Genetic predisposition to altered blood cell homeostasis is associated with glioma risk and survival.

Glioma is a highly fatal and heterogeneous brain tumor with few known risk factors. Our study examines genetically predicted variability in blood cell indices in relation to glioma risk and survival in 3418 cases and 8156 controls. We find that increased platelet to lymphocyte ratio (PLR) confers an increased risk of glioma (odds ratio (OR) = 1.

A phase I study of convection-enhanced delivery (CED) of liposomal-irinotecan using real-time magnetic resonance imaging in patients with recurrent high-grade glioma.

Background: Irinotecan demonstrates anti-tumor efficacy in preclinical glioma models but clinical results are modest due to drug delivery limitations. Convection enhanced delivery (CED) improves drug delivery by increasing intratumoral drug concentration. Real-time magnetic resonance imaging of infusate delivery during CED may optimize tumor coverage.

Functional germline variants in DNA damage repair pathways are associated with altered survival in adults with glioma treated with temozolomide.

Background: Temozolomide (TMZ) treatment has demonstrated, but variable, impact on glioma prognosis. This study examines associations of survival with DNA repair gene germline polymorphisms among glioma patients who did and did not have TMZ treatment. Identifying genetic markers which sensitize tumor cells to TMZ could personalize therapy and improve outcomes.

Practical and statistical aspects of subgroup analyses in surgical neuro-oncology: A comprehensive review from the PIONEER Consortium.

Subgroup analyses are essential to generate new hypotheses or to estimate treatment effects in clinically meaningful subgroups of patients. They play an important role in taking the next step towards personalized surgical treatment for brain tumor patients. However, subgroup analyses must be used with consideration and care because they have significant potential risks.

Construction and performance of a clinical prediction rule for ureteral stone without the use of race or ethnicity: A new STONE score.

Objectives: The original STONE score was designed to predict the presence of uncomplicated renal colic and the corresponding absence of alternate serious etiologies. It was retrospectively derived and prospectively validated and resulted in five variables: Sex (male gender), Timing (acute onset of pain), "Origin" (non-Black race), Nausea/vomiting (present), and Erythrocytes (microscopic hematuria). With recent increased awareness of the potential adverse impacts of including race (a socially constructed identity) in clinical prediction rules, we sought to determine if a revised STONE score without race could be constructed with similar diagnostic accuracy.

Development and validation of a clinical risk model for postoperative outcome in newly diagnosed glioblastoma: a report of the RANO resect group.

Background: Following surgery, patients with newly diagnosed glioblastoma frequently enter clinical trials. Nuanced risk assessment is warranted to reduce imbalances between study arms. Here, we aimed (I) to analyze the interactive effects of residual tumor with clinical and molecular factors on outcome and (II) to define a postoperative risk assessment tool.

Glioma immune microenvironment composition calculator (GIMiCC): a method of estimating the proportions of eighteen cell types from DNA methylation microarray data.

A scalable platform for cell typing in the glioma microenvironment can improve tumor subtyping and immune landscape detection as successful immunotherapy strategies continue to be sought and evaluated. DNA methylation (DNAm) biomarkers for molecular classification of tumor subtypes have been developed for clinical use. However, tools that predict the cellular landscape of the tumor are not well-defined or readily available.

Association of immunoglobulin E levels with glioma risk and survival.

Background: Previous epidemiologic studies have reported an association of serum immunoglobulin E (IgE) levels with reduced glioma risk, but the association between IgE and glioma prognosis has not been characterized. This study aimed to examine how sex, tumor subtype, and IgE class modulate the association of serum IgE levels with glioma risk and survival.

Methods: We conducted a case-control study using participants from the University of California, San Francisco Adult Glioma Study (1997-2010).

Functional germline variants in DNA damage repair pathways are associated with altered survival in adults with glioma treated with temozolomide.

Background: Temozolomide (TMZ) treatment has demonstrated, but variable, impact on glioma prognosis. This study examines associations of survival with DNA repair gene germline polymorphisms among glioma patients who did and did not have TMZ treatment. Identifying genetic markers which sensitize tumor cells to TMZ could personalize therapy and improve outcomes.

Oligodendroglioma patient survival is associated with circulating B-cells and age.

Background: Variations in survival among patients with oligodendroglioma are unexplained by known prognostic factors. To assess the impact of peripheral immune profiles on prognosis, we applied immunomethylomics analyses-DNA methylation of archived whole blood samples, to characterize immune cells.

Methods: We compared the proportions of immune cells from patients with oligodendroglioma to other glioma subtypes and controls.

Improving glioma drug delivery: A multifaceted approach for glioma drug development.

Glioma is one of the most common central nervous system (CNS) cancers that can be found within the brain and the spinal cord. One of the pressing issues plaguing the development of therapeutics for glioma originates from the selective and semipermeable CNS membranes: the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB). It is difficult to bypass these membranes and target the desired cancerous tissue because the purpose of the BBB and BSCB is to filter toxins and foreign material from invading CNS spaces.

Enhancing neuro-oncology care through equity-driven applications of artificial intelligence.

The disease course and clinical outcome for brain tumor patients depend not only on the molecular and histological features of the tumor but also on the patient's demographics and social determinants of health. While current investigations in neuro-oncology have broadly utilized artificial intelligence (AI) to enrich tumor diagnosis and more accurately predict treatment response, postoperative complications, and survival, equity-driven applications of AI have been limited. However, AI applications to advance health equity in the broader medical field have the potential to serve as practical blueprints to address known disparities in neuro-oncologic care.

An assessment of compositional methods for the analysis of DNA methylation-based deconvolution estimates.

DNA methylation (DNAm)-based deconvolution estimates contain relative data, forming a composition, that standard methods (testing directly on cell proportions) are ill-suited to handle. In this study we examined the performance of an alternative method, analysis of compositions of microbiomes (ANCOM), for the analysis of DNAm-based deconvolution estimates. We performed two different simulation studies comparing ANCOM to a standard approach (two sample -test performed directly on cell proportions) and analyzed a real-world data from the Women's Health Initiative to evaluate the applicability of ANCOM to DNAm-based deconvolution estimates.

Improving the Generalizability of Deep Learning for T2-Lesion Segmentation of Gliomas in the Post-Treatment Setting.

Although fully automated volumetric approaches for monitoring brain tumor response have many advantages, most available deep learning models are optimized for highly curated, multi-contrast MRI from newly diagnosed gliomas, which are not representative of post-treatment cases in the clinic. Improving segmentation for treated patients is critical to accurately tracking changes in response to therapy. We investigated mixing data from newly diagnosed ( = 208) and treated ( = 221) gliomas in training, applying transfer learning (TL) from pre- to post-treatment imaging domains, and incorporating spatial regularization for T2-lesion segmentation using only T2 FLAIR images as input to improve generalization post-treatment.

Association of immunoglobulin E levels with glioma risk and survival.

Background: Previous epidemiologic studies have reported an association of serum immunoglobulin E (IgE) levels with reduced glioma risk, but the association between IgE and glioma prognosis has not been characterized. This study aimed to examine how sex, tumor subtype, and IgE class modulate the association of serum IgE levels with glioma risk and survival.

Methods: We conducted a case-control study using participants from the University of California, San Francisco Adult Glioma Study (1997-2010).

Use of External Control Cohorts in Pediatric Brain Tumor Clinical Trials.

Why, when, and how to consider external control cohorts in pediatric brain tumor clinical trials.

Enrichment of a neutrophil-like monocyte transcriptional state in glioblastoma myeloid suppressor cells.

Glioblastomas (GBM) are lethal central nervous system cancers associated with tumor and systemic immunosuppression. Heterogeneous monocyte myeloid-derived suppressor cells (M-MDSC) are implicated in the altered immune response in GBM, but M-MDSC ontogeny and definitive phenotypic markers are unknown. Using single-cell transcriptomics, we revealed heterogeneity in blood M-MDSC from GBM subjects and an enrichment in a transcriptional state reminiscent of neutrophil-like monocytes (NeuMo), a newly described pathway of monopoiesis in mice.

Matched analysis of detailed peripheral blood and tumor immune microenvironment profiles in bladder cancer.

Bladder cancer and therapy responses hinge on immune profiles in the tumor microenvironment (TME) and blood, yet studies linking tumor-infiltrating immune cells to peripheral immune profiles are limited. DNA methylation cytometry quantified TME and matched peripheral blood immune cell proportions. With tumor immune profile data as the input, subjects were grouped by immune infiltration status and consensus clustering.

Rational combination platform trial design for children and young adults with diffuse midline glioma: A report from PNOC.

Background Diffuse midline glioma (DMG) is a devastating pediatric brain tumor unresponsive to hundreds of clinical trials. Approximately 80% of DMGs harbor H3K27M oncohistones, which reprogram the epigenome to increase the metabolic profile of the tumor cells. Methods We have previously shown preclinical efficacy of targeting both oxidative phosphorylation and glycolysis through treatment with ONC201, which activates the mitochondrial protease ClpP, and paxalisib, which inhibits PI3K/mTOR, respectively.

Everolimus for Children With Recurrent or Progressive Low-Grade Glioma: Results From the Phase II PNOC001 Trial.

Purpose: The PNOC001 phase II single-arm trial sought to estimate progression-free survival (PFS) associated with everolimus therapy for progressive/recurrent pediatric low-grade glioma (pLGG) on the basis of phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway activation as measured by phosphorylated-ribosomal protein S6 and to identify prognostic and predictive biomarkers.

Patients And Methods: Patients, age 3-21 years, with progressive/recurrent pLGG received everolimus orally, 5 mg/m once daily. Frequency of driver gene alterations was compared among independent pLGG cohorts of newly diagnosed and progressive/recurrent patients.