scholarly journals PATH-13. PLEOMORPHIC XANTHOASTROCYTOMA INTEGRATED GENOMIC CHARACTERIZATION - WHAT HAVE WE LEARNED?

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii426-iii427
Author(s):  
Rachael Vaubel ◽  
Valentina Zschernack ◽  
Alissa Caron ◽  
Dragana Milosevic ◽  
Robert Jenkins ◽  
...  
Keyword(s):  
Overall Survival ◽  
Strong Predictor ◽  
Progression Free Survival ◽  
Genetic Alterations ◽  
Pleomorphic Xanthoastrocytoma ◽  
Who Grade ◽  
Targeted Next Generation Sequencing ◽  
Genomic Characterization ◽  
Promoter Mutations ◽  
Methylation Profiling

Abstract Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytoma occurring predominantly in children and young adults. It is characterized histologically by large pleomorphic, spindled and lipidized cells with frequent eosinophilic granular bodies and pericellular reticulin deposition. BRAF p.V600E mutation and CKDN2A/B deletion are the most common genetic alterations. We report the integrated genomic characterization of a cohort of 67 patients (37 F, 30 M; median age 20.3 years (interquartile 13.4–32.9) with histologically defined PXA (52, 78%) or anaplastic PXA (A-PXA) (15, 22%), using genome-wide cytogenetic (ThermoFisher Oncoscan, n=67), methylation profiling (Illumina EPIC array, n=43), and targeted next generation sequencing (n=32). BRAF p.V600E mutation (n=51, 76.1%) and CDKN2A/B deletion (n=63; 94%) were the most frequent alterations. Of 16 BRAF p.V600E negative cases, 7 showed an alternative BRAF activating mutation (n=2), NF1 (n=3) mutation or ATG7-RAF1 fusion (n=2). Targeted TERT analysis found promoter mutations in 3 (of 58) cases, but TERT amplification was absent. Supervised and unsupervised methylation profiling against a comprehensive reference cohort demonstrated consensus grouping with the PXA class in 36 of 43 cases; while the minority grouped with a ganglioglioma class (n=3), with reactive brain or had no resolvable subgroup (n=4). Follow-up was available in 61 patients (91.0%) (median 63 months). Overall survival was significantly different between PXA and A-PXA (5-year:80.4% vs. 55.1%; p=0.001), but not progression-free survival (5-year:61.7% vs. 39.8%; p=0.128). Our data confirm the high frequency of MAP-K abnormalities and CDKN2A/B deletion in PXA. WHO grade remains a strong predictor of patient overall survival.

scholarly journals P14.95 Is the pathological-grade relevant in “IDH-wild type, TERT-mutant” diffuse-gliomas? An analysis in 147 patients

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii90-iii90
Author(s):  
A E Danyeli ◽  
C B Akyerli ◽  
A Dinçer ◽  
E Coşgun ◽  
U Abacıoğlu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Progression Free Survival ◽  
Genetic Alterations ◽  
Lower Grade ◽  
Wild Type ◽  
Ki 67 ◽  
Who Grade ◽  
Free Survival ◽  
Tert Promoter ◽  
Diffuse Gliomas

Abstract BACKGROUND Although the word “glioblastoma” still denotes a grade-IV pathology, basic molecular studies have clearly indicated that a significant proportion of lower-grade gliomas harbor genetic alterations typical of glioblastomas. Based on these findings cIMPACT-NOW update 3 has defined an entity called the “diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV”. A TERT-promoter mutation is one of these typical molecular markers of glioblastomas. In this study we analyzed IDH-wild type, TERT-mutant diffuse gliomas of different pathological grades to look for differences in demographic, clinical and survival characteristics. MATERIAL AND METHODS 147 adult hemispheric diffuse-gliomas with wild-type IDH1/2 and mutant TERT-promoter (C228T or C250T) were retrospectively analyzed. Primary thalamic, cerebellar brainstem or spinal cases were excluded. 126 (86%), 16(11%) and 5(3%) patients were WHO grade IV, III and II respectively. After surgical treatment or stereotactic biopsy all patients underwent chemoradiation. Median follow-up was 16mo (1–110). Tumors of different grades were compared for age, gender, multifocality, gliomatosis pattern, Ki-67 index, progression-free survival and overall-survival. RESULTS Mean age at presentation for grade II, III and IV were comparable (58.1, 58 and 58.1; ANOVA, p=0.72). There was a slight male predominance in both lower-grades and WHO-grade IV (M:F ratios 1.625 and 1.74). Mean Ki-67 index was significantly higher in higher grades (0.06, 0.14 and 0.25 for grades II, III and IV; ANOVA, p=0.001). Multifocality was comparable (chi-sq, p=1) in lower-grades (3/21; 14.3%) vs. WHO-grade IV (18/126; 14.3%). Gliomatosis pattern was comparable (chi-sq, p=0.095) in lower-grades (2/21; 9.5%) vs. (3/126; 2.3%). Median recurrence free survival (RFS) was 16 months (0–63) in lower-grades and 8months (1–50) in WHO-grade IV. PFS was significantly different between 3 WHO-grades (Log rank, p=0.007) and also between lower-grades and WHO-grade IV (Log rank, p=0.002). Median overall survival was 26 months(2–110) in lower-grades and 15mo(1–91) in WHO-grade IV. OS was significantly different between 3 WHO-grades (Log rank, p=0.014) and also between lower-grades and WHO-grade IV (Log rank, p=0.007). CONCLUSION Increasing pathological grades of hemispheric “IDH-wild type, TERT-mutant diffuse gliomas” have similar demographic and clinical characteristics but incrasing proliferation indices, decrasing progression free survival and shorter overall survival. The findings may be suggesitve of different grades of one common tumor entity.

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.

Efficacy of Fractionated Stereotactic Reirradiation in Recurrent Gliomas: Long-Term Results in 172 Patients Treated in a Single Institution

2005 ◽  
Vol 23 (34) ◽  
pp. 8863-8869 ◽  
Author(s):  
Stephanie E. Combs ◽  
Christoph Thilmann ◽  
Lutz Edler ◽  
Jürgen Debus ◽  
Daniela Schulz-Ertner
Keyword(s):  
Overall Survival ◽  
Progression Free Survival ◽  
Primary Diagnosis ◽  
Long Term Results ◽  
Low Grade ◽  
Single Institution ◽  
Who Grade ◽  
Low Grade Gliomas ◽  
Recurrent Gliomas ◽  
Grade 3

Purpose To evaluate the efficacy of fractionated stereotactic radiotherapy (FSRT) performed as reirradiation in 172 patients with recurrent low- and high-grade gliomas. Patients and Methods Between 1990 and 2004, 172 patients with recurrent gliomas were treated with FSRT as reirradiation in a single institution. Seventy-one patients suffered from WHO grade 2 gliomas. WHO grade 3 gliomas were diagnosed in 42 patients, and 59 patients were diagnosed with glioblastoma multiforme (GBM). The median time between primary radiotherapy and reirradiation was 10 months for GBM, 32 months for WHO grade 3 tumors, and 48 months for grade 2 astrocytomas. FSRT was performed with a median dose of 36 Gy in a median fractionation of 5 × 2 Gy/wk. Results Median overall survival after primary diagnosis was 21 months for patients with GBM, 50 months for patients with WHO grade 3 gliomas, and 111 months for patients with WHO grade 2 gliomas. Histologic grading was the strongest predictor for overall survival, together with the extent of neurosurgical resection and age at primary diagnosis. Median survival after reirradiation was 8 months for patients with GBM, 16 months for patients with grade 3 tumors, and 22 months for patients with low-grade gliomas. Only time to progression and histology were significant in influencing survival after reirradiation. Progression-free survival after FSRT was 5 months for GBM, 8 months for WHO grade 3 tumors, and 12 months for low-grade gliomas. Conclusion FSRT is well tolerated and may be effective in patients with recurrent gliomas. Prospective studies are warranted for further evaluation.

Loss of Heterozygosity 1p36 and 19q13 Is a Prognostic Factor for Overall Survival in Patients With Diffuse WHO Grade 2 Gliomas Treated Without Chemotherapy

2006 ◽  
Vol 24 (29) ◽  
pp. 4758-4763 ◽  
Author(s):  
Luigi Mariani ◽  
Gianluca Deiana ◽  
Erik Vassella ◽  
Ali-Reza Fathi ◽  
Christine Murtin ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Malignant Transformation ◽  
Loss Of Heterozygosity ◽  
Progression Free Survival ◽  
Who Grade ◽  
Free Survival ◽  
Extent Of Surgery ◽  
Oligodendroglial Component ◽  
The Impact

Purpose This study was conducted to elucidate the impact of loss of heterozygosity (LOH) for chromosomes 1p36 and 19q13 on the overall survival of patients with diffusely infiltrating WHO grade 2 gliomas treated without chemotherapy. Patients and Methods We assessed the LOH status of tumors from patients harboring WHO grade 2 gliomas diagnosed between 1991 and 2000. Patients were either followed after initial biopsy or treated by surgery and/or radiation therapy (RT). Overall survival, time to malignant transformation, and progression-free survival were last updated as of March 2005. Results Of a total of 79 patients, LOH 1p36 and LOH 19q13 could be assessed in 67 and 66 patients, respectively. The median follow-up after diagnosis was 6 years. Loss of either 1p or 19q, in particular codeletion(s) at both loci, was found to positively impact on both overall survival (log-rank P < .01), progression-free survival, and survival without malignant transformation (P < .05). Tumor volume (P < .0001), neurologic deficits at diagnosis (P < .01), involvement of more than one lobe (P < .01), and absence of an oligodendroglial component (P < .05) were also predictors of shorter overall survival. The extent of surgery was similar in patients with or without LOH 1p and/or 19q; RT was more frequently resorted to for patients without than for patients with LOH 1p/19q (30% v 60%). Conclusion The presence of LOH on either 1p36 or 19q13, and in particular codeletion of both loci is a strong, nontreatment-related, prognostic factor for overall survival in patients with diffusely infiltrating WHO grade 2 gliomas.

scholarly journals Exploring DNA Methylation for Prognosis and Analyzing the Tumor Microenvironment in Pleomorphic Xanthoastrocytoma

2020 ◽  
Vol 79 (8) ◽  
pp. 880-890
Author(s):  
Karen Tang ◽  
David Kurland ◽  
Varshini Vasudevaraja ◽  
Jonathan Serrano ◽  
Michael Delorenzo ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Overall Survival ◽  
Tumor Microenvironment ◽  
Immune Cell ◽  
Progression Free Survival ◽  
Cell Types ◽  
Homozygous Deletion ◽  
Pleomorphic Xanthoastrocytoma ◽  
Braf V600e ◽  
Rare Type

Abstract Pleomorphic xanthoastrocytoma (PXA) is a rare type of brain tumor that affects children and young adults. Molecular prognostic markers of PXAs remain poorly established. Similar to gangliogliomas, PXAs show prominent immune cell infiltrate, but its composition also remains unknown. In this study, we correlated DNA methylation and BRAF status with clinical outcome and explored the tumor microenvironment. We performed DNA methylation in 21 tumor samples from 18 subjects with a histological diagnosis of PXA. MethylCIBERSORT was used to deconvolute the PXA microenvironment by analyzing the associated immune cell-types. Median age at diagnosis was 16 years (range 7–32). At median follow-up of 30 months, 3-year and 5-year overall survival was 73% and 71%, respectively. Overall survival ranged from 1 to 139 months. Eleven out of 18 subjects (61%) showed disease progression. Progression-free survival ranged from 1 to 89 months. Trisomy 7 and CDKN2A/B (p16) homozygous deletion did not show any association with overall survival (p = 0.67 and p = 0.74, respectively). Decreased overall survival was observed for subjects with tumors lacking the BRAF V600E mutation (p = 0.02). PXAs had significantly increased CD8 T-cell epigenetic signatures compared with previously profiled gangliogliomas (p = 0.0019). The characterization of immune cell-types in PXAs may have implications for future development of immunotherapy.

scholarly journals A Retrospective Interventional Cohort Study to Assess the Safety and Efficacy of Sandostatin LAR(octreotide) for Treatment of Recurrent and/or Refractory Meningiomas

2019 ◽  
Author(s):  
Daniela Annenelie Bota ◽  
Maya Hrachova ◽  
Beverly D. Fu ◽  
Xiao–Tang Kong ◽  
Gilbert Cadena ◽  
...  
Keyword(s):  
Overall Survival ◽  
Somatostatin Receptors ◽  
Somatostatin Analogs ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
The United States ◽  
High Recurrence Rate ◽  
Who Grade ◽  
Free Survival ◽  
The University

Abstract Background Meningiomas are the most common adult primary intracranial tumors in the United States. Despite, high recurrence rate of atypical and malignant subtypes, there is no approved drug indicated specifically for meningioma. Majority of meningiomas exhibit high density (70%) of somatostatin receptors subtypes, and somatostatin analogs have been under close investigation as a potential treatment option for management of progressive or recurrent meningiomas. The aim of this study was to evaluate efficacy and safety of Sandostatin LAR (octreotide) in patients with progressive and/or recurrent meningioma. Methods A total of 44 patients ≥ 18 years old were included in retrospective chart review. They were diagnosed with meningioma and underwent therapy with Sandostatin LAR (octreotide) from 01/01/10 until 06/01/17 at the University of California, Irvine. Six months progression free survival (PFS6) was defined as a primary endpoint, and the overall survival (OS) was a secondary endpoint along with safety and toxicity. Results The PFS6 months for all tumor grades was 80.6%. The OS for 6 months, 1 year, and 3 years for all WHO grades was 94.9% (95% confidence interval [CI]: 0.88-1.00), 88.4% (95% CI: 0.78-0.99), and 67.2% (95% CI: 0.36-0.99) respectively. Median TTP for WHO grade I, II and III was 3.1, 2.40, and 0.20 years respectively. Sandostatin LAR (octreotide) was well tolerated. Conclusions This is the largest reported retrospective analysis of meningioma patients treated with Sandostatin LAR (octreotide) and suggests that this treatment has minimal to no adverse events and could prolong overall survival and progression free survival.

Correlation of MTAP Immunohistochemistry With CDKN2A Status Assessed by Fluorescence In Situ Hybridization and Clinicopathological Features in CNS WHO Grade 2 and 3 Meningiomas: A Single Center Cohort Study

2021 ◽  
Author(s):  
Shoh Sasaki ◽  
Maiko Takeda ◽  
Takanori Hirose ◽  
Tomomi Fujii ◽  
Hiroe Itami ◽  
...  
Keyword(s):  
Cellular Proliferation ◽  
Surrogate Marker ◽  
Progression Free Survival ◽  
Mitotic Rate ◽  
Genetic Alterations ◽  
Homozygous Deletion ◽  
Clinicopathological Features ◽  
Ki 67 ◽  
Who Grade ◽  
Grade 3

Abstract CDKN2A homozygous deletion has occasionally been reported in atypical and anaplastic meningiomas and is considered as one of the genetic alterations commonly involved in their recurrence and malignant progression. Methylthioadenosine phosphorylase (MTAP) immunohistochemistry is a promising surrogate marker for CDKN2A homozygous deletion in different cancers but has not been examined in meningiomas. We performed CDKN2A FISH and MTAP immunohistochemistry on specimens from 30 patients with CNS WHO grade 2 (n = 27) and 3 (n = 3) meningiomas, including specimens from primary and recurrent tumors and then determined whether MTAP immunohistochemistry correlated with CDKN2A homozygous deletion and clinicopathological features. CDKN2A homozygous deletion was detected in 12% (3/26) of CNS WHO grade 2 and 67% (2/3) of CNS WHO grade 3 meningiomas; 3 cases exhibited temporal and/or spatial heterogeneity. MTAP loss was in excellent concordance with CDKN2A homozygous deletion (sensitivity; 100%, specificity; 100%). MTAP loss/CDKN2A homozygous deletion correlated with cellular proliferation (mitotic rate; p = 0.001, Ki-67 labeling index; p = 0.03) and poor prognosis (overall survival; p = 0.01, progression free survival; p &lt; 0.001). Thus, MTAP immunostaining can be a surrogate marker for CDKN2A homozygous deletion in meningiomas, and MTAP loss/CDKN2A homozygous deletion may be an important prognostic factor for meningiomas.

Alternating versus continuous “FOLFIRI” in advanced colorectal cancer (ACC): A randomized “GISCAD” trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3505-3505 ◽  
Author(s):  
R. Labianca ◽  
I. Floriani ◽  
E. Cortesi ◽  
L. Isa ◽  
A. Zaniboni ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Experimental Studies ◽  
Progression Free Survival ◽  
Continuous Treatment ◽  
Who Grade ◽  
Free Survival ◽  
Alternating Chemotherapy ◽  
Grade 3

3505 Background: In ACC “FOLFIRI” is one of the standard regimens and is able to obtain about 40% response rate (RR) with an overall survival (OS) of 17–18 months. Experimental studies (Sobrero, 2000) indicate that an alternating chemotherapy could delay the appearance of cell resistance and reduce the therapeutic load for patients (pts). Methods: In order to evaluate whether intermittent “FOLFIRI” (CPT-11: 180 mg/sqm d1 + l-folinic acid -FA: 100 mg/sqm in 2 hr + 5fluorouracil-5FU: 400 mg/sqm bolus + 600 mg/sqm 22 hr infusion, d 1 and 2 every 2 weeks, for 2 months on and 2 months off) (arm A) was at least as effective as continuous “FOLFIRI” (same regimen, every month) (arm B), until progression in both arms, 336 pts from 27 Centers were randomised from 7/2001 to 6/2005. The characteristics of pts were: median age 64 years (r 29–75), males 214 (63%), PS 0: 222 (66%), liver mets only 166 (49%), multiple mts including liver 80 (24%). Results: RR was 29% in arm A and 35% in arm B, with a median progression-free survival (PFS) of 8.8 and 7.3 months respectively (HR = 1.00, 95% CI: 0.74 - 1.36). At a median follow-up of 27 months, median overall survival (OS), the primary endpoint of the trial, was 16.9 months in arm A and 17.6 in arm B (HR = 1.11, 95% CI: 0.83 - 1.48). Toxicity was acceptable and similar in the 2 arms (WHO grade 3–4 toxicity: neutropenia in 12% pts, diarrhoea in 11%, nausea/vomiting in 4% and fatigue in 3%). Conclusions: Our results demonstrate that alternating “FOLFIRI” obtains the same survival as a continuous treatment, thus reducing the discomfort to pts and the economic costs. No significant financial relationships to disclose.

Gastrointestinal stromal tumors: Institute of Oncology—Dr. “Luis Razetti” experience, Caracas, Venezuela.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e21512-e21512
Author(s):  
Luis Chirinos ◽  
Maria Belen Fuentes ◽  
Maria Angelina Perez ◽  
Gustavo Gotera ◽  
Jesus Felipe Parra ◽  
...  
Keyword(s):  
Overall Survival ◽  
Gastrointestinal Stromal Tumors ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Genetic Alterations ◽  
Adjuvant Imatinib ◽  
Free Survival ◽  
Stromal Tumors ◽  
Localized Disease ◽  
Disease Free

e21512 Background: Gastrointestinal Stromal Tumors are a heterogeneous group of tumors with clinical features and specific genetic alterations, which represent 1-3% of all gastrointestinal cancers. Imatinib, is the standard treatment in advanced and localized disease, and has demonstrated benefit in overall survival, progression free survival and disease free survival. Methods: The primary end point was to evaluate overall survival in patients with locally advanced, metastatic and early stage GIST treated with Imatinib; secondary end points were to evaluate disease-free survival and progression free survival. We included 34 patients with GIST treated between January 2005 and December 2011. Results: The most affected gender was male (55.88%), the average age was 51-60 years (26.47%), and most had localized disease at diagnosis (73.52%), mainly in the stomach (52.94%). As for the primary treatment, 25 underwent surgery (73.5%), applying adjuvant Imatinib in 18 patients (75%).The OS and DFS was higher in patients with localized disease compared with age (p = 0.0001 respectively). Regarding the use of adjuvant Imatinib, it produced clinical benefit in DFS and OS of 50 and 60 months respectively, regardless of risk. In patients with advanced or metastatic disease Imatinib was associated with higher PFS (p = 0.055) and OS (p = 0.1120). Relapses occurred in 24% of patients regardless of risk and the use of Imatinib. Conclusions: In our study we concluded that radical surgery and the use of Imatinib in GIST patients produce important clinical benefits which translate into higher survival rates.

scholarly journals P04.10 IDH-wildtype low grade gliomas: overall survival and prognostic indicators

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii30-iii31
Author(s):  
G Berzero ◽  
A Di Stefano ◽  
S Ronchi ◽  
C Villa ◽  
Y Marie ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Genetic Alterations ◽  
Biological Behavior ◽  
Low Grade ◽  
Rare Tumor ◽  
Who Grade ◽  
Grade Ii ◽  
Chromosome 9P ◽  
Who Grade Ii Gliomas

Abstract BACKGROUND IDH-wildtype WHO grade II diffuse gliomas represent a rare subgroup of low grade tumors characterized by poor prognosis. The clinical and molecular profile associated with these tumors has not been fully elucidated yet, and the ongoing uncertainties regarding their biological behavior hamper to establish a standard of treatment. The aim of this study is to define the median overall survival and the main prognostic factors associated with this rare tumor entity. MATERIALS AND METHODS We performed a retrospective research in our center for all patients diagnosed with diffuse WHO grade II and III gliomas from 1976 to 2018. WHO grade II and III gliomas were divided into three molecular subgroups according to the IDH1/2 mutation and the 1p/19q codeletion status (1: IDH-mutant, 1p/19q codeleted; 2: IDH-mutant, 1p/19q non codeleted; 3: IDH-wildtype). We analyzed the clinical and molecular characteristics of the three subgroups, and then the clinical, radiological, histological and molecular features of IDH-wildtype WHO grade II gliomas. RESULTS We identified 445 patients with diffuse WHO grade II gliomas, including 59 IDH1/2-wildtype tumors. IDH-wildtype grade II gliomas affected more frequently male (75% vs. 55%, p = 0.004) and older (mean age: 50.0 vs. 39.6 years, p<0.0001) patients, had frequent fronto-temporo-insular location (41%) and commonly underwent biopsy (53%) rather than resection. We found TERT promoter mutations (18/42, 43%), chromosome 7q gains (12/30, 40%), chromosome 10q losses (12/44, 27%), chromosome 9p losses (7/47, 15%), EGFR amplifications (5/51, 10%) and p16 deletions (4/50, 8%) but no P53 (0/16) mutations. Median overall survival was 46 months (vs. 98 for IDH-mutant non codeleted and 175 for IDH-mutant codeleted WHO grade II gliomas (p<0.0001); vs. 20 months for IDH-wildtype WHO grade III gliomas (p = 0.001)). Survival was not significantly influenced by age, preoperative KPS, tumor location, extent of resection or adjuvant treatment schemes. Chromosome 9p loss had a strong negative impact on overall survival (p=0.002). CONCLUSION The median overall survival associated with IDH-wildtype WHO grade II gliomas does not exceed 4 years from diagnosis. As some genetic alterations seem to have a strong prognostic impact, an exhaustive genetic assessment can be helpful in this rare tumor group for purposes of prognostic stratification and treatment decision.

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