Metastatic Brain Tumors Research Articles

Practical guidance for direct oral anticoagulant use in the treatment of venous thromboembolism in primary and metastatic brain tumor patients.

Management of venous thromboembolism (VTE) in patients with primary and metastatic brain tumors (BT) is challenging because of the risk of intracranial hemorrhage (ICH). There are no prospective clinical trials evaluating safety and efficacy of direct oral anticoagulants (DOACs), specifically in patients with BT, but they are widely used for VTE in this population. A group of neuro-oncology experts convened to provide practical clinical guidance for the off-label use of DOACs in treating VTE in patients with BT. We searched PubMed for the following terms: BTs, glioma, glioblastoma (GBM), brain metastasis, VTE, heparin, low-molecular-weight heparin (LWMH), DOACs, and ICH. Although prospective clinical trials are needed, the recommendations presented aim to assist clinicians in making informed decisions regarding DOACs for VTE in patients with BT.

Reprimo (RPRM) mediates neuronal ferroptosis via CREB-Nrf2/SCD1 pathways in radiation-induced brain injury

Neuronal ferroptosis has been found to contribute to degenerative brain disorders and traumatic and hemorrhagic brain injury, but whether radiation-induced brain injury (RIBI), a critical deleterious effect of cranial radiation therapy for primary and metastatic brain tumors, involves neuronal ferroptosis remains unclear. We have recently discovered that deletion of reprimo (RPRM), a tumor suppressor gene, ameliorates RIBI, in which its protective effect on neurons is one of the underlying mechanisms. In this study, we found that whole brain irradiation (WBI) induced ferroptosis in mouse brain, manifesting as alterations in mitochondrial morphology, iron accumulation, lipid peroxidation and a dramatic reduction in glutathione peroxidase 4 (GPX4) level. Moreover, the hippocampal ferroptosis induced by ionizing irradiation (IR) mainly happened in neurons. Intriguingly, RPRM deletion protected the brain and primary neurons against IR-induced ferroptosis. Mechanistically, RPRM deletion prevented iron accumulation by reversing the significant increase in the expression of iron storage protein ferritin heavy chain (Fth), ferritin light chain (Ftl) and iron importer transferrin receptor 1 (Tfr1), as well as enhancing the expression of iron exporter ferroportin (Fpn) after IR. RPRM deletion also inhibited lipid peroxidation by abolishing the reduction of GPX4 and stearoyl coenzyme A desaturase-1 (SCD1) induced by IR. Importantly, RPRM deletion restored or even increased the expression of nuclear factor, erythroid 2 like 2 (Nrf2) in irradiated neurons. On top of that, compromised cyclic AMP response element (CRE)-binding protein (CREB) signaling was found to be responsible for the down-regulation of Nrf2 and SCD1 after irradiation, specifically, RPRM bound to CREB and promoted its degradation after IR, leading to a reduction of CREB protein level, which in turn down-regulated Nrf2 and SCD1. Thus, RPRM deletion recovered Nrf2 and SCD1 through its impact on CREB. Taken together, neuronal ferroptosis is involved in RIBI, RPRM deletion prevents IR-induced neuronal ferroptosis through restoring CREB-Nrf2/SCD1 pathways.

Neuropathological Applications of Microscopy with Ultraviolet Surface Excitation (MUSE): A Concordance Study of Human Primary and Metastatic Brain Tumors.

Whereas traditional histology and light microscopy require multiple steps of formalin fixation, paraffin embedding, and sectioning to generate images for pathologic diagnosis, Microscopy using Ultraviolet Surface Excitation (MUSE) operates through UV excitation on the cut surface of tissue, generating images of high resolution without the need to fix or section tissue and allowing for potential use for downstream molecular tests. Here, we present the first study of the use and suitability of MUSE microscopy for neuropathological samples. MUSE images were generated from surgical biopsy samples of primary and metastatic brain tumor biopsy samples (n = 27), and blinded assessments of diagnoses, tumor grades, and cellular features were compared to corresponding hematoxylin and eosin (H&E) images. A set of MUSE-treated samples subsequently underwent exome and targeted sequencing, and quality metrics were compared to those from fresh frozen specimens. Diagnostic accuracy was relatively high, and DNA and RNA integrity appeared to be preserved for this cohort. This suggests that MUSE may be a reliable method of generating high-quality diagnostic-grade histologic images for neuropathology on a rapid and sample-sparing basis and for subsequent molecular analysis of DNA and RNA.

Animal models of brain and spinal cord metastases of NSCLC established using a brain stereotactic instrument

ObjectiveAnimal models of brain and spinal cord metastases of non-small cell lung cancer were established through the intracranial injection of PC-9 Luc cells with a brain stereotaxic device. This method provides a reliable modeling method for studying brain and spinal cord metastases of non-small cell lung cancer. MethodsPC-9 Luc cells at logarithmic growth stage were injected into the skulls of 5-week-old BALB/c nude mice at different cell volumes (30 × 104, 80 × 104) and different locations (using anterior fontanel as a location point, 1 mm from the coronal suture, and 1.5 mm from the sagittal suture on the right upper and right lower side of the skull). After 1 week of cell inoculation, fluorescence signals of tumor cells in the brain and spinal were detected using the IVIS Xenogen Imaging system. After 4 weeks, brain and spinal tissues from the nude mice were harvested. Following paraffin-embedded sectioning, HE staining was performed on the tissues. ResultsThe fluorescence signals revealed that both brain and spinal cord metastasis occurred in the mice where the cells were injected at the lower right side of the skull. There was only brain metastasis in the nude mice injected with 30 × 104 cells at the upper right side of the skull. Both brain and spinal cord metastasis occurred in the nude mice injected with 80 × 104 cells. The HE staining revealed that both brain and spinal cord metastasis occurred in the mice injected with different amounts of PC-9 Luc cells, consistent with the results detected using the IVIS Xenogen Imaging system, thereby demonstrating the reliability of detecting fluorescent signals in vivo to determine tumor growth. ConclusionIt is a reliable method to establish the animal model of brain and spinal cord metastases of non-small cell lung cancer by injecting different quantities of cells from different positions with a brain stereotaxic device. The IVIS Xenogen Imaging system has high reliability in detecting the fluorescence signals of brain and spinal cord metastatic tumors.

Non-neoplastic astrocytes: key players for brain tumor progression.

Astrocytes are highly plastic cells whose activity is essential to maintain the cerebral homeostasis, regulating synaptogenesis and synaptic transmission, vascular and metabolic functions, ions, neuro- and gliotransmitters concentrations. In pathological conditions, astrocytes may undergo transient or long-lasting molecular and functional changes that contribute to disease resolution or exacerbation. In recent years, many studies demonstrated that non-neoplastic astrocytes are key cells of the tumor microenvironment that contribute to the pathogenesis of glioblastoma, the most common primary malignant brain tumor and of secondary metastatic brain tumors. This Mini Review covers the recent development of research on non-neoplastic astrocytes as tumor-modulators. Their double-edged capability to promote cancer progression or to represent potential tools to counteract brain tumors will be discussed.

Leksell Frame-Based Stereotactic Biopsy for Infratentorial Tumor : Practical Tips and Considerations.

The Leksell frame-based transcerebellar approach was proposed with the arc support frame attached upside down to the Z coordinate. This study presented practical tips and considerations for obtaining adequate tissue samples for deep-seated cerebellar lesions or lower brainstem lesions specifically those accessible via the cerebellar peduncle. For practical insights, the Leksell coordinate frame G was fixed to prevent the anterior screw implantation within the temporalis muscle, to avoid interference with the magnetic resonance (MR)-adapter, and taking into account the magnetic field of MR in close proximity to the tentorium. After mounting of indicator box, the MR imaging evaluation should cover both the indicator box and the infratentorial region that deviated from it. The coordinates [X, Y, Za, Arc0, Ringa0] obtained from Leksell SurgiPlan® software (Elekta, Stockholm, Sweden) with arc 00 located on the patient's right side were converted to [X, Y, Zb=360-Za, Arc0, Ringb0=Ringa0-1800]. The operation was performed in the prone position under general anesthesia in four patients with deep cerebellar (n=3) and brainstem (n=1) tumors. The biopsy results showed two cases of diffuse large B-cell lymphoma, one metastatic braintumor and one glioblastoma. One patient required frame repositioning as a complication. Drawing upon the methodology outlined in existing literature, we anticipate that imparting supplementary expertise could render the stereotactic biopsy of infratentorial tumors more consistent and manageable for the practitioner, thereby facilitating adequate tissue samples and minimizing patient complications.

Clinical applications of cerebrospinal fluid liquid biopsies in central nervous system tumors

For patients with central nervous system (CNS) malignancies, liquid biopsies of the cerebrospinal fluid (CSF) may offer an unparalleled source of information about the tumor, with much less risk than traditional biopsies. Two techniques have been adapted to CSF in clinical settings: circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). CTCs have been employed mostly as a diagnostic tool for leptomeningeal metastases in epithelial tumors, although they may also have value in the prognostication and monitoring of this disease. The ctDNA technology has been studied in a variety of primary and metastatic brain and spinal cord tumors, where it can be used for diagnosis and molecular classification, with some work suggesting that it may also be useful for longitudinal tracking of tumor evolution or as a marker of residual disease. This review summarizes recent publications on the use of these two tests in CSF, focusing on their established and potential clinical applications.

Prognostic impact of the number and total tumor burden of secondary cerebral lesions in patients with resected brain metastases of non-small cell lung cancers.

Systemic therapeutic advancements have improved the prognosis of cancer patients, leading to surgery more frequently being carried out for patients with multiple brain metastases (BM). The underlying evidence for the strategy is currently lacking. This study aimed to evaluate the prognostic significance of the number of BM and total tumor burden (TTB) on the overall survival (OS) of patients with resected BM of non-small cell lung cancer (NSCLC) in a modern series. In this monocentric retrospective series, patients who underwent resection of BM of NSCLC between 2015 and 2021 were included. Demographic, clinical, and histological parameters were collected, and formal radiological volumetric analyses were performed. Prognostic biomarkers for cerebral progression-free survival (C-PFS) and OS were analyzed with univariate and multivariate Cox proportional hazards analysis. One hundred eighty-four patients were included in the study. Among these, 108 patients (58.7%) presented with a single brain metastasis, 36 patients (19.6%) with 2 BM, 22 patients (11.9%) with 3 BM, and 18 patients (9.8%) with more than 3 BM (maximum 15 BM). The mean ± SD (range) preoperative tumor burden was 23.1 ± 25.3 (1.1-145.3) cm3. The mean residual tumor burden after surgery was 0.3 ± 0.8 (0.0-6.3) cm3. By the time of the analysis, 128 patients (69.6%) had died. The median follow-up duration was 49.0 months (95% CI 39.6-63.6). The median OS was 19.2 months (95% CI 13.2-24.0), and the survival rates at 6 months, 1 year, and 2 years were 76% (95% CI 69%-82%), 61% (95% CI 53%-67%), and 43% (95% CI 35%-50%), respectively. The median C-PFS was 8.4 months (95% CI 7.2-12.0). In the Cox multivariate regression model, younger age (< 65 years), single brain metastasis, adjuvant brain radiation therapy, adjuvant use of targeted therapy, and TTB < 7 cm3 were all independent predictors of longer OS. In this era of modern systemic treatments for cancer, the number of BM and total cerebral tumor burden remain significant prognostic factors of OS. However, resection should be considered as an option even in those patients with multiple BM in order to enhance patient clinical status, enable further local and systemic treatment delivery, and improve their survival and quality of life.

Pivotal Role of Cranial Irradiation-Induced Peripheral, Intrinsic, and Brain-Engrafting Macrophages in Malignant Glioma.

Malignant (high-grade) gliomas are aggressive intrinsic brain tumors that diffusely infiltrate the brain parenchyma. They comprise of World Health Organization (WHO) grade III and IV gliomas. Ionizing radiation or irradiation (IR) is frequently utilized in the treatment of both primary as well as metastatic brain tumors. On the contrary, macrophages (MΦ) are the most copious infiltrating immune cells of all the different cell types colonizing glioma. MΦ at tumor milieu are referred to as tumor-associated macrophages (TAMΦ). In malignant gliomas milieu, TAMΦ are also polarized into two distinct phenotypes such as M1 TAMΦ or M2 TAMΦ, which are capable of inhibiting or promoting tumor growth, respectively. Cranial-IR such as x- and γ-IR are sufficient to induce the migration of peripherally derived MΦ into the brain parenchyma. The IR facilitate a more immunosuppressive milieu via the stimulation of efferocytosis in TAMΦ, and an upsurge of tumor cell engulfment by TAMΦ exhibited detrimental effect of the anti-tumoral immune response in glioma. The MΦ inside the tumor mass are associated with multiple phenomena that include IR resistance and enrichment of the M2 MΦ after IR is able to facilitate glioblastoma multiforme (GBM) recurrence. Reviews on the role of cranial IR-induced peripheral and brain-engrafting macrophages (BeMΦ) in glioma are lacking. Specifically, most studies on peripheral, intrinsic as well as beMΦ on IR focus on WHO grade III and IV. Thus, this review precisely focuses primary on WHO grade III as well as IV gliomas.

Environment-responsive dendrobium polysaccharide hydrogel embedding manganese microsphere as a post-operative adjuvant to boost cascaded immune cycle against melanoma.

Rationale: Surgical resection is a primary treatment for solid tumors, but high rates of tumor recurrence and metastasis post-surgery present significant challenges. Manganese (Mn2+), known to enhance dendritic cell-mediated cancer immunotherapy by activating the cGAS-STING pathway, has potential in post-operative cancer management. However, achieving prolonged and localized delivery of Mn2+ to stimulate immune responses without systemic toxicity remains a challenge. Methods: We developed a post-operative microenvironment-responsive dendrobium polysaccharide hydrogel embedded with Mn2+-pectin microspheres (MnP@DOP-Gel). This hydrogel system releases Mn2+-pectin microspheres (MnP) in response to ROS, and MnP shows a dual effect in vitro: promoting immunogenic cell death and activating immune cells (dendritic cells and macrophages). The efficacy of MnP@DOP-Gel as a post-surgical treatment and its potential for immune activation were assessed in both subcutaneous and metastatic melanoma models in mice, exploring its synergistic effect with anti-PD1 antibody. Result: MnP@DOP-Gel exhibited ROS-responsive release of MnP, which could exert dual effects by inducing immunogenic cell death of tumor cells and activating dendritic cells and macrophages to initiate a cascade of anti-tumor immune responses. In vivo experiments showed that the implanted MnP@DOP-Gel significantly inhibited residual tumor growth and metastasis. Moreover, the combination of MnP@DOP-Gel and anti-PD1 antibody displayed superior therapeutic potency in preventing either metastasis or abscopal brain tumor growth. Conclusions: MnP@DOP-Gel represents a promising drug-free strategy for cancer post-operative management. Utilizing this Mn2+-embedding and ROS-responsive delivery system, it regulates surgery-induced immune responses and promotes sustained anti-tumor responses, potentially increasing the effectiveness of surgical cancer treatments.

Assessing the impact of distortion correction on Gamma Knife radiosurgery for multiple metastasis: Volumetric and dosimetric analysis

IntroductionMagnetic resonance imaging (MRI) is a robust neuroimaging technique and is the preferred method for stereotactic radiosurgery (SRS) planning. However, MRI data always contain distortions caused by hardware and patient factors. Research questionCan these distortions potentially compromise the effectiveness and safety of SRS treatments? Material and methodsTwenty-six MR datasets with multiple metastatic brain tumors (METs) used for Gamma Knife radiosurgery (GKRS) were retrospectively evaluated. A commercially available software was used for distortion correction. Geometrical agreement between corrected and uncorrected tumor volumes was evaluated using MacDonald criteria, Euclidian distance, and Dice similarity coefficient (DSC). SRS plans were generated using uncorrected tumor volumes, which were assessed to determine their coverage of the corrected tumor volumes. ResultsThe median target volume was 0.38 cm3 (range,0.01–12.38 cm3). A maximum displacement of METs of up to 2.87 mm and a median displacement of 0.55 mm (range,0.1–2.87 mm) were noted. The median DSC between uncorrected and corrected MRI was 0.92, and the most concerning case had a DSC of 0.46. Although all plans met the optimization criterion of at least 98% of the uncorrected tumor volume (median 99.55%, range 98.1–100%) receiving at least 100% of the prescription dose, the percent of the corrected tumor volume receiving the total prescription dose was a median of 95.45% (range,23.1–99.5%). Discussion and conclusionMRI distortion, though visually subtle, has significant implications for SRS planning. Regular utilization of corrected MRI is recommended for SRS planning as distortion is sometimes enough to cause a volumetric miss of SRS targets.

Endometrioid Karsinomanın Çoklu Beyin Metastazında Eşzamanlı Tümöriçi Kanama: Nadir Bir Metastazın Nadir Bir Bulgusu

Metastasis of endometrioid carcinomas to the brain is rare, usually solitary, and has a poor prognosis. Intratumoral bleeding is also a poor prognostic factor for metastatic brain tumors but rarely occurs in gynecological cancers. A female patient who was under chemotherapy for endometrioid carcinoma was admitted to the emergency department for recent deterioration and seizures. She had confusion and left hemiparesis, along with an elevated systolic blood pressure and platelet count of 45,000 /mL. An emergent computerized tomography and subsequent magnetic resonance imaging revealed multiple hemorrhagic metastatic lesions in both hemispheres and cerebellum. Brain metastasis of endometrioid carcinoma is rare and can present with intratumoral hemorrhage, which is associated with a poor prognosis and is more likely to occur in the setting of low platelet counts. This case highlights the importance of monitoring brain metastasis in patients with endometrioid carcinoma and considering the possibility of intratumoral hemorrhage.

Whole-Brain Radiotherapy Alone vs Preceded by Bevacizumab, Etoposide, and Cisplatin for Untreated Brain Metastases From Breast Cancer

The incidence of brain metastasis is increasing in patients with metastatic breast cancer. Treatments to extend the control of brain metastasis are urgently required. To investigate whether the addition of an induction treatment of bevacizumab, etoposide, and cisplatin (BEEP) improves brain-specific progression-free survival (PFS) after whole-brain radiotherapy (WBRT). This open-label, randomized, multicenter clinical trial assessed patients with brain metastases from breast cancer (BMBC) in Taiwan from September 9, 2014, to December 24, 2018, with survival follow-up until December 31, 2021. Key inclusion criteria included metastatic brain tumors not suitable for focal treatment, WBRT naivety, age 20 to 75 years, and at least 1 measurable brain metastatic lesion. The primary end point was brain-specific PFS, with an expected hazard ratio of 0.60, a 2-sided α ≤ .20, and power of 0.8. Eligible patients were randomly assigned at a ratio of 2:1 to the experimental arm, which involved 3 cycles of BEEP followed by WBRT, or the control arm, which involved WBRT alone. The primary end point was the determination of brain-specific PFS by local investigators according to the Response Evaluation Criteria in Solid Tumors, version 1.1, the initiation of other brain-directed treatment after WBRT, or death. Other key end points included brain-specific objective response rate after 8 weeks of BEEP treatment or WBRT and 8-month brain-specific PFS rate, PFS, and overall survival. A total of 118 patients with BMBC were randomized, with the intention-to-treat cohort comprising 112 patients. The median age was 56 years (range, 34-71 years), and 61 patients (54.5%) had ERBB2 (formerly HER2 or HER2/neu)-positive disease. The median (range) brain-specific PFS was 8.1 (0.3-29.5) vs 6.5 (0.9-25.5) months in the experimental and control arms, respectively (hazard ratio, 0.71; 95% CI, 0.44-1.13; P = .15; significant at predefined α ≤ .20). The brain-specific objective response rate at 2 months was not significantly different (BEEP treatment vs WBRT, 41.9% vs 52.6%), but the 8-month brain-specific PFS rate was significantly higher in the experimental group (48.7% vs 26.3%; P = .03). Adverse events were generally manageable with prophylactic granulocyte colony-stimulating factor treatment. The findings show that induction BEEP before WBRT may improve the control of BMBC compared with using upfront WBRT, which could address an unmet need for an effective systemic treatment for intractable brain and extracranial metastases from metastatic breast cancer. ClinicalTrials.gov Identifier: NCT02185352.

10167-MET-8 CLINICAL CHARACTERISTICS AND TREATMENT STRATEGY OF CANCER CASES PRESENTING WITH CENTRAL NERVOUS SYSTEM SYMPTOMS

Abstract Metastatic brain tumors were previously reported with prognoses of approximately 6 months. The accuracy of diagnostic imaging and advances in drug therapy have improved the treatment outcomes of various types of cancer. On the other hand, patients with advanced cancer who are detected with neurological symptoms caused by metastatic brain tumors usually face difficulty in deciding on a treatment strategy. In this study, we reported the results of cancer patients who were first detected with central nervous system symptoms in the last 10 years and treated at our hospital.There were 14 patients treated at our hospital from 2013 to 2022 with CNS symptoms as the initial symptom. The mean age was 65.5 years, and the most common primary cancer was lung cancer in 11 cases (9 NSCLC and 2 SCLC). The OS examined in the 11 lung cancer cases was 14 months. Among NSCLC, only 2 cases had EGFR mutation and no cases had ALK fusion gene. The mean Lung-molGPA was 0.89 in 9 patients with NSCLC and 0.75 in 2 patients with SCLC, and the expected survival time was 6.9 months and 2.8 months.With advances in drug therapy, median survival for patients with NSCLC brain metastases has been reported to range from 7 months to 2 years for patients with EGFR mutations and 4 years for patients with ALK fusion gene. Thus, it is necessary to consider treatment strategies according to primary tumor, histology, and genetic information, rather than considering metastatic brain tumors as a single entity.The results of this study suggest that aggressive therapeutic intervention may prolong the survival period expected at the time of initial diagnosis, even in cancer patients who are found to have metastatic brain tumors.

10195-MET-11 THE PREDICTIVE FACTORS OF EFFICACY OF PEMBROLIZUMAB IN BRAIN METASTASES OF LUNG CANER

Abstract The main treatment for metastatic brain tumors is radiation therapy or surgical removal. Since the pembrolizumab, an anti-PD1 monoclonal antibody, was revealed to be effective for brain metastases of lung cancer, it has been used as a therapeutic option. However, the predictive factors of its efficacy have been unclear. If the efficacy of pembrolizumab can be predicted prior to the treatment of metastatic brain tumors, it will have a significant impact on subsequent treatment strategies. In this study, we performed a retrospective analysis of patients with metastatic brain tumors from lung cancer treated with pembrolizumab to investigate predictive factors of pembrolizumab efficacy. From January 2018 to July 2023, 73 patients were treated with pembrolizumab for brain metastases of lung cancer at our institution. Among them, 16 patients who had received pembrolizumab for at least 1 year were included. Median age was 68 years (45-86), 10 were male (63%), and median period of pembrolizumab treatment was 105 months (49-319). Patients with brain metastasis which was well controlled for at least 2 years after starting pembrolizumab were defined as effective, and those who required new treatment were defined as invalid. There were 11 effective cases and 5 invalid cases. We compared clinical characteristics, genetic characteristics of the primary tumor, and imaging characteristics of metastatic brain tumors between the effective and ineffective cases, and identified predictive factors for efficacy of pembrolizumab.

10022-MET-2 CLINICAL FEATURES OF RENAL CELL CARCINOMA BRAIN METASTASES COMPARED WITH OTHER CARCINOMAS

Abstract INTRODUCTION In recent years, the positioning of surgical treatment for metastatic brain tumors has changed. To extract conditions suitable for surgical treatment, the background factors for each primary lesion were verified by retrospective analysis of our case. SUBJECTS AND METHODS From 2014 to 2022, 425 patients with metastatic brain tumors diagnosed and treated at our university were included. There were 219 lung cancers, 46 breast cancers, 64 gastrointestinal cancers, 26 renal cell carcinomas, and 70 others. First, the tumor volume and edema volume were measured, and the ROC curve was drawn for the presence or absence of symptoms to determine the cutoff value. After that, statistical analysis was performed on the following items for each primary lesion. The items were tumor volume (T), edema volume (E), tumor edema ratio (E/T), age, KPS, hemorrhage, cyst formation, meningitis, metastasis to other organs, posterior fossa, simultaneous detection, and single tumor. RESULTS The symptomatic cutoff was 1514mm3 for tumor volume (sensitivity 0.86 specificity 0.74) and 15616 mm3 for edema volume (sensitivity 0.85 specificity 0.85). The tumor edema ratio was significantly higher in renal cell carcinoma. Factors with significant differences were older age and multiple lesions in lung cancer, younger age and posterior fossa in breast cancer, lower KPS in gastrointestinal cancer, and solitary cases and bleeding in renal cell carcinoma. DISCUSSION/CONCLUSION In this analysis, many cases of brain metastasis from renal cell carcinoma are solitary, and because they exhibit extensive edema that seems to be affected by VEGF, they tend to develop symptoms while they are small, and they are characterized by hemorrhage easily during the course. These findings suggest that patients with brain metastases from renal cell carcinoma should be given priority for surgical treatment.

10159-STMO-7 INTRAOPERATIVE MRI SURGERY FOR POSTERIOR FOSSA LESIONS

Abstract Background: Intraoperative MRI (iMRI) is an important modality in brain tumor surgery to identify residual tumors, however, it is problematic due to patient positional limitations. In this study, we investigated the usefulness of iMRI for posterior fossa lesions. Materials and Methods: Of 320 cases of brain tumors removed using iMRI from June 2016 to April 2023, 24 cases of posterior fossa lesions were included. Tumor type, approach method, imaging availability, tumor removal rate, and complications were examined retrospectively. Results: Tumor types included 8 gliomas, 5 epidermoid cysts, 4 meningiomas, 3 metastatic brain tumors, 1 schwannoma, and 3 others. Eleven patients underwent midline suboccipital approach in the supine position, 8 patients underwent lateral suboccipital approach, 2 patients underwent occipital transtentorial approach, and 2 patients underwent anterior transpetrosal approach in the supine position. transpetrosal approach in 2 cases and subtemporal approach in 1 case. iMRI showed residual lesion in 14 of 24 patients. More than half of the gliomas and epidermoid cysts had intraoperative residual disease, whereas only one meningioma did. Total resection was achieved except for one case of intentional residual schwannoma and two cases of glioma. Discussion: iMRI requires the upper body to fit within a gantry, and it is difficult to image in the park bench position. However, various approaches is possible by using a supine-lateral or semi-prone position. In the concorde position, where the fourth ventricle and upper cerebellum are approached, it is useful to insert a mat in the anterior thoracic and raise the upper body. For tumors in the dorsal brainstem and upper cerebellum, the occipital transtentorial approach was used. iMRI is effective in the removal of all tumors, including gliomas in intramedullary tumors and epidermoid cysts in extramedullary tumors. Conclusion: iMRI can be used in posterior cranial fossa lesions.

10054-STMO-1 5-ALA INTENSITY ANALYSIS OF NON-NEOPLASTIC LESIONS BY IMAGE J

Abstract PURPOSE We used 5-ALA during surgery for malignant brain tumors, and analyzed the brightness using Image J for positive findings during surgery. We report on three cases that were positive for intraoperative 5-ALA and had high brightness but were diagnosed as non-tumor, including the results of brightness analysis by Image J. METHODS 5-ALA was administered according to the protocol, and intraoperative 5-ALA-positive findings were analyzed with Image J (Wayne Rasband: NIH), brightness was measured with histograms, and maximum brightness was compared. RESULTS Case 1 was suspected malignant tumor before surgery, but the diagnosis was inflammation, different from lymphoma. The intraoperative maximum brightness was as high as 239, but there was no finding of' blazing fire' characteristic of malignant tumors, and the lesion and its surroundings were uniformly red. Case 2 required differentiation between metastatic brain tumor and radiation necrosis, and case 3 required differentiation between recurrent anaplastic astrocytoma and radiation necrosis, both of which had high intraoperative brightness (113,166). CONCLUSION Measuring the brightness of 5-ALA-positive findings during surgery can help in the rapid pathological diagnosis of tumors and the determination of peripheral edema.

10031-GGE-2 GENOMIC ANALYSIS OF MENINGIOMA USING GENE PANEL TESTING

Abstract Recently, cancer gene panel tests have been covered by insurance and their usefulness has been reported. In addition to the cancer gene panel tests covered by insurance, we are conducting the PleSSision-Rapid test, a cancer gene panel test that can measure 143 genes, as a clinical research project. The former has been used for 14 cases brain tumors, and the latter has been used for brain tumors in about 100 cases, respectively. The PleSSision-Rapid test has now completed analysis of 87 cases, with gliomas accounting for 33, meningiomas for 29, and metastatic brain tumors for 14 cases. Tumor mutation burden (TMB) was high in 18 cases, and microsatellite instability was high in none. NTRK gene fusion was observed in 1 case. Of the 29 meningiomas, 9 were male and 20 female, ranging in age from 31 to 79 years (mean 57). Twenty of the cases were located at the skull base. Twenty four were primary cases, whereas 5 were recurrent cases. WHO grade 1, 2, and 3 were 23, 4, and 2, respectively. There was no difference in TMB among grades, and Ki-67 values increased with increasing grade. Comparing grade 1 and grade 2/3, NF2 and KDM6A were found to be significantly different in the rate of gene mutations. Grade 2/3 patients had a significantly higher frequency of copy number aberrations such as genes related to DNA repair, histone modification, and chromatin remodeling, than grade 1 patients,

Antiepileptic therapy algorithms in patients with primary and metastatic brain tumors

Up to date the brain tumors incidence keeps growing worldwide. Epilepsy and epileptic seizures are one of the most common clinical features of brain tumors. The aim of the study was to invent the algorithms antiepileptic treatment of patients with primary and metastatic brain tumors based on literature data. We searched eLIBRARY, PubMed databases by keywords. We concluded, that preventive antiepileptic drugs administration in patients with primary or metastatic brain lesions does not lower the risk of acute symptomatic postoperative seizures or epilepsy incidence, and therefore should not be recommended. Experts’ opinion states that in patients with brain tumors even one unprovoked seizure makes it feasible to initiate antiepileptic drugs therapy as soon as possible. In case of two or more unprovoked episodes (with over 24 hours difference) the diagnosis of “epilepsy” is legitimate and antiepileptic therapy should be started. The treating physician’s choice of antiepileptic therapy is based on type of seizures, age and sex of the patient, the comorbidity and potential antiepileptic drugs pharmacokinetic interactions with other drugs (including chemotherapy), in particular, one should avoid the use of liver microsomal-inducing antiepileptic drugs. The presented algorithms provide the decision-making guidelines in case of intraoperative focal seizures, acute symptomatic seizures and status epilepticus occurrence in early postoperative period.