Distinct IDH1/IDH2 mutation profiles in purely insular versus paralimbic WHO Grade II gliomas

2013 ◽  
Vol 118 (4) ◽  
pp. 866-872 ◽  
Author(s):  
Catherine Gozé ◽  
Lamisse Mansour ◽  
Valérie Rigau ◽  
Hugues Duffau

Object The molecular profile of diffuse WHO Grade II gliomas involving the insular lobe, with a possible impact on outcome, is controversial. The authors undertook this study to investigate a possible difference of molecular patterns between purely insular Grade II gliomas and paralimbic Grade II gliomas that involve both the insular lobe and the frontal and/or temporal structures. Methods From a consecutive series of 47 patients who underwent resection of a Grade II glioma invading the insula, 2 subgroups were identified. The first subgroup included 11 patients with a purely insular tumor. The second subgroup included 36 patients with a paralimbic Grade II glioma also involving the frontal and/or temporal lobe. The authors searched systematically for TP53 mutations, 1p19q codeletion, and IDH1/IDH2 mutations. Results There was no significant difference between the 2 subgroups with respect to 1p19q codeletion or TP53 mutations rates. Conversely, IDH1/IDH2 mutations were found in all 11 (100%) of the insular Grade II gliomas but only 20 (55%) of 36 paralimbic Grade II gliomas (p = 0.008). Ten (28%) of the 36 patients in the paralimbic tumor group experienced a malignant transformation, and 6 of them died; whereas neither transformation nor death occurred in the insular tumor group (trend toward significance, p = 0.088). Conclusions These findings demonstrate for the first time distinct IDH1/IDH2 and consequently distinct “triplenegative” patterns in purely insular versus paralimbic Grade II gliomas. Such findings could explain discrepancies reported in the literature, because insular and paralimbic gliomas have not been separated in previous reports. These results may enable physicians to refine the management of Grade II gliomas involving the insula according to the presence or lack of invasion of the frontal and/or temporal areas.

2009 ◽  
Vol 110 (4) ◽  
pp. 696-708 ◽  
Author(s):  
Hugues Duffau

Object Few experiences of insular surgery have been reported. Moreover, there are no large surgical studies with long-term follow-up specifically dedicated to WHO Grade II gliomas involving the insula. In this paper, the author describes a personal consecutive series of 51 cases in which patients underwent surgery for an insular Grade II glioma. On the basis of the functional and oncological results, advances and limitations of this challenging surgery are discussed. Methods Fifty-one patients harboring an insular Grade II glioma (revealed by seizures in 50 cases) underwent surgery. Findings on preoperative neurological examination were normal in 45 patients (88%). All surgeries were conducted under cortico-subcortical stimulation, and in the case of 16 patients while awake. Results Despite an immediate postoperative worsening in 30 cases (59%), the condition of all but 2 patients (96%) returned to baseline or better. Postoperative MR imaging demonstrated that 77% of resections were total or subtotal. Ten patients underwent a second or third surgery, with no additional deficit. Forty-two patients (82%) are alive with a median follow-up of 4 years. Conclusions This is the largest reported experience with insular Grade II glioma surgery. The better knowledge of the insular pathophysiology and the use of intraoperative functional mapping allow the risk of permanent deficit to be minimized (and even enable improvement in quality of life) while increasing the extent of resection and thus the impact on the course of the disease. Therefore, surgical removal must always be considered for insular Grade II glioma. However, this surgery remains challenging, especially within the anterior perforating substance and the posterior part of the (dominant) insula. Additional surgery can be suggested in cases in which the first resection is not complete.


Oncotarget ◽  
2015 ◽  
Vol 6 (30) ◽  
pp. 30295-30305 ◽  
Author(s):  
Heather E. Leeper ◽  
Alissa A. Caron ◽  
Paul A. Decker ◽  
Robert B. Jenkins ◽  
Daniel H. Lachance ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Ziwen Fan ◽  
Zhiyan Sun ◽  
Shengyu Fang ◽  
Yiming Li ◽  
Xing Liu ◽  
...  

PurposeThe present study aimed to preoperatively predict the status of 1p/19q based on radiomics analysis in patients with World Health Organization (WHO) grade II gliomas.MethodsThis retrospective study enrolled 157 patients with WHO grade II gliomas (76 patients with astrocytomas with mutant IDH, 16 patients with astrocytomas with wild-type IDH, and 65 patients with oligodendrogliomas with mutant IDH and 1p/19q codeletion). Radiomic features were extracted from magnetic resonance images, including T1-weighted, T2-weighted, and contrast T1-weighted images. Elastic net and support vector machines with radial basis function kernel were applied in nested 10-fold cross-validation loops to predict the 1p/19q status. Receiver operating characteristic analysis and precision-recall analysis were used to evaluate the model performance. Student’s t-tests were then used to compare the posterior probabilities of 1p/19q co-deletion prediction in the group with different 1p/19q status.ResultsSix valuable radiomic features, along with age, were selected with the nested 10-fold cross-validation loops. Five features showed significant difference in patients with different 1p/19q status. The area under curve and accuracy of the predictive model were 0.8079 (95% confidence interval, 0.733–0.8755) and 0.758 (0.6879–0.8217), respectively, and the F1-score of the precision-recall curve achieved 0.6667 (0.5201–0.7705). The posterior probabilities in the 1p/19q co-deletion group were significantly different from the non-deletion group.ConclusionCombined radiomics analysis and machine learning showed potential clinical utility in the preoperative prediction of 1p/19q status, which can aid in making customized neurosurgery plans and glioma management strategies before postoperative pathology.


Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 342 ◽  
Author(s):  
Enrico Franceschi ◽  
Dario De Biase ◽  
Vincenzo Di Nunno ◽  
Annalisa Pession ◽  
Alicia Tosoni ◽  
...  

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.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii83-ii83
Author(s):  
Nilan Vaghjiani ◽  
Andrew Schwieder ◽  
Sravya Uppalapati ◽  
Zachary Kons ◽  
Elizabeth Kazarian ◽  
...  

Abstract PURPOSE Radiation-induced meningiomas (RIMs) are associated with previous exposure to therapeutic irradiation. RIMs are rare and have not been well characterized relative to spontaneous meningiomas (SMs). METHODS 1003 patients with proven or presumed meningiomas were identified from the VCU brain tumor database. Chart review classified RIM patients and their characteristics. RESULTS Of the 1003 total patients, 76.47% were female with a mean ± SD age of 67.55 ± 15.50 years. 15 RIM patients were identified (66.67% female), with a mean ± SD age of 52.67 ± 15.46 years, 5 were African American and 10 were Caucasian. The incidence of RIMs was 1.49% in our data set. The mean age at diagnosis was 43.27 ± 15.06 years. The mean latency was 356.27 ± 116.96 months. The mean initiating dose was 44.28 ± 14.68 Gy. There was a significant difference between mean latency period and ethnicity, 258.3 months for African American population, and 405.2 months for Caucasian population (p = 0.003). There was a significant difference between the mean number of lesions in females (2.8) versus males (1.2; p = 0.046). Of the RIMs with characterized histology, 6 (55%) were WHO grade II and 5 (45%) were WHO grade I, demonstrating a prevalence of grade II tumors approximately double that found with SMs. RIMs were treated with combinations of observation, surgery, radiation, and medical therapy. Of the 8 patients treated with radiation, 4 demonstrated response. 8 of the 15 patients (53%) demonstrated recurrence/progression despite treatment. CONCLUSION RIMs are important because of the associated higher grade histology, gender, and ethnic incidences, and increased recurrence/progression compared to SMs. Despite the presumed contributory role of prior radiation, RIMs demonstrate a significant rate of responsiveness to radiation treatment.


2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii28-ii28
Author(s):  
X Xue ◽  
Q Gao

Abstract OBJECTIVE WHO grade II glioma has the characteristics of heterogeneity, and this disease progresses rapidly in some patients, in whom the malignant degree is equivalent to that of high-grade glioma. In order to accurately predict the prognosis of patients, an effective clinical prediction model based on relevant risk factors is needed which could provide a theoretical basis for optimization of clinical individualized treatment. METHODS According to the inclusion and exclusion criteria, eligible patients from January 2010 to December 2018 in our hospital were selected, and those who met the criteria were randomly assigned 4:1 to the training group and the validation group, respectively. The predictors were screened by univariate and multivariate Cox regression analysis, the prediction model was established, and the model was verified and evaluated. RESULTS A total of 258 patients with WHO grade II glioma were recruited, including 208 patients as the training group and 50 patients as the validation group. Six independent risk factors, including patient age, preoperative Karnofsky performance status (KPS) score, preoperative seizure symptoms, surgical resection range, tumor size and IDH status, were selected and included into the prediction model by univariate and multivariate Cox regression analysis, and were visualized in the form of Nomogram. The concordance index (C index) was used to evaluate the predictive ability of the model. Results showed that the C-index was 0.832 in the training group and 0.853 in the validation group, respectively, indicating good performance for the prediction model. The calibration charts were drawn in both groups respectively, which showed that the calibration lines were in good agreement with the standard lines, indicating good consistency between the two groups. CONCLUSIONS In this study, a clinical prediction model for WHO grade II glioma was established, and it was verified that the model has good predictive ability, which may be beneficial for clinical work.


Neurosurgery ◽  
2019 ◽  
Vol 86 (1) ◽  
pp. E64-E74 ◽  
Author(s):  
Moritz Scherer ◽  
Hajrulla Ahmeti ◽  
Constantin Roder ◽  
Florian Gessler ◽  
Christine Jungk ◽  
...  

Abstract BACKGROUND In diffuse WHO grade II gliomas (LGG), the extent of resection (EOR) required to achieve significant survival benefits remains elusive. OBJECTIVE To evaluate the association of residual volume (RV) and EOR with progression-free survival (PFS) or overall survival (OS) in LGG in a retrospective, multicenter series by the German study group of intraoperative MRI (GeSGIM). METHODS Consecutive cases were retrospectively assessed from 5 centers. Tumors were volumetrically quantified before and after surgery, and clinical data were analyzed, including IDH mutations and neurologic deficits. Kaplan–Meier estimates, accelerated failure time models (AFT), and multivariate Cox regression models were calculated to identify determinants of survival. RESULTS A total of 140 cases were analyzed. Gross total resection (GTR) was associated with significantly longer PFS compared to any incomplete resection (P = .009). A significant survival disadvantage was evident even for small (&gt;0-5 ml) residuals and increased for moderate (&gt;5-20 ml) and large remnants (&gt;20 ml) P = .001). Accordingly, PFS increased continuously for 20% incremental steps of EOR (P &lt; .001). AFT models supported the notion of a continuous association of RV and EOR with PFS. Multivariate Cox regression models confirmed RV (P = .01) and EOR (P = .005) as continuous prognosticators of PFS. Univariate analysis showed significant associations of RV and EOR with OS. CONCLUSION Our data support the hypothesis of a continuous relationship of RV and EOR with survival for LGG with superiority seen for GTR. Hence, GTR should be achieved whenever safely feasible, and resections should be maximized whenever tumor has to be left behind to spare function.


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