P04.11 10-Year Institutional Retrospective Case Series of WHO Grade II Gliomas and Correlation of Seizures, Lobar Location, Histopathological Subtype and IDH-1 Mutation (2010–2020)

BACKGROUND A 10-year retrospective case series was undertaken of all patients who had a tissue diagnosis of a World Health Organisation (WHO) Grade II glioma, i.e. low grade glioma (LGGM), at the Institute of Neurological Sciences (INS) between January 2010 and January 2020 (NB: pre-2016 World Health Organisation classification). The objective was to assess the correlation of World Health Organisation (WHO) Grade II gliomas to seizure symptomology, intracerebral tumour location, histopathological glioma sub-type and molecular markers including isocitrate dehydrogenase-1 (IDH-1) mutation. MATERIAL AND METHODS We extracted data regarding clinical, radiological, histological, molecular discriminators and functional outcomes in patients. The pre-operative symptomology was restricted to seizures, headache and focal neurological deficits. RESULTS 84 patients underwent resection and had a mean age of 42rs (range: 21-77yrs]). Seizures (NB: pre-2017 International League against Epilepsy classification [ILAE]) occurred in 71% and of these 52% were generalised, 37% partial and 11% mixed. 31% had ongoing seizures postoperatively. Headache occurred in 38% (of these 50% had headache and seizures). Focal neurological deficits (FNDs) occurred in 21% (of these 61% had FNDs and seizures). Seizure, as an isolated pre-operative symptom occurred in 48% patients compared to isolated headache in 10% and isolated FNDs in 4%. Anatomically, 58% of lesions were frontal. The seizure spatial frequency was 60% frontal. Histologically, 60% were diffuse astrocytomas and 40% oligodendrogliomas. Furthermore, 71% of oligodendrogliomas and 49% of diffuse astrocytomas had a frontal location. IDH-1 mutation occurred in 80% patients (75% of these had seizures) and of these 66% were frontal. CONCLUSIONS Our analysis confirms a correlation between incidence of seizures, frontal lobar location, histopathological subtype and IDH-1 mutations (p = <0.05

Preoperative Radiomics Analysis of 1p/19q Status in WHO Grade II Gliomas

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.

Radiomics Features Predict Telomerase Reverse Transcriptase Promoter Mutations in World Health Organization Grade II Gliomas via a Machine-Learning Approach

The detection of mutations in telomerase reverse transcriptase promoter (pTERT) is important since preoperative diagnosis of pTERT status helps with evaluating prognosis and determining the surgical strategy. Here, we aimed to establish a radiomics-based machine-learning algorithm and evaluated its performance with regard to the prediction of mutations in pTERT in patients with World Health Organization (WHO) grade II gliomas. In total, 164 patients with WHO grade II gliomas were enrolled in this retrospective study. We extracted a total of 1,293 radiomics features from multi-parametric magnetic resonance imaging scans. Elastic net (used for feature selection) and support vector machine with linear kernel were applied in nested 10-fold cross-validation loops. The predictive model was evaluated by receiver operating characteristic and precision-recall analyses. We performed an unpaired t-test to compare the posterior predictive probabilities among patients with differing pTERT statuses. We selected 12 valuable radiomics features using nested 10-fold cross-validation loops. The area under the curve (AUC) was 0.8446 (95% confidence interval [CI], 0.7735–0.9065) with an optimal summed value of sensitivity of 0.9355 (95% CI, 0.8802–0.9788) and specificity of 0.6197 (95% CI, 0.5071–0.7371). The overall accuracy was 0.7988 (95% CI, 0.7378–0.8598). The F1-score was 0.8406 (95% CI, 0.7684–0.902) with an optimal precision of 0.7632 (95% CI, 0.6818–0.8364) and recall of 0.9355 (95% CI, 0.8802–0.9788). Posterior probabilities of pTERT mutations were significantly different between patients with wild-type and mutant TERT promoters. Our findings suggest that a radiomics analysis with a machine-learning algorithm can be useful for predicting pTERT status in patients with WHO grade II glioma and may aid in glioma management.

ACTR-20. EFFICACY OF INITIAL TEMOZOLOMIDE FOR HIGH-RISK LOW GRADE GLIOMAS IN A PHASE II AINO (ITALIAN ASSOCIATION FOR NEURO-ONCOLOGY) STUDY: A POST-HOC ANALYSIS WITHIN MOLECULAR SUBGROUPS OF WHO 2016

BACKGROUND The optimal management of high risk WHO grade II gliomas after surgery is still debated. The efficacy of initial temozolomide to delay radiotherapy and risk of cognitive defects could vary across the molecular subgroups of WHO 2016, but information on this issue are lacking. PATIENTS AND METHODS A post-hoc analysis has been performed on a cohort of high risk WHO grade II gliomas, who received initial temozolomide alone in phase II multicenter study, with the objective of re-evaluating the long-term results across the different molecular subgroups of the WHO 2016 classification. The primary endpoint of the study, carried out between 2007 and 2010, was response rate according to RANO, being seizure response, PFS and OS secondary endpoints. RESULTS Response rate (partial and minor responses) among oligodendrogliomas IDH-mutant and 1p/19q codeleted (76%) was significantly higher than that among diffuse astrocytomas either mutant (55%) or wild-type (36%). A reduction of seizure frequency >50% was observed in 87% patients and a seizure freedom in 72%. The probability of seizure reduction >50% was significantly associated with the presence of an IDH mutation. Median PFS, PFS at 5 and 10 years, median OS and OS at 5 and 10 years were all significantly longer in oligodendrogliomas IDH-mutant and 1p/19q codeleted. Of patients who did not recur or delay radiotherapy at recurrence for a median follow-up of 8.2 years, 67% and 59%, respectively, were oligodendrogliomas IDH-mutant and 1p/19q codeleted. CONCLUSIONS The post-hoc analysis of this phase II trial suggests that the beneficial effects of initial temozolomide prevail in oligodendrogliomas IDH-mutant and 1p/19q codeleted: thus, these tumors, when incompletely resected or progressive after surgery, especially when suffering from pharmacoresistant seizures, could receive temozolomide as initial treatment with radiotherapy and chemotherapy at recurrence. The trial was registered with EU Clinical Trials Register, EudraCT n. 2007/000386-38.

Surgery for Diffuse WHO Grade II Gliomas: Volumetric Analysis of a Multicenter Retrospective Cohort From the German Study Group for Intraoperative Magnetic Resonance Imaging

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 (>0-5 ml) residuals and increased for moderate (>5-20 ml) and large remnants (>20 ml) P = .001). Accordingly, PFS increased continuously for 20% incremental steps of EOR (P < .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.

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

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.