Publications by authors named "Benjamin M Ellingson"

A radio-pathomic machine learning (ML) model has been developed to estimate tumor cell density, cytoplasm density (Cyt) and extracellular fluid density (ECF) from multimodal MR images and autopsy pathology. In this multicenter study, we implemented this model to test its ability to predict survival in patients with recurrent glioblastoma (rGBM) treated with chemotherapy. Pre- and post-contrast T-weighted, FLAIR and ADC images were used to generate radio-pathomic maps for 51 patients with longitudinal pre- and post-treatment scans.

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  • Glioblastoma patients typically have a poor prognosis even after standard treatments, prompting research into new combinations of therapy.
  • The study evaluated the effectiveness of veliparib combined with temozolomide for glioblastoma patients with MGMT promoter hypermethylation, hoping to enhance treatment outcomes.
  • Results showed a slight improvement in median overall survival for the veliparib group compared to the placebo, but the difference wasn't significant enough to meet efficacy goals, though the combination treatment was generally well tolerated.
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  • This study evaluates the effectiveness of normalized apparent diffusion coefficient (nADC) versus percentage T2-FLAIR mismatch-volume (%T2FM-volume) in distinguishing IDH-mutant astrocytoma from other glioma types.* -
  • The analysis involved 105 non-enhancing gliomas, utilizing T2-FLAIR digital subtraction maps to identify tumor subregions, yielding results that showed nADC was significantly higher in IDH-mutant astrocytomas compared to other glioma subtypes.* -
  • Overall, nADC was found to be a more reliable classifier than %T2FM-volume, demonstrating higher sensitivity and specificity in identifying IDH-mutant astrocytomas, while survival analysis results indicated a trend
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  • Targeted radionuclide therapy is a new treatment option for metastatic cancer that uses nuclear medicine to identify and target tumors based on specific markers.
  • This therapy can complement traditional radiotherapy, especially when imaging techniques like MRI miss microscopic metastases.
  • Current approved uses include treating certain thyroid and prostate cancers, while ongoing research is exploring additional targets, with potential effectiveness against brain metastases if the necessary targets are present.
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  • The study investigates the biological basis of stress reactivity (SR) differences in individuals, focusing on irritable bowel syndrome (IBS) patients and healthy controls (HCs) to understand how these differences impact their health.
  • It uses data from 291 participants, applying methods like transcriptomics profiling and brain imaging to categorize individuals into high and low SR groups and analyze their differences.
  • Results indicate that those with high SR have greater sympathetic nervous system activation and brain changes linked to heightened stress responses, suggesting that this increased activity could be a risk factor for IBS and may inform personalized treatment approaches.
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  • The study investigates the effects of Jardiance® (Empagliflozin), a specific SGLT2 inhibitor, on glucose uptake in astrocytomas by using a glucose tracer and PET imaging.
  • Five patients participated, four with grade IV glioblastomas and one with grade II astrocytoma, undergoing two PET scans before and after taking Jardiance.
  • Results showed a significant reduction in tumor glucose accumulation after treatment, suggesting SGLT2 is an active glucose transporter in astrocytomas and prompting recommendations for further clinical trials.
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Purpose Of Review: The Response Assessment in Neuro-Oncology (RANO) 2.0 criteria aim at improving the standardization and reliability of treatment response assessment in clinical trials studying central nervous system (CNS) gliomas. This review presents the evidence supporting RANO 2.

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Patients with degenerative cervical myelopathy (DCM) experience structural and functional brain reorganization. However, few studies have investigated the influence of sex on cerebral alterations. The present study investigates the role of sex on brain functional connectivity (FC) and global network topology in DCM and healthy controls (HCs).

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Radiographic assessment plays a crucial role in the management of patients with central nervous system (CNS) tumors, aiding in treatment planning and evaluation of therapeutic efficacy by quantifying response. Recently, an updated version of the Response Assessment in Neuro-Oncology (RANO) criteria (RANO 2.0) was developed to improve upon prior criteria and provide an updated, standardized framework for assessing treatment response in clinical trials for gliomas in adults.

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  • The 2016 and 2021 WHO classifications of CNS tumors have improved how we categorize IDH-mutant gliomas, leading to better treatment options and longer survival for patients.
  • Current treatment guidelines are still largely based on older data that mix different tumor types, often focusing on high-risk factors like age and residual tumor post-surgery.
  • New insights from recent studies suggest that postponing aggressive treatments like radiation and chemotherapy may be safe for many patients with lower-grade IDH-mutant gliomas, and that newer medications like vorasidenib could be beneficial before resorting to traditional therapies.
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Typical longitudinal radiographic assessment of brain tumors relies on side-by-side qualitative visualization of serial magnetic resonance images (MRIs) aided by quantitative measurements of tumor size. However, when assessing slowly growing tumors and/or complex tumors, side-by-side visualization and quantification may be difficult or unreliable. Whole-brain, patient-specific "digital flipbooks" of longitudinal scans are a potential method to augment radiographic side-by-side reads in clinical settings by enhancing the visual perception of changes in tumor size, mass effect, and infiltration across multiple slices over time.

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In this randomized phase II clinical trial, we evaluated the effectiveness of adding the TLR agonists, poly-ICLC or resiquimod, to autologous tumor lysate-pulsed dendritic cell (ATL-DC) vaccination in patients with newly-diagnosed or recurrent WHO Grade III-IV malignant gliomas. The primary endpoints were to assess the most effective combination of vaccine and adjuvant in order to enhance the immune potency, along with safety. The combination of ATL-DC vaccination and TLR agonist was safe and found to enhance systemic immune responses, as indicated by increased interferon gene expression and changes in immune cell activation.

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  • The study explores the use of resting-state functional MRI (rs-fMRI) and its potential to evaluate functional connectivity (FC) in patients with brain tumors, highlighting the limitations in clinical assessments due to time and cost.
  • The researchers propose deriving a "pseudo-rs-fMRI" signal from DSC perfusion MRI, which is routinely used in clinical settings, to assess both perfusion metrics and cognitive impairment simultaneously.
  • Results show that the pseudo-rs-fMRI technique produced comparable network maps for default mode, motor, and language functions, indicating its viability as an alternative method for assessing cognitive dysfunction in glioma patients.
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Background: Non-enhancing (NE) infiltrating tumor cells beyond the contrast-enhancing (CE) bulk of tumor are potential propagators of recurrence after gross total resection of high-grade glioma.

Methods: We leveraged single-nucleus RNA sequencing on 15 specimens from recurrent high-grade gliomas ( = 5) to compare prospectively identified biopsy specimens acquired from CE and NE regions. Additionally, 24 CE and 22 NE biopsies had immunohistochemical staining to validate RNA findings.

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Background And Objectives: This study identified a clinically significant subset of patients with glioma with tumor outside of contrast enhancement present at autopsy and subsequently developed a method for detecting nonenhancing tumor using radio-pathomic mapping. We tested the hypothesis that autopsy-based radio-pathomic tumor probability maps would be able to noninvasively identify areas of infiltrative tumor beyond traditional imaging signatures.

Methods: A total of 159 tissue samples from 65 subjects were aligned to MRI acquired nearest to death for this retrospective study.

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Purpose: Although fewer than 5% of high-grade gliomas (HGG) are BRAF-V600E mutated, these tumors are notable as BRAF-targeted therapy shows efficacy for some populations. The purpose of this study was to evaluate response to the combination of encorafenib with binimetinib in adults with recurrent BRAF-V600-mutated HGG.

Patients And Methods: In this phase 2, open-label, Adult Brain Tumor Consortium (ABTC) trial (NCT03973918), encorafenib and binimetinib were administered at their FDA-approved doses continuously in 28-day cycles.

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Response Assessment in Neuro-Oncology (RANO) response criteria have been established and were updated in 2023 for MRI-based response evaluation of diffuse gliomas in clinical trials. In addition, PET-based imaging with amino acid tracers is increasingly considered for disease monitoring in both clinical practice and clinical trials. So far, a standardised framework defining timepoints for baseline and follow-up investigations and response evaluation criteria for PET imaging of diffuse gliomas has not been established.

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Standardized MRI acquisition protocols are crucial for reducing the measurement and interpretation variability associated with response assessment in brain tumor clinical trials. The main challenge is that standardized protocols should ensure high image quality while maximizing the number of institutions meeting the acquisition requirements. In recent years, extensive effort has been made by consensus groups to propose different "ideal" and "minimum requirements" brain tumor imaging protocols (BTIPs) for gliomas, brain metastases (BM), and primary central nervous system lymphomas (PCSNL).

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Study Design: Prospective single institutional cohort study on degenerative cervical myelopathy (DCM) from 2009 to 2022.

Objective: This study aims to assess the relationship among preoperative spinal cord signal change, postoperative signal change evolution, and functional outcome in patients undergoing surgery for DCM.

Summary Of Background Data: There is conflicting evidence on whether spinal cord signal intensity influences functional outcomes in patients with DCM.

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  • * The Response Assessment in Neuro-Oncology (RANO) consortium has created standardized recommendations to improve tumor evaluation in a field known for its inherent tissue variability, detailing how to properly sample and analyze tumor regions based on preoperative imaging.
  • * The guidelines also include practical tissue sampling advice for different grades of gliomas and the handling of liquid biopsies, aiming to optimize research practices and ensure high-quality tissue for future studies.
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  • The study aimed to assess the effectiveness of dynamic SAGE-EPI imaging to measure blood flow and contrast leakage in gliomas during one contrast injection.
  • The research involved 38 patients and evaluated various imaging metrics, which were then analyzed based on treatment history and biological factors like IDH mutation status and Ki67 expression.
  • The findings revealed that these imaging metrics vary significantly between treatment-naïve and recurrent gliomas, highlighting the potential of using TRATE values as a predictor for tumor characteristics.
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Background: There is an immunologic rationale to evaluate immunotherapy in the older glioblastoma population, who have been underrepresented in prior trials. The NUTMEG study evaluated the combination of nivolumab and temozolomide in patients with glioblastoma aged 65 years and older.

Methods: NUTMEG was a multicenter 2:1 randomized phase II trial for patients with newly diagnosed glioblastoma aged 65 years and older.

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