Extracellular Vesicles from Cerebrospinal Fluid of Leptomeningeal Metastasis Patients Deliver MiR-21 and Induce Methotrexate Resistance in Lung Cancer Cells.

Leptomeningeal metastasis (LM) is a common and fatal complication of advanced non-small cell lung cancer (NSCLC) caused by the spread of malignant cells to the leptomeninges and cerebrospinal fluid (CSF). While intra-CSF methotrexate (MTX) chemotherapy can improve prognosis, eventual MTX resistance deters continued chemotherapy. Recent studies have shown that increased miRNA-21 (miR-21) expression in the CSF of patients with LM after intraventricular MTX-chemotherapy is associated with poor overall survival; however, the molecular mechanisms underlying this resistance are poorly understood. Here, we confirm, in 36 patients with NSCLC-LM, that elevated miR-21 expression prior to treatment correlates with poor prognosis. MiR-21 overexpression or sponging results in a corresponding increase or decrease in MTX resistance, demonstrating that cellular miR-21 expression correlates with drug resistance. MiR-21-monitoring sensor and fluorescent extracellular vesicle (EV) staining revealed that EV-mediated delivery of miR-21 could modulate MTX resistance. Moreover, EVs isolated from the CSF of LM patients containing miR-21 could enhance the cell proliferation and MTX resistance of recipient cells. These results indicate that miR-21 can be transferred from cell-to-cell via EVs and potentially modulate MTX sensitivity, suggesting that miR-21 in CSF EVs may be a prognostic and therapeutic target for overcoming MTX resistance in patients with NSCLC-LM.

Optimal mask fixation method for frameless radiosurgery with Leksell Gamma Knife IconTM.

The Leksell Gamma Knife (LGK) IconTM is used for mask-based and frame-based fixation. The mask fixation provides a noninvasive method. However, an optimal mask fixation method is yet to be established. We evaluated the characteristics of three mask fixation methods (Plain, Folded, and Wide) for the LGK IconTM . Force-sensitive resistor sensors were attached to the forehead, supraorbital, zygoma, mandible, and occipital bone of the phantom, and digital humidity and temperature sensors were attached to both temporal lobes. Cone-beam computed tomography (CBCT) and high-definition motion management (HDMM) for each mask fixation method were used to evaluate the phantom motion during the initial application. Subsequently, the mask was removed and reapplied on the second (1st reapplication) and third days (2nd reapplication). In the initial application, forces acting on most portions of the phantom were stabilized within 1.5 h. The largest force acted on the occipital bone for the Plain and Wide methods and on the mandible for the Folded method. The temperature rapidly approaches the initial temperature, whereas the humidity gradually approached the initial humidity in all fixation methods. The Folded method exhibited a significantly lower translation along the Y-axis of the Leksell coordinate system, and rotations along all axes were under 0.5°. The HDMM values remained at 0.1 mm for all fixation methods. In the reapplications, the force acting on the occipital bone was significantly greater than that during the initial application for all mask fixation methods; the temperature and humidity remained unchanged. All mask fixation methods in the 1st reapplication were not significantly different from those in the 2nd reapplication. The Folded method is recommended as an optimal mask fixation for patients who require tight fixation; the Wide method can be considered if patient comfort is a priority.

Development of an inside-out augmented reality technique for neurosurgical navigation.

OBJECTIVE: With the advancement of 3D modeling techniques and visualization devices, augmented reality (AR)-based navigation (AR navigation) is being developed actively. The authors developed a pilot model of their newly developed inside-out tracking AR navigation system. METHODS: The inside-out AR navigation technique was developed based on the visual inertial odometry (VIO) algorithm. The Quick Response (QR) marker was created and used for the image feature-detection algorithm. Inside-out AR navigation works through the steps of visualization device recognition, marker recognition, AR implementation, and registration within the running environment. A virtual 3D patient model for AR rendering and a 3D-printed patient model for validating registration accuracy were created. Inside-out tracking was used for the registration. The registration accuracy was validated by using intuitive, visualization, and quantitative methods for identifying coordinates by matching errors. Fine-tuning and opacity-adjustment functions were developed. RESULTS: ARKit-based inside-out AR navigation was developed. The fiducial marker of the AR model and those of the 3D-printed patient model were correctly overlapped at all locations without errors. The tumor and anatomical structures of AR navigation and the tumors and structures placed in the intracranial space of the 3D-printed patient model precisely overlapped. The registration accuracy was quantified using coordinates, and the average moving errors of the x-axis and y-axis were 0.52 ± 0.35 and 0.05 ± 0.16 mm, respectively. The gradients from the x-axis and y-axis were 0.35° and 1.02°, respectively. Application of the fine-tuning and opacity-adjustment functions was proven by the videos. CONCLUSIONS: The authors developed a novel inside-out tracking-based AR navigation system and validated its registration accuracy. This technical system could be applied in the novel navigation system for patient-specific neurosurgery.

Clinical observation of lymphopenia in patients with newly diagnosed glioblastoma.

PURPOSE: Lymphopenia in patients with glioblastoma (GBM) is related to treatment as well as disease progression. This retrospective study investigated the prevalence, influencing factors, recoverability, and clinical significance of lymphopenia in GBM patients treated with concomitant chemoradiotherapy (CCRT). PATIENTS AND METHODS: A total of 219 patients with newly diagnosed GBM who had received at least 3 cycles of adjuvant temozolomide (TMZ) followed by CCRT with TMZ were enrolled. Serial data on complete blood cell counts, including differential cell counts, were collected just before a new phase and before every treatment cycle of the regimen. Relationships between white blood cell (WBC) variable changes and treatment modalities as well as survival were analyzed. Lymphopenia was classified using the definition of the Common Terminology Criteria for Adverse Events version 5.0. RESULTS: A total of 92 patients (42.0%) showed decreased levels of lymphocytes (< 1500/µL) at baseline. The WBC count, absolute neutrophil count, lymphocyte count, and neutrophil-to-lymphocyte ratio were all significantly decreased after RT/TMZ treatment and did not recover during the adjuvant TMZ period. However, these metrics all began to recover 3 months after the last TMZ cycle, except for the lymphocyte count. The proportion of lymphopenia patients (< 1500 lymphocytes/µL) increased to 74.8% after RT/TMZ and remained steady at approximately 71.5% (range 63.7-75.3%) throughout the management period. Moreover, the number of patients with grade 3 lymphopenia (< 500 lymphocytes/µL) also increased significantly after treatment to reach 2.9% (from 0.9% at baseline). Statistically, 75.7% of lymphopenia patients were predicted to recover in a median time of 240.3 days (95% confidence interval ± 104.7 days) after TMZ withdrawal. There were no dose-dependent relationships between RT or TMZ and lymphopenia. Grade 3 (< 500 lymphocytes/µL) lymphopenia measured at 1 month after RT/TMZ predicted significantly reduced survival (13.0 months vs. 19.5 months, p = 0.011). CONCLUSION: Lymphopenia is a frequent event during GBM disease progression and treatment. Treatment-related lymphopenia is profound and prolonged and can be used as a prognostic factor for GBM patients.

Preoperative 5-aminolevulinic acid administration for brain tumor surgery is associated with an increase in postoperative liver enzymes: a retrospective cohort study.

BACKGROUND: Besides 5-aminolevulinic acid (5-ALA), liver enzyme elevation after brain tumor surgery can be caused by anesthesia and medications. In this retrospective study, we determined whether preoperative 5-ALA administration is associated with postoperative elevation of liver enzymes (PELE) in brain tumor patients and identified predictive factors for PELE in patients treated with 5-ALA. METHODS: In 179 patients undergoing brain tumor surgery with preoperative normal values of liver enzymes, laboratory data on serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and total bilirubin (T.bil) levels were collected preoperatively and through postoperative day (POD) 45. RESULTS: Ninety-nine PELEs (ALT, 56; AST, 34; ALP, 5; and TB, 4) were observed in 62 (34.6%) patients. Four (4.2%) patients treated with 5-ALA showed grade 3 elevation of transaminases based on the Common Terminology Criteria for Adverse Effects. Preoperative 5-ALA treatment was predictive of PELE (odds ratio [95% confidence interval], 2.30 [1.14-4.67]; P = 0.021). In patients treated with 5-ALA (n = 95), 70 PELEs (ALT, 39; AST, 22; ALP, 5; and TB, 4) were observed in 41 (43.2%) patients and significant predictive factors for PELE were preoperative ALT level (1.10 [1.04-1.17]; P = 0.001) and body mass index (BMI, 1.29 [1.08-1.56]; P = 0.006). In patients treated with 5-ALA, 13 and 36 patients, of 39 patients whose maximum postoperative ALT levels > 40 U/L, showed the normal value of serum ALT on PODs 14 and 45, respectively. Only three patients showed ALT elevation > 40 U/L on PODs 15-45, with a downward trend. CONCLUSIONS: The use of 5-ALA for brain tumor surgery in patients with preoperative normal values of liver enzymes was associated with increased transient PELE, but a low incidence of severely elevated liver transaminases levels. When 5-ALA is administered to patients with the upper normal value of preoperative serum ALT and overweight, attention is paid to PELE.

Genomic analysis of synchronous intracranial meningiomas with different histological grades.

Although meningioma is the most common primary tumor of the central nervous system, the mechanism of progression from benign to atypical or anaplastic grade remains elusive. The present case reports the genomic evaluation of two synchronous meningiomas with different histological grades (benign and atypical) in the same patient. Under the assumption that the atypical tumor may have progressed from the benign tumor, the clonal origin of the lesions was investigated to identify genomic events responsible for the oncogenic process of evolution to higher grades in meningioma. A 59 year-old female patient was diagnosed with two synchronous meningiomas with different histological grades, benign and atypical. Whole-exome sequencing (WES) and RNA sequencing (RNA-seq) analysis of both tumors were done. WES analysis showed that each meningioma harbored distinct mutation profiles, and RNA-seq analysis revealed distinct gene expression profiles between the two tumors. The only apparent common genetic abnormality found in both tumors was the loss of heterozygosity of chromosome 22, raising the possibility that this event is the initial step in tumor formation, after which distinct subsequent mutations lead to the evolvement of two separate tumors of different grades. The result provides additional evidence on previous reports suggesting separate, independent mechanism of progression into higher grades in meningioma.

Optimal strategy of gamma knife radiosurgery for craniopharyngiomas.

OBJECT: To analyze the outcomes of gamma knife radiosurgery (GKS) for craniopharyngiomas and elucidate the optimal strategy. METHODS: Between 1998 and 2016, 35 patients underwent GKS for the treatment of 40 recurrent or residual craniopharyngiomas. Among 40 GKSs, 22 procedures were single-session GKSs and 18 procedures were fractionated GKSs. In cases of single-session GKS, the median marginal dose was 15 Gy (range 10-20 Gy). In cases of fractionated GKS, the median marginal dose was 6 Gy (range 5-7.5 Gy) of three fractions. The radiation dose was calculated to the biologic equivalent dose (BED) using α/ß ratios of 10 and 2. RESULT: The location of the tumor, the distance between the optic nerve and tumor (> 10 mm), BED 10 (> 35 Gy), and BED2 (> 80 Gy) were statistically significant with overall response rate (P = 0.008, 0.02, 0.03, and 0.002, respectively). There was a statistically significant difference in progression-free survival according to the distance between the optic nerve and tumor (> 10 mm) and the location of tumor (P = 0.03 and 0.03, respectively). Multivariate logistic regression analysis showed the hypothalamus group had an odds ratio of 0.04 compared with the suprasellar group for tumor progression. The group with BED2 > 80 Gy had an odds ratio of 0.049 compared with the group with BED2 < 80 Gy. CONCLUSION: A sufficient dose is required for treating craniopharyngiomas using single-session and fractionated GKS. The outcomes of GKS can be predicted according to the location of tumor, the distance between the optic nerve and tumor and BED value.

Impact of adjuvant treatments on survival in Korean patients with WHO grade II gliomas: KNOG 15-02 and KROG 16-04 intergroup study.

INTRODUCTION: Optimal treatment strategies for low-grade glioma (LGG) remain controversial. We analyzed treatment outcomes and evaluated prognostic factors of adult LGG patients in Korea. METHODS: We reviewed the medical records of 555 patients diagnosed with WHO grade II LGG (astrocytoma 37.8%, oligoastrocytoma 15.3%, and oligodendroglioma 46.8%) at 14 institutions between 2000 and 2010. Primary and secondary endpoints were progression-free survival (PFS) and overall survival (OS). Propensity-score matching (PSM) analyses were performed to correct imbalances in patient/tumor characteristics among adjuvant treatment groups. RESULTS: The median follow-up time was 83.4 months, and the 5-year PFS and OS rates were 52.2% and 83.0%, respectively. Male, older age, poorer performance status, multiple lobe involvement, and astrocytoma histology were associated with poorer survival. Among the treatment factors, gross total resection (GTR) was associated with better PFS and OS, and adjuvant chemotherapy with improved PFS. Interestingly, adjuvant radiotherapy (RT) did not improve PFS; rather, it was related with poorer OS. Regarding patient/tumor characteristics, the RT group had poorer characteristics than the non-RT group. After PSM, we detected a tendency for improved PFS in the matched RT group, and no significant difference in OS compared with the matched non-RT group. CONCLUSIONS: The achievement of GTR is important to improve survival in LGG patients. Adjuvant chemotherapy may enhance PFS, but adjuvant RT did not improve survival outcomes. After PSM, we observed potential impacts of adjuvant RT on PFS. Our results may reflect real-world practice and consequently may help to optimize treatment strategies for LGG.

A Retrospective Analysis of the Outcomes of Dural Arteriovenous Fistulas Treated with Gamma Knife Radiosurgery: A Single-Institution Experience.

BACKGROUND: Gamma knife radiosurgery (GKRS) has recently been used as a treatment modality for dural arteriovenous fistula (DAVF). OBJECTIVE: To retrospectively analyze the outcomes of GKRS for DAVF at a single institute. METHODS: Between 1998 and 2016, a total of 20 patients underwent GKRS for DAVF. After excluding 4 patients with > 12 months of follow-up, 16 patients were enrolled in this study. Twelve patients had undergone embolization prior to GKRS. The most common location was the cavernous sinus (CS). The median clinical and radiological follow-up durations were 87.5 (range 24-186) months and 44.5 (range 14-174) months. RESULTS: Ten (62.5%) of the 16 DAVFs were obliterated; 8 were confirmed on angiography. Five cases resulted in small, residual DAVFs, and one case remained unchanged. The obliteration rate of GKRS for CS DAVF was significantly higher than that for non-CS DAVF (100 vs. 40%; p = 0.034). Fifteen out of 16 patients (94%) had a favorable outcome, and the remaining patient had an unfavorable outcome. Hemorrhage after GKRS occurred in only 1 patient, who presented with seizure. CONCLUSIONS: GKRS is a safe and effective treatment modality for DAVF in combination with a traditional treatment option such as endovascular embolization or microsurgery.

Restoration of miR-29b exerts anti-cancer effects on glioblastoma.

BACKGROUND: Glioblastoma multiforme (GBM) is known as one of the most fatal forms of cancer. MicroRNAs have been widely implicated in the regulation of mammalian development and pathogenesis. The brain-enriched miR-29 subfamilies are known to be exclusively expressed in the developing brain, and they are aberrantly down-regulated in GBM. This study aims to elucidate the role of miR-29b in GBM development and the feasibility of therapeutic targeting using conjugated nanoparticles. METHODS: After confirmation of miR-29b expression levels in GBM tissues by analysis of open source data, the anticancer effect of miR-29b was tested by the introduction of syn-hsa-miR-29b-3p in the A172 GBM cell line. In vitro studies of cell viability and apoptosis and ex vivo study using GBM tissue slice cultures from 3 patients and nanoparticle delivery of miR-29b were performed. RESULTS: We discovered an increase in apoptotic cell populations with the introduction of miR-29b in the GBM cell line. An established human-derived GBM tissue slice culture system confirmed the anticancer effect of miR-29b-conjugated nanoparticles. Using PCR array, we found that exogenous miR-29b inhibits the expression of COL1A2, COL3A1, COL4A1, ELN, ITGA11, MMP24, and SPARC, which mediates an anticancer effect. CONCLUSIONS: miR-29b may serve as a putative therapeutic molecule when its expression is restored using a nanoparticle delivery system in GBM.

Ruptured de novo Aneurysm following Gamma Knife Surgery for Arteriovenous Malformation: Case Report.

Stereotactic radiosurgery is a well-known treatment tool for arteriovenous malformations (AVMs). The method has high validity and minimal invasiveness, but late-onset problems involving tumor formation and vasculopathy induced by radiation have been reported. We present a rare case of a radiation-induced ruptured de novo aneurysm following Gamma Knife surgery (GKS) for an AVM. A 17-year-old, right-handed male underwent GKS for AVM at the left parietal lobe. After 3 years, a follow-up angiogram showed a residual AVM at the angular gyrus. Then, a 2nd GKS was performed for the residual lesion. Six years after the 1st GKS, the AVM disappeared on the angiogram. Seven years later, he suffered a sudden onset of headache. A left carotid angiogram revealed a ruptured aneurysm at the M2-M3 junction of the middle cerebral artery parietal branch. Coil embolization was performed, and the aneurysm was occluded. The patient was discharged without any neurologic deficits.

Investigation of the location of atypical teratoid/rhabdoid tumor.

INTRODUCTION: The location of a brain tumor is a fundamental characteristic, because various brain tumors develop in relatively specific locations. An atypical teratoid/rhabdoid tumor (AT/RT) is a highly age-specific tumor that occurs in infants and young children. However, AT/RTs develop in a variety of locations in the brain. This study aimed at uncovering the tumor location pattern of AT/RTs to enhance diagnoses. MATERIAL AND METHODS: Neuroimages from 27 patients with a pathologically proven AT/RT were reviewed, and the specific tumor locations were described and categorized. The association of imaging characteristics and tumor location was analyzed. RESULTS: The posterior fossa was the most frequent locations accounting for 19 patients (70%), followed by the diencephalon (four patients; 15%), cerebrum (three patients; 11%), and midbrain (one patient; 4%). In the posterior fossa, the superior medullary velum (SMV) and cerebellopontine angle (CPA) areas were the most common sites (eight patients each) and three patients had a tumor in the inferior medullary velum (IMV) region. AT/RTs in the SMV area had a significantly higher chance of no/minimal enhancement compared with tumors in other locations (P = 0.001) and a lower likelihood of leptomeningeal tumor seeding at presentation (P = 0.053). CONCLUSION: The location spectrum of AT/RT follows a specific pattern, and some of the locations are linked with intriguing clinical characteristics. This information may not only help make correct preoperative diagnosis but also occasionally aid in postoperative pathological diagnosis.

Validation of real-time inside-out tracking and depth realization technologies for augmented reality-based neuronavigation.

PURPOSE: Concomitant with the significant advances in computing technology, the utilization of augmented reality-based navigation in clinical applications is being actively researched. In this light, we developed novel object tracking and depth realization technologies to apply augmented reality-based neuronavigation to brain surgery. METHODS: We developed real-time inside-out tracking based on visual inertial odometry and a visual inertial simultaneous localization and mapping algorithm. The cube quick response marker and depth data obtained from light detection and ranging sensors are used for continuous tracking. For depth realization, order-independent transparency, clipping, and annotation and measurement functions were developed. In this study, the augmented reality model of a brain tumor patient was applied to its life-size three-dimensional (3D) printed model. RESULTS: Using real-time inside-out tracking, we confirmed that the augmented reality model remained consistent with the 3D printed patient model without flutter, regardless of the movement of the visualization device. The coordination accuracy during real-time inside-out tracking was also validated. The average movement error of the X and Y axes was 0.34 ± 0.21 and 0.04 ± 0.08 mm, respectively. Further, the application of order-independent transparency with multilayer alpha blending and filtered alpha compositing improved the perception of overlapping internal brain structures. Clipping, and annotation and measurement functions were also developed to aid depth perception and worked perfectly during real-time coordination. We named this system METAMEDIP navigation. CONCLUSIONS: The results validate the efficacy of the real-time inside-out tracking and depth realization technology. With these novel technologies developed for continuous tracking and depth perception in augmented reality environments, we are able to overcome the critical obstacles in the development of clinically applicable augmented reality neuronavigation.

Disseminating Necrotizing Leukoencephalopathy Associated With Intra-CSF Methotrexate Chemotherapy: A Retrospective Observational Study.

BACKGROUND AND OBJECTIVES: Leptomeningeal metastases (LMs) are neoplasms that proliferate to membranes lining the brain and spinal cord. Intra-CSF methotrexate (MTX) chemotherapy is a prevalent treatment option. However, resultant long-term neurotoxicity can lead to irreversible disseminated necrotizing leukoencephalopathy (DNL). This study aims to determine the incidence, characteristics, risk factors, and outcomes of DNL following intra-CSF MTX chemotherapy for LM. METHODS: We retrospectively reviewed patients with LM who received intra-CSF MTX between 2001 and 2021 at the National Cancer Center of Korea. Patients with a follow-up duration of <3 months and those without follow-up MRI after MTX administration were excluded. The primary outcome was the development of DNL, evaluated based on the clinical and radiologic definitions of DNL. Logistic and Cox proportional regression models were used to assess the risk of DNL in patients with LM receiving intra-CSF MTX chemotherapy. RESULTS: Of the 577 patients included in the DNL investigation, 13 (2.3%) were identified to have irreversible DNL. The MRI features of DNL typically include necrotic changes in the bilateral anterior temporal region, extensive white matter, and/or brainstem lesions. All patients with DNL experienced fatal clinical course despite MTX cessation. Logistic regression analysis revealed that a cumulative dose of MTX significantly affected DNL occurrence. Multivariable analysis showed that the factor of ≥10 MTX rounds was significant for DNL development after adjusting for route of MTX administration and prior brain radiotherapy (odds ratio 7.32, 95% CI 1.42-37.77 at MTX rounds ≥10 vs < 10). In the Cox proportional hazards model considering time to occurrence of DNL, ≥10 rounds of MTX were identified as an independent predictor of DNL (hazard ratio 12.57, 95% CI 1.62-97.28, p = 0.015), even after adjusting for the synergistic effect of brain radiotherapy. DISCUSSION: DNL is a rare but fatal complication of intra-CSF MTX chemotherapy, and its progression cannot be prevented despite early recognition. The cumulative dose of intra-CSF MTX was an independent risk factor for DNL occurrence. Thus, intra-CSF MTX treatment for patients with LM should be administered with caution considering the possibility of the cumulative irreversible neurotoxicity.

Avoiding a Collision in Gamma Knife Radiosurgery : A Modified Mask Fixation Method.

OBJECTIVE: The latest version of the Leksell Gamma Knife IconTM allows for mask- and frame-based fixation. Although mask fixation provides fractionated treatment and immobilization using a noninvasive method, it is not free from collision. The authors investigated the collision problem with a modified mask fixation method. METHODS: This study presents a case of two meningiomas in the frontal area, where a collision occurs in the occipital area. A modified mask fixation method was introduced to avoid the collision : first, the edges of the head cushion were cut off and polystyrene beads with a diameter of approximately 5 cm were removed. Next, the head cushion was sealed using a stapler. Finally, the head cushion was flattened in the adapter. We compared the shot coordinates, 3-dimensional (3D) error, clearance distance, and vertical depth of the head cushion between the initial and modified mask fixations. RESULTS: When comparing the initial and modified mask fixations, the difference in the shot coordinates was +10.5 mm along the y-axis, the difference in the 3D error was approximately 18 mm, and the difference in clearance was -10.2 mm. The head cushion was approximately 8 mm deeper in the modified mask fixation. CONCLUSION: Based on these findings, we recommend a modified mask fixation method for gamma knife radiosurgery using ICON with a collision.

A 3-month survival model after Gamma Knife surgery in patients with brain metastasis from lung cancer with Karnofsky performance status ≤ 70.

Gamma Knife surgery (GKS) for brain metastasis (BM) has been generally advocated for patients with a Karnofsky performance status (KPS) scale of ≥ 70. However, some patients with a poor KPS scale of < 70 are recoverable after GKS and show durable survival. A purpose of this study is to devise a 3-month survival prediction model to screen patients with BM with a KPS of ≤ 70 in whom GKS is needed. A retrospective analysis of 67 patients with a KPS scale of 60-70 undergoing GKS for BM of non-small cell lung cancer (NSCLC) from 2016 to 2020 in our institute was performed. Univariate and multivariate logistic regression analyses were performed to investigate factors related to survival for more than 3 months after GKS. The probability (P) prediction model was designed by giving a weight corresponding to the odds ratio of the variables. The overall survival was 9.9 ± 12.7 months (range 0.2-53.2), with a 3-month survival rate of 59.7% (n = 40). In multivariate logistic regression analysis, extracranial disease (ECD) control (p = .033), focal neurological deficit (FND) (p = .014), and cumulative tumor volume (∑ TV) (p = .005) were associated with 3-month survival. The prediction model of 3-month survival (Harrell's C index = 0.767) was devised based on associated factors. In conclusion, GKS for BMs is recommended in selected patients, even if the KPS scale is ≤ 70.

Changes of Resection Goal After Using 3-Dimensional Printing Brain Tumor Model for Presurgical Planning.

BACKGROUND: Conventional 2-Dimensional magnetic resonance imaging-based neuronavigation systems can improve the maximal safe resection in brain tumor surgery but can be unintuitive. A 3-Dimensional (3D)-printed brain tumor model allows for a more intuitive and stereoscopic understanding of brain tumors and adjacent neurovascular structures. This study aimed to identify the clinical efficacy of a 3D-printed brain tumor model in presurgical planning by focusing on differences in the extent of resection (EOR). METHODS: Thirty two neurosurgeons (14 faculty members, 11 fellows, 7 residents) randomly selected the two 3D-printed brain tumor models from the 10 manufactured models and performed presurgical planning following a standardized questionnaire. To compare the 2-Dimensional magnetic resonance imaging-based planning results with the 3D-printed model-based planning results, we analyzed the changing patterns and characteristics of the EOR. RESULTS: Of 64 randomly generated cases, the resection goal changed in 12 cases (18.8%). When the tumor was located intra-axially, the surgical posture required a prone position, and when the neurosurgeon was dexterous in surgery, there was a higher rate of EOR changes. 3D-printed models 2, 4, and 10, which all represented tumors in the posterior of the brain, had high rates of changing EOR. CONCLUSIONS: A 3D-printed brain tumor model could be utilized in presurgical planning to effectively determine the EOR.

Functional Magnetic Resonance Imaging and Diffusion Tensor Imaging for Language Mapping in Brain Tumor Surgery: Validation With Direct Cortical Stimulation and Cortico-Cortical Evoked Potential.

OBJECTIVE: Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging-derived tractography (DTI-t) contribute to the localization of language areas, but their accuracy remains controversial. This study aimed to investigate the diagnostic performance of preoperative fMRI and DTI-t obtained with a simultaneous multi-slice technique using intraoperative direct cortical stimulation (DCS) or corticocortical evoked potential (CCEP) as reference standards. MATERIALS AND METHODS: This prospective study included 26 patients (23-74 years; male:female, 13:13) with tumors in the vicinity of Broca's area who underwent preoperative fMRI and DTI-t. A site-by-site comparison between preoperative (fMRI and DTI-t) and intraoperative language mapping (DCS or CCEP) was performed for 226 cortical sites to calculate the sensitivity and specificity of fMRI and DTI-t for mapping Broca's areas. For sites with positive signals on fMRI or DTI-t, the true-positive rate (TPR) was calculated based on the concordance and discordance between fMRI and DTI-t. RESULTS: Among 226 cortical sites, DCS was performed in 100 sites and CCEP was performed in 166 sites. The specificities of fMRI and DTI-t ranged from 72.4% (63/87) to 96.8% (122/126), respectively. The sensitivities of fMRI (except for verb generation) and DTI-t were 69.2% (9/13) to 92.3% (12/13) with DCS as the reference standard, and 40.0% (16/40) or lower with CCEP as the reference standard. For sites with preoperative fMRI or DTI-t positivity (n = 82), the TPR was high when fMRI and DTI-t were concordant (81.2% and 100% using DCS and CCEP, respectively, as the reference standards) and low when fMRI and DTI-t were discordant (≤ 24.2%). CONCLUSION: fMRI and DTI-t are sensitive and specific for mapping Broca's area compared with DCS and specific but insensitive compared with CCEP. A site with a positive signal on both fMRI and DTI-t represents a high probability of being an essential language area.

The Korean Society for Neuro-Oncology (KSNO) Guideline for the Management of Brain Tumor Patients During the Crisis Period: A Consensus Recommendation Using the Delphi Method (Version 2023.1).

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, the need for appropriate treatment guidelines for patients with brain tumors was indispensable due to the lack and limitations of medical resources. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. METHODS: The KSNO Guideline Working Group was composed of 22 multidisciplinary experts on neuro-oncology in Korea. In order to reach consensus among the experts, the Delphi method was used to build up the final recommendations. RESULTS: All participating experts completed the series of surveys, and the results of final survey were used to draft the current consensus recommendations. Priority levels of surgery and radiotherapy during crises were proposed using appropriate time window-based criteria for management outcome. The highest priority for surgery is assigned to patients who are life-threatening or have a risk of significant impact on a patient's prognosis unless immediate intervention is given within 24-48 hours. As for the radiotherapy, patients who are at risk of compromising their overall survival or neurological status within 4-6 weeks are assigned to the highest priority. Curative-intent chemotherapy has the highest priority, followed by neoadjuvant/adjuvant and palliative chemotherapy during a crisis period. Telemedicine should be actively considered as a management tool for brain tumor patients during the mass infection crises such as the COVID-19 pandemic. CONCLUSION: It is crucial that adequate medical care for patients with brain tumors is maintained and provided, even during times of crisis. This guideline will serve as a valuable resource, assisting in the delivery of treatment to brain tumor patients in the event of any future crisis.

The Korean Society for Neuro-Oncology (KSNO) Guideline for the Management of Brain Tumor Patients During the Crisis Period: A Consensus Survey About Specific Clinical Scenarios (Version 2023.1).

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, there was a shortage of medical resources and the need for proper treatment guidelines for brain tumor patients became more pressing. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. As part II of the guideline, this consensus survey is to suggest management options in specific clinical scenarios during the crisis period. METHODS: The KSNO Guideline Working Group consisted of 22 multidisciplinary experts on neuro-oncology in Korea. In order to confirm a consensus reached by the experts, opinions on 5 specific clinical scenarios about the management of brain tumor patients during the crisis period were devised and asked. To build-up the consensus process, Delphi method was employed. RESULTS: The summary of the final consensus from each scenario are as follows. For patients with newly diagnosed astrocytoma with isocitrate dehydrogenase (IDH)-mutant and oligodendroglioma with IDH-mutant/1p19q codeleted, observation was preferred for patients with low-risk, World Health Organization (WHO) grade 2, and Karnofsky Performance Scale (KPS) ≥60, while adjuvant radiotherapy alone was preferred for patients with high-risk, WHO grade 2, and KPS ≥60. For newly diagnosed patients with glioblastoma, the most preferred adjuvant treatment strategy after surgery was radiotherapy plus temozolomide except for patients aged ≥70 years with KPS of 60 and unmethylated MGMT promoters. In patients with symptomatic brain metastasis, the preferred treatment differed according to the number of brain metastasis and performance status. For patients with newly diagnosed atypical meningioma, adjuvant radiation was deferred in patients with older age, poor performance status, complete resection, or low mitotic count. CONCLUSION: It is imperative that proper medical care for brain tumor patients be sustained and provided, even during the crisis period. The findings of this consensus survey will be a useful reference in determining appropriate treatment options for brain tumor patients in the specific clinical scenarios covered by the survey during the future crisis.