Diffuse astrocytic glioma, IDH-Wildtype, with molecular features of glioblastoma, WHO grade IV: A single-institution case series and review

Abstract Objectives Analyse clinical characteristics and treatment provided to an adult population diagnosed with intracranial ependymomas between 2009–2018. Methods Single centre retrospective cohort study. Variables reviewed: demographics, extent of resection, adjuvant oncological treatment and molecular genetics. Results 17 patients were included (6 females, 11 males). Average age at presentation was 51.3 yrs (range 19-74yrs). 4 supratentorial (2 intraventricular, 1 temporal lobe and 1 frontal lobe) and 13 infratentorial lesions were identified. In the supratentorial subgroup the following treatment was performed: GTR (1 patient), STR (1 patient) and Biopsy (2 patients); 2 patients underwent post-operative radiotherapy. 3 patients had a WHO grade 2 tumour (1 patient - insufficient tissue for grading). 3 recurrences were identified and 2 patients had re-debulking. 2 patients had postoperative hemiparesis, 1 patient died during treatment and 3 are currently being followed up. In the infratentorial subgroup the following treatment was performed: GTR (5 patients), STR (7 patients) and biopsy (1 patient). 3 patients underwent post-operative radiotherapy. 1 patient was WHO grade 1, 11 patients were WHO grade 2 and 1 patient was WHO grade 3. 2 patients had tumour recurrences of which 1 was re-operated. 7 patients develop new post-operative deficits after surgery; 1 patient died and the rest are currently being followed up. Conclusion Even though this case series supports the good prognosis in terms of overall survival in adults with intracranial ependymomas, they represent a challenge to manage given the morbidity of optimal surgical resection and their poor response to adjuvant treatment.

Download Full-text

Clinical, radiologic & prognostic profile of IDH wild type diffuse astrocytic glioma with molecular features of glioblastoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.2557 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 2557-2557

Author(s):

Oluwatosin Akintola ◽

Wesley Samore ◽

Maria Martinez-Lage Alvarez ◽

Elizabeth Robins Gerstner

Keyword(s):

Clinical Trials ◽

Methylation Status ◽

Diffuse Astrocytoma ◽

Tert Promoter Mutation ◽

Promoter Mutation ◽

Who Grade ◽

Egfr Amplification ◽

Astrocytic Glioma ◽

Molecular Features ◽

Tert Promoter

2557 Background: In 2018, The Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) recommended that IDH-wildtype diffuse astrocytic glioma Grade II/III with either EGFR amplification, combined whole chromosome 7 gain and whole chromosome 10 loss (+7/−10), or TERT promoter mutation should receive an integrated histological and molecular grade classification: Diffuse astrocytic glioma, IDH-wildtype with molecular features of glioblastoma, WHO grade IV. The natural history, radiologic characteristics and standard management for these patients has not been well described. They are typically excluded from clinical trials for WHO Grade IV gliomas. Methods: Adults diagnosed at Massachusetts General Hospital with IDH wildtype diffuse astrocytoma and EGFR amplification or TERT promoter mutation from 2011-2019 were identified. Demographics, functional status, radiologic features, MGMT promoter methylation status, time to progression, and overall survival were collected retrospectively. Qualitative MRI data was analyzed using the VASARI feature set. Response assessment was performed using the RANO criteria. Results: 50 patients were identified (table). 37/50 patients received standard Stupp protocol, 2/50 received hypofractionated radiotherapy with temozolomide, 6/50 received radiotherapy alone, and 1 patient received a MEK inhibitor. None were enrolled in clinical trials at diagnosis. mPFS was 10 months in the 47/50 with confirmed progression and mOS in the patients with confirmed deaths (40/50) was 17.5 months (4-47). 9/50 patients are alive with survival ranging 6-52 months. Conclusions: Outcomes for patients with molecularly defined GBM were variable. Analysis of the cohort to characterize factors that led to the observed variability is in progress. More studies on molecularly defined glioblastomas are required to better understand their behavior and to provide guidance for their inclusion or exclusion in clinical trials. [Table: see text]

Download Full-text

Outcomes of Single-Institution Retrospective Case Series on Observation Alone Following Atypical Meningioma Resection

Neurosurgery ◽

10.1093/neuros/nyz310_647 ◽

2019 ◽

Vol 66 (Supplement_1) ◽

Author(s):

Lauren Stone ◽

Hugh D Moulding ◽

Nimisha Deb ◽

Charles T Lee

Keyword(s):

Median Time ◽

Tumor Resection ◽

Case Series ◽

Single Institution ◽

Retrospective Case ◽

Who Grade ◽

Entire Cohort ◽

Simpson Grade ◽

Retrospective Case Series ◽

Significant Difference

Abstract INTRODUCTION Observation alone vs adjuvant radiotherapy (RT) following gross total resection (GTR) of WHO Grade II (G2) meningiomas is controversial. Local recurrence (LR) rates have been reported to be similar. We present LR rates in patients who were observed following G2 meningioma resection and correlate with Simpson grades. METHODS Patients from 2005 to 2018 who underwent observation alone following surgical resection of G2 meningiomas at a single institution were analyzed in a retrospective case series. Simpson grades were used to classify extent of tumor resection. Patients were followed with magnetic resonance imaging (MRI) or computed tomography (CT) imaging at 1-mo, 3-mo, 6-mo, and 12-mo postoperatively, then annually thereafter to monitor for recurrence. Descriptive 2-yr, and 5-yr LR rates for our entire cohort and time to recurrence by Simpson grade are reported. RESULTS A total of 28 patients with Simpson 1 to 4 resections for G2 meningiomas did not undergo adjuvant RT and were included. Median follow-up (FU) was 34 mo [Interquartile range (IQR): 18-55 mo]. Median time to LR was 55 mo (IQR: 44-65 mo) across our entire cohort. Of 14 patients with Simpson 1 resection, there was 1 LR at 68 mo. Of 3 patients with Simpson 2 resection, there was 1 LR at 49 mo. Of 9 patients with Simpson 3 resection, there were 5 recurrences; median time to LR was 61 mo. Of 2 patients with Simpson 4 resections, there was 1 LR at 3 mo. Overall, 2-yr LR was 3.6% and 5-yr LR was 10.7%. There was no statistically significant difference in LR rate between Simpson 1 vs Simpson 2 to 4 resections (P = .11). CONCLUSION Our results are consistent with the low recurrence rate of G2 meningiomas undergoing observation along following GTR in current literature. Simpson grade 1 resections have low overall LR rate and larger scale studies are needed to determine if statistical significance exists.

Download Full-text

Survival of diffuse astrocytic glioma, IDH1/2 wildtype, with molecular features of glioblastoma, WHO grade IV: a confirmation of the cIMPACT-NOW criteria

Neuro-Oncology ◽

10.1093/neuonc/noz200 ◽

2019 ◽

Vol 22 (4) ◽

pp. 515-523 ◽

Cited By ~ 14

Author(s):

C Mircea S Tesileanu ◽

Linda Dirven ◽

Maarten M J Wijnenga ◽

Johan A F Koekkoek ◽

Arnaud J P E Vincent ◽

...

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

World Health ◽

Lower Grade ◽

Isocitrate Dehydrogenase 1 ◽

Who Grade ◽

Astrocytic Glioma ◽

Molecular Features

Abstract Background The Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) has recommended that isocitrate dehydrogenase 1 and 2 wildtype (IDH1/2wt) diffuse lower-grade gliomas (LGGs) World Health Organization (WHO) grade II or III that present with (i) a telomerase reverse transcriptase promoter mutation (pTERTmt), and/or (ii) gain of chromosome 7 combined with loss of chromosome 10, and/or (iii) epidermal growth factor receptor (EGFR) amplification should be reclassified as diffuse astrocytic glioma, IDH1/2 wildtype, with molecular features of glioblastoma, WHO grade IV (IDH1/2wt astrocytomas WHO IV). This paper describes the overall survival (OS) of IDH1/2wt astrocytoma WHO IV patients, and more in detail patients with tumors with pTERTmt only. Methods In this retrospective multicenter study, we compared the OS of 71 IDH1/2wt astrocytomas WHO IV patients, with radiological characteristics of LGGs, with the OS of 197 IDH1/2wt glioblastoma patients. Moreover, we compared the OS of 22 pTERTmt only astrocytoma patients with the OS of the IDH1/2wt glioblastoma patients. Results Median OS was similar for IDH1/2wt astrocytoma WHO IV patients (23.8 mo) and IDH1/2wt glioblastoma patients (19.2 mo) (Cox proportional hazards model: hazard ratio [HR] 1.27, 95% CI: 0.85–1.88, P = 0.242). OS was also similar in patients with IDH1/2wt astrocytomas WHO IV, pTERTmt only, and IDH1/2wt glioblastomas (HR 1.15, 95% CI: 0.64–2.10, P = 0.641). Conclusions The presented data confirm the cIMPACT-NOW recommendation and we propose that IDH1/2wt astrocytomas WHO IV in the absence of other qualifying mutations should be classified as IDH1/2wt glioblastomas.

Download Full-text

cIMPACT-NOW update 3: recommended diagnostic criteria for “Diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV”

Acta Neuropathologica ◽

10.1007/s00401-018-1913-0 ◽

2018 ◽

Vol 136 (5) ◽

pp. 805-810 ◽

Cited By ~ 173

Author(s):

Daniel J. Brat ◽

Kenneth Aldape ◽

Howard Colman ◽

Eric C. Holland ◽

David N. Louis ◽

...

Keyword(s):

Diagnostic Criteria ◽

Who Grade ◽

Astrocytic Glioma ◽

Molecular Features

Download Full-text

Progestin-related WHO grade II meningiomas behavior—a single-institution comparative case series

Neurosurgical Review ◽

10.1007/s10143-021-01708-w ◽

2021 ◽

Author(s):

Antoine Devalckeneer ◽

Rabih Aboukais ◽

Maxime Faisant ◽

Philippe Bourgeois ◽

Vannod-Michel Quentin ◽

...

Keyword(s):

Case Series ◽

Single Institution ◽

Who Grade ◽

Grade Ii

Download Full-text

PATH-27. CLINICAL, RADIOLOGIC AND PROGNOSTIC PROFILE OF IDH WILD TYPE DIFFUSE ASTROCYTOMA WITH MOLECULAR FEATURES OF GLIOBLASTOMA

Neuro-Oncology ◽

10.1093/neuonc/noaa215.708 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii170-ii170

Author(s):

Oluwatosin Akintola ◽

Wesley Samore ◽

Maria Martinez-Lage Alvarez ◽

Elizabeth Gerstner

Keyword(s):

Clinical Trial ◽

Chromosome 7 ◽

Diffuse Astrocytoma ◽

Wild Type ◽

Who Grade ◽

Probability Of Survival ◽

Astrocytic Glioma ◽

Molecular Features ◽

Initial Surgery ◽

Grade Ii

Abstract BACKGROUND cIMPACT-NOW-3 recommends that IDH-wildtype diffuse astrocytic glioma Grade II or III with EGFR amplification, or combined whole chromosome 7 gain and whole chromosome 10 loss, or TERT promoter mutation should receive an integrated classification: Diffuse astrocytic glioma, IDH-wildtype with molecular features of glioblastoma, WHO grade IV. The aims of this study were: Outline the features of a cohort of patients with molecular glioblastoma according to the above criteria; Assess clinical and molecular factors that may inform prognosis; Determine if cIMPACT-NOW-3 recommendation changed clinical practice and clinical trial enrolment. METHODS 61 patients diagnosed with IDH-wildtype diffuse astrocytic glioma Grade II or III and EGFR amp or mTERT or chromosome (+7/-10) between 2011 and 2019 at MGH were included in this single center retrospective cohort study. Data collected: sex, age, extent of surgery, functional status, histological grade, molecular diagnostics and treatment. Progression was defined using RANO criteria, progression was quantified in terms of months from the initial surgery. Survival was defined in terms of months from initial surgery to date of death or last known visit. RESULTS mOS was 16 months, mPFS was 9 months. 14 patients (23%) survived > 24 months, 7 ≥ 36 months (mOS 32 months; 9 deceased). The probability of survival in patients with markedly enhancing tumors was 0.5 at 3 months versus 0.5 at 11 months in non-enhancing tumors. The probability of survival in patients who underwent biopsy only was 0.5 at 5 months compared to 0.5 at 12 months in patients with maximally resected tumors. 1 patient was enrolled in a clinical trial at diagnosis. 6 were enrolled at time of recurrence. CONCLUSIONS mOS and pFS in the deceased patients was comparable to historical data on survival in IDH wild-type glioblastomas. Inclusion criteria in clinical trials have not reflected the cIMPACT-NOW-3 recommendation so far.

Download Full-text

Long-term outcomes of lumbar microdiscectomy in the pediatric population: a large single-institution case series

Journal of Neurosurgery Pediatrics ◽

10.3171/2019.6.peds18716 ◽

2019 ◽

Vol 24 (5) ◽

pp. 549-557

Author(s):

Malia McAvoy ◽

Heather J. McCrea ◽

Vamsidhar Chavakula ◽

Hoon Choi ◽

Wenya Linda Bi ◽

...

Keyword(s):

Conservative Management ◽

Functional Outcomes ◽

Pediatric Patients ◽

Clinical Presentation ◽

Case Series ◽

Csf Leak ◽

Single Institution ◽

The Mean

OBJECTIVEFew studies describe long-term functional outcomes of pediatric patients who have undergone lumbar microdiscectomy (LMD) because of the rarity of pediatric disc herniation and the short follow-up periods. The authors analyzed risk factors, clinical presentation, complications, and functional outcomes of a single-institution series of LMD patients over a 19-year period.METHODSA retrospective case series was conducted of pediatric LMD patients at a large pediatric academic hospital from 1998 to 2017. The authors examined premorbid risk factors, clinical presentation, physical examination findings, type and duration of conservative management, indications for surgical intervention, complications, and postoperative outcomes.RESULTSOver the 19-year study period, 199 patients underwent LMD at the authors’ institution. The mean age at presentation was 16.0 years (range 12–18 years), and 55.8% were female. Of these patients, 70.9% participated in competitive sports, and among those who did not play sports, 65.0% had a body mass index greater than 25 kg/m2. Prior to surgery, conservative management had failed in 98.0% of the patients. Only 3 patients (1.5%) presented with cauda equina syndrome requiring emergent microdiscectomy. Complications included 4 cases of postoperative CSF leak (2.0%), 1 case of a noted intraoperative CSF leak, and 3 cases of wound infection (1.5%). At the first postoperative follow-up appointment, minimal or no pain was reported by 93.3% of patients. The mean time to return to sports was 9.8 weeks. During a mean follow-up duration of 8.2 years, 72.9% of patients did not present again after routine postoperative appointments. The total risk of reoperation was a rate of 7.5% (3.5% of patients underwent reoperation for the same level; 4.5% underwent adjacent-level decompression, and one patient [0.5%] ultimately underwent a fusion).CONCLUSIONSMicrodiscectomy is a safe and effective treatment for long-term relief of pain and return to daily activities among pediatric patients with symptomatic lumbar disc disease in whom conservative management has failed.

Download Full-text

Toxoplasma encephalitis presenting as neoplastic disease: A single institution case series

Interdisciplinary Neurosurgery ◽

10.1016/j.inat.2021.101174 ◽

2021 ◽

Vol 25 ◽

pp. 101174

Author(s):

Jennifer L. Perez ◽

Zachary C. Gersey ◽

Daniel F. Marker ◽

Georgios A. Zenonos ◽

Pascal O. Zinn

Keyword(s):

Case Series ◽

Neoplastic Disease ◽

Single Institution ◽

Toxoplasma Encephalitis

Download Full-text

Ultrasound Biomicroscopy Documented Anterior Uveal Melanoma Regression after Ruthenium-106 Plaque Therapy

Ocular Oncology and Pathology ◽

10.1159/000512030 ◽

2021 ◽

pp. 1-9

Author(s):

Biljana Kuzmanović Elabjer ◽

Mladen Bušić ◽

Andrej Pleše ◽

Mirjana Bjeloš ◽

Daliborka Miletić ◽

...

Keyword(s):

Uveal Melanoma ◽

Tumor Regression ◽

Corneal Thickness ◽

Case Series ◽

Ultrasound Biomicroscopy ◽

Close Monitoring ◽

Single Institution ◽

Retrospective Case ◽

Caucasian Patients

Introduction: Ultrasound biomicroscopy (UBM) is the only widely used method for the evaluation of anterior uveal melanoma (AUM). Objective: Documentation of regression of AUM treated with ruthenium-106 (Ru-106) plaque types CCB and CCC using UBM. Methods: This single institution-based retrospective case series involved 10 Caucasian patients with AUM followed after brachytherapy with UBM from January 2014 until February 2019. The largest prominence of the tumor perpendicular to the sclera or the cornea (including scleral/corneal thickness) (D) and the largest basal dimension (B) were measured in millimeters with UBM for all patients prior to the brachytherapy and at 4-month interval follow-up. Tumor regression was calculated as a percentage of decrease in the initial D and B values. Results: The study involved 10 patients with a mean age of 64.4 years (yr) (range 46–80 yr). D ranged from 1.82 to 5.5 mm (median 2.99 mm) and B from 2.32 to 12.38 mm (median 4.18 mm). The apical radiation dose in all patients was 100 Gy. The median follow-up was 42.02 months. Regression for D was 21.11 ± 13.66%, 31.09 ± 14.66%, and 34.92 ± 19.86% at 1st, 2nd, and 3rd year of the follow-up, respectively, while for B it was 21.58 ± 16.05%, 28.98 ± 17.71%, and 32.06 ± 18.96%, respectively. Tumor recurrence was documented in 2/10 patients. Conclusion: The major regression of AUM, treated with Ru-106 plaque types CCB and CCC, was documented in the first 2 years after brachytherapy in our study group. In the following years, only minimal regression was documented that warns of the need for close monitoring and active search for local recurrences.

Download Full-text