Stereotactic radiosurgery for brain metastases from extra-renal clear cell carcinoma: A series of four patients and review of the literature.

Background: Clear cell carcinoma occurring outside of the kidney represents an aggressive histological subtype which is frequently resistant to standard chemotherapy. Brain metastases (BM) from extra-renal clear cell carcinoma (erCCC) are exceedingly rare, and the optimal treatment approach for this histology remains uncertain. To our knowledge, stereotactic radiosurgery (SRS) has not been specifically investigated for this patient population.

Adaptive cohort design and LAT1 expression scale: study protocol for a Phase 2a trial of QBS72S in breast cancer brain metastases.

Background: Breast cancer is the most common cause of cancer death among women and frequently metastasizes to the brain. Up to 30% of patients with breast-to-brain metastases will develop leptomeningeal disease (LMD), with poor survival, rapid neurologic decline, and no durable treatment options. The novel agent QBS72S, also known as QBS10072S, is designed to leverage the high expression of L-type amino acid transporter 1 (LAT1) on breast cancer cells and the blood-brain barrier.

Nanopore-based cell-free DNA fragmentation and methylation profiles from the cerebral spinal fluid of patients with lung cancer brain metastases.

Background: Non-small cell lung cancer () patients with brain metastases () have a poor prognosis. Cerebrospinal fluid () is a source of cell free DNA () from the brain and its methylation and fragmentation properties may be an indicator of NSCLC-BMET.

Methods: We applied a nanopore single-molecule sequencing approach to characterize the fragmentation, methylation and hydroxymethylation patterns present in CSF-derived cfDNA from NSCLC-BMET patients (N=15).

Stereotactic radiosurgery for intracranial and spinal adenoid cystic carcinoma: systematic review and illustrative case presentation.

Purpose: Adenoid cystic carcinoma (ACC) is a rare, aggressive malignancy with a predilection for perineural spread and distant metastases. Given the limited but emerging evidence on the role of stereotactic radiosurgery (SRS) in managing intracranial and spinal ACC, a systematic review was deemed necessary to synthesize relevant parameters related to clinical features and management of ACC patients, SRS treatment characteristics, and clinical outcomes across published studies.

Methods: This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Multi-omic landscape of human gliomas from diagnosis to treatment and recurrence.

Gliomas are among the most lethal cancers, with limited treatment options. To uncover hallmarks of therapeutic escape and tumor microenvironment (TME) evolution, we applied spatial proteomics, transcriptomics, and glycomics to 670 lesions from 310 adult and pediatric patients. Single-cell analysis shows high B7H3+ tumor cell prevalence in glioblastoma (GBM) and pleomorphic xanthoastrocytoma (PXA), while most gliomas, including pediatric cases, express targetable tumor antigens in less than 50% of tumor cells, potentially explaining trial failures.

Use of Carbon Fiber Implants to Improve the Safety and Efficacy of Radiation Therapy for Spine Tumor Patients.

Current standard of care treatment for patients with spine tumors includes multidisciplinary approaches, including the following: (1) surgical tumor debulking, epidural spinal cord decompression, and spine stabilization techniques; (2) systemic chemo/targeted therapies; (3) radiation therapy; and (4) surveillance imaging for local disease control and recurrence. Titanium pedicle screw and rod fixation have become commonplace in the spine surgeon's armamentarium for the stabilization of the spine following tumor resection and separation surgery. However, the high degree of imaging artifacts seen with titanium implants on postoperative CT and MRI scans can significantly hinder the accurate delineation of vertebral anatomy and adjacent neurovascular structures to allow for the safe and effective planning of downstream radiation therapies and detection of disease recurrence.

Single- versus multi-fraction spine stereotactic radiosurgery (ALL-STAR) for patients with spinal metastases: a randomized phase III trial protocol.

Background: For patients with spine metastases, stereotactic radiosurgery (SRS) provides excellent local control and pain response. Despite increasing use of this treatment modality, there is no consensus on the optimal dose and fractionation of spine SRS for efficacy and toxicity. We have initiated a single-center phase III randomized trial that compares two dose regimens with similar biological equivalent dose (BED) to determine the isolated effect of SRS fractionation on local control.

Spatial Profiling Reveals Equivalence-Derived Molecular Signatures of Brain Mimicry and Adaptation in Breast Cancer Brain Metastases.

Brain metastases (BrMets), common for advanced-stage breast cancer patients, are associated with poor median survival and accompanied by severe neurologic decline. Halting the progression of breast cancer brain metastases (BCBMs) may require modulation of the tumor microenvironment (TME), yet little is known about the impact of the primary breast TME on brain tropism, or how, once there, metastatic breast cancer cells coexist with brain-resident cells (e.g.

Monitoring of cancer ferroptosis with [F]hGTS13, a system xc- specific radiotracer.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults, characterized by resistance to conventional therapies and poor survival. Ferroptosis, a form of regulated cell death driven by lipid peroxidation, has recently emerged as a promising therapeutic target for GBM treatment. However, there are currently no non-invasive imaging techniques to monitor the engagement of pro-ferroptotic compounds with their respective targets, or to monitor the efficacy of ferroptosis-based therapies.

Robust, fully-automated assessment of cerebral perivascular spaces and white matter lesions: a multicentre MRI longitudinal study of their evolution and association with risk of dementia and accelerated brain atrophy.

Background: Perivascular spaces (PVS) on brain MRI are surrogates for small parenchymal blood vessels and their perivascular compartment, and may relate to brain health. However, it is unknown whether PVS can predict dementia risk and brain atrophy trajectories in participants without dementia, as longitudinal studies on PVS are scarce and current methods for PVS assessment lack robustness and inter-scanner reproducibility.

Methods: We developed a robust algorithm to automatically assess PVS count and size on clinical MRI, and investigated 1) their relationship with dementia risk and brain atrophy in participants without dementia, 2) their longitudinal evolution, and 3) their potential use as a screening tool in simulated clinical trials.

Brain Metastases from Esophageal Cancer: A Retrospective Review from a Single Institution.

Background: Patients with brain metastases (BrMs) from esophageal cancer have poor prognosis, the incidence of which is expected to rise due to improved survival from the primary tumor and increased neuroimaging. We aimed to identify patient and esophageal cancer characteristics associated with longer survival in patients with BrMs and, secondly, to compare the prognosis of patients with HER2 overexpression.

Methods: We retrospectively reviewed patients with BrMs from esophageal cancer at a single institution from 2008-2021.

Quantification of cerebrospinal fluid tumor DNA in lung cancer patients with suspected leptomeningeal carcinomatosis.

Cerebrospinal fluid tumor-derived DNA (CSF-tDNA) analysis is a promising approach for monitoring the neoplastic processes of the central nervous system. We applied a lung cancer-specific sequencing panel (CAPP-Seq) to 81 CSF, blood, and tissue samples from 24 lung cancer patients who underwent lumbar puncture (LP) for suspected leptomeningeal disease (LMD). A subset of the cohort (N = 12) participated in a prospective trial of osimertinib for refractory LMD in which serial LPs were performed before and during treatment.

Cerebral perivascular spaces as predictors of dementia risk and accelerated brain atrophy.

Cerebral small vessel disease, an important risk factor for dementia, lacks robust, measurement methods. Perivascular spaces (PVS) on brain MRI are surrogates for small parenchymal blood vessels and their perivascular compartment, and may relate to brain health. We developed a novel, robust algorithm to automatically assess PVS count and size on MRI, and investigated their relationship with dementia risk and brain atrophy.

Repurposing mebendazole against triple-negative breast cancer CNS metastasis.

Purpose: Triple-negative breast cancer (TNBC) often metastasizes to the central nervous system (CNS) and has the highest propensity among breast cancer subtypes to develop leptomeningeal disease (LMD). LMD is a spread of cancer into leptomeningeal space that speeds up the disease progression and severely aggravates the prognosis. LMD has limited treatment options.

Executive summary of the American Radium Society appropriate use criteria for brain metastases in epidermal growth factor receptor mutated-mutated and ALK-fusion non-small cell lung cancer.

The American Radium Society (ARS) Central Nervous System (CNS) committee reviewed literature on epidermal growth factor receptor mutated (EGFRm) and ALK-fusion (ALK+) tyrosine kinase inhibitors (TKIs) for the treatment of brain metastases (BrMs) from non-small cell lung cancers (NSCLC) to generate appropriate use guidelines addressing use of TKIs in conjunction with or in lieu of radiotherapy (RT). The panel developed three key questions to guide systematic review: can radiotherapy be deferred in patients receiving EGFR or ALK TKIs at (1) diagnosis or (2) recurrence? Should TKI be administered concurrently with RT (3)? Two literature searches were performed (May 2019 and December 2023). The panel developed 8 model cases and voted on treatment options using a 9-point scale, with 1-3, 4-6 and 7-9 corresponding to usually not appropriate, may be appropriate, and usually appropriate (respectively), per the UCLA/RAND Appropriateness Method.

Repurposing mebendazole against triple-negative breast cancer leptomeningeal disease.

Purpose: Triple-negative breast cancer (TNBC) is an aggressive subtype that often metastasizes to the brain. Leptomeningeal disease (LMD), a devastating brain metastasis common in TNBC, has limited treatment options. We sought to test whether the common anti-helminthic drug mebendazole (MBZ) may be effective against murine TNBC LMD.

Effect of Language Barriers and Use of Interpreters on Hope Among Patients With Central Nervous System Malignancies and Bone Metastases.

Purpose: Hope is important in serious illnesses, as it has been linked to patient quality of life. We aimed to determine factors associated with lower hope scores among patients with central nervous system disease or bone metastases.

Methods And Materials: The Adult Dispositional Hope Scale (AHS) is a 12-item questionnaire that measures hope through 2 qualities: agency (goal-directed energy) and pathways (plan to meet goals).

Roadmap for Development of a Strong, Diverse Research Workforce in Neurosurgery.

A benchmark of success for the neurosurgeon-scientist includes obtaining individual research funding from the National Institutes of Health. Successful roadmaps to this goal highlight diversity, individual commitment and resiliency, innovative research goals, intentional mentoring, protected research time, and financial support. We must equip neurosurgery residents to surmount obstacles such as long periods of training, gaps in research productivity, and limited protected time for research to ensure successful transition to independent research careers.

Roadmap for Successful Research Training in Neurosurgery.

A benchmark of success for the neurosurgeon-scientist includes obtaining individual research funding from the National Institutes of Health. Successful roadmaps to this goal highlight individual commitment and resiliency, innovative research goals, intentional mentoring, protected research time, and financial support. Neurosurgery residents must carefully plan their training career to surmount obstacles such as long clinical training period, gaps in research productivity during clinical training, and limited protected time for research to ensure successful transition to independent research careers.

National Cancer Institute Collaborative Workshop on Shaping the Landscape of Brain Metastases Research: challenges and recommended priorities.

Brain metastases are an increasing global public health concern, even as survival rates improve for patients with metastatic disease. Both metastases and the sequelae of their treatment are key determinants of the inter-related priorities of patient survival, function, and quality of life, mandating a multidimensional approach to clinical care and research. At a virtual National Cancer Institute Workshop in September, 2022, key stakeholders convened to define research priorities to address the crucial areas of unmet need for patients with brain metastases to achieve meaningful advances in patient outcomes.

Patterns of Progression in Patients With Newly Diagnosed Glioblastoma Treated With 5-mm Margins in a Phase 1/2 Trial of 5-Fraction Stereotactic Radiosurgery With Concurrent and Adjuvant Temozolomide.

Purpose: In patients with newly diagnosed glioblastoma (GBM), tumor margins of at least 20 mm are the standard of care. We sought to determine the pattern of tumor progression in patients treated with 5-fraction stereotactic radiosurgery with 5-mm margins.

Methods And Materials: Thirty adult patients with newly diagnosed GBM were treated with 5-fraction stereotactic radiosurgery in escalated doses from 25 to 40 Gy with a 5-mm total treatment margin.

A Protocol for Reducing Intensive Care Utilization After Craniotomy: A 3-Year Assessment.

Background: Craniotomy patients have traditionally received intensive care unit (ICU) care postoperatively. Our institution developed the "Non-Intensive CarE" (NICE) protocol to identify craniotomy patients who did not require postoperative ICU care.

Objective: To determine the longitudinal impact of the NICE protocol on postoperative length of stay (LOS), ICU utilization, readmissions, and complications.

Stereotactic radiosurgery for trigeminal neuralgia secondary to tumor: a single-institution retrospective series.

Objective: Trigeminal neuralgia (TN) secondary to tumor represents a rare and diverse entity, and treatment for secondary TN remains controversial. This report reviews a single institution's experience in treating secondary TN with stereotactic radiosurgery (SRS) and focuses on the durability of pain relief with respect to various treatment targets, i.e.

Elevated ETV6 Expression in Glioma Promotes an Aggressive In Vitro Phenotype Associated with Shorter Patient Survival.

: GBM astrocytes may adopt fetal astrocyte transcriptomic signatures involved in brain development and migration programs to facilitate diffuse tumor infiltration. Our previous data show that ETS variant 6 (ETV6) is highly expressed in human GBM and fetal astrocytes compared to normal mature astrocytes. We hypothesized that ETV6 played a role in GBM tumor progression.

5-Aminolevulinic Acid Imaging of Malignant Glioma.

High-grade glioma is the most common malignant primary brain tumor in adults. Glioma infiltration renders it difficult to treat and likely to recur. Increasing the extent of resection has been associated with improving progression-free survival and overall survival by several months.