scholarly journals BRAF Mutations and the Utility of RAF and MEK Inhibitors in Primary Brain Tumors

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1262 ◽  
Author(s):  
Karisa C. Schreck ◽  
Stuart A. Grossman ◽  
Christine A. Pratilas
Keyword(s):  
Brain Tumors ◽  
Poor Prognosis ◽  
Primary Brain Tumor ◽  
High Grade ◽  
Braf Mutations ◽  
Mek Inhibitors ◽  
Primary Brain Tumors ◽  
The Poor ◽  
Oncogenic Mutations ◽  
Tumor Types

BRAF mutations have been identified as targetable, oncogenic mutations in many cancers. Given the paucity of treatments for primary brain tumors and the poor prognosis associated with high-grade gliomas, BRAF mutations in glioma are of considerable interest. In this review, we present the spectrum of BRAF mutations and fusion alterations present in each class of primary brain tumor based on publicly available databases and publications. We also summarize clinical experience with RAF and MEK inhibitors in patients with primary brain tumors and describe ongoing clinical trials of RAF inhibitors in glioma. Sensitivity to RAF and MEK inhibitors varies among BRAF mutations and between tumor types as only class I BRAF V600 mutations are sensitive to clinically available RAF inhibitors. While class II and III BRAF mutations are found in primary brain tumors, further research is necessary to determine their sensitivity to third-generation RAF inhibitors and/or MEK inhibitors. We recommend that the neuro-oncologist consider using these drugs primarily in the setting of a clinical trial for patients with BRAF-altered glioma in order to advance our knowledge of their efficacy in this patient population.

scholarly journals Concurrent BRAF/MEK Inhibitors in BRAF V600–Mutant High-Grade Primary Brain Tumors

2018 ◽  
Vol 16 (4) ◽  
pp. 343-347 ◽  
Author(s):  
Karisa C. Schreck ◽  
Andrew Guajardo ◽  
Doris D.M. Lin ◽  
Charles G. Eberhart ◽  
Stuart A. Grossman
Keyword(s):  
Brain Tumors ◽  
High Grade ◽  
Mek Inhibitors ◽  
Primary Brain Tumors

scholarly journals The Interplay between Glioblastoma and Its Microenvironment

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2257
Author(s):  
Mark Dapash ◽  
David Hou ◽  
Brandyn Castro ◽  
Catalina Lee-Chang ◽  
Maciej S. Lesniak
Keyword(s):  
Tumor Microenvironment ◽  
Patient Outcomes ◽  
Poor Prognosis ◽  
Primary Brain Tumor ◽  
Major Contributor ◽  
Complex Interplay ◽  
Environmental Pressures ◽  
The Poor ◽  
Adaptive Nature ◽  
Poor Efficacy

GBM is the most common primary brain tumor in adults, and the aggressive nature of this tumor contributes to its extremely poor prognosis. Over the years, the heterogeneous and adaptive nature of GBM has been highlighted as a major contributor to the poor efficacy of many treatments including various immunotherapies. The major challenge lies in understanding and manipulating the complex interplay among the different components within the tumor microenvironment (TME). This interplay varies not only by the type of cells interacting but also by their spatial distribution with the TME. This review highlights the various immune and non-immune components of the tumor microenvironment and their consequences f the efficacy of immunotherapies. Understanding the independent and interdependent aspects of the various sub-populations encapsulated by the immune and non-immune components will allow for more targeted therapies. Meanwhile, understanding how the TME creates and responds to different environmental pressures such as hypoxia may allow for other multimodal approaches in the treatment of GBM. Ultimately, a better understanding of the GBM TME will aid in the development and advancement of more effective treatments and in improving patient outcomes.

scholarly journals PS1 - 188 Rehabilitation Consultation: An Integrated Model for Addressing Rehabilitation Concerns in the Primary Brain Tumor Population

2016 ◽  
Vol 43 (S4) ◽  
pp. S9-S10
Author(s):  
I. Lax ◽  
M. Daniels ◽  
C. Kanter ◽  
W. Mason ◽  
K. Edelstein
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Disease Process ◽  
Primary Brain Tumor ◽  
Rehabilitation Services ◽  
Face To Face ◽  
Primary Brain Tumors ◽  
Common Diagnosis ◽  
Consultation Model ◽  
Oncology Treatment

Individuals with primary brain tumors experience a range of physical, cognitive and psychosocial sequelae which impact their independence, safety and quality of life. These impairments may be addressed through rehabilitation intervention. Despite acknowledgement that timely rehabilitation services over the course of the disease process is of benefit, few outpatient neuro-oncology treatment teams include a rehabilitation professional. Purpose: The aims are: (1) to describe a rehabilitation consultation model of care integrated into outpatient neuro-oncology treatment for individuals with primary brain tumors; and (2) to describe the characteristics of individuals referred for rehabilitation services. Methods: This retrospective descriptive study examined data from 200 individuals that received rehabilitation consultation from January 2015 to March 2016 at Princess Margaret Hospital, Pencer Brain Tumor Centre. Information on patient demographics, referral characteristics, and number of patient care visits was collected. Descriptive statistics were calculated. Preliminary Results: Of all patients, (n=195), the most common diagnosis is glioblastoma, 39% (n=76), and 50% are 50-69 years of age (M=55, SD=15.0). The most common reason for initial referral was decline in physical functioning, strength and balance (41%). In 77% of cases, patients were seen immediately at the time of referral. In total, 540 consultations were completed (face-to-face=230, telephone=310) with 2.78 on average (SD=4.0) per patient. Conclusion: Given the range of symptoms that individuals with primary brain tumors experience coupled with changes in functional status as the disease progresses, integrated and timely rehabilitation consultation is feasible.

scholarly journals Brain tumors risk factors - current state of knowledge review

2021 ◽  
Vol 11 (9) ◽  
pp. 101-107
Author(s):  
Zygmunt Siedlecki ◽  
Małgorzata Szafrańska ◽  
Emilia Główczewska-Siedlecka ◽  
Maciej Śniegocki
Keyword(s):  
Risk Factors ◽  
Brain Tumor ◽  
Ionizing Radiation ◽  
Brain Tumors ◽  
Poor Prognosis ◽  
Primary Brain Tumor ◽  
Evidence Based ◽  
Raw Meat ◽  
The Public ◽  
Current State

Brain tumors cause widespread apprehension in society, associated with poor prognosis and death. Laymen most often associate them with glioblastoma multiforme which is in fact the most common malignant primary brain tumor (formerly it was considered the most common primary brain tumor, now it is thought that meningiomas are the most common). The interest of both the public and physicians is aroused by potential brain tumors risk factors. The only evidence based risk factor is ionizing radiation of head and neck. Other risk factors are also under consideration, however are not conclusive and different studies give different results. Given the widespread apprehension of brain tumors, knowledge of the risk factors seems obvious. In this manuscript, we have reviewed the current state of knowledge aboutf risk factors based on research. They confirm that apart from ionizing radiation, the existence of other risk factors is considered: cell phones, electromagnetic field, occupational exposure to raw meat, viruses. However, all these risk factors are not confirmed by reference results.

scholarly journals Tumor-Associated Microglia and Macrophages in the Glioblastoma Microenvironment and their Implications for Therapy

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4255
Author(s):  
Rikke Sick Andersen ◽  
Atul Anand ◽  
Dylan Scott Lykke Harwood ◽  
Bjarne Winther Kristensen
Keyword(s):  
Poor Prognosis ◽  
Therapeutic Strategy ◽  
Treatment Strategies ◽  
Treatment Resistance ◽  
Standard Of Care ◽  
Primary Brain Tumor ◽  
Therapeutic Strategies ◽  
The Poor ◽  
Temozolomide Chemotherapy

Glioblastoma is the most frequent and malignant primary brain tumor. Standard of care includes surgery followed by radiation and temozolomide chemotherapy. Despite treatment, patients have a poor prognosis with a median survival of less than 15 months. The poor prognosis is associated with an increased abundance of tumor-associated microglia and macrophages (TAMs), which are known to play a role in creating a pro-tumorigenic environment and aiding tumor progression. Most treatment strategies are directed against glioblastoma cells; however, accumulating evidence suggests targeting of TAMs as a promising therapeutic strategy. While TAMs are typically dichotomously classified as M1 and M2 phenotypes, recent studies utilizing single cell technologies have identified expression pattern differences, which is beginning to give a deeper understanding of the heterogeneous subpopulations of TAMs in glioblastomas. In this review, we evaluate the role of TAMs in the glioblastoma microenvironment and discuss how their interactions with cancer cells have an extensive impact on glioblastoma progression and treatment resistance. Finally, we summarize the effects and challenges of therapeutic strategies, which specifically aim to target TAMs.

scholarly journals From first symptoms to diagnosis: Initial clinical presentation of primary brain tumors

2020 ◽  
Vol 4 (2) ◽  
pp. 2514183X2096836
Author(s):  
B Alther ◽  
V Mylius ◽  
M Weller ◽  
AR Gantenbein
Keyword(s):  
Brain Tumors ◽  
Clinical Presentation ◽  
Personality Change ◽  
University Hospital ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Primary Brain Tumors ◽  
Presenting Symptoms ◽  
Time To Diagnosis

Background: Despite modern imaging methods, a long symptom-to-diagnosis interval can be observed in patients with primary brain tumors. Objective: The study evaluated the initial and subsequent clinical presentation of patients with brain tumors in the context of time to diagnosis, localization, histology, and tumor grading. Methods: In this retrospective analysis of 85 consecutive patients with primary brain tumors, we assessed the presenting symptoms and signs. The analyses were based on entries from medical records at the Department of Neurology of Zurich University Hospital between 2005 and 2010. Results: A total of 54 men and 31 women with a mean age at diagnosis of 48 years were included. 60% of the patients present with a malignant tumor (World Health Organization grading III–IV), 24.7% with a benign tumor (I–II), and 15.3% were not classified. The interval between symptom onset and diagnosis varied from 1 day to 96 months (median: 39 days). High-grade tumors (III–IV) were diagnosed significantly earlier than low-grade tumors (II) after the first symptoms occurred (median: 26 vs. 138 days; z = −3.847, p < 0.001). Conclusions: Symptoms with a short symptom-to-diagnosis interval such as nausea/vomiting, seizures, as well as of personality change are assumed to contribute to a faster diagnosis in high-grade tumors. Visual disturbances and headaches, although occurring relatively seldom, did not contribute to a decrease in time to diagnosis and should therefore be considered for further diagnostic workup.

Measurement Methodologies for Assessing the Glycolysis Effect in the Discrimination and Therapy of Brain Gliomas

2013 ◽  
Vol 1 (1) ◽  
pp. 34-55 ◽  
Author(s):  
Michalis G Kounelakis ◽  
Ekaterini S Bei ◽  
Michalis E Zervakis ◽  
Georgios C Giakos ◽  
Lin Zhang ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Molecular Classification ◽  
Scientific Basis ◽  
World Health ◽  
Primary Brain Tumors ◽  
Glycolysis Pathway ◽  
Health Organization ◽  
Tumor Types ◽  
Brain Gliomas ◽  
The Brain

Primary brain tumors refer to those developing from the various types of cells that compose the brain. Gliomas represent about 50% of all primary brain tumors and include a variety of different histological tumor types and malignancy grades. The World Health Organization (WHO) classifies gliomas into four histological types and four grades. The goal of molecular classification using advanced pattern recognition tools is to identify subgroups of tumors with distinct biological and clinical features and initiate the challenge of classifying complex gliomas of similar histology and malignancy status into distinct categories. The aim of this paper is to i) present the measurement procedures and analysis methodologies, ii) summarize the currently available knowledge related to the utilization of ’omics’ measurements in the discrimination of brain gliomas, and iii) provide a scientific basis for future medical practice in the discrimination and treatment of brain gliomas based specifically on the metabolic process of glycolysis. In particular, the paper explores the idea of the glycolysis pathway as a critical concept for the development of therapeutic strategies for brain gliomas.

scholarly journals Use of fluorescence to guide resection or biopsy of primary brain tumors and brain metastases

2014 ◽  
Vol 36 (2) ◽  
pp. E10 ◽  
Author(s):  
Serge Marbacher ◽  
Elisabeth Klinger ◽  
Lucia Schwyzer ◽  
Ingeborg Fischer ◽  
Edin Nevzati ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Brain Tumors ◽  
Brain Metastases ◽  
Low Grade ◽  
High Grade ◽  
Open Resection ◽  
Who Grade ◽  
Primary Brain Tumors ◽  
High Grade Gliomas ◽  
Surgical Adjunct

Object The accurate discrimination between tumor and normal tissue is crucial for determining how much to resect and therefore for the clinical outcome of patients with brain tumors. In recent years, guidance with 5-aminolevulinic acid (5-ALA)–induced intraoperative fluorescence has proven to be a useful surgical adjunct for gross-total resection of high-grade gliomas. The clinical utility of 5-ALA in resection of brain tumors other than glioblastomas has not yet been established. The authors assessed the frequency of positive 5-ALA fluorescence in a cohort of patients with primary brain tumors and metastases. Methods The authors conducted a single-center retrospective analysis of 531 patients with intracranial tumors treated by 5-ALA–guided resection or biopsy. They analyzed patient characteristics, preoperative and postoperative liver function test results, intraoperative tumor fluorescence, and histological data. They also screened discharge summaries for clinical adverse effects resulting from the administration of 5-ALA. Intraoperative qualitative 5-ALA fluorescence (none, mild, moderate, and strong) was documented by the surgeon and dichotomized into negative and positive fluorescence. Results A total of 458 cases qualified for final analysis. The highest percentage of 5-ALA–positive fluorescence in open resection was found in glioblastomas (96%, n = 99/103). Among other tumors, 5-ALA–positive fluorescence was detected in 88% (n = 21/32) of anaplastic gliomas (WHO Grade III), 40% (n = 8/19) of low-grade gliomas (WHO Grade II), no (n = 0/3) WHO Grade I gliomas, and 77% (n = 85/110) of meningiomas. Among metastases, the highest percentage of 5-ALA–positive fluorescence was detected in adenocarcinomas (48%, n = 13/27). Low rates or absence of positive fluorescence was found among pituitary adenomas (8%, n = 1/12) and schwannomas (0%, n = 0/7). Biopsies of high-grade primary brain tumors showed positive rates of fluorescence similar to those recorded for open resection. No clinical adverse effects associated with use of 5-ALA were observed. Only 1 patient had clinically silent transient elevation of liver enzymes. Conclusions Study findings suggest that the administration of 5-ALA as a surgical adjunct for resection and biopsy of primary brain tumors and brain metastases is safe. In light of the high rate of positive fluorescence in high-grade gliomas other than glioblastomas, meningiomas, and a variety of metastatic cancers, 5-ALA seems to be a promising tool for enhancing intraoperative identification of neoplastic tissue and optimizing the extent of resection.

CTNI-55. THE CDK4/6 INHIBITOR ABEMACICLIB IN PATIENTS WITH RECURRENT MENINGIOMA AND OTHER PRIMARY CNS TUMORS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi72-vi73
Author(s):  
Elizabeth Coffee ◽  
Katherine Panageas ◽  
Robert Young ◽  
Tara Morrison ◽  
Ahmad Daher ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Single Agent ◽  
Pituitary Tumors ◽  
Molecular Characteristics ◽  
Multiple Cancer ◽  
Who Grade ◽  
Multiple Tumor ◽  
Primary Brain Tumors ◽  
Basket Trial ◽  
Tumor Types

Abstract BACKGROUND Medical therapies for recurrent brain tumors are limited. Abemaciclib is a small molecule CDK4/6 inhibitor that has demonstrated antitumor activity in multiple cancer types and crosses the blood-brain barrier. METHODS We conducted a phase II trial of single-agent abemaciclib in patients with recurrent primary brain tumors utilizing a novel CNS basket trial design with multiple tumor types accrued to separate cohorts including patients with recurrent IDH-wildtype gliomas (Cohort A), any recurrent gliomas requiring cytoreductive surgery (Cohort B), and any other recurrent primary brain tumors (Cohort C) including IDH-mutant gliomas, meningiomas, and other tumor types. In all patients, abemaciclib was administered orally at 200mg twice daily for each 28-day cycle. In cohort B abemaciclib was administered 4-7 days prior to surgery then resumed after recovery. Neuroimaging disease assessments were performed every two cycles. Cohorts were individually assessed for efficacy, tumoral molecular characteristics, and exploratory biomarker analyses. Next generation sequencing was performed on patients who had prior surgery. RESULTS To date, a total of 61 patients have enrolled and initiated treatment with abemaciclib. Cohort A enrolled 9 patients with IDH-wildtype WHO grade II and III astrocytomas. Cohort B enrolled 10 patients with astrocytomas of varying IDH-status. Cohort C is a diverse group of 42 patients including 22 treatment-refractory meningiomas, 10 IDH-mutant gliomas (5 astrocytomas, 5 oligodendrogliomas), 3 ependymomas, 3 primary CNS lymphomas, 2 pituitary tumors, 1 glioneuronal rosette forming tumor, and 1 diffuse midline glioma. A total of 7 grade 3 toxicities occurred in 6 patients: fatigue (3), neutropenia (2), colitis (1) and seizure (1); no grade 4 toxicities occurred. CONCLUSIONS We present the results of a novel CNS basket trial looking at the efficacy of abemaciclib across multiple recurrent primary brain tumors. Efficacy results will be presented, highlighting an update on promising results in the 22 patients with recurrent meningiomas.

scholarly journals Fertility preservation in primary brain tumor patients

2016 ◽  
Vol 4 (1) ◽  
pp. 40-45 ◽  
Author(s):  
Jacqueline B. Stone ◽  
Joanne F. Kelvin ◽  
Lisa M. DeAngelis
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Fertility Preservation ◽  
Primary Brain Tumor ◽  
Nurse Specialist ◽  
Tumor Patients ◽  
Related Factors ◽  
Patients Âgés ◽  
Primary Brain Tumors ◽  
Significant Difference

Abstract Background Fertility preservation (FP) is an infrequently addressed issue for young adults with primary brain tumors. Given the improved prognosis and enhanced technology in reproductive medicine, more primary brain tumor patients see procreation as feasible, making the discussion of FP increasingly important. The goals of this study were to describe patients who received FP counseling by a fertility nurse specialist (FNS) and determine which sociodemographic and disease-related factors predict acceptance of referral to a reproductive specialist. Methods Institutional review board-approved retrospective review of primary brain tumor patients, ages 18 to 45, who were referred for FP counseling with a FNS from 2009 to 2013. Results Seventy patients were referred for FP counseling: 38 men, 32 women, with a median age of 32 years and median KPS of 90. Eighty-nine percent had gliomas; 58% grade III, 17% grade IV. Sixty-seven percent were referred for counseling at initial diagnosis. Of those referred, 73% accepted referral to a sperm bank (87% of men) or reproductive endocrinologist (56% of women). Patients were more likely to accept referral if they had no prior children (P = .048). There was no statistically significant difference in referral acceptance by age, race/ethnicity, marital status, religion, or tumor grade. After treatment, 3 men conceived naturally, 2 men conceived using banked sperm, and 2 women conceived naturally. Conclusions Despite the historically poor prognosis of patients with primary brain tumors, there is significant interest in FP among these patients, particularly if they have no prior children. Clinicians should develop strategies to incorporate FP counseling into practice.

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