scholarly journals Effectiveness of BRAF inhibitors in patients with BRAF V600 mutation positive glioma: a systematic review

2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv14-iv14
Author(s):  
Ian Yao ◽  
Sarah Dawson ◽  
Julian Higgins ◽  
Luke McGuinness ◽  
Alexandra McAleenan ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Objective Response ◽  
Braf Inhibitor ◽  
High Grade Glioma ◽  
Low Grade ◽  
High Grade ◽  
Braf Inhibitors ◽  
Duration Of Treatment ◽  
Braf V600 Mutation

Abstract Background BRAF inhibitor treatment with vemurafenib and dabrafenib have produced significant increases in median overall survival for BRAF V600 mutation-positive melanoma patients and are in wide clinical use. BRAF inhibitors have also been used in an ad hoc fashion in BRAF V600 mutation-positive glioma in a number of glioma subtypes with varying prognoses. Methods An electronic search was performed on MEDLINE and Embase on February 1, 2019 to identify studies of any design that reported the outcome of patients with BRAF V600 mutation-positive glioma treated with BRAF inhibitors. Data was collected for demographic information, tumour information (type and grading), BRAF mutation type, prior treatment regimens, type of BRAF inhibitor, dose and duration of treatment, best objective response, progression free survival (PFS), overall survival (OS), glioma specific symptomatic relief and adverse events. Preliminary Results Seventy-nine case reports, case series and single arm cohort studies with a total of 286 patients were included. Duration of treatment was available for 197 patients and varied from 0.1 to 54 months, with 104 patients still undergoing treatment at the time of publication. Progression occurred in 158 patients (including both low-grade and high-grade glioma) at between 0.805 and 36 months following the start of treatment. 34 people died, at between 0.329 and 40.1 months following the start of treatment. Conclusions Our systematic review shows varying clinical effectiveness of BRAF inhibitors in BRAF V600 mutation-positive glioma depending on low-grade or high-grade glioma. This evidence may inform future trials of BRAF inhibitors for glioma patients.

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 Exploring the lived experience of a high grade glioma

2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv14-iv14
Author(s):  
Shivani Soni ◽  
Matthew Williamas ◽  
Antonia Lannie
Keyword(s):  
Systematic Review ◽  
Lived Experience ◽  
High Grade Glioma ◽  
Low Grade ◽  
High Grade ◽  
Comprehensive Overview ◽  
Needs Assessments ◽  
Search Terms ◽  
James Lind Alliance ◽  
Common Problems

Abstract Introduction Brain tumour patients face a variety of challenges during diagnosis and treatment. Although most treating clinicians are familiar with these, it can be difficult to obtain a comprehensive overview of which are the most common problems, which patients they affect and how to address them. Methods We conducted a systematic review of all work relating to the lived experience of patients and carers of a glioblastoma. We identified articles published between 2008 and 2018 these had to be published in English, using the search terms cares and patients, lived experience, glioblastoma and perspective with relative alternative terms. We excluded articles that were previous systematic reviews, included low grade/brain metastasis from another primary site and articles that combined results for patients and carers. We extracted key theme and concerns, and summarised and tabulated and developed a discussion/recommendation. Results We identified 405 potential studies. We rejected 374 after screening abstract and titles, and a further 23 on further review. This left a set of 8 unique publications. The 8 publications included were comprised of qualitative studies that explored patient and carers experience at different points in the patient pathway. The main concerns/themes identified were issues around communication specifically the shock of diagnosis, re-negotiating relationships and finally accessing support. Conclusions This is the first systematic review that collates the lived experience of patients with high grade gliomas. It differs from the palliative care literature and from the James Lind Alliance, and is more specific than generic health needs assessments that are being used in practice.

scholarly journals Homotopic functional connectivity disruptions in glioma patients are associated with tumor malignancy and overall survival

2021 ◽  
Author(s):  
Andy G S Daniel ◽  
Carl D Hacker ◽  
John J Lee ◽  
Donna Dierker ◽  
Joseph B Humphries ◽  
...  
Keyword(s):  
Overall Survival ◽  
Functional Connectivity ◽  
Healthy Subjects ◽  
High Grade Glioma ◽  
Tumor Grade ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Healthy Controls ◽  
Who Grade

Abstract Background Gliomas exhibit widespread bilateral functional connectivity (FC) alterations that may be associated with tumor grade. Limited studies have examined the connection-level mechanisms responsible for these effects. Given the typically strong FC observed between mirroring/homotopic brain regions in healthy subjects, we hypothesized that homotopic connectivity (HC) is altered in low-grade and high-grade glioma patients and the extent of disruption is associated with tumor grade and predictive of overall survival (OS) in a cohort of de novo high-grade glioma (World Health Organization [WHO] grade 4) patients. Methods We used a mirrored FC-derived cortical parcellation to extract blood-oxygen-level-dependent (BOLD) signals and to quantify FC differences between homotopic pairs in normal-appearing brain in a retrospective cohort of glioma patients and healthy controls. Results Fifty-nine glioma patients (WHO grade 2, n = 9; grade 4 = 50; mean age, 57.5 years) and thirty healthy subjects (mean age, 65.9 years) were analyzed. High-grade glioma patients showed lower HC compared to low-grade glioma patients and healthy controls across several cortical locations and resting-state networks. Connectivity disruptions were also strongly correlated with hemodynamic lags between homotopic regions. Finally, in high-grade glioma patients with known survival times (n = 42), HC in somatomotor and dorsal attention networks were significantly correlated with OS. Conclusions These findings demonstrate an association between tumor grade and HC alterations that may underlie global FC changes and provide prognostic information.

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.

scholarly journals Anlotinib Alone or in Combination With Temozolomide in the Treatment of Recurrent High-Grade Glioma: A Retrospective Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Qunying Yang ◽  
Chengcheng Guo ◽  
Xiaoping Lin ◽  
Lili Luo ◽  
Zhenqiang He ◽  
...  
Keyword(s):  
Overall Survival ◽  
Objective Response ◽  
Progression Free Survival ◽  
High Grade Glioma ◽  
Rank Test ◽  
Cancer Center ◽  
High Grade ◽  
Karnofsky Score ◽  
Free Survival ◽  
Grade 3

Background: Anlotinib is a multi-target anti-angiogenic agent. This retrospective study aimed to evaluate the efficacy and safety of anlotinib alone or in combination with temozolomide for the treatment of recurrent high-grade glioma.Materials and Methods: The clinical data of patients with recurrent high-grade glioma treated with anlotinib alone or in combination with temozolomide in our cancer center were collected and analyzed. Treatment response was evaluated according to the response assessment for neuro-oncology criteria. Progression-free survival, progression-free survival at 6 months, overall survival, and overall survival at 12 months were evaluated by Kaplan–Meier method and compared by log-rank test.Results: Between August 2019 and December 2020, 31 patients with recurrent high-grade glioma (21 of grade 4 and 10 of grade 3) were enrolled in this study. Seventeen patients received anlotinib alone and 14 received anlotinib plus temozolomide. All patients were heavily treated, the median lines of previous treatments were 2, and the median Karnofsky score was 60. At the data cutoff date, the median progression-free survival was 4.5 months and the progression-free survival at 6 months was 43.5%. The median overall survival was 7.7 months, and the overall survival at 12 months was 26.7%. The progression-free survival at 6 months and the overall survival at 12 months for 21 patients with grade 4 glioma was 40.2 and 27.9%, respectively. The tumor objective response rate was 41.9% in all patients and 33.3% in patients with grade 4 glioma. No grade 3 or worse treatment-related adverse events were recorded during the treatment.Conclusion: Anlotinib alone or in combination with temozolomide showed encouraging efficacy and favorable tolerability in patients with recurrent high-grade glioma who had been heavily treated.

EPID-06. ASSOCIATIONS BETWEEN GERMLINE GENETIC VARIANTS AND OVERALL SURVIVAL IN PATIENTS WITH GLIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi86-vi86
Author(s):  
Kunal Potnis ◽  
Quinn Ostrom ◽  
Elizabeth Claus
Keyword(s):  
Overall Survival ◽  
Genetic Variation ◽  
Genetic Variants ◽  
Cancer Susceptibility ◽  
High Grade Glioma ◽  
Cox Proportional Hazards ◽  
Small Sample ◽  
Hazard Ratio ◽  
Low Grade ◽  
High Grade

Abstract BACKGROUND In addition to somatic genetic variation in tumors, germline genetic variation can better define cancer susceptibility risk, guide therapy, and predict survival. Most prior research into associations between germline genetic variants and survival outcomes in patients with glioma has been limited by small sample sizes and to high-grade glioma only. This study is the first to use data from Brigham and Women’s Hospital (BWH) and to include both low-grade and high-grade glioma cases to explore associations between germline genetic variants and overall survival. METHODS This study included 211 patients enrolled at BWH from April 2010 to January 2020. Ninety-two candidate germline genetic variants were identified via literature review. Fifty-five variants with minor allele frequency >0.05 were included preliminarily, for which bivariate Cox proportional hazards regression models were employed. Twenty-two variants with P< 0.5 were included in the final multivariable model, adjusted for patient sex, age, race, and glioma grade. Stratified sub-analyses were also conducted by sex. Associations were considered statistically significant at P< 0.05. RESULTS Among all patients, homozygous C/C genotype at rs17655 (ERCC5 gene) was significantly associated with worse overall survival (hazard ratio=2.61, P=0.0095). Among females only, worse survival was associated with homozygous T/T genotype at rs1381057 (POLQ, hazard ratio=2.58, P=0.046). Among males only, heterozygous status for the A genotype at rs487848 (POLQ, hazard ratio=0.31, P=0.018) and the A genotype at rs1468923 variant (PIK3CA, hazard ratio=0.51, P=0.016) were associated with improved survival. CONCLUSION We identified statistically significant associations between overall survival and four variants in genes involved in DNA repair and the PIK3 pathway, three of which were sex-specific. Our results contribute to improving patient stratification in glioma and may lead to increased targeting of treatment strategies.

scholarly journals ACTR-30. UPDATED EFFICACY AND SAFETY OF DABRAFENIB PLUS TRAMETINIB IN PATIENTS WITH RECURRENT/REFRACTORY BRAF V600E–MUTATED HIGH-GRADE GLIOMA (HGG) AND LOW-GRADE GLIOMA (LGG)

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi19-vi20 ◽  
Author(s):  
Patrick Wen ◽  
Alexander Stein ◽  
Martin van den Bent ◽  
Jacques De Greve ◽  
Sascha Dietrich ◽  
...  
Keyword(s):  
Treatment Options ◽  
Objective Response ◽  
Braf Inhibitor ◽  
Progression Free Survival ◽  
High Grade Glioma ◽  
Braf V600e ◽  
Low Grade ◽  
Open Label ◽  
Ongoing Treatment ◽  
Grade 3

Abstract BACKGROUND There is a lack of treatment options for HGG and LGG patients. BRAFV600E mutations are uncommon in glioma, with a poor long-term prognosis. Combined BRAF/MEK inhibition extends progression-free survival (PFS) and overall survival (OS) in BRAF V600E–mutated melanoma, non small-cell lung cancer, and anaplastic thyroid cancer. METHODS This phase 2, open-label trial (NCT02034110) evaluated dabrafenib (BRAF inhibitor, 150mg BID) plus trametinib (MEK inhibitor, 2mg QD) in patients with BRAF V600E mutations in 9 rare tumor types, including HGG and LGG. Eligible patients had histologically-confirmed recurrent or progressive glioma (LGG:WHO grade 1 or 2; HGG:WHO grade 3 or 4), with HGG patients required to have received radiotherapy and first-line chemotherapy, or concurrent chemoradiation. Treatment continued until unacceptable toxicity, disease progression, or death. Primary endpoint was investigator-assessed objective response rate (ORR) using RANO criteria. Secondary endpoints included duration of response (DOR), PFS, OS, and safety. RESULTS Interim analysis (IA) #14 (data cutoff: April 2, 2018) reported additional 3 months follow-up, with 49 patients enrolled (HGG, n=39; LGG, n=10) and 3 patients not evaluable for response. In HGG patients, ORR was 27% (10/37; 95%CI: 13.8%-44.1%), including CR (n=1), PR (n=9), and SD (n=11), with 16 patients currently ongoing treatment. In LGG patients, ORR was 56% (5/9; 95%CI: 26.8%-79.3%), including PR (n=5) and SD (n=4), with 6 patients currently ongoing treatment. OS, PFS, and DOR will be presented (IA#15). In HGG patients, adverse events (AEs) included fatigue (33%), headache (31%), rash (28%), and pyrexia (23%); grade 3/4 AEs included neutropenia (8%) and fatigue (5%). In LGG patients, AEs included headache (70%), fatigue, pyrexia (60% each), nausea, and arthralgia (50% each); grade 3/4 AEs included fatigue (20%). CONCLUSIONS Dabrafenib plus trametinib demonstrated promising efficacy in patients with recurrent or refractory BRAF V600E‒mutated HGG or LGG, with manageable AEs and no new safety signals.

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