What’s New in Brain Tumor Progress
Progress in 2019
Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma
Glioblastoma is the most common primary malignant brain tumor in adults and is associated with poor survival. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi-institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma.
Diffuse gliomas are the most common malignant brain tumours in adults and include glioblastomas and World Health Organization (WHO) grade II and grade III tumours (sometimes referred to as lower-grade gliomas). Genetic tumour profiling is used to classify disease and guide therapy, but involves brain surgery for tissue collection; repeated tumour biopsies may be necessary for accurate genotyping over the course of the disease
Solid stress in brain tumors causes neuronal loss and neurological dysfunction and can be reversed by lithium
Brain tumors cause “solid stress” — a compression of nearby tissue that can kill cells and result in some of the symptoms patients with brain cancer exhibit. In a new study, researchers set out to find what types of tumors are more likely to cause solid stress and if it can be alleviated. By both imaging patients’ brain tumors and investigating tumors in mice, they found that tumors that remain a mass cause more stress than tumors that snake out into healthy tissue. These “nodular” tumors were more likely to decrease the blood flow in neighboring vessels and damage nearby cells. The researchers also explored ways of relieving the compression and found that in mice, the drug lithium reduced the surrounding cellular damage the tumors caused.
Progress in 2018
One web-based group, Integrative Cancer Answers, states that as many as 83 percent of cancer patients choose to use one or more forms of alternative medicine, ranging from acupuncture and herbs to vitamins and yoga, most often in conjunction with therapies clinically proven to be effective.
Association of MGMT Promoter Methylation Status With Survival Outcomes in Patients With High-Risk Glioma Treated With Radiotherapy and Temozolomide
In this correlative analysis of the NRG Oncology/RTOG 0424 trial, the proportion of patients with MGMT promoter methylation was 57 of 75 (76%) vs 18 of 75 (24%) unmethylated. MGMT promoter methylation was significantly correlated with progression-free and overall survival on univariate and multivariate analyses with and without adjusting for IDH1/2 status (wild type vs mutant).
A modified version of the polio vaccine, infused straight into aggressive brain tumors, helped some patients live for years longer than they normally would have, doctors reported Tuesday.
A large, randomized, controlled Phase III clinical trial is traditionally the last, pivotal step in the evaluation of a potential new medicine before it is approved for use by all patients with the indicated disease.
New brain tumor clinical trials open around the country all the time, and it can be hard for patients and care-partners to keep track of new opportunities to potentially participate in leading-edge clinical research. This report, generated by the National Brain Tumor Society, provides you with a summary of clinical trials that have started or begun recruitment since our last quarterly report
The field of cancer immunotherapy has made exciting progress for some cancer types in recent years. However, recent failures of late phase clinical trials evaluating checkpoint blockade in glioblastoma (GBM) patients represent continued challenges for brain cancer immunotherapy.
New Cleveland Clinic research shows for the first time that ibrutinib, an FDA-approved drug for lymphoma and leukemia, may also help treat the most common—and deadliest—type of brain tumor. The findings, published in Science Translational Medicine, offer hope that the drug may one day be used in patients with glioblastoma and improve poor survival rates.
Glioblastoma is a lethal and difficult to treat primary brain tumor. Similar to many cancers, glioblastoma contains a population of stem cells, which are particularly treatment-resistant and promote tumor growth. A protein called bone marrow and X-linked (BMX) nonreceptor tyrosine kinase is active in these cells and can be targeted with ibrutinib, an approved drug used in other cancers.
Gliomas exhibit high proportions of glioma stem cells (GSCs), anoikis resistance, increased brain parenchyma invasion, and resistance to therapy with high recurrence. GSCs display protective autophagy, a self-mediated lysosomal degradation process that balances sources of energy at critical times of stress.
Discordant inheritance of chromosomal and extrachromosomal DNA elements contributes to dynamic disease evolution in glioblastoma
To understand how genomic heterogeneity of glioblastoma (GBM) contributes to poor therapy response, we performed DNA and RNA sequencing on GBM samples and the neurospheres and orthotopic xenograft models derived from them.
At the time of their clinical manifestation, the heterogeneous group of adult and pediatric gliomas carries a wide range of diverse somatic genomic alterations, ranging from somatic single-nucleotide variants to structural chromosomal rearrangements.
Minimally Invasive Resection of Deep-seated High-grade Gliomas Using Tubular Retractors and Exoscopic Visualization.
Deep-seated high-grade gliomas (HGGs) represent a unique surgical challenge because they reside deep to critical cortical and subcortical structures and infiltrate functional areas of the brain. Therefore, accessing and resecting these tumors can often be challenging and associated with significant morbidity. We describe the use of minimally invasive approaches to access deep-seated HGGs to achieve extensive resections while minimizing surgical morbidity.
Launched in 2013, Defeat GBM is now in its fourth year of funding toward a five-year, $10 million commitment. The disease trajectory goal of Defeat GBM is to conduct “team science” that ultimately leads to doubling the percentage of glioblastoma patients living five years or longer.
Predicting the expected outcome of patients diagnosed with cancer is a critical step in treatment. Advances in genomic and imaging technologies provide physicians with vast amounts of data, yet prognostication remains largely subjective, leading to suboptimal clinical management.
Phase I Study of DNX-2401 (Delta-24-RGD) Oncolytic Adenovirus: Replication and Immunotherapeutic Effects in Recurrent Malignant Glioma
DNX-2401 (Delta-24-RGD; tasadenoturev) is a tumor-selective, replication-competent oncolytic adenovirus. Preclinical studies demonstrated antiglioma efficacy, but the effects and mechanisms of action have not been evaluated in patients.
New brain tumor clinical trials open around the world all the time, and it can be hard for patients and care-partners to keep track of new opportunities to potentially participate in leading-edge clinical research.
2018 Crystal Ball: Predictions & Hopes for Advances in Brain Tumor Research and Treatments in the New Year
Last year, progress continued to build in the fight against brain tumors. Two products were given FDA approval for use in the treatment of brain tumors, the first such approvals since the Optune device was approved for use in newly diagnosed glioblastoma patients in 2015.
Progress in 2017
Targeted therapeutics elicit age-dependent long-term consequences on the developing brain that can be ameliorated with environmental enrichment
Machine-based-learning approaches are being developed to aid the diagnosis of clinical samples, and in a paper in Nature, Capper et al.1 report such a method for classifying brain tumours on the basis of molecular patterns.