scholarly journals Phase II open-label, global study evaluating dabrafenib in combination with trametinib in pediatric patients with BRAF V600–mutant high-grade glioma (HGG) or low-grade glioma (LGG)

2018 ◽  
Vol 29 ◽  
pp. viii132 ◽  
Author(s):  
D. Hargrave ◽  
O. Witt ◽  
K. Cohen ◽  
R. Packer ◽  
A. Lissat ◽  
...  
Keyword(s):  
Phase Ii ◽  
Pediatric Patients ◽  
High Grade Glioma ◽  
Low Grade Glioma ◽  
Low Grade ◽  
High Grade ◽  
Open Label ◽  
Global Study

scholarly journals SURG-32. THE USE OF 5-AMINOLEVULINIC ACID IN LOW-GRADE GLIOMA RESECTION: A SYSTEMATIC REVIEW

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi246-vi246
Author(s):  
Ahmad Almekkawi ◽  
Tarek El Ahmadieh ◽  
Karl Abi-Aad ◽  
Salah Aoun ◽  
Najib EL Tecle ◽  
...  
Keyword(s):  
Systematic Review ◽  
Quality Index ◽  
Aminolevulinic Acid ◽  
High Grade Glioma ◽  
Extent Of Resection ◽  
Low Grade Glioma ◽  
Low Grade ◽  
High Grade ◽  
Visualization Technology ◽  
Glioma Resection

Abstract BACKGROUND 5-aminolevulinic acid is a reliable tool for optimizing high-grade glioma resection. However, its efficacy in low-grade glioma resection remains unclear. OBJECTIVE To study the role of 5-aminolevulinic acid in low-grade glioma resection and assess positive fluorescence rates and effect on the extent of resection. METHODS A systematic review of PubMed, Google Scholar, and Cochrane was performed from the date of inception to February 1, 2019. Studies that correlated 5-aminolevulinic acid fluorescence with low-grade glioma in the setting of operative resection were selected. Studies with biopsy only were excluded. Positive fluorescence rates were calculated. Quality index of the selected papers using the Downs and Black criteria checklist was provided. RESULTS Twelve articles met the selection criteria with 244 histologically-confirmed low-grade glioma patients who underwent microsurgical resection. All patients received 20 mg/kg body weight of 5-aminolevulinic acid. Only 60 patients (n=60/244; 24.5%) demonstrated visual intra-operative 5-aminolevulinic acid fluorescence. The extent of resection was reported in 4 studies, however, the data combined low- and high-grade tumors. Only 2 studies reported on tumor location. Only 3 studies reported on clinical outcomes. The Zeiss OPMI Pentero microscope was most commonly used across all studies. The average quality index was 14.58 (range: 10–17) which correlated with an overall good quality. CONCLUSION There is an overall low correlation between 5-aminolevulinic acid fluorescence and low-grade glioma. Advances in visualization technology and using standardized fluorescence quantification methods may further improve the visualization and reliability of 5-aminolevulinic acid fluorescence in low-grade glioma resection.

scholarly journals Phase II, Open-Label, Randomized, Multicenter Trial (HERBY) of Bevacizumab in Pediatric Patients With Newly Diagnosed High-Grade Glioma

2018 ◽  
Vol 36 (10) ◽  
pp. 951-958 ◽  
Author(s):  
Jacques Grill ◽  
Maura Massimino ◽  
Eric Bouffet ◽  
Amedeo A. Azizi ◽  
Geoffrey McCowage ◽  
...  
Keyword(s):  
Adverse Events ◽  
Pediatric Patients ◽  
Group Versus ◽  
High Grade Glioma ◽  
Hazard Ratio ◽  
High Grade ◽  
Newly Diagnosed ◽  
Review Committee ◽  
Open Label ◽  
Risk Of Death

Purpose Bevacizumab (BEV) is approved in more than 60 countries for use in adults with recurrent glioblastoma. We evaluated the addition of BEV to radiotherapy plus temozolomide (RT+TMZ) in pediatric patients with newly diagnosed high-grade glioma (HGG). Methods The randomized, parallel group, multicenter, open-label HERBY trial ( ClinicalTrials.gov identifier: NCT01390948) enrolled patients age ≥ 3 years to ≤ 18 years with localized, centrally neuropathology-confirmed, nonbrainstem HGG. Eligible patients were randomly assigned to receive RT + TMZ (RT: 1.8 Gy, 5 days per week, and TMZ: 75 mg/m2 per day for 6 weeks; 4-week treatment break; then up to 12 × 28-day cycles of TMZ [cycle 1: 150 mg/m2 per day, days 1 to 5; cycles 2 to 12: 200 mg/m2 per day, days 1 to 5]) with or without BEV (10 mg/kg every 2 weeks). The primary end point was event-free survival (EFS) as assessed by a central radiology review committee that was blinded to treatment. We report findings of EFS at 12 months after the enrollment of the last patient. Results One hundred twenty-one patients were enrolled (RT+TMZ [n = 59]; BEV plus RT+TMZ [n = 62]). Central radiology review committee–assessed median EFS did not differ significantly between treatment groups (RT+TMZ, 11.8 months; 95% CI, 7.9 to 16.4 months; BEV plus RT+TMZ, 8.2 months; 95% CI, 7.8 to 12.7 months; hazard ratio, 1.44; P = .13 [stratified log-rank test]). In the overall survival analysis, the addition of BEV did not reduce the risk of death (hazard ratio, 1.23; 95% CI, 0.72 to 2.09). More patients in the BEV plus RT+TMZ group versus the RT+TMZ group experienced one or more serious adverse events (n = 35 [58%] v n = 27 [48%]), and more patients who received BEV discontinued study treatment as a result of adverse events (n = 13 [22%] v n = 3 [5%]). Conclusion Adding BEV to RT+TMZ did not improve EFS in pediatric patients with newly diagnosed HGG. Our findings were not comparable to those of previous adult trials, which highlights the importance of performing pediatric-specific studies.

scholarly journals RARE-07. EFFICACY AND SAFETY OF LAROTRECTINIB IN PEDIATRIC PATIENTS WITH TROPOMYOSIN RECEPTOR KINASE (TRK) FUSION-POSITIVE PRIMARY CENTRAL NERVOUS SYSTEM (CNS) TUMORS

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i42-i42
Author(s):  
Sébastien Perreault ◽  
François Doz ◽  
Birgit Geoerger ◽  
Karsten Nysom ◽  
Ingrid Øra ◽  
...  
Keyword(s):  
Disease Control ◽  
Pediatric Patients ◽  
Objective Response ◽  
High Grade Glioma ◽  
Disease Control Rate ◽  
Cns Tumors ◽  
Glioneuronal Tumor ◽  
Low Grade ◽  
High Grade ◽  
Gene Fusions

Abstract Background NTRK gene fusions are oncogenic drivers in various CNS and non-CNS tumors. Larotrectinib is a highly selective TRK inhibitor approved to treat patients with TRK fusion cancer, with an objective response rate (ORR) of 78% across multiple non-CNS cancers (McDermott et al, ESMO 2020). We report updated data on pediatric patients with TRK fusion-positive primary CNS tumors. Methods Patients aged <18 years with primary CNS tumors harboring an NTRK gene fusion enrolled in two clinical trials (NCT02637687, NCT02576431) were identified. Larotrectinib was administered until disease progression, withdrawal, or unacceptable toxicity. Response was investigator assessed. Results By July 2020, 26 pediatric patients with TRK fusion-positive CNS tumors were treated. Tumor histologic subtypes included high-grade glioma (n=13), low-grade glioma (n=7), glioneuronal tumor (n=2), neuroepithelial tumor (n=2), CNS neuroblastoma (n=1), and small round blue cell tumor (n=1). Median age was 7.0 years (range 1.3–16.7). The ORR was 38% (95% CI 20–59%): 3 complete responses, 7 partial responses (including 2 pending confirmation), 14 stable disease, and 2 progressive disease. The ORR in patients with high-grade glioma was 38% (95% CI 14–68%). Nineteen of 21 patients (90%) with measurable disease had tumor shrinkage. The 24-week disease control rate was 77% (95% CI 56–91%). Median duration of response (DoR), PFS and overall survival (OS) were not reached. The 12-month rates for DoR, PFS and OS were 75%, 65%, and 86%, respectively. Duration of treatment ranged from 1.2 to 31.3+ months. Treatment-related adverse events were reported for 15 patients (58%) and were Grade 3–4 in 3 patients (12%), with no discontinuations related to larotrectinib. Conclusions In pediatric patients with TRK fusion-positive CNS tumors, larotrectinib demonstrated durable responses, high disease control rate, and good tolerability. These results support testing for NTRK gene fusions in pediatric patients with CNS tumors.

Brain Tumor Classification into High Grade and Low Grade Gliomas

2019 ◽  
pp. 785-790
Author(s):  
Sanjeet Pandey ◽  
Brijesh Bharadwaj ◽  
Himanshu Pandey ◽  
Vineet Kr. Singh
Keyword(s):  
Invasive Procedure ◽  
High Grade Glioma ◽  
Low Grade Glioma ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Learning Approaches ◽  
Sampling Errors ◽  
Promising Alternative ◽  
Glioma Grading

Brain is recognized as one of the complex organ of the human body. Abnormal formation of cells may affect the normal functioning of the brain. These abnormal cells may belong to category of benign cells resulting in low grade glioma or malignant cells resulting in high grade glioma. The treatment plans vary according to grade of glioma detected. This results in need of precise glioma grading. As per World Health Organization, biopsy is considered to be gold standard in glioma grading. Biopsy is an invasive procedure which may contains sampling errors. Biopsy may also contain subjectivity errors. This motivated the clinician to look for other methods which may overcome the limitations of biopsy reports. Machine learning and deep learning approaches using MRI is considered to be most promising alternative approach reported by scientist in literature. The presented work were based on the concept of AdaBoost approach which is an ensemble learning approach. The developed model was optimized w.r.t to two hyper parameters i.e. no. of estimators and learning rate keeping the base model fixed. The decision tree was us ed as a base model. The proposed developed model was trained and validated on BraTS 2018 dataset. The developed optimized model achieves reasonable accuracy in carrying out classification task i.e. high grade glioma vs. low grade glioma.

Diffusion Weighted Imaging of Brain Gliomas in the Differential Diagnosis Value

2020 ◽  
Author(s):  
Jian JIANG ◽  
Liangcai BAI ◽  
Xueling ZHANG ◽  
Jianli LIU ◽  
Junlin ZHOU
Keyword(s):  
Brain Metastases ◽  
Diffusion Weighted Imaging ◽  
High Grade Glioma ◽  
Low Grade Glioma ◽  
Control Group ◽  
Low Grade ◽  
High Grade ◽  
Imaging Data ◽  
Grade Group ◽  
Diffusion Weighted

Background: To evaluate the diagnostic value of diffusion weighted imaging (DWI) and apparent diffusion coefficient measurement (ADC) in glioma. cient measurement (ADC) in glioma. Methods: Thirty two low-grade glioma patients and 31 high-grade glioma patients who were confirmed by pathology in Lanzhou University Second Hospital, Lanzhou, China from February 2016 to January 2019 were selected. The other 30 patients with brain metastases were selected as a control group. DWI imaging data of the three groups were collected, and ADC, relative ADC (rADC) values in tumor parenchyma, peritumor edema area, and contralateral normal white matter area were measured, and the levels of n-acetyl aspartic acid (NAA), choline (Cho), creatine (Cr) of tumor metabolites were analyzed. Results: rADC values in the peri-tumor edema areas of the high-grade glioma group were significantly lower than those in the low-grade group and the metastatic group （P=0.011）, and the low-grade group was significantly lower than that in the metastatic group (P < 0.05). NAA/Cho and NAA/Cr in parenchymal and peritumor edema areas of patients in the advanced group were significantly lower than those in the metastatic group (P < 0.05), and Cho /Cr was significantly higher than those in the metastatic group (P < 0.05). Conclusion: the rADC value, NAA/Cho, NAA/Cr and Cho/Cr in parenchymal and peritumor edema areas of the tumor can help to distinguish high-grade glioma, low-grade glioma and brain metastases.

Long-term outcomes after irradiation (RT) for pediatric low-grade glioma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10549-10549
Author(s):  
Derek S. Tsang ◽  
Erin Sennett Murphy ◽  
Thomas E. Merchant
Keyword(s):  
Systemic Therapy ◽  
Cumulative Incidence ◽  
High Grade Glioma ◽  
Tumor Location ◽  
Low Grade Glioma ◽  
Low Grade ◽  
High Grade ◽  
Who Grade ◽  
Extent Of Surgery

10549 Background: Treatment for pediatric low-grade glioma (LGG) is variable, depending on age and tumor location. Systemic therapy (ST) is often used to delay RT, but ST does not result in durable local control. The goal of this study was to evaluate event-free survival (EFS) and toxicities for pediatric LGG treated with RT over a 30-year period. Methods: All patients age ≤21 with intracranial pediatric LGG (WHO grade I-II) treated with RT at a single institution since May 1986 were included in this retrospective review. Patients with metastatic disease (M+) received craniospinal irradiation (CSI); otherwise, RT was conformal. EFS and overall survival (OS) were measured from the first day of RT. Events included death, progression, or secondary high-grade glioma. Results: 221 patients were eligible. Median follow-up was 11.3 yrs (range, 0.1-30.5). Median RT dose was 54 Gy. 10-yr EFS and OS were 67.9% (95% CI 60.4-74.3) and 91.1% (95% CI 85.8-94.5) for non-metastatic patients, respectively. For 12 M+ patients treated with CSI, 10-yr EFS and OS were 58.9% (95% CI 23.4-82.5) and 70.0% (32.9-89.2), respectively. 28.6% developed pseudoprogression (PP) with median time to onset and resolution of 6.1 months (IQR 3.6-14.6) and 6.4 months (IQR 3.5-11.7), respectively. Patients with PP had improved 10-yr EFS (83.4% vs. 61.0%, HR 0.40, p = .006). Patients with grade II tumors and who received pre-RT ST had lower EFS (Table). Sex, NF-1, tumor location, extent of surgery and CSI were not independently associated with EFS. 10-yr cumulative incidence of grade ≥2 vasculopathy was 7.5% (95% CI 4.9-11.4). There were 12 cases of secondary high-grade glioma, with a 20-yr cumulative incidence of 5.5% (95% CI 2.6-11.4). Conclusions: Irradiation provides long-term control of pediatric LGG in a majority of patients. Receipt of pre-RT systemic therapy was associated with reduced EFS; this association requires further investigation. [Table: see text]

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