Macrophage migration inhibitory factor as a therapeutic target in neuro-oncology: A review.

Primary central nervous system (CNS) tumors affect tens of thousands of patients each year, and there is a significant need for new treatments. Macrophage migration inhibitory factor (MIF) is a cytokine implicated in multiple tumorigenic processes such as cell proliferation, vascularization, and immune evasion and is therefore a promising therapeutic target in primary CNS tumors. There are several MIF-directed treatments available, including small-molecule inhibitors, peptide drugs, and monoclonal antibodies.

Tumor cell-derived spermidine promotes a pro-tumorigenic immune microenvironment in glioblastoma via CD8+ T cell inhibition.

The glioblastoma microenvironment is enriched in immunosuppressive factors that potently interfere with the function of cytotoxic T lymphocytes. Cancer cells can directly impact the immune system, but the mechanisms driving these interactions are not completely clear. Here we demonstrate that the polyamine metabolite spermidine is elevated in the glioblastoma tumor microenvironment.

Sex-Biased T-cell Exhaustion Drives Differential Immune Responses in Glioblastoma.

Unlabelled: Sex differences in glioblastoma (GBM) incidence and outcome are well recognized, and emerging evidence suggests that these extend to genetic/epigenetic and cellular differences, including immune responses. However, the mechanisms driving immunologic sex differences are not fully understood. Here, we demonstrate that T cells play a critical role in driving GBM sex differences.

The MIF promoter SNP rs755622 is associated with immune activation in glioblastoma.

Intratumoral heterogeneity is a defining hallmark of glioblastoma, driving drug resistance and ultimately recurrence. Many somatic drivers of microenvironmental change have been shown to affect this heterogeneity and, ultimately, the treatment response. However, little is known about how germline mutations affect the tumoral microenvironment.

Spatial immunosampling of MRI-defined glioblastoma regions reveals immunologic fingerprint of non-contrast enhancing, infiltrative tumor margins.

Glioblastoma (GBM) treatment includes maximal safe resection of the core and MRI contrast-enhancing (CE) tumor. Complete resection of the infiltrative non-contrast-enhancing (NCE) tumor rim is rarely achieved. We established a safe, semi-automated workflow for spatially-registered sampling of MRI-defined GBM regions in 19 patients with downstream analysis and biobanking, enabling studies of NCE, wherefrom recurrence/progression typically occurs.

The Impact of Extent of Ablation on Survival of Patients With Newly Diagnosed Glioblastoma Treated With Laser Interstitial Thermal Therapy: A Large Single-Institutional Cohort.

Background: Upfront laser interstitial thermal therapy (LITT) can be used as part of the treatment paradigm in difficult-to-access newly diagnosed glioblastoma multiforme (ndGBM) cases. The extent of ablation, though, is not routinely quantified; thus, its specific effect on patients' oncological outcomes is unclear.

Objective: To methodically measure the extent of ablation in the cohort of patients with ndGBM and its effect, and other treatment-related parameters, on patients' progression-free survival (PFS) and overall survival (OS).

Tumor Treating Fields: killing two birds with one stone.

Given its aggressive natural history and immunosuppressive nature, glioblastoma (GBM) remains difficult to treat. Tumor Treating Fields (TTFields) are a promising treatment for GBM patients, yet the entirety of their antitumor action has not been fully elucidated. In a recent issue of the JCI, Chen et al.

Time to Steroid Independence After Laser Interstitial Thermal Therapy vs Medical Management for Treatment of Biopsy-Proven Radiation Necrosis Secondary to Stereotactic Radiosurgery for Brain Metastasis.

Background: Radiation necrosis (RN) after stereotactic radiosurgery (SRS) for brain metastases (BM) can result in significant morbidity, compounded by the effects of extended steroid therapy. Laser interstitial thermal therapy (LITT) is a minimally invasive procedure that can offer definitive treatment for RN while potentially obviating the need for prolonged steroid use.

Objective: To compare LITT vs medical management (MM) in the treatment of RN.

Laser interstitial thermal therapy for brain metastases.

Laser interstitial thermal therapy (LITT) is a minimally invasive treatment for intracranial lesions entailing thermal ablation via a stereotactically placed laser probe. In metastatic disease, it has shown the most promise in the treatment of radiographically progressive lesions after initial stereotactic radiosurgery, whether due to recurrent metastatic disease or radiation necrosis. LITT has been demonstrated to provide clinical benefit in both cases, as discussed in the review below.

The Translocator Protein () Genetic Polymorphism A147T Is Associated with Worse Survival in Male Glioblastoma Patients.

Glioblastoma (GBM) is the most common primary brain tumor in adults, with few available therapies and a five-year survival rate of 7.2%. Hence, strategies for improving GBM prognosis are urgently needed.

Late-week surgery and discharge to specialty care associated with higher costs and longer lengths of stay after elective lumbar laminectomy.

Objective: In a healthcare landscape in which costs increasingly matter, the authors sought to distinguish among the clinical and nonclinical drivers of patient length of stay (LOS) in the hospital following elective lumbar laminectomy-a common spinal surgery that may be reimbursed using bundled payments-and to understand their relationships with patient outcomes and costs.

Methods: Patients ≥ 18 years of age undergoing laminectomy surgery for degenerative lumbar spinal stenosis within the Cleveland Clinic health system between March 1, 2016, and February 1, 2019, were included in this analysis. Generalized linear modeling was used to assess the relationships between the day of surgery, patient discharge disposition, and hospital LOS, while adjusting for underlying patient health risks and other nonclinical factors, including the hospital surgery site and health insurance.

Preclinical Modeling of Surgery and Steroid Therapy for Glioblastoma Reveals Changes in Immunophenotype that are Associated with Tumor Growth and Outcome.

Purpose: Glioblastoma (GBM) immunotherapy clinical trials are generally initiated after standard-of-care treatment-including surgical resection, perioperative high-dose steroid therapy, chemotherapy, and radiation treatment-has either begun or failed. However, the impact of these interventions on the antitumoral immune response is not well studied. While discoveries regarding the impact of chemotherapy and radiation on immune response have been made and translated into clinical trial design, the impact of surgical resection and steroids on the antitumor immune response has yet to be determined.

resources for optimizing care and practice in spinal oncology.

As the diagnosis and treatment of systemic cancers continues to improve, increased patient survival has resulted in a rise in the number of patients who develop spinal metastases (SM). Within many areas of oncology, utilization of multidisciplinary care models in the management and decision making of SM patients has proven effective for optimizing care and improving patient safety. Three main goals of an effective clinical pathway include improving outcomes and quality, improving the patient experience, and lowering cost.

Stereotactic Laser Ablation of Glioblastoma.

The previous decade has seen an expansion in the use of laser interstitial thermal therapy (LITT) for a variety of pathologies. LITT has been used to treat both newly diagnosed and recurrent glioblastoma (GBM), especially in deep-seated, difficult-to-access lesions where open resection is otherwise infeasible or in patients who would not tolerate craniotomy. This review aims to describe the current state of the technology and operative technique, as well as summarize the outcomes data and future research regarding LITT as a treatment of GBM.

Defining best practices for tissue procurement in immuno-oncology clinical trials: consensus statement from the Society for Immunotherapy of Cancer Surgery Committee.

Immunotherapy is now a cornerstone for cancer treatment, and much attention has been placed on the identification of prognostic and predictive biomarkers. The success of biomarker development is dependent on accurate and timely collection of biospecimens and high-quality processing, storage and shipping. Tumors are also increasingly used as source material for the generation of therapeutic T cells.

The intersection between immunotherapy and laser interstitial thermal therapy: a multipronged future of neuro-oncology.

The rise of immunotherapy (IT) in oncological treatment has greatly improved outcomes in a number of disease states. However, its use in tumors of the central nervous system (CNS) remains limited for multiple reasons related to the unique immunologic tumor microenvironment. As such, it is valuable to consider the intersection of IT with additional treatment methods that may improve access to the CNS and effectiveness of existing IT modalities.

Immune suppression in gliomas.

Introduction: The overall survival in patients with gliomas has not significantly increased in the modern era, despite advances such as immunotherapy. This is in part due to their notorious ability to suppress local and systemic immune responses, severely restricting treatment efficacy.

Methods: We have reviewed the preclinical and clinical evidence for immunosuppression seen throughout the disease process in gliomas.

Myeloid-Derived Suppressor Cell Subsets Drive Glioblastoma Growth in a Sex-Specific Manner.

Myeloid-derived suppressor cells (MDSC) that block antitumor immunity are elevated in glioblastoma (GBM) patient blood and tumors. However, the distinct contributions of monocytic (mMDSC) versus granulocytic (gMDSC) subsets have yet to be determined. In mouse models of GBM, we observed that mMDSCs were enriched in the male tumors, whereas gMDSCs were elevated in the blood of females.

The Impact of Artificial Intelligence on Quality and Safety.

As exponential expansion of computing capacity converges with unsustainable health care spending, a hopeful opportunity has emerged: the use of artificial intelligence to enhance health care quality and safety. These computer-based algorithms can perform the intricate and extremely complex mathematical operations of classification or regression on immense amounts of data to detect intricate and potentially previously unknown patterns in that data, with the end result of creating predictive models that can be utilized in clinical practice. Such models are designed to distinguish relevant from irrelevant data regarding a particular patient; choose appropriate perioperative care, intervention or surgery; predict cost of care and reimbursement; and predict future outcomes on a variety of anchored measures.

Metronomic capecitabine as an immune modulator in glioblastoma patients reduces myeloid-derived suppressor cells.

BACKGROUNDMyeloid-derived suppressor cells (MDSCs) are elevated in the circulation of patients with glioblastoma (GBM), present in tumor tissue, and associated with poor prognosis. While low-dose chemotherapy reduces MDSCs in preclinical models, the use of this strategy to reduce MDSCs in GBM patients has yet to be evaluated.METHODSA phase 0/I dose-escalation clinical trial was conducted in patients with recurrent GBM treated 5-7 days before surgery with low-dose chemotherapy via capecitabine, followed by concomitant low-dose capecitabine and bevacizumab.

Operative and peri-operative considerations in the management of brain metastasis.

The number of patients who develop metastatic brain lesions is increasing as the diagnosis and treatment of systemic cancers continues to improve, resulting in longer patient survival. The role of surgery in the management of brain metastasis (BM), particularly multiple and recurrent metastases, remains controversial and continues to evolve. However, with appropriate patient selection, outcomes after surgery are typically favorable.

Global immune fingerprinting in glioblastoma patient peripheral blood reveals immune-suppression signatures associated with prognosis.

Glioblastoma (GBM) remains uniformly lethal, and despite a large accumulation of immune cells in the microenvironment, there is limited antitumor immune response. To overcome these challenges, a comprehensive understanding of GBM systemic immune response during disease progression is required. Here, we integrated multiparameter flow cytometry and mass cytometry TOF (CyTOF) analysis of patient blood to determine changes in the immune system among tumor types and over disease progression.