse Gliomas ◽  
Unadjusted Analysis

Abstract BACKGROUND Diffuse gliomas have an increased biological aggressiveness across the World Health Organization (WHO) grading system. The implications of glioma grading on the primary motor cortex (M1)-corticospinal tract (CST) excitability is unknown. OBJECTIVE To assess the excitability of the motor pathway with navigated transcranial magnetic stimulation (nTMS). METHODS Retrospective cohort study of patients admitted for surgery with diffuse gliomas within motor eloquent areas. Demographic, clinical, and nTMS-related variables were collected. The Cortical Excitability Score (CES 0 to 2 according to the number of abnormal interhemispheric resting motor threshold (RMT) ratios) was calculated for patients where bilateral upper and lower limb mapping was performed. RESULTS A total of 45 patients were included: 9 patients had a low-grade glioma and 36 patients had a high-grade glioma. The unadjusted analysis revealed an increase in the latency of the motor evoked potential of the lower limb with an increase of the WHO grade (P = .038). The adjusted analysis confirmed this finding (P = .013) and showed a relation between the increase in the WHO and a decreased RMT (P = .037) of the motor evoked responses in the lower limb. When CES was calculated, an increase in the score was related with an increase in the WHO grade (unadjusted analysis—P = .0001; adjusted analysis—P = .001) and in isocitrate dehydrogenase (IDH) wild-type tumors (unadjusted analysis—P = .020). CONCLUSION An increase in the WHO grading system and IDH wild-type tumors are associated with an abnormal excitability of the motor eloquent areas in patients with diffuse gliomas.

scholarly journals SURG-14. AWAKE CRANIOTOMY VS CRANIOTOMY UNDER GENERAL ANESTHESIA FOR GLIOBLASTOMAS: EVALUATING THE IMPACT ON OVERALL SURVIVAL AND RISK OF RECURRENCE

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii206-ii206
Author(s):  
Mario Moro
Keyword(s):  
Overall Survival ◽  
General Anesthesia ◽  
Tumor Resection ◽  
Extent Of Resection ◽  
Neurological Deficits ◽  
Awake Surgery ◽  
Tumor Control ◽  
Risk Of Recurrence ◽  
Eloquent Areas ◽  
The Impact

Abstract Maximum safe resection for eloquent glioblastomas (GBMs) is the maximum tumor resection achievable without causing neurological deficits. Although challenging, it must be considered the therapeutic target for GBMs. Indeed, the extension of resection positively correlates with the overall survival and recurrences risk. Awake surgery (AS) has become paramount for achieving maximum safe resection for tumors in eloquent areas. However, there is not a unanimous consensus on the extent of resection of eloquent GBMs, especially for what concerns the so-called supratotal resection (i.e.: resection over the contrast-enhancing limits of the lesion). Recently, several studies focused their attention on the residual tumor volume as estimated from T1-contrast enhanced sequences, but few analyzed the outcomes of patients with a more extended resection. Some authors speculated that increased surgical aggressiveness, thus removing peritumoral edematous area, correlates with improved overall survival and tumor control, without increasing adverse events rates. This study aimed to assess, through quantitative volumetric analysis, the outcomes of a prospectively collected cohort of patients with primary GBM located in eloquent areas. We furtherly subdivided our population into two treatment groups: awake surgery (AS) and general anesthesia (GA) craniotomies. We analyzed the overall outcomes, especially for what concerns MRI T2-Flair signal extent of resection, related to patients’ survival and recurrences formation. Eventually, we stratified our analysis by type of treatment (awake surgery vs. general anesthesia) to rule out any significant differences in survival and postoperative GBMs behaviors. Our data confirmed extensive that T2-Flair resection (EOR≥30%) and AS could improve overall survival and reduce risk of recurrence without, at the same time, causing an increase of surgical and medical complications

Formation of Lunar Craters and Bright Rays as a Result of Meteorite Impacts

1962 ◽  
Vol 14 ◽  
pp. 415-418
Author(s):  
K. P. Stanyukovich ◽  
V. A. Bronshten
Keyword(s):  
Explosive Charge ◽  
The Moon ◽  
Meteorite Impacts ◽  
The Earth ◽  
Lunar Craters ◽  
The Impact

The phenomena accompanying the impact of large meteorites on the surface of the Moon or of the Earth can be examined on the basis of the theory of explosive phenomena if we assume that, instead of an exploding meteorite moving inside the rock, we have an explosive charge (equivalent in energy), situated at a certain distance under the surface.

The Geosciences Applied to Lunar Exploration

1962 ◽  
Vol 14 ◽  
pp. 169-257 ◽  
Author(s):  
J. Green
Keyword(s):  
Lunar Surface ◽  
Probable Mechanism ◽  
Point Of View ◽  
Lunar Exploration ◽  
Geological Model ◽  
Apply Geophysics ◽  
Surface Features ◽  
The Impact

The term geo-sciences has been used here to include the disciplines geology, geophysics and geochemistry. However, in order to apply geophysics and geochemistry effectively one must begin with a geological model. Therefore, the science of geology should be used as the basis for lunar exploration. From an astronomical point of view, a lunar terrain heavily impacted with meteors appears the more reasonable; although from a geological standpoint, volcanism seems the more probable mechanism. A surface liberally marked with volcanic features has been advocated by such geologists as Bülow, Dana, Suess, von Wolff, Shaler, Spurr, and Kuno. In this paper, both the impact and volcanic hypotheses are considered in the application of the geo-sciences to manned lunar exploration. However, more emphasis is placed on the volcanic, or more correctly the defluidization, hypothesis to account for lunar surface features.

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