VISTA Emerges as a Promising Target against Immune Evasion Mechanisms in Medulloblastoma.

Background: Relapsed medulloblastoma (MB) poses a significant therapeutic challenge due to its highly immunosuppressive tumor microenvironment. Immune checkpoint inhibitors (ICIs) have struggled to mitigate this challenge, largely due to low T-cell infiltration and minimal PD-L1 expression. Identifying the mechanisms driving low T-cell infiltration is crucial for developing more effective immunotherapies.

Clear cell meningiomas-case presentation, review of radiographic identifiers, and treatment approaches.

Spinal clear cell meningiomas (CCMs) are a rare histological subtype of meningiomas that pose preoperative diagnostic challenges due to their radiographic similarities with other lesions. They are also more aggressive, exhibiting higher rates of recurrence, particularly in pediatric patients. Overcoming diagnostic challenges of these tumors can improve patient outcomes.

DNA methylation landscapes in DIPG reveal methylome variability that can be modified pharmacologically.

Background: Diffuse intrinsic pontine glioma (DIPG) is a uniformly lethal brainstem tumor of childhood, driven by histone H3 K27M mutation and resultant epigenetic dysregulation. Epigenomic analyses of DIPG have shown global loss of repressive chromatin marks accompanied by DNA hypomethylation. However, studies providing a static view of the epigenome do not adequately capture the regulatory underpinnings of DIPG cellular heterogeneity and plasticity.

Oncolytic HSV-1 G207 Immunovirotherapy for Pediatric High-Grade Gliomas.

Background: Outcomes in children and adolescents with recurrent or progressive high-grade glioma are poor, with a historical median overall survival of 5.6 months. Pediatric high-grade gliomas are largely immunologically silent or "cold," with few tumor-infiltrating lymphocytes.

Response rate and local recurrence after concurrent immune checkpoint therapy and radiotherapy for non-small cell lung cancer and melanoma brain metastases.

Background: Prior literature has suggested synergy between immune checkpoint therapy (ICT) and radiotherapy (RT) for the treatment of brain metastases (BrM), but to the authors' knowledge the optimal timing of therapy to maximize this synergy is unclear.

Methods: A total of 199 patients with melanoma and non-small cell lung cancer with BrM received ICT and RT between 2007 and 2016 at the study institution. To reduce selection biases, individual metastases were included only if they were treated with RT within 90 days of ICT.

PD-L1 Expression in Pediatric Low-Grade Gliomas Is Independent of BRAF V600E Mutational Status.

To evaluate a potential relationship between BRAF V600E mutation and PD-L1 expression, we examined the expression of PD-L1 in pediatric high- and low-grade glioma cell lines as well as a cohort of pediatric low-grade glioma patient samples. Half of the tumors in our patient cohort were V600-wildtype and half were V600E mutant. All tumors expressed PD-L1.

Orally bioavailable glutamine antagonist prodrug JHU-083 penetrates mouse brain and suppresses the growth of MYC-driven medulloblastoma.

A subset of poor-prognosis medulloblastoma has genomic amplification of MYC. MYC regulates glutamine metabolism in multiple cellular contexts. We modified the glutamine analog 6-diazo-5-oxo-l-norleucine (DON) to mask its carboxylate and amine functionalities, creating a prodrug termed JHU-083 with increased oral bioavailability.

Breast cancer subtype and intracranial recurrence patterns after brain-directed radiation for brain metastases.

Purpose: Brain metastases from breast cancer are frequently managed with brain-directed radiation but the impact of subtype on intracranial recurrence patterns after radiation has not been well-described. We investigated intracranial recurrence patterns of brain metastases from breast cancer after brain-directed radiation to facilitate subtype-specific management paradigms.

Methods: We retrospectively analyzed 349 patients with newly diagnosed brain metastases from breast cancer treated with brain-directed radiation at Brigham and Women's Hospital/Dana-Farber Cancer Institute between 2000 and 2015.

Local control after brain-directed radiation in patients with cystic versus solid brain metastases.

Purpose: Brain metastases can be radiographically cystic or solid. Cystic metastases are associated with a greater intracranial disease burden and poorer oncologic outcomes, but the impact of cystic versus solid appearance on local control after radiation remains unknown. We investigated whether cystic versus solid nature is predictive of local control after management with stereotactic or whole brain radiation (WBRT) and whether the radiation modality utilized is an effect modifier.

Neurosurgical Resection and Stereotactic Radiation Versus Stereotactic Radiation Alone in Patients with a Single or Solitary Brain Metastasis.

Background: Brain metastases commonly manifest in patients with cancer, with ∼20%-50% presenting with 1 intracranial lesion. Among patients with 1, small brain metastasis and controlled or absent extracranial disease, it remains unclear whether aggressive intracranial management using neurosurgical resection plus cavity stereotactic radiosurgery/stereotactic radiotherapy (SRS/SRT) rather than SRS/SRT alone is beneficial. In patients with controlled or absent extracranial disease and 1 brain metastasis ≤2 cm in size, we evaluated the effect of surgery plus SRS/SRT compared with SRS/SRT on oncologic outcomes, including overall survival.

Expression of LAG-3 and efficacy of combination treatment with anti-LAG-3 and anti-PD-1 monoclonal antibodies in glioblastoma.

Like in many tumor types, immunotherapy is currently under investigation to assess its potential efficacy in glioblastoma patients. Trials are under way to assess the efficacy of new immune checkpoint inhibitors including anti-PD-1 or CTLA4. We here investigate the expression and efficacy of a novel immune-checkpoint inhibitor, called LAG-3.

Postchemotherapy Immunization Practices for Non-HSCT Pediatric Oncology Patients.

Pediatric oncology patients treated with antineoplastic therapy have impaired immune systems that lead to loss of protective antibodies. They require reimmunization to protect against vaccine-preventable diseases. There are a paucity of studies on the clinical practice of pediatric oncologists and the available recommendations are heterogenous.

Unilateral application of an external pneumatic compression therapy improves skin blood flow and vascular reactivity bilaterally.

Background: We sought to determine the effects of unilateral lower-limb external pneumatic compression (EPC) on bilateral lower-limb vascular reactivity and skin blood flow.

Methods: Thirty-two participants completed this two-aim study. In AIM1 ( = 18, age: 25.

Implications of Screening for Brain Metastases in Patients With Breast Cancer and Non-Small Cell Lung Cancer.

This study analyzes the value of magnetic resonance imaging of the brain for patients with cancers that frequently metastasize to the brain.

PD-L1 expression in medulloblastoma: an evaluation by subgroup.

Background: This study evaluated the expression of PD-L1 and markers of immune mediated resistance in human medulloblastoma (MB), the most common malignant pediatric brain tumor.

Results: Overall levels of PD-L1 in human MB were low; however, some cases demonstrated robust focal expression associated with increased immune infiltrates. The case with highest PD-L1 expression was a sonic hedgehog (SHH) MB.

Secondary Acute Leukemia in Sarcoma Patients: A Population-Based Study.

Purpose: To compare rates of secondary acute leukemia between sarcoma patients and the general population, using data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) registry, and to examine whether various patient, tumor, and treatment factors were associated with development of a secondary acute leukemia.

Methods And Materials: Patients with a primary diagnosis of connective tissue malignancy between 1973 and 2008 in the SEER database were included. Multivariable competing risk analysis was used to determine risk factors associated with subsequent development of acute leukemia.

Impact of pemetrexed on intracranial disease control and radiation necrosis in patients with brain metastases from non-small cell lung cancer receiving stereotactic radiation.

Background: Pemetrexed is a folate antimetabolite used in the management of advanced adenocarcinoma of the lung. We sought to assess the impact of pemetrexed on intracranial disease control and radiation-related toxicity among patients with adenocarcinoma of the lung who received stereotactic radiation for brain metastases.

Materials/methods: We identified 149 patients with adenocarcinoma of the lung and newly diagnosed brain metastases without a targetable mutation receiving stereotactic radiation.

Immunotherapy and Symptomatic Radiation Necrosis in Patients With Brain Metastases Treated With Stereotactic Radiation.

This study investigates the association between immunotherapy and symptomatic radiation necrosis in patients with melanoma, non–small-cell lung cancer, or renal cell carcinoma and newly diagnosed brain metastases treated with stereotactic radiation therapy.

Incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy: a population-based study.

Background: Brain metastases are associated with significant morbidity and mortality. Population-level data describing the incidence and prognosis of patients with brain metastases are lacking. The aim of this study was to characterize the incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy using recently released data from the Surveillance, Epidemiology, and End Results (SEER) program.

Brain Metastases in Newly Diagnosed Breast Cancer: A Population-Based Study.

Importance: Population-based estimates of the incidence and prognosis of brain metastases at diagnosis of breast cancer are lacking.

Objective: To characterize the incidence proportions and median survivals of patients with breast cancer and brain metastases at the time of cancer diagnosis.

Design, Setting, And Participants: Patients with breast cancer and brain metastases at the time of diagnosis were identified using the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute.

Anti-PD-1 antitumor immunity is enhanced by local and abrogated by systemic chemotherapy in GBM.

The immunosuppressive effects of chemotherapy present a challenge for designing effective cancer immunotherapy strategies. We hypothesized that although systemic chemotherapy (SC) exhibits negative immunologic effects, local chemotherapy (LC) can potentiate an antitumor immune response. We show that LC combined with anti-programmed cell death protein 1 (PD-1) facilitates an antitumor immune response and improves survival (P < 0.

Combination Therapy with Anti-PD-1, Anti-TIM-3, and Focal Radiation Results in Regression of Murine Gliomas.

Purpose: Checkpoint molecules like programmed death-1 (PD-1) and T-cell immunoglobulin mucin-3 (TIM-3) are negative immune regulators that may be upregulated in the setting of glioblastoma multiforme. Combined PD-1 blockade and stereotactic radiosurgery (SRS) have been shown to improve antitumor immunity and produce long-term survivors in a murine glioma model. However, tumor-infiltrating lymphocytes (TIL) can express multiple checkpoints, and expression of ≥2 checkpoints corresponds to a more exhausted T-cell phenotype.