scholarly journals Tumor-associated macrophage infiltration in meningioma

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Dustin T Proctor ◽  
Jordan Huang ◽  
Sanju Lama ◽  
Abdulrahman Albakr ◽  
Guido Van Marle ◽  
...  
Keyword(s):  
Potential Role ◽  
Immune Cell ◽  
Phenotypic Diversity ◽  
High Rate ◽  
Potential Contribution ◽  
Who Grade ◽  
Cell Ratio ◽  
Patient Demographics ◽  
Tumor Associated Macrophage ◽  
Grade Ii

Abstract Background Meningioma, a most common brain tumor, has a high rate of recurrence. Tumor-associated macrophages (TAMs) are the most abundant immune cell type in meningioma. TAMs display functional phenotypic diversity and may establish either an inflammatory and anti-tumoral or an immunosuppressive and pro-tumoral microenvironment. TAM subtypes present in meningioma and potential contribution to growth and recurrence is unknown. Methods Immunofluorescence staining was used to quantify M1 and M2 TAM populations in tissues obtained from 30 meningioma patients. Associations between M1 and M2 cells, M1:M2 cell ratio to tumor characteristics, WHO grade, recurrence, size, location, peri-tumoral edema, and patient demographics such as age and sex were examined. Results TAM cells accounted for ~18% of all cells in meningioma tissues. More than 80% of infiltrating TAMs were found to be of pro-tumoral M2 phenotype and correlated to tumor size (P = .0409). M1:M2 cell ratio was significantly decreased in WHO grade II, compared to grade I tumors (P = .009). Furthermore, a 2.3-fold difference in M1:M2 ratio between primary (0.14) and recurrent (0.06) tumors was observed (n = 18 and 12 respectively, P = .044). Conclusion This study is the first to confirm existence of pro-tumoral M2 TAMs in the meningioma microenvironment, emphasizing its potential role in tumor growth and recurrence.

scholarly journals GENE-27. MENINGIOMA RECURRENCE: ROLE OF M1/M2 TUMOUR-ASSOCIATED MACROPHAGE INFILTRATION

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi103-vi103
Author(s):  
Dustin Proctor ◽  
Jordan Huang ◽  
Sanju Lama ◽  
Abdulrahman Albakr ◽  
Guido Van Marle ◽  
...  
Keyword(s):  
Immune Cell ◽  
Phenotypic Diversity ◽  
Tumour Size ◽  
High Rate ◽  
Potential Contribution ◽  
Who Grade ◽  
Patient Demographics ◽  
Meningioma Recurrence ◽  
Tumour Characteristics

Abstract BACKGROUND Meningioma, a most common brain tumour, has a high rate of recurrence. Tumour-associated macrophages (TAMs) are the most abundant immune cell type in meningioma. TAMs display functional phenotypic diversity and may establish either an inflammatory and anti-tumoural or an immunosuppressive and pro-tumoural microenvironment. TAM subtypes present in meningioma and potential contribution to growth and recurrence is unknown. METHODS Fluorescence immunohistochemistry was used to evaluate the distribution and quantify M1 and M2 TAM populations in 30 meningioma tissues. Association between quantified M1 and M2 cells and M1/M2 ratio to tumour characteristics including WHO grade, tumour recurrence, size, location, peri-tumoural edema and patient demographics such as age and sex was examined. RESULTS TAM cells accounted for ~17% of all cells in tumour tissues. Importantly, greater than 80% of infiltrating TAMs were discovered to be of a polarized pro-tumoural M2 phenotype which positively associated with tumour size. TAM subtype profiles differed significantly between non-recurrent (n=18) and recurrent meningioma (n=12) (P=0.044). Specifically, the M1/M2 cell ratio was decreased by ~250% in recurrent tumours. CONCLUSION This study is the first to confirm existence of pro-tumoural M2 TAMs in the meningioma microenvironment and a potential role in tumour growth and recurrence.

Forniceal glioma in children

2009 ◽  
Vol 4 (3) ◽  
pp. 249-253 ◽  
Author(s):  
Thomas Blauwblomme ◽  
Pascale Varlet ◽  
John R. Goodden ◽  
Marie Laure Cuny ◽  
Helene Piana ◽  
...  
Keyword(s):  
Residual Disease ◽  
Surgical Excision ◽  
Pediatric Brain Tumors ◽  
Additional Treatment ◽  
High Rate ◽  
Low Grade ◽  
Who Grade ◽  
Retrograde Memory ◽  
Grade Ii

Object Five to ten percent of pediatric brain tumors are located in the ventricles. Among them, forniceal lesions are rare and their management has not often been described. The aim of this study was to review the clinical, radiological, and histopathological features as well as the feasibility of surgical excision and the outcomes in these patients. Methods From a retrospective analysis of 250 cases of supratentorial pediatric glioma, the records of 8 children presenting with forniceal lesions were selected and reviewed. Results The median age of patients in the cohort was 13.5 years. Presenting features included intracranial hypertension (7 cases), hypothalamic dysfunction (2), and memory dysfunction (3). Complete resection was possible in only 1 case, where the lesion was mainly exophytic; the remaining patients had either a partial resection or biopsy. On histological review, the tumors were confirmed as pilocytic astrocytoma (4 lesions), WHO Grade II astrocytoma (3), and ganglioglioma (1). Postoperatively, working and retrograde memory was normal for all patients, but the authors found a mild alteration in verbal episodic memory in 5 patients. Despite fatigability for 5 patients, academic achievement was normal for all but 2, both of whom had preoperative school difficulties. Additional treatment was required for 5 patients for tumor progression, with a median interval of 19 months from surgery. At a median follow-up duration of 4.9 years, all patients had stable disease. Conclusions In this series, forniceal gliomas were found to be low-grade gliomas. They are surgically challenging, and only exophytic lesions may be cured surgically. Due to the high rate of progression of residual disease, adjuvant therapy is recommended for infiltrative tumors, and it yielded excellent results.

scholarly journals Cranial Meningiomas Requiring Cranioplasty

2021 ◽  
Vol 23 (Supplement_4) ◽  
pp. iv14-iv15
Author(s):  
Max Norrington ◽  
Christopher Millward ◽  
John Doherty ◽  
Mohammad Mustafa ◽  
Thomas Humphries ◽  
...  
Keyword(s):  
Surgical Techniques ◽  
Intracranial Meningioma ◽  
Who Grade ◽  
Patient Demographics ◽  
Included Patient ◽  
Grade Ii ◽  
Bone Infiltration ◽  
Materials Used ◽  
Intraosseous Meningioma ◽  
Tumour Characteristics

Abstract Aims Bone infiltration in association with intracranial meningioma (4.5% of cases) and primary intraosseous meningioma (2%) are rare. Management can be challenging, as cranial vault reconstruction may be required. This study aimed to examine the surgical techniques used and outcomes in this patient population. Method A single-centre, retrospective cohort study was conducted between January 2010 and September 2020. All adult patients who required cranial reconstruction due to bone involvement of their meningioma were included. Patient demographics, tumour characteristics, operative details, complications, and outcomes were examined. Statistical analyses were performed using SPSS v24.0. Results There were 30 patients (17 female; 56.7%), median age 54 yrs (range 28-86 yrs), of whom 25 (83.3%) had bone infiltration, and 5 (16.7%) had primary intraosseous meningioma. Only 10 patients had a Simpson I or II resection. Twenty-eight had 'on-table' primary cranioplasties. Materials used were titanium (n=13; 43.3%), acrylic (n=10; 33.3%), PMMA (n=5; 16.7%), and hydroxyapatite (n=2; 6.7%). There were 9 (mostly minor) surgical complications and only one wound infection. Twelve patients had WHO grade II tumours, and 14 required radiotherapy. Ten patients (33.3%) had re-operation for recurrent tumour, with a median time to progression of 41 months. At 6 months, 24 patients had a performance score less than 2. Conclusion On-table cranioplasty provides a lower risk surgical option for patients with high risk meningiomas.

scholarly journals Case Report: Identification of a Novel GNAS Mutation and 1p/22q Co-Deletion in a Patient With Multiple Recurrent Meningiomas Sensitive to Sunitinib

2021 ◽  
Vol 11 ◽  
Author(s):  
Weiping Hong ◽  
Changguo Shan ◽  
Minting Ye ◽  
Yanying Yang ◽  
Hui Wang ◽  
...  
Keyword(s):  
Case Report ◽  
Potential Role ◽  
Molecular Classification ◽  
Who Grade ◽  
Case Presentation ◽  
Grade Ii ◽  
Residual Lesions ◽  
Generation Sequencing ◽  
Gnas Mutation

BackgroundAlthough surgical resection can cure the majority of meningiomas, there are still approximately 20% of patients suffering from an aggressive course with recurrence or progression. In this study, we reported a novel GNAS mutation and 1p/22q co-deletion responding to sunitinib in a patient with multiple recurrent meningiomas.Case PresentationA 53-year-old woman with meningioma was hospitalized due to postoperative tumor progression for 3 weeks. WHO grade I meningioma was pathologically diagnosed after the first three surgeries, but the second recurrence occurred approximately 3 years following the third surgery. Next-generation sequencing was performed on the first two recurrent samples. GNAS mutations and 1p/22q co-deletion were both identified, and amplification at 17q and chromosome 19 was also found in the second recurrent sample, based on which WHO grade II/III meningioma was diagnosed. The lesion in the left cerebellopontine angle area enlarged after use of radiotherapy combined with temozolomide chemotherapy for 2 months. When sunitinib was added, the residual lesions began to lessen and continuously reduced.ConclusionThis typical case suggested that timely molecular diagnosis for refractory meningiomas contributed to guiding the molecular classification and clinicians to make more reasonable individualized therapeutic regimens, consequently benefiting the patients. This case report also highlighted the potential role of sunitinib in the treatment of refractory meningiomas.

scholarly journals Influence of VEGF-A, VEGFR-1-3, and neuropilin 1-2 on progression-free: and overall survival in WHO grade II and III meningioma patients

2021 ◽  
Vol 52 (2) ◽  
pp. 233-243
Author(s):  
Simon Bernatz ◽  
Daniel Monden ◽  
Florian Gessler ◽  
Tijana Radic ◽  
Elke Hattingen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Cells ◽  
Progression Free Survival ◽  
Staining Intensity ◽  
Who Grade ◽  
Positive Correlation ◽  
Protein Levels ◽  
Angiogenic Therapy ◽  
Neuropilin 1 ◽  
Grade Ii

AbstractHigher grade meningiomas tend to recur. We aimed to evaluate protein levels of vascular endothelial growth factor (VEGF)-A with the VEGF-receptors 1-3 and the co-receptors Neuropilin (NRP)-1 and -2 in WHO grade II and III meningiomas to elucidate the rationale for targeted treatments. We investigated 232 specimens of 147 patients suffering from cranial meningioma, including recurrent tumors. Immunohistochemistry for VEGF-A, VEGFR-1-3, and NRP-1/-2 was performed on tissue micro arrays. We applied a semiquantitative score (staining intensity x frequency). VEGF-A, VEGFR-1-3, and NRP-1 were heterogeneously expressed. NRP-2 was mainly absent. We demonstrated a significant increase of VEGF-A levels on tumor cells in WHO grade III meningiomas (p = 0.0098). We found a positive correlation between expression levels of VEGF-A and VEGFR-1 on tumor cells and vessels (p < 0.0001). In addition, there was a positive correlation of VEGF-A and VEGFR-3 expression on tumor vessels (p = 0.0034). VEGFR-2 expression was positively associated with progression-free survival (p = 0.0340). VEGF-A on tumor cells was negatively correlated with overall survival (p = 0.0084). The VEGF-A-driven system of tumor angiogenesis might still present a suitable target for adjuvant therapy in malignant meningioma disease. However, its role in malignant tumor progression may not be as crucial as expected. The value of comprehensive testing of the ligand and all receptors prior to administration of anti-angiogenic therapy needs to be evaluated in clinical trials.

Clear cell histology portends a worse prognosis than other WHO grade II histologies

2021 ◽  
Author(s):  
Pranay Soni ◽  
Jianning Shao ◽  
Arbaz Momin ◽  
Diana Lopez ◽  
Lilyana Angelov ◽  
...  
Keyword(s):  
Clear Cell ◽  
Who Grade ◽  
Grade Ii ◽  
Worse Prognosis

scholarly journals IDH1 Non-Canonical Mutations and Survival in Patients with Glioma

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 342 ◽  
Author(s):  
Enrico Franceschi ◽  
Dario De Biase ◽  
Vincenzo Di Nunno ◽  
Annalisa Pession ◽  
Alicia Tosoni ◽  
...  
Keyword(s):  
Idh1 Mutation ◽  
Who Grade ◽  
Tissue Samples ◽  
1P19q Codeletion ◽  
Idh1 R132h ◽  
Rare Mutations ◽  
Grade Ii ◽  
Idh1 Mutations ◽  
R132h Mutation ◽  
Generation Sequencing

Background: Non-canonical mutations of the isocitrate dehydrogenase (IDH) genes have been described in about 20–25% and 5–12% of patients with WHO grade II and III gliomas, respectively. To date, the prognostic value of these rare mutations is still a topic of debate. Methods: We selected patients with WHO grade II and III gliomas and IDH1 mutations with available tissue samples for next-generation sequencing. The clinical outcomes and baseline behaviors of patients with canonical IDH1 R132H and non-canonical IDH1 mutations were compared. Results: We evaluated 433 patients harboring IDH1 mutations. Three hundred and ninety patients (90.1%) had a canonical IDH1 R132H mutation while 43 patients (9.9%) had a non-canonical IDH1 mutation. Compared to those with the IDH1 canonical mutation, patients with non-canonical mutations were younger (p < 0.001) and less frequently presented the 1p19q codeletion (p = 0.017). Multivariate analysis confirmed that the extension of surgery (p = 0.003), the presence of the 1p19q codeletion (p = 0.001), and the presence of a non-canonical mutation (p = 0.041) were variables correlated with improved overall survival. Conclusion: the presence of non-canonical IDH1 mutations could be associated with improved survival among patients with IDH1 mutated grade II–III glioma.

scholarly journals RTID-05. INDIGO: A GLOBAL, RANDOMIZED, DOUBLE-BLIND, PHASE 3 STUDY OF VORASIDENIB (AG-881) VS PLACEBO IN PATIENTS WITH RESIDUAL/RECURRENT GRADE II GLIOMA WITH AN ISOCITRATE DEHYDROGENASE 1/2 (IDH1/2) MUTATION

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii194-ii194
Author(s):  
Ingo Mellinghoff ◽  
Martin van den Bent ◽  
Jennifer Clarke ◽  
Elizabeth Maher ◽  
Katherine Peters ◽  
...  
Keyword(s):  
High Risk ◽  
Dose Escalation ◽  
Objective Response ◽  
Data Monitoring Committee ◽  
Progression Free Survival ◽  
High Risk Population ◽  
Low Grade ◽  
Who Grade ◽  
Free Survival ◽  
Grade Ii

Abstract BACKGROUND Low-grade gliomas (LGGs; WHO grade II) are incurable and ultimately progress to high-grade gliomas. The current treatment options are surgery followed by observation (“watch and wait”) for patients with lower risk for disease progression or postoperative chemoradiotherapy (high-risk population). There are no approved targeted therapies. IDH1 and IDH2 mutations (mIDH1/2) occur in approximately 80% and 4% of LGGs, respectively, and promote tumorigenesis via neomorphic production of D-2-hydroxyglutarate. Vorasidenib, an oral, potent, reversible, brain-penetrant pan-inhibitor of mIDH1/2, was evaluated in 76 patients with glioma in two phase 1 studies (dose escalation and perioperative) and was associated with a favorable safety profile at daily doses below 100 mg. Preliminary clinical activity was observed in non-enhancing glioma patients in both studies, with an objective response rate (ORR) of 18.2% and median progression-free survival of 31.4 months in the dose escalation study. METHODS Approximately 366 patients will be randomized 1:1 to vorasidenib (50 mg QD) or matched placebo and stratified by 1p19q status (intact vs co-deleted). Key eligibility criteria: age ≥ 12 years; grade II oligodendroglioma or astrocytoma (per WHO 2016 criteria) not in need of immediate treatment and without high-risk features; centrally confirmed mIDH1/2 status; ≥ 1 surgery for glioma with most recent ≥ 1 year but ≤ 5 years before randomization, and no other anticancer therapy; Karnofsky performance status ≥ 80%; and centrally confirmed measurable, non-enhancing disease evaluable by magnetic resonance imaging. Crossover from placebo to the vorasidenib arm is permitted upon centrally confirmed radiographic progression per RANO-LGG criteria. Primary endpoint: progression-free survival assessed by independent review. Secondary endpoints: safety and tolerability, tumor growth rate assessed by volume, ORR, overall survival, and quality of life. Clinical data will be reviewed regularly by an independent data monitoring committee. The study is currently enrolling patients in the US, with additional countries planned (NCT04164901).

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