Diagnosis Of High-grade Glioma Research Articles

Diagnostic Accuracy of PET/CT or PET/MRI Using PSMA-Targeting Radiopharmaceuticals in High-Grade Gliomas: A Systematic Review and a Bivariate Meta-Analysis.

Background: Several studies proposed the use of positron emission tomography (PET) with Prostate Specific Membrane Antigen (PSMA)-targeting radiopharmaceuticals in brain tumors. Our aim is to calculate the diagnostic accuracy of these methods in high-grade gliomas (HGG) with a bivariate meta-analysis. Methods: A comprehensive literature search of studies on the diagnostic accuracy of PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals in HGG was performed. Original articles evaluating these imaging methods both in the differential diagnosis between HGG and low-grade gliomas (LGG) and in the assessment of suspicious HGG recurrence were included. Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and diagnostic odds ratio (DOR) including 95% confidence intervals (95% CI) were calculated. Statistical heterogeneity was also assessed using the I2 test. Results: The meta-analysis of six selected studies (157 patients) provided the following results about PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals in the diagnosis of HGG: sensitivity 98.2% (95% CI: 75.3–99.9%), specificity 91.2% (95% CI: 68.4–98.1%), LR+ 4.5 (95% CI: 2.2–9.3), LR− 0.07 (95% CI: 0.04–0.15), and DOR 70.1 (95% CI: 19.6–250.9). No significant statistical heterogeneity among the included studies was found (I2 = 0%). Conclusions: the quantitative data provided demonstrate the high diagnostic accuracy of PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals for HGG detection. However, more studies are needed to confirm the promising role of PSMA-targeted PET in this clinical setting.

Artificial intelligence for radiomics; diagnostic biomarkers for neuro-oncology

Recent advances in medical image analysis have been made to improve our understanding of how disease develops, behaves, and responds to treatment. Magnetic resonance imaging (MRI) and positron emission tomography (PET) advanced imaging strategies provide structural and functional phenotypic biomarkers that correlate with key disease processes. Through radiomics and radiogenomics, ML-medical imaging has opened up new perspectives in high-grade glioma diagnosis. As a result, non-invasive and in vivo biomarkers for patient survival, tumor recurrence, and genomics are identified. Tumor genomic imaging signatures can help identify patients who benefit from targeted therapies. Molecular characterization of gliomas and prediction of their evolution would allow treatment optimization. Radiomics-based biomarkers allow for a more in-depth analysis of pathophysiologic processes and insights into diagnosing better, classifying, stratifying, and prognosticating brain tumors and assessing their response to therapy. Radiomics is a new data-driven approach that can help answer clinical questions like diagnosis, prognosis, and treatment response. With encouraging outcomes in brain tumor patients, radiomics and deep learning are still not widely used in clinical practice, requiring more extensive and practical clinical studies.

3D-CRT versus RapidArc in Deep Tempero-Parietal High Grade Gliomas: Do We Really Need Higher Technology?

Purpose:The aim of this study was to dosimetrically compare single arc RapidArc with conventional 3D-CRT plans for tempero-parietal high grade gliomas with respect to PTV coverage and doses perceived by surrounding critical organs at risk. Methods:Thirty patients with the pathological diagnosis of high grade gliomas (WHO grade III-IV) were selected to be enrolled in our study. Patients were referred to our center (center of Clinical Oncology and Radiotherapy, Cairo University) during the period March 2020 till June 2021 for post-operative irradiation using 3D-CRT technique. For all patients, the dose prescribed to the planning target volume (PTV) was 60 Gy in 30 fractions. A RA plan was performed for each patient and dosimetrically was compared to the 3D-CRT plan. Results:The PTV coverage in terms of V95% was significantly superior in the RA plans with values of 98.4 ± 1.7 compared to 94.4 ± 2.6 for the 3D-CRT plans (p-value of 0.004). The doses risk structures ( eyes, optic nerves and cochleae) was lower with the RA plans as contrasted to the 3D-CRT plan with an exception for the intraocular lens which received higher doses in the RA plan with a statistically significant p-value of 0.001 and 0.002 for the Ipsilateral and contralateral lens, respectively. The average number of MUs ± SD was 358.6± 44.4 for the RA plans versus 247.6 ± 16.1 for 3D-CRT plans (p-value 0.001). The Dmean of healthy brain tissue was nearly equal for both plans (p-value of 0.071). Conclusion:The plans achieved by RA showed superior dose conformity, PTV coverage, more homogeneous dose distribution when contrasted to 3D-CRT plans. With the exception of both intraocular lenses, the RA plans showed better OAR sparing and utilized a higher number of MUs compared to the 3D-CRT.

Arterial Spin Labeling Perfusion in Determining the IDH1 Status and Ki-67 Index in Brain Gliomas.

The aim of the study was to evaluate the relationship between tumor blood flow (TBF) measured by the pseudo-continuous arterial spin labeling (PCASL) method and IDH1 mutation status of gliomas as well as Ki-67 proliferative index. Methods. The study included 116 patients with newly diagnosed gliomas of various grades. They received no chemotherapy or radiotherapy before MRI. IDH1 status assessment was performed after tumor removal in 106 cases—48 patients were diagnosed with wildtype gliomas (Grade 1–2—6 patients, Grade 3–4—42 patients) and 58 patients were diagnosed with mutant forms of gliomas (Grade 1–2—28 patients, Grade 3–4—30 patients). In 64 cases out of 116 Ki-67 index was measured. Absolute and normalized tumor blood flow values were measured on 3D PCASL maps. Results. TBF and normalized TBF (nTBF) in wildtype gliomas were significantly higher than in IDH1-mutant gliomas (p < 0.001). ASL perfusion showed high values of sensitivity and specificity in the differential diagnosis of gliomas with distinct IDH1 status (for TBF: specificity 75%, sensitivity 77.6%, AUC 0.783, cutoff 80.57 mL/100 g/min, for nTBF: specificity 77.1%, sensitivity 79.3%, AUC 0.791, cutoff 4.7). TBF and nTBF in wildtype high-grade gliomas (HGG) were significantly higher than in mutant forms (p < 0.001). ASL perfusion showed the following values of sensitivity and specificity in the diagnosis of mutant HGG and wildtype HGG (for TBF: specificity 83.3%, sensitivity 60%, AUC 0.719, cutoff 84.18 mL/100 g/min, for nTBF: specificity 88.1%, sensitivity 60%, AUC 0.729, cutoff 4.7). There was a significant positive correlation between tumor blood flow and Ki-67 (for TBF Rs = 0.63, for nTBF Rs = 0.61). Conclusion. ASL perfusion may be an informative factor in determining the IDH1 status in brain gliomas preoperative and tumor proliferative activity.

HIGH GRADE GLIOMA IN A 2 1/2 YEAR OLD: A CASE REPORT

Gliomas are the tumor of glial cells found in Central nervous System. High Grade Gliomas are rare in pediatric age group. Definitive diagnosis is made by histopathological examination. A 2 ½ year old male admitted with the complaint of abnormal tonic-clonic body movements along with headache, nausea, vomiting and fever. CT scan showed a poorly circumscribed hypodense lesion involving frontoparietal region. Surgery was performed and specimen sent for histopathological examination. Histopathological examination showed mfeatures of high grade glioma like microvascular proliferation, necrosis and haemorrhage. Cerebral tumors are the most common childhood neoplastic tumors. Gliomas are generally classified into low grade glioma and high grade glioma. High Grade glioma is rare in pediatric age group. Most commonly they present in supra tentorial compartment. The most common cerebral cortex involved are frontal lobe followed by parietal and temporal. Clinical signs and symptoms of High grade gliomas are seizure, headache, nausea, vomiting and visual disturbances. CT scan showed a poorly circumscribed hypodense lesion involving left frontoparietal region mainly. Definitive diagnosis of high grade glioma is by histopathological examination. Histopathological examination showed hypercellular heterogeneous tumor lying on a fibrillary background. Areas of microvascular proliferation along with necrosis and haemorrhage are also seen. Surgical resection followed by chemotherapy and local radiotherapy are the present recommendation. High grade gliomas are rare pediatric tumor associated with poor outcome. Surgery was performed due to neurological worsening, which was unsuccessful and patient died. Diagnosis was confirmed on histopathological examination. Poor prognosis and high morbidity even after evolution of treatment, demands further research to improve the prognosis and reduce morbidities.

Treatment patterns and outcomes of patients with high-grade glioma during the COVID-19 pandemic.

e14009 Background: During the first year of the COVID-19 pandemic there was global disruption in the provision of healthcare, causing significant pressure on hospital resources. High-grade gliomas (HGG) are rapidly progressive tumors, so patients with delays in diagnosis or treatment due to COVID-19-related disruptions might have poor outcomes. Therefore, we retrospectively evaluated the impact of the COVID-19 pandemic on treatment patterns and outcomes of patients with HGG in British Columbia (BC). Methods: A case cohort with a pathologic diagnosis of HGG (grade 4 astrocytoma and glioblastoma) treated at BC Cancer centers with radiotherapy between March 1, 2020 – March 1, 2021 (“COVID era”), and a control cohort treated between March 1, 2018 – March 1, 2019 (“pre-COVID era”) were identified. Patient demographics, tumor characteristics, treatment details, and dates of radiographic progression and death were included in the chart review. Analyses were performed with one-way ANOVA and Chi-squared tests for comparisons between eras. The Kaplan-Meier method was used to assess progression-free survival (PFS) and overall survival (OS) and differences in outcome between eras were investigated using the log-rank test. Results: 164 patients were identified: 85 in the pre-COVID era and 79 in the COVID era. There was no statistically significant baseline difference in age, sex, comorbidities, ECOG, tumor diameter, IDH mutation status, or MGMT methylation status between eras. There was also no statistically significant difference between time from symptom onset to first imaging, time from first imaging to surgery, time from surgery to oncologic consultation between eras, and time from surgery to radiotherapy. Significantly more patients were managed with biopsy relative to partial or gross total resection during the COVID era 22% (17/79) than the pre-COVID era 13% (11/85) (p = 0.04). However, radiation treatment (RT) did not differ between eras, with similar rates of conventionally fractionated RT in the pre-COVID era (87%, 74/85) and the COVID era (82%, 65/79) (p = 0.23). Use of concurrent and/or adjuvant temozolomide also was not significantly different between eras (p = 0.27 and p = 0.19, respectively). Median PFS was 7.0 months in both eras (CI95 = 5.5 – 8.5 months for pre-COVID era, CI95 = 5.8 – 8.2 months for COVID era, p = 0.3), and median OS was 13 months in the pre-COVID era (CI95 = 10.3 – 15.7 months) and 16 months in the COVID era (CI95 = 11.5 – 20.5 months), though this difference was not significant (p = 0.09). Conclusions: To our knowledge, this is the first study to assess outcomes of patients treated for HGG during the COVID-19 pandemic. We found that, despite less use of surgery in the COVID era, the outcomes of patients with HGG were not affected.

High-grade gliomas: a literature review. Part 2. Radiosurgical treatment

Malignant brain tumors remain one of the most complex problem in modern oncology, being among the most dangerous types of cancer not only because of their poor prognosis, but also due to the immediate consequences for quality of life and cognitive functions. It is expected that the number of such patients will increase as the life expectancy of the population increases.The mortality rate of patients with malignant gliomas remains the highest among all cancer patients. The median survival rate in this population does not exceed 24.5 months. Despite serious progress in the study of the molecular biology of this type of tumor, the question of effective application of this knowledge in the treatment process remains open.The review highlights the most advanced diagnostic methods and analyzes the effectiveness of a multidisciplinary therapeutic strategy. Special attention is given to the search for new approaches to radiosurgical treatment of high-grade gliomas in order to increase the duration and improve the quality of life of patients. The literature review is divided into 2 parts. Part 1 covers the epidemiology, clinic, and diagnosis of high-grade gliomas, as well as a combined approach to the treatment of the disease. In the 2nd part, the issues of stereotactic radiosurgery of high-grade gliomas, the features of the practical application of the “gamma knife” device in this pathology are highlighted; the effectiveness of the multimodal approach to the treatment of malignant gliomas is analyzed.

Re-irradiation for recurrent high grade glioma (HGG) patients: Results of a single arm prospective phase 2 study

Background and purposeStandard of care for recurrent high grade glioma (HGG) is missing. Several treatment options have been investigated including re-irradiation (re-RT). Results are promising but provided by retrospective studies. We designed a single arm prospective phase II study aiming to evaluate efficacy, and toxicity of re-irradiation. Materials and methodsAdults patients with good performance status, HGG diagnosis reclassified according to the new 2021 fifth edition WHO CNS classification, an interval time (IT) from previous RT ≥ 6 months were included. Outcome was evaluated by MRI imaging at 1 month, and every 3 months thereafter. Toxicities were evaluated in terms of radionecrosis occurrence, and neurocognitive status. ResultsNinety recurrent HGG patients were treated, 11 oligodendroglioma grade 3, 18 astrocytoma grade 3 and 4, and 61 glioblastoma grade 4. The median age was 54 years, and majority had KPS 90–100. The median IT between first-RT and re-RT was 24 months. Re-surgery has been performed in 56.6%, and chemotherapy in 53.3%. The median follow up time was 64 months; median overall survival (OS) time,1,2,3-year OS rates were 17 months (95%CI 14–19), 66.7%±4.9, 32.6%±5.0, and 22.2 ± 4.7. Prognostic factors impacting on survival were age (p = 0.0154), IT between first RT and re-RT (p = 0.0051), glioma grade (p = 0.0090), and IDH status (p = 0.0001). Radionecrosis grade 2–3 occurred in 9 (10%) patients; neurocognitive functions remained stable until disease progression. ConclusionRe-RT proved to be a safe and feasible treatment option with low toxicity. Younger patients with grade 3 IDH mutated gliomas, and a longer IT had the better outcome.Trial registration number: NCT02567539

Tracking the Corticospinal Tract in Patients With High-Grade Glioma: Clinical Evaluation of Multi-Level Fiber Tracking and Comparison to Conventional Deterministic Approaches.

While the diagnosis of high-grade glioma (HGG) is still associated with a considerably poor prognosis, neurosurgical tumor resection provides an opportunity for prolonged survival and improved quality of life for affected patients. However, successful tumor resection is dependent on a proper surgical planning to avoid surgery-induced functional deficits whilst achieving a maximum extent of resection (EOR). With diffusion magnetic resonance imaging (MRI) providing insight into individual white matter neuroanatomy, the challenge remains to disentangle that information as correctly and as completely as possible. In particular, due to the lack of sensitivity and accuracy, the clinical value of widely used diffusion tensor imaging (DTI)-based tractography is increasingly questioned. We evaluated whether the recently developed multi-level fiber tracking (MLFT) technique can improve tractography of the corticospinal tract (CST) in patients with motor-eloquent HGGs. Forty patients with therapy-naïve HGGs (mean age: 62.6 ± 13.4 years, 57.5% males) and preoperative diffusion MRI [repetition time (TR)/echo time (TE): 5000/78 ms, voxel size: 2x2x2 mm3, one volume at b=0 s/mm2, 32 volumes at b=1000 s/mm2] underwent reconstruction of the CST of the tumor-affected and unaffected hemispheres using MLFT in addition to deterministic DTI-based and deterministic constrained spherical deconvolution (CSD)-based fiber tractography. The brain stem was used as a seeding region, with a motor cortex mask serving as a target region for MLFT and a region of interest (ROI) for the other two algorithms. Application of the MLFT method substantially improved bundle reconstruction, leading to CST bundles with higher radial extent compared to the two other algorithms (delineation of CST fanning with a wider range; median radial extent for tumor-affected vs. unaffected hemisphere – DTI: 19.46° vs. 18.99°, p=0.8931; CSD: 30.54° vs. 27.63°, p=0.0546; MLFT: 81.17° vs. 74.59°, p=0.0134). In addition, reconstructions by MLFT and CSD-based tractography nearly completely included respective bundles derived from DTI-based tractography, which was however favorable for MLFT compared to CSD-based tractography (median coverage of the DTI-based CST for affected vs. unaffected hemispheres – CSD: 68.16% vs. 77.59%, p=0.0075; MLFT: 93.09% vs. 95.49%; p=0.0046). Thus, a more complete picture of the CST in patients with motor-eloquent HGGs might be achieved based on routinely acquired diffusion MRI data using MLFT.

AI and High-Grade Glioma for Diagnosis and Outcome Prediction: Do All Machine Learning Models Perform Equally Well?

Radiomic models outperform clinical data for outcome prediction in high-grade gliomas (HGG). However, lack of parameter standardization limits clinical applications. Many machine learning (ML) radiomic models employ single classifiers rather than ensemble learning, which is known to boost performance, and comparative analyses are lacking in the literature. We aimed to compare ML classifiers to predict clinically relevant tasks for HGG: overall survival (OS), isocitrate dehydrogenase (IDH) mutation, O-6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, epidermal growth factor receptor vIII (EGFR) amplification, and Ki-67 expression, based on radiomic features from conventional and advanced magnetic resonance imaging (MRI). Our objective was to identify the best algorithm for each task. One hundred fifty-six adult patients with pathologic diagnosis of HGG were included. Three tumoral regions were manually segmented: contrast-enhancing tumor, necrosis, and non-enhancing tumor. Radiomic features were extracted with a custom version of Pyradiomics and selected through Boruta algorithm. A Grid Search algorithm was applied when computing ten times K-fold cross-validation (K=10) to get the highest mean and lowest spread of accuracy. Model performance was assessed as AUC-ROC curve mean values with 95% confidence intervals (CI). Extreme Gradient Boosting (xGB) obtained highest accuracy for OS (74,5%), Adaboost (AB) for IDH mutation (87.5%), MGMT methylation (70,8%), Ki-67 expression (86%), and EGFR amplification (81%). Ensemble classifiers showed the best performance across tasks. High-scoring radiomic features shed light on possible correlations between MRI and tumor histology.

NCMP-06. THE RISK AND BURDEN OF THROMBOEMBOLIC AND HEMORRHAGIC EVENTS IN PATIENTS WITH MALIGNANT GLIOMA RECEIVING BEVACIZUMAB

Abstract BACKGROUND Patients with high-grade gliomas (HGG) often receive anti-angiogenic therapy with bevacizumab to slow disease progression and/or palliate neurological symptoms. Bevacizumab has been associated with an increased risk of two major vascular complications: venous thromboembolism (VTE) and intracranial hemorrhage (ICH). We sought to identify clinical, pathologic, and radiographic variables correlated with risk of either event occurring in patients with HGG receiving bevacizumab. METHODS We retrospectively identified 94 patients with HGG who received bevacizumab at our center from 2015-2021. Variables included demographics, performance status, IDH, MGMT, vascular risk factors, baseline anti-coagulant/anti-platelet use, concurrent chemotherapy, and presence of macrobleeds on MRI (&amp;gt;1 cm3 susceptibility) at the time of bevacizumab initiation. We conducted competing risk analysis using subdistribution hazard models with death as competing risk for ICH or VTE. The effects of covariates on the incidence of hemorrhage or VTE were evaluated in univariate and multivariate settings. RESULTS Of 94 patients, 36 (38.3%) and 27 (28.7%) developed VTE and ICH, respectively. 31 (33%) did not develop either. ICH and VTE events occurred after a mean of 4.46 and 5.94 cycles of bevacizumab, respectively. 20 had baseline anti-platelet/anticoagulant use, and 16 had prior VTEs. Patients with macrobleeds on MRI had a larger HR of developing acute hemorrhage [HR=2.368 (1.112, 5.043), p=0.0254]. Patients older than 50 trended toward larger HR of developing VTE in univariate analysis that approached significance [HR=1.799 (0.889, 3.637), p=0.1023]. Sex, performance status, IDH, MGMT, vascular risk factors, baseline anticoagulant/anti-platelet use and concurrent chemotherapy were not significantly associated with occurrence of VTE. CONCLUSIONS The presence of macrobleeds on MRI is associated with increased risk of developing acute ICH while on bevacizumab. Older age at diagnosis of HGG may be associated with an increased risk of VTE in patients receiving bevacizumab. Larger studies are needed to confirm these findings.

High-grade gliomas: a literature review. Part 1. Epidemiology, classification and approaches to combination treatment

Malignant brain tumors remain one of the most complex problem in modern oncology, being among the most dangerous types of cancer not only because of their poor prognosis, but also due to the immediate consequences for quality of life and cognitive functions. It is expected that the number of such patients will increase as the life expectancy of the population increases.The mortality rate of patients with malignant gliomas remains the highest among all cancer patients. The median survival rate in this population does not exceed 24.5 months. Despite serious progress in the study of the molecular biology of this type of tumor, the question of effective application of this knowledge in the treatment process remains open.The review highlights the most advanced diagnostic methods and analyzes the effectiveness of a multidisciplinary therapeutic strategy. Special attention is given to the search for new approaches to radiosurgical treatment of highgrade gliomas in order to increase the duration and improve the quality of life of patients.The literature review is divided into 2 parts. Part 1 covers the epidemiology, clinic, and diagnosis of high-grade gliomas, as well as a combined approach to the treatment of the disease.

99mTc]Tc-iPSMA SPECT brain imaging as a potential specific diagnosis of metastatic brain tumors and high-grade gliomas

BackgroundPSMA (prostate-specific membrane antigen) protein is heavily expressed in the proliferating microvasculature of high-grade gliomas (HGG) and brain metastases (BM). This research aimed to assess [99mTc]Tc-iPSMA SPECT brain imaging as a potential specific diagnosis of HGG and BM by PSMA-targeting in their proliferating vasculature. MethodsForty-one patients, with suspected brain tumors, as detected by enhanced MRI scanning, were enrolled to undergo preoperative [99mTc]Tc-iPSMA SPECT brain imaging. Semiquantitative image analyses, to evaluate the maximum target-to-background ratio (TBRmax), were performed. All diagnoses were histopathologically confirmed. PSMA expression was evaluated by immunohistochemistry (IHC) in 11 brain tumor tissues. TBRmax values were correlated with IHC results and tumor WHO grade (HGG vs LGG). Results[99mTc]Tc-iPSMA images showed increased uptake in BM, HGG, and recurrent gliomas (TBRmax of 25.1 ± 7.1, 18.5 ± 9.0, 15.0 ± 9.9, respectively), and was negative in treatment-naive patients with LGG and reactive gliosis. PSMA was highly expressed in the vascular endothelium of grade IV gliomas and BM, while its expression was extremely low in LGG and completely absent in gliosis. By using 2.8 as a threshold value for TBRmax, the specificity, sensitivity, PPV, NPV and accuracy were 100%, 94%, 100%, 77% and 95%, respectively. ConclusionsThe results of this pilot study show that [99mTc]Tc-iPSMA SPECT brain imaging is a specific and potentially useful neuroimaging tool for assessing tumoral neovasculature formation in gliomas and brain metastases.

HGG-11. HIGH-GRADE GLIOMAS IN ADOLESCENTS AND YOUNG ADULTS HIGHLIGHT HISTOMOLECULAR DIFFERENCES WITH THEIR ADULT AND PAEDIATRIC COUNTERPARTS

BACKGROUNDConsidering that paediatric high-grade gliomas (HGGs) are biologically distinct from their adult counterparts, the objective of this study was to define the landscape of HGGs in adolescents and young adults (AYAs).METHODSWe performed a multicentric retrospective study of 112 AYAs from adult and paediatric Ile-de-France neurosurgical units, treated between 1998 and 2013 to analyse their clinicoradiological and histomolecular profiles. The inclusion criteria were age between 15 and 25-years, histopathological HGG diagnosis, available clinical data, pre-operative and follow-up MRI. MRI and tumoral samples were centrally reviewed. Immunohistochemistry and complementary molecular techniques such as targeted/next generation sequencing, whole exome sequencing and DNA-methylation analyses were performed to achieve an integrated diagnosis according to the 2016 WHO classification.RESULTSBased on 80 documented AYA patients, HGGs constitute heterogeneous clinicopathological and molecular groups, with a predominant representation of paediatric-subtypes (Histone H3-mutants, 40%) but also adult-subtypes (IDH-mutants, 28%) characterized by the rarity of oligodendrogliomas, IDH-mutant and 1p/19q co-deleted and the relative high frequency of “rare adult IDH mutations” (20%). H3G34-mutants (14%) represent the most specific subgroup in AYAs. In the H3K27-mutant subgroup, the non-brainstem diffuse midline gliomas are more frequent (66.7%) than diffuse intrinsic pontine gliomas (23.8%), contrary to children. We found that WHO grade has no prognostic value, but molecular subgrouping has major prognostic importance.CONCLUSIONSHGGs in AYAs could benefit from a more personalized neuro-oncological management, driven by molecular subtyping rather than age group. Collaborative efforts are needed from paediatric and adult neuro-oncology teams to improve the management of HGGs in AYAs.

Pediatric Diffuse Midline Gliomas H3 K27M-Mutant and Non-Histone Mutant Midline High-Grade Gliomas in Neurofibromatosis Type 1 in Comparison With Non-Syndromic Children: A Single-Center Pilot Study.

Background: Pediatric neurofibromatosis type 1 (NF1) patients rarely develop aggressive central nervous system tumors. Among high-grade gliomas (HGGs), histone mutant diffuse midline gliomas (DMGs H3 K27M-mutant) have exceptionally been reported. The aim of this retrospectives single-center study was to compare the clinical behavior of DMGs H3 K27M-mutant and non-histone mutant midline HGGs in NF1 vs. non-syndromic children and to report imaging features of NF1 HGGs.Method: We conducted a retrospective review of cerebral DMGs H3 K27M-mutant or non-histone mutant HGGs in 18 patients with or without NF1 followed at our institution between 2010 and 2018. Differences in outcomes, notably progression-free survival (PFS) and overall survival (OS), were evaluated.Results: Two patients were identified with genetically confirmed diagnosis of NF1 and cerebral HGGs (one DMG H3 K27M-mutant and one histone wild type). Both subjects presented with midline mass lesions with imaging features of aggressive biological activity on advanced MRI or amino-acid PET. During the same time period, 16 non-NF1 patients (11 subjects with DMGs H3 K27M-mutant and 5 with non-histone mutant midline HGGs) were treated at our institution. The two patients with NF1 and HGGs presented a PFS of 3 months and an OS of 5 and 7 months. Median PFS and OS of children without NF1 were respectively 6 and 10 months in DMGs H3 K27M-mutant, and 6 and 11 months in H3 K27M wild-type tumors. Seventy-five percent of subjects with non-NF1 HGGs presented a PFS >4 months compared to 0% in NF1 patients. The 8-month OS of patients with non-NF1 HGGs was 81% compared to 0% in NF1 patients.Conclusions: Cerebral HGGs arising in midline structures rarely occur in pediatric patients with NF1 and present with extremely poor prognosis, worse than HGGs developing in non-NF1 patients, independent of the presence or absence of H3 K27M mutation. Imaging features of aggressive biological activity on advanced MRI or amino-acid PET imaging suggest prompt neuropathological and molecular investigations.

External beam radiation dose escalation for high grade glioma.

External beam radiation dose escalation for high grade glioma.

High-grade gliomas in adolescents and young adults highlight histomolecular differences from their adult and pediatric counterparts

Considering that pediatric high-grade gliomas (HGGs) are biologically distinct from their adult counterparts, the objective of this study was to define the landscape of HGGs in adolescents and young adults (AYAs). We performed a multicentric retrospective study of 112 AYAs from adult and pediatric Ile-de-France neurosurgical units, treated between 1998 and 2013 to analyze their clinicoradiological and histomolecular profiles. The inclusion criteria were age between 15 and 25 years, histopathological HGG diagnosis, available clinical data, and preoperative and follow-up MRI. MRI and tumoral samples were centrally reviewed. Immunohistochemistry and complementary molecular techniques such as targeted/next-generation sequencing, whole exome sequencing, and DNA-methylation analyses were performed to achieve an integrated diagnosis according to the 2016 World Health Organization (WHO) classification. Based on 80 documented AYA patients, HGGs constitute heterogeneous clinicopathological and molecular groups, with a predominant representation of pediatric subtypes (histone H3-mutants, 40%) but also adult subtypes (isocitrate dehydrogenase [IDH] mutants, 28%) characterized by the rarity of oligodendrogliomas, IDH mutants, and 1p/19q codeletion and the relative high frequency of "rare adult IDH mutations" (20%). H3G34-mutants (14%) represent the most specific subgroup in AYAs. In the H3K27-mutant subgroup, non-brainstem diffuse midline gliomas are more frequent (66.7%) than diffuse intrinsic pontine gliomas (23.8%), contrary to what is observed in children. We found that WHO grade has no prognostic value, but molecular subgrouping has major prognostic importance. HGGs in AYAs could benefit from a specific classification, driven by molecular subtyping rather than age group. Collaborative efforts are needed from pediatric and adult neuro-oncology teams to improve the management of HGGs in AYAs.

419P - Venous thromboembolism and intracranial hemorrhage in patients with high-grade glioma

BackgroundPatients with high-grade glioma (HGG) are at increased risk of venous thromboembolism (VTE), throughout the course of disease. Prophylactic anticoagulation is not established outside of perioperative context, due to potential for intracranial hemorrhage (ICH) and the limited data available for predictive VTE scores. Our study aims to characterize VTE risk and assess anticoagulation safety in HGG. MethodsRetrospective analysis of adult patients with HGG diagnosis, proposed to systemic treatment between 2009 and 2018. Exclusion criteria was anticoagulation previous to diagnosis. VTE was defined as radiographic-confirmed thrombus in venous system. Risk factors for VTE and ICH were analyzed by chi-squared test and multivariate logistic regression; survival analysis by Kaplan-Meier method. ResultsOf 410 patients, 31 (7,8%) developed a VTE, including 22 deep, 6 pulmonary and 3 central vein thrombosis. Twenty-nine patients with VTE had WHO grade 4 glioma and 2 patients had grade 3 (anaplastic astrocytoma and oligodendroglioma). In 22 cases, the VTE occurred during systemic treatment, more frequently during Temozolomide (n=15), followed by Irinotecan+Bevacizumab (n=6). The median time to VTE was 10,11 months. Khorana score, age, ECOG performance status, smoking and obesity did not significantly differ in the VTE population. All VTE were initially treated with low molecular weight heparin (LMWH), of which 64.5% maintained LMWH, and the remainder switched to warfarin (19.4%) or to direct oral anticoagulant (16.1%). Six patients (19,4%) had spontaneous ICH under anticoagulation. Patients with grade 3 glioma (p=0,032) had significantly higher rates of ICH. Patients with higher ECOG had significantly higher risk of ICH (OR 3,23 (95CI 1,18-8,81), p=0,022). HAS-BLED and ACCP bleeding scores were not associated with ICH. There was no significant difference in overall survival for TVE or ICH. ConclusionsAccording to our data, ICH occurred in nearly 20% anticoagulated patients with HGG, as described in literature, and did not correlate with poorer prognosis. High ECOG performance status was an independent risk factor for ICH. Further effort towards better prediction models for VTE and ICH in HGG is warranted. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Palliative Care in Patients With High-Grade Gliomas in the Neurological Intensive Care Unit.

Palliative care improves quality of life in patients with malignancy; however, it may be underutilized in patients with high-grade gliomas (HGGs). We examined the practices regarding palliative care consultation (PCC) in treating patients with HGGs in the neurological intensive care unit (NICU) of an academic medical center. We conducted a retrospective cohort study of patients admitted to the NICU from 2011 to 2016 with a previously confirmed histopathological diagnosis of HGG. The primary outcome was the incidence of an inpatient PCC. We also evaluated the impact of PCC on patient care by examining its association with prespecified secondary outcomes of code status amendment to do not resuscitate (DNR), discharge disposition, 30-day mortality, and 30-day readmission rate, length of stay, and place of death. Ninety (36% female) patients with HGGs were identified. Palliative care consultation was obtained in 16 (18%) patients. Palliative care consultation was associated with a greater odds of code status amendment to DNR (odds ratio [OR]: 18.15, 95% confidence interval [CI]: 5.01-65.73), which remained significant after adjustment for confounders (OR: 27.20, 95% CI: 5.49-134.84), a greater odds of discharge to hospice (OR: 24.93, 95% CI: 6.48-95.88), and 30-day mortality (OR: 6.40, 95% CI: 1.96-20.94). In this retrospective study of patients with HGGs admitted to a university-based NICU, PCC was seen in a minority of the sample. Palliative care consultation was associated with code status change to DNR and hospice utilization. Further study is required to determine whether these findings are generalizable and whether interventions that increase PCC utilization are associated with improved quality of life and resource allocation for patients with HGGs.

Evaluation of the Impact of Magnetic Resonance Imaging (MRI) on Gross Tumor Volume (GTV) Definition for Radiation Treatment Planning (RTP) of Inoperable High Grade Gliomas (HGGs)

Aim and Background. Inoperable high-grade gliomas (HGGs) comprise a specific group of brain tumors portending a very poor prognosis. In the absence of surgical management, radiation therapy (RT) offers the primary local treatment modality for inoperable HGGs. Optimal target definition for radiation treatment planning (RTP) of HGGs is a difficult task given the diffusely infiltrative nature of the disease. In this context, detailed multimodality imaging information may add to the accuracy of target definition in HGGs. We evaluated the impact of Magnetic Resonance Imaging (MRI) on Gross Tumor Volume (GTV) definition for RTP of inoperable HGGs in this study. Materials and Methods. Twenty-five inoperable patients with a clinical diagnosis of HGG were included in the study. GTV definition was based on Computed Tomography- (CT-) simulation images only or both CT-simulation and MR images, and a comparative assessment was performed to investigate the incorporation of MRI into RTP of HGGs. Results. Median volume of GTV acquired by using CT-simulation images only and by use of CT and MR images was 65.3 (39.6-94.3) cc and 76.1 (46.8-108.9) cc, respectively. Incorporation of MRI into GTV definition has resulted in a median increase of 12.61% (6%-19%) in the volume of GTV defined by using the CT-simulation images only, which was statistically significant (p &lt; 0.05). Conclusion. Incorporation of MRI into RTP of inoperable HGGs may improve GTV definition and may have implications for dose escalation/intensification strategies despite the need for further supporting evidence.