scholarly journals Activation of PI3K/mTOR pathway occurs in most adult low-grade gliomas and predicts patient survival

2009 ◽  
Vol 97 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Sean M. McBride ◽  
Daniel A. Perez ◽  
Mei-Yin Polley ◽  
Scott R. Vandenberg ◽  
Justin S. Smith ◽  
...  
Keyword(s):  
Patient Survival ◽  
Mtor Pathway ◽  
Low Grade ◽  
Low Grade Gliomas

scholarly journals Genetic variants related to angiogenesis and apoptosis in patients with glioma

2018 ◽  
Vol 76 (6) ◽  
pp. 393-398
Author(s):  
Maria Clara Jessica Calastri ◽  
Nicolas Luz Toledo Ortega Rodrigues ◽  
Gabriela Hatori ◽  
Michele Lima Gregório ◽  
Camila Ive Ferreira Oliveira Brancati ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genetic Variants ◽  
Medical Records ◽  
Patient Survival ◽  
Response To Treatment ◽  
Low Grade ◽  
Significance Level ◽  
Low Grade Gliomas ◽  
Homozygous Genotype ◽  
Independent Risk Factors

ABSTRACT Background Glioma, the most common primary malignant brain tumor in adults, is highly aggressive and associated with a poor prognosis. The objectives of this study were to evaluate the association of genetic polymorphisms related to angiogenesis and apoptosis with gliomas, as well as comorbidities, lifestyle, clinical profile, survival and response to treatment (temozolomide [TMZ] and radiotherapy [RT]) in patients with the disease. Methods In a total of 303 individuals, genotypes were performed by real-time PCR, and clinical data, lifestyle and comorbidities were obtained from medical records and questionnaires. The significance level was set at 5%. Results Smoking, alcohol consumption, systemic arterial hypertension, diabetes mellitus and body mass index prevailed among patients, compared to controls (p < 0.05). The heterozygous genotype rs1468727 (T/C) and the homozygous genotype rs2010963 (G/G) (p > 0.05) were observed in both groups. Lifestyle and comorbidities showed independent risk factors for the disease (p < 0.0001, p = 0.0069, p = 0.0394, respectively). Patients with low-grade gliomas had a survival rate of 80.0 ± 1.7% in three years. For the combination of TMZ+RT, survival was 78.7 ± 7.6% in 20 months, compared to TMZ only (21.9 ± 5.1%, p = 0.8711). Conclusions Genetic variants were not associated with gliomas. Specific lifestyle habits and comorbidities stood out as independent risk factors for the disease. Low-grade gliomas showed an increase in patient survival with TMZ+RT treatment.

scholarly journals ACTR-42. PI3K/mTOR PATHWAY ACTIVATION SELECTED PHASE II STUDY OF EVEROLIMUS (RAD001) WITH AND WITHOUT TEMOZOLOMIDE IN THE TREATMENT OF ADULT PATIENTS WITH SUPRATENTORIAL LOW-GRADE GLIOMA [NCT NCT02023905]

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi22-vi23
Author(s):  
Jennie Taylor ◽  
Annette Molinaro ◽  
Eduardo Rodriguez Almaraz ◽  
Ciara Downey ◽  
Joanna Phillips ◽  
...  
Keyword(s):  
Survival Data ◽  
Primary Outcome ◽  
Pi3k Pathway ◽  
Mtor Pathway ◽  
Low Grade ◽  
Diffuse Glioma ◽  
Eligibility Criteria ◽  
Low Grade Gliomas ◽  
Pathway Activation ◽  
Central Pathology

Abstract Functional activation of the PI3K/AKT/mTOR pathway is seen in ~50% of low-grade gliomas and correlates with worse survival. Everolimus is a selective inhibitor of mTOR that targets mTOR-raptor signaling, halting proliferation and indirectly inhibiting angiogenesis. This phase 2 study evaluated the efficacy of everolimus in untreated grade II diffuse glioma. Patients were stratified by 1p19q status and PI3K pathway activation (via phosphorylation of PRAS-40) into three arms: 1) 1p19q intact, PRAS-40 phosphorylated received everolimus monotherapy; 2) 1p19q intact, PRAS-40 not phosphorylated received everolimus with temozolomide; and 3) 1p19q co-deleted received everolimus monotherapy. Primary outcome was landmark PFS-33 months for Arms 1 and 2; and PFS-38 months for Arm 3 (null hypothesis 50% for all arms individually). Key eligibility criteria included central pathology confirmation, no prior treatment, and initiation of everolimus within 120 days of most recent tissue sampling. From 05/2014 to 07/2018, 27 patients were enrolled – 16 into Arm 1; 2 into Arm 2; and 9 into Arm 3. Median age at enrollment was 38 years (range 21 – 65); median KPS 90 (range 70 – 100) and a majority were male (74%). Although follow-up is not complete, as of 05/2019 11 of 16 patients had progressed prior to 33 months in Arm 1, and 5 of 9 patients had progressed prior to 38 months in Arm 3. Toxicity was as expected with frequent grade 1/2 AEs of diarrhea, rash, and mucositis. Headache was the most common grade 3 AE and was seen in three cases. The study was closed prematurely secondary to slow accrual and loss of drug support. Updated survival data as well as results of secondary and exploratory analyses will be reported. In summary, everolimus was well tolerated in previously untreated low-grade gliomas. However, it failed to meet primary outcome of extending PFS in this population.

scholarly journals EVEROLIMUS (RAD001) AND THE MTOR PATHWAY IN LOW-GRADE GLIOMAS

2014 ◽  
Vol 16 (suppl 3) ◽  
pp. iii48-iii48
Author(s):  
J. L. Clarke ◽  
S. Chang ◽  
J. Phillips ◽  
A. Molinaro ◽  
M. Berger ◽  
...  
Keyword(s):  
Mtor Pathway ◽  
Low Grade ◽  
Low Grade Gliomas

scholarly journals Domain Mapping and Deep Learning from Multiple MRI Clinical Datasets for Prediction of Molecular Subtypes in Low Grade Gliomas

2020 ◽  
Vol 10 (7) ◽  
pp. 463 ◽  
Author(s):  
Muhaddisa Barat Ali ◽  
Irene Yu-Hua Gu ◽  
Mitchel S. Berger ◽  
Johan Pallud ◽  
Derek Southwell ◽  
...  
Keyword(s):  
Molecular Subtypes ◽  
Negative Impact ◽  
Molecular Classification ◽  
Tumor Segmentation ◽  
Test Accuracy ◽  
Low Grade ◽  
Idh Mutation ◽  
Molecular Type ◽  
Low Grade Gliomas ◽  
Domain Mapping

Brain tumors, such as low grade gliomas (LGG), are molecularly classified which require the surgical collection of tissue samples. The pre-surgical or non-operative identification of LGG molecular type could improve patient counseling and treatment decisions. However, radiographic approaches to LGG molecular classification are currently lacking, as clinicians are unable to reliably predict LGG molecular type using magnetic resonance imaging (MRI) studies. Machine learning approaches may improve the prediction of LGG molecular classification through MRI, however, the development of these techniques requires large annotated data sets. Merging clinical data from different hospitals to increase case numbers is needed, but the use of different scanners and settings can affect the results and simply combining them into a large dataset often have a significant negative impact on performance. This calls for efficient domain adaption methods. Despite some previous studies on domain adaptations, mapping MR images from different datasets to a common domain without affecting subtitle molecular-biomarker information has not been reported yet. In this paper, we propose an effective domain adaptation method based on Cycle Generative Adversarial Network (CycleGAN). The dataset is further enlarged by augmenting more MRIs using another GAN approach. Further, to tackle the issue of brain tumor segmentation that requires time and anatomical expertise to put exact boundary around the tumor, we have used a tight bounding box as a strategy. Finally, an efficient deep feature learning method, multi-stream convolutional autoencoder (CAE) and feature fusion, is proposed for the prediction of molecular subtypes (1p/19q-codeletion and IDH mutation). The experiments were conducted on a total of 161 patients consisting of FLAIR and T1 weighted with contrast enhanced (T1ce) MRIs from two different institutions in the USA and France. The proposed scheme is shown to achieve the test accuracy of 74 . 81 % on 1p/19q codeletion and 81 . 19 % on IDH mutation, with marked improvement over the results obtained without domain mapping. This approach is also shown to have comparable performance to several state-of-the-art methods.

scholarly journals LGG-18. EVEROLIMUS TREATMENT IN PEDIATRIC PATIENTS AFFECTED BY LOW-GRADE GLIOMAS (pLGG) NON-TSC, BRAF v600-WT

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii369-iii369
Author(s):  
Antonella Cacchione ◽  
Evelina Miele ◽  
Maria Chiara Lodi ◽  
Andrea Carai ◽  
Giovanna Stefania Colafati ◽  
...  
Keyword(s):  
Adverse Event ◽  
Disease Progression ◽  
Mapk Pathway ◽  
Brain Mri ◽  
Mammalian Target Of Rapamycin ◽  
Low Grade ◽  
Duration Of Treatment ◽  
Tumor Biopsy ◽  
Low Grade Gliomas ◽  
Personalized Approach

Abstract BACKGROUND MAPK pathway is the hallmark of pediatric low grade gliomas (pLGGs); hyperactivation of mTOR (mammalian target of rapamycin) might be a suitable biomarker for therapeutic response. We investigated the feasibility of Everolimus, mTOR inhibitor, in patients affected by pLGGs. METHODS Patients 1 to 18 years old, diagnosed with pLGG, with a positive tumor biopsy for mTOR/phospho-mTOR and radiological and / or clinical disease progression, treated at Bambino Gesù Children’s Hospital in Rome were evaluated. Tumor DNA methylation analysis was performed in 10 cases. Exclusion criteria included: Tuberous Sclerosis patients, Sub Ependymal Giant Astrocytoma. Everolimus was administered orally at a dose of 2.5 mg or 5 mg daily based on body weight. Patients were evaluated with brain MRI every 4, 8 and 12 months after treatment start and every six months thereafter. RESULTS 16 patients were enrolled from September 2014 and 2019. The median age was 7.5 years old. All patients had at least one adverse event. Events rated as severe (grade 3/4) were reported in 6 patients. Stomatitis was the most frequent adverse event. One patient discontinued treatment due to grade 4 toxicity (ulcerative stomatitis and fatigue). The median duration of treatment was 21 months (4–57 months). Brain MRI evaluations have showed disease stability in 11 patients, partial response in 2 patients and disease progression in 3 patients. CONCLUSIONS Everolimus has proven to be well tolerated and effective treatment in terms of disease stability in patients with pLGGs. It’s also an excellent example of chemo-free personalized approach.

scholarly journals Hemispheric low-grade gliomas

2016 ◽  
Vol 32 (10) ◽  
pp. 1787-1787
Author(s):  
Gianpiero Tamburrini ◽  
Jose Hinojosa
Keyword(s):  
Low Grade ◽  
Low Grade Gliomas
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