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OBJECTIVE Meningiomas are the most common primary intracranial tumors, and their clinical and biological characteristics vary by location. Convexity, parasagittal, and falx meningiomas account for approximately 50%–65% of intracranial meningiomas. Focusing only on these locations, the aim of this study was to determine the typical speed of tumor growth, to assess the growth risk, and to show the possible tumor volume that many lesions can reach after 5 years. METHODS Patients with radiologically suspected convexity, parasagittal, or falx meningiomas at the authors’ institution were studied retrospectively. The relative growth rate (RGR) and annual volume change (AVC) were calculated from MRI at more than 3-month intervals. Based on sex, age, and signal intensity on T2-weighted MRI, the cases were classified into three groups: extremely high-growth, high-growth, and low-growth groups. RESULTS The data of 313 cases were analyzed. The median RGR and AVC for this entire cohort were 6.1% (interquartile range [IQR] 2.4%–16.0%) and 0.20 (IQR 0.04–1.18) cm3/year, respectively. There were significant differences in sex (p = 0.018) and T2-weighted MRI signal intensity (p < 0.001) for RGR, and T2-weighted MRI signal intensity (p < 0.001), tumor location (p = 0.025), and initial tumor volume (p < 0.001) for AVC. The median RGR and AVC were 17.5% (IQR 8.3%–44.1%) and 1.05 (IQR 0.18–3.53) cm3/year, 8.2% (IQR 2.9%–18.6%) and 0.33 (IQR 0.06–1.66) cm3/year, and 3.4% (IQR 1.2%–5.8%) and 0.04 (IQR 0.02–0.21) cm3/year for the extremely high-growth, high-growth, and low-growth groups, respectively, with a significant difference among the groups (p < 0.001). A 2.24-times, or 5.24 cm3, increase in tumor volume over 5 years was typical in the extremely high-growth group, whereas the low-growth group showed little change in tumor volume even over a 5-year follow-up period. CONCLUSIONS For the first time, the typical speed of tumor growth was calculated, focusing only on patients with convexity, parasagittal, and falx meningiomas. In addition, the possible tumor volume that many lesions in these locations can reach after 5 years was shown based on objective indicators. These results may allow clinicians to easily detect lesions that require frequent follow-up or early treatment by determining whether they deviate from the typical range of the growth rate, similar to a growth chart for children.

The blood-brain barrier is a major obstacle to the delivery of drugs to the central nervous system. In the blood-brain barrier, the spaces between adjacent brain microvascular endothelial cells are sealed by multiprotein complexes known as tight junctions. Among the many components of the tight junction, claudin-5 has received the most attention as a target for loosening the tight-junction seal and allowing drugs to be delivered to the brain. In mice, transient knockdown of claudin-5 and the use of claudin-5 binders have been shown to enhance the permeation of small molecules from the blood into the brain without apparent adverse effects. However, sustained knockdown of claudin-5 in mice is lethal within 40 days, and administration of an anti-claudin-5 antibody induced convulsions in a nonhuman primate. Here, we review the safety concerns of claudin-5-targeted technologies with respect to their clinical application.

We conducted a prospective multicenter trial to compare the usefulness of C-11-methionine (MET) and F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) for identifying tumor recurrence. Patients with clinically suspected tumor recurrence after radiotherapy underwent both C-11-MET and F-18-FDG PET. When a lesion showed a visually detected uptake of either tracer, it was surgically resected for histopathological analysis. Patients with a lesion negative to both tracers were revaluated by magnetic resonance imaging (MRI) at 3 months after the PET studies. The primary outcome measure was the sensitivity of each tracer in cases with histopathologically confirmed recurrence, as determined by the McNemar test. Sixty-one cases were enrolled, and 56 cases could be evaluated. The 38 cases where the lesions showed uptake of either C-11-MET or F-18-FDG underwent surgery; 32 of these cases were confirmed to be subject to recurrence. Eighteen cases where the lesions showed uptake of neither tracer received follow-up MRI; the lesion size increased in one of these cases. Among the cases with histologically confirmed recurrence, the sensitivities of C-11-MET PET and F-18-FDG PET were 0.97 (32/33, 95% confidence interval [CI]: 0.85-0.99) and 0.48 (16/33, 95% CI: 0.33-0.65), respectively, and the difference was statistically significant (P < .0001). The diagnostic accuracy of C-11-MET PET was significantly better than that of F-18-FDG PET (87.5% vs. 69.6%, P = .033). No examination-related adverse events were observed. The results of the study demonstrated that C-11-MET PET was superior to F-18-FDG PET for discriminating between tumor recurrence and radiation-induced necrosis.

Background New therapies for glioblastoma (GBM) are urgently needed because the disease prognosis is poor. Chimeric antigen receptor (CAR)-T cell therapy that targets GBM-specific cell surface antigens is a promising therapeutic strategy. However, extensive transcriptome analyses have uncovered few GBM-specific target antigens. Methods We established a library of monoclonal antibodies (mAbs) against a tumor cell line derived from a patient with GBM. We identified mAbs that reacted with tumor cell lines from patients with GBM but not with nonmalignant human brain cells. We then detected the antigens they recognized using expression cloning. CAR-T cells derived from a candidate mAb were generated and tested in vitro and in vivo. Results We detected 507 mAbs that bound to tumor cell lines from patients with GBM. Among them, E61 and A13 reacted with tumor cell lines from most patients with GBM, but not with nonmalignant human brain cells. We found that B7-H3 was the antigen recognized but E61. CAR-T cells were established using the antigen-recognition domain of E61-secreted cytokines and exerted cytotoxicity in co-culture with tumor cells from patients with GBM. Conclusions Cancer-specific targets for CAR-T cells were identified using a mAb library raised against primary GBM tumor cells from a patient. We identified a GBM-specific mAb and its antigen. More mAbs against various GBM samples and novel target antigens are expected to be identified using this strategy.

Claudin-5 (CLDN-5) is an essential component of the tight junction seal in the blood–brain barrier. Previously, we showed that CLDN-5 modulation in vitro via an anti-CLDN-5 monoclonal antibody (mAb) may be useful for increasing the permeability of the blood–brain barrier for drug delivery to the brain. Based on these findings, here we examined the safety and efficacy of the anti-CLDN-5 mAb in a non-human primate. Cynomolgus monkeys were intravenously administered the anti-CLDN-5 mAb followed by fluorescein dye (376 Da), and the concentrations of the dye in the cerebrospinal fluid was examined. When the mAb was administered at 3.0 mg/kg, the concentration of dye in the cerebrospinal fluid was increased, and no behavioral changes or changes in plasma biomarkers for inflammation or liver or kidney injury were observed. However, a monkey that received the mAb at 6 mg/kg experienced convulsions, and subsequent histopathological examination of this animal revealed vasodilation in the liver, lung, and kidney; hemorrhage in the lung; and edema in the brain. Together, our data indicate that CLDN-5 might be a potential target for enhancing drug delivery to the brain, but also that the therapeutic window of the anti-CLDN-5 mAb may be narrow for separating efficacy and toxicity.

Meningiomas are the most frequent primary brain tumors. The long-term natural history of asymptomatic meningiomas remains unclear and difficult to predict accurately, however. The purpose of this study was to determine the subsequent course of asymptomatic meningiomas preceded by 5 years of no treatment.We retrospectively studied patients with radiologically suspected intracranial asymptomatic meningiomas preceded by 5 years of no treatment. We volumetrically measured the lesions' chronological changes during the initial 5 years to obtain the 5-year tumor doubling time (5y-TdT).A total of 201 cases met the inclusion criteria. They were further divided into 3 subgroups: those who remained asymptomatic (group A; 174 cases), those who developed neurological symptoms and underwent treatment (group B; 8 cases), and those who received intentional intervention for a preventative reason (group C; 19 cases). 5y-TdT of group B (median: 46.5 months) was significantly shorter than that of group A (median: 216.3 months) (P 0.001). Progression-free survival (PFS) was significantly different between tumors that exhibited 5y-TdT ≥ 98.8 months and98.8 months (P0.001). When we combined groups B and C and set the PFS endpoint as either disease progression or treatment, we found that more than 20% of patients would require treatment within 15 years.The present study revealed the subsequent course of asymptomatic meningiomas after 5 years of no treatment and demonstrated that 5y-TdT is useful to detect patients who may require treatment.

Introduction Recently, CAR-T cell (chimertic antigen receptor T-cell) therapy has been attracting and has shown high therapeutic efficacy, especially in the hematological tumors. The T cells from patient are then genetically engineered to specifically bind to and attack the target tumor cell antigen. In the brain, EGFRvIII or HER2 have been used as antigens, but have yet to show positive results. It is necessary to find antibodies that are more specific and have a therapeutic effect. Methods A primary culture line was prepared from glioblastoma surgical specimens, and immunized to Balb/c mice with it.The B cells from the mice were fused with myeloma cells, immortalized, and cultured monoclonally to obtain a number of monoclonal antibodies reacted glioblastoma cells. The obtained antibodies were reacted with glioblastoma cells and normal brain cells, and those that specifically react to glioblastoma were selected by flowcytometry to obtain antibody candidates that could be specifically expressed on the surface of glioblastoma cells. Results Approximately 20,000 antibody-producing strains were generated. From these, about 3,200 strains were selected as the reacted with immunized glioblastoma. About 560 strains was selected that reacted with at least one other glioblastoma, and from these, we selected 30 strains that did not react with normal brain cells. Finally, the cells were frozen and thawed at least once, and 13 stably growing strains selected. Discussion We have been identified one antibody among approximately 500 strains in past our study, and have confirmed that it is B7H3, a pan-tumor antibody. We will generate more antibody candidates in the future, as well as identify antibodies in 13 strains that have already been selected and confirmed to be glioblastoma-specific antibodies. We will also create CAR-T cells targeting these antibodies and confirm their anti-tumor effects.

Background Glioblastomas are highly infiltrative tumors, and differentiating between infiltrating tumors and vasogenic edema occurring in the non-enhancing T2-weighted hyperintense area is challenging. Here, we differentiated between infiltrating tumors and edemas in glioblastomas using dynamic perfusion-weighted MR imaging. Methods Data were collected from 33 patients with glioblastomas and 15 with meningioma as controls, who underwent resection at our institution between January 2019 and March 2022. The MRI data included T2 weighted images and contrast-enhanced T1 weighted images, and dynamic perfusion-weighted MR imaging. Two neurosurgeons manually assigned regions of interest (ROIs) to infiltrating tumors and vasogenic edema based on a previous report using conventional MRI features. The ratio of cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) in the ROIs to that contralateral normal regions were calculated. We also histological analysis using histological specimens obtained by stereotactic biopsy in each ROI. Results CBF and MTT ratios of infiltrating tumors and edemas differed significantly (p Conclusions Using dynamic perfusion-weighted MR imaging may prove useful in differentiating infiltrating tumors from edemas in the non-contrast T2 hyperintensity region of glioblastomas.

Background The natural history of meningiomas is still unclear, and no guidelines have been established based on objective indices regarding the necessity and timing of therapeutic intervention.Objective: We attempted to provide statistics on the characteristics of tumor volume change, stratify tumor growth by risk factors, and generate a predictive tumor volume curve based on the statistics, with the aim of describing the natural history of meningiomas. Methods 313 cases were included in the study, with the origin of meningioma being the circumflex and parasagittal sinus areas and the cerebral sickle region, and with multiple MRI scans performed at intervals of at least 3 months. Relative growth rate (RGR) and annual volume change (AVC) were calculated by measuring tumor volume, and the patients were classified into three groups according to the combination of gender, age, and MRI T2WI signal intensity, and compared. Results The median RGR and AVC of the entire cohort were 6.1% and 0.20 cm3/year, respectively, and there were significant differences between groups in gender (p=0.018) and MRI T2WI (p < 0.001) for RGR and tumor location (p=0.025) and initial tumor volume (p < 0.001)for AVC. The median RGR and AVC in the classification were 17.5% and 1.05 cm3/year for the very high growth group, 8.2% and 0.33 cm3/year for the high growth group, and 3.4% and 0.04 cm3/year for the low growth group, showing significant differences between the groups (p < 0.001). The predicted tumor volume curve showed an average 2.24-fold or 5.24 cm3 increase in volume over 5 years in the very high-growth group, while little tumor volume change was observed in the low-growth group. Conclusion The combination of growth risk factors allowed stratification of tumor growth and provided a predictive tumor volume curve for each county. The results may assist in the treatment of meningiomas.

The prognosis for glioblastoma is still very poor despite intensive treatment by surgery, radiation, and chemotherapy. One of the reasons for poor prognosis of glioblastoma is blood-brain-barrier (BBB), which limits the delivery of chemotherapeutic agents to the brain. Focused ultrasound (FUS) therapy is approved for essential tremor and Parkinson disease in Japan and preclinical studies suggest low-intensity focused ultrasound (LIFU) administered with microbubbles (MB) can disrupt BBB and can improve the delivery of chemotherapeutic agents. Thus, currently, focused ultrasound therapy has gained attention in neuro-oncology and a number of clinical trials using FUS for the treatment of glioblastoma are underway. Our institutions (Osaka University Hospital and Saito Yukoukai Hospital) are the first in Japan to join the international multicenter study to examine the safety and feasibility of BBB disruption by FUS and MB combined with intravenous carboplatin for the treatment of recurrent glioblastoma. We are planning to enroll one recurrent glioblastoma patient for this study soon. BBB disruption strategies using FUS and MB for the treatment of neuro-oncological disease has potentials to improve the outcome of patients and many clinical trials will be performed in future.

New therapies for GBM are urgently needed due to its poor prognosis and chimeric antigen receptor T (CAR-T) cell therapy is thought to be a promising strategy. To develop CAR-T cell therapy, cell surface targets that is highly specific for GBM cells are needed.Although extensive transcriptome analyses of GBM cells were performed, few transcripts highly specific for GBM cells have been identified. However, GBM cell-specific antigen epitopes formed by post-translational modifications of proteins may have been missed, and could still be discovered by thoroughly searching for cancer-specific monoclonal antibodies and characterizing the antigens they recognize. In this study, we applied this strategy to search for GBM-specific cell surface targets using patient derived tumor spheres. We identified two monoclonal antibodies E61 and A13 as those reacting with GBM cells but not with normal brain parenchymal cells. CAR-T cells derived from both monoclonal antibodies produced IL-2 and IFNɤ and exerted cytotoxicity to GBM cells by chromium 51 release assay. In addition, we identified B7-H3, which is frequently used for a CAR-T cell target against GBM, as the antigen recognized by B7-H3 by the expression cloning method. These results indicate that the strategy shown in this study is useful for identifying antigens that are expressed on patient-derived GBM cells and potentially useful as targets for CAR T cells.

Background Wilms’ tumor gene 1 (WT1) peptide vaccine and anti-programmed cell death-1 (anti-PD-1) antibody are expected as immunotherapies to improve the clinical outcome of glioblastoma. The aims of this study were to clarify how each immunotherapy affects tumor-infiltrating immune cells (TIIs) and to determine whether the combination of these two therapies could synergistically work. Methods Mice were transplanted with WT1 and programmed cell death-ligand 1 doubly expressing glioblastoma cells into brain followed by treatment with WT1 peptide vaccine, anti-PD-1 antibody, or the combination of the two, and survival of each therapy was compared. CD45+ cells were positively selected as TIIs from the brains with tumors, and TIIs were compared between WT1 peptide vaccine and anti-PD-1 antibody therapies. Results Most mice seemed to be cured by the combination therapy with WT1 peptide vaccine and anti-PD-1 antibody, which was much better survival than each monotherapy. A large number of CD4+ T cells, CD8+ T cells, and NK cells including WT1-specific CD8+ and CD4+ T cells infiltrated into the glioblastoma in WT1 peptide vaccine-treated mice. On the other hand, the number of TIIs did not increase, but instead PD-1 molecule expression was decreased on the majority of the tumor-infiltrating CD8+ T cells in the anti-PD-1 antibody-treated mice. Conclusion Our results clearly demonstrated that WT1 peptide vaccine and anti-PD-1 antibody therapies worked in the different steps of cancer-immunity cycle and that the combination of the two therapies could work synergistically against glioblastoma.

We conducted a prospective multicenter trial to compare the usefulness of 11C‐methionine (MET) and 18F‐fluorodeoxyglucose (FDG) positron emission tomography (PET) for identifying tumor recurrence. Patients with clinically suspected tumor recurrence after radiotherapy underwent both 11C‐MET and 18F‐FDG PET. When a lesion showed a visually detected uptake of either tracer, it was surgically resected for histopathological analysis. Patients with a lesion negative to both tracers were revaluated by magnetic resonance imaging (MRI) at 3 months after the PET studies. The primary outcome measure was the sensitivity of each tracer in cases with histopathologically confirmed recurrence, as determined by the McNemar test. Sixty‐one cases were enrolled, and 56 cases could be evaluated. The 38 cases where the lesions showed uptake of either 11C‐MET or 18F‐FDG underwent surgery; 32 of these cases were confirmed to be subject to recurrence. Eighteen cases where the lesions showed uptake of neither tracer received follow‐up MRI; the lesion size increased in one of these cases. Among the cases with histologically confirmed recurrence, the sensitivities of 11C‐MET PET and 18F‐FDG PET were 0.97 (32/33, 95% confidence interval [CI]: 0.85‐0.99) and 0.48 (16/33, 95% CI: 0.33‐0.65), respectively, and the difference was statistically significant (P, This prospective multicenter study using positron emission tomography (PET) demonstrated the uptake of 11C‐methionine at a significantly higher sensitivity with brain tumor recurrence after radiotherapy than that of 18F‐fluorodeoxyglucose, based on histopathological evidence. The 11C‐methionine PET can be a useful diagnostic tool for the detection of tumor recurrence, distinguishable from radiation‐induced necrosis after radiotherapy in brain tumors.

BACKGROUNDConjoined twins represent a rare congenital malformation. Pygopagus twins are fused at the sacrum and perineum, with union of the spine. The authors report a successful separation of a unique case of pygopagus twins sharing a U-shaped spinal cord, which the authors identified through aberrant nerves by intraoperative physiological spinal root examination.OBSERVATIONSThe 6-month-old male pygopagus conjoined twins, who were diagnosed in the prenatal period, underwent separation. They had a single dural sac containing a U-shaped continuous spinal cord; their filum terminale appeared completely fused and the anatomical border of the spinal cord was not distinguishable. A triggered electromyogram (tEMG) was used on each nerve root to determine which belonged to one twin versus the other, to detect nerve cross, and to identify functional midline cleavage. Finally, the twins were separated after spinal division. Both twins recovered uneventfully with no lower limb neurological deficits or walking impairment for 16 months.LESSONSPygopagus twins with a conjoined spinal cord are very rare, but a good long-term functional prognosis can be expected with successful separation. Intraoperative tEMG is useful in spinal separation surgery for twins with a conjoined spinal cord.

Background: Neuroendocrine tumors (NETs) are uncommon neoplasms arising from neuroendocrine cells and are rarely associated with intracranial metastases. Case Description: We discuss the case of a 74-year-old woman with a right CPA tumor. She had a history of retroperitoneal NET, but was diagnosed with vestibular schwannoma due to a right-sided hearing loss and a right CPA tumor along the VII and VIII nerves. After a 3-year follow-up, she presented with repetitive vomiting, a 1-month history of gait instability, and a 3-month history of general fatigue. Brain imaging revealed tumor growth and edematous changes in the right cerebellum. She underwent retrosigmoid craniotomy and partial resection. Histopathological examination revealed metastatic NET. She underwent stereotactic radiosurgery for residual lesion and, at 11 months of follow-up, the lesion was confirmed to have shrunk on magnetic resonance imaging (MRI). Conclusion: This is the first case to report the natural course of cerebellopontine metastasis of a NET. The differential diagnosis of CPA tumors is diverse, and, in our case, we suspected a vestibular schwannoma because of the typical symptoms and imaging features. However, the tumor grew relatively faster than expected and showed intratumoral hemorrhage during the 3-year follow-up. Therefore, in patients with a history of a NET, a careful follow-up is advisable even for lesions highly suspected to be another benign tumor on MRI. Careful follow-up imaging and appropriate treatment strategies were useful to manage the brain metastasis. Although NETs metastasizing to the CPA are extremely rare, this possibility should be considered when patients with NETs have intracranial lesions.

BACKGROUND: Intracranial germ cell tumors (iGCT) are heterogeneous tumors with several histopathology. Chemoradiotherapy is effective and required for treatment against them, but optimal treatment intensity should be selected from the viewpoint of both improvement of clinical outcome and avoidance of late complications. We introduced a protocol with reduced-dose radiotherapy and intensified chemotherapy for iGCT. OBJECTIVE: We retrospectively analysed the clinical outcome, especially for non-germinomatous germ cell tumors and long-term clinical outcome of late complications, enrollment and employment, as indicators of quality of life (QOL). MATERIALS AND METHODS: Thirty-eight children and young adults (28 men and 10 women) with iGCTs treated in our institution from 1997 to 2013 were enrolled in this study. They consisted of 26 germinomas including HCG-producing cases and 12 non-germinomatous GCTs (NGGCT). Local irradiation was selected for all patients, and the dose of irradiation was 23.4-54 Gy. The whole-brain irradiation was made in patients who had intracranial dissemination, but any prophylactic irradiation to the whole brain and spinal cord was not performed. For NGGCT, high-dose chemotherapy and peripheral blood stem cell transplantation (PBSCT) were introduced. Second-look surgeries were performed for cases with residual tumors after induction chemotherapies. RESULTS: In germinoma group and NGGCT group, 10-year progression-free survival was 86% and 84%, 10-year overall survival was 93% and 91%, respectively. About late complications, endocrinological replacement (39%), cerebrovascular disease such as cavernous hemangioma and arterial stenosis (18%), secondary neoplasm (2.6%) were observed. Regarding QOL, enrollment and return to school rate was 92% and employment and the return rate was 89%, which were influenced by hemipararesis associated with basal ganglia lesion, intractable epilepsy and whole-brain irradiation. CONCLUSION: Reduced-dose radiotherapy and intensified chemotherapy for iGCT, especially NGGCT, improved the clinical outcome and QOL of long-term survivors, suppressing late complications. Further comprehensive follow-up and analysis are needed.

The Japanese conditional and time-limited (CTL) approval framework, a tiered system for regenerative medical products, was initiated in 2014. Here, we compare the dossiers of six regenerative medical products with either direct full approval or CTL approval, and we discuss the regulatory considerations for obtaining approval under the CTL approval framework.

Background: Molecular heterogeneity among and within tumors are one of the reasons for the poor survival rate of brain tumors even with the current standard therapy. However, monolayer culture and neuro-sphere culture (NS) use exogenous growth factors, so may not show the true nature of the tumor. And the culture establishment rate is low, especially low-grade tumors. Therefore, we used the glioblastoma organoid (GBO) culture method showed by Fadi to create culture models of various brain tumors and investigated their characteristics. Methods: We examined the establishment rate in pathological and genotypic types of 56 patients who underwent brain tumor resection at our hospital between January 2020 and June 2021 and were cultured with GBO or NS. If tumor cells are increased visually at 1 month after culture, we defined establishment. Results: There were 15 cases of glioblastoma, 7 cases of anaplastic astrocytoma, 7 cases of diffuse astrocytoma, 3 cases of diffuse midline glioma, 2 cases of anaplastic oligodendroglioma, 5 cases of oligodendroglioma, and 16 cases of others. The establishment rate was 76.5% by the GBO method and 40% by the N S method. By histological type, GBO: 80% in glioblastoma, NS: 58.3% in glioblastoma, GBO: 83.3% in AA, NS: 40% in AA, and GBO: 100% in DA. The IDH mutation and pTERT mutation were investigated in GBO: IDHwt/TERT+ 87.5%, IDHwt/TERT- 64.3%, IDHmt/TERT- 100%, and in NS: IDHwt/TERT+ 75%, IDHwt/TERT- 33.3%, IDHmt/ TERT- 20% in NS. In addition, establishment was observed in GBO 2 case in medulloblastoma, 1 case in ependymoma. Discussion and Conclusion: This suggest that GBO can be used to establish culture models for low-grade tumors. In addition, GBO can establish culture earlier, so it is expected to be applicable to personalized therapies such as preclinical drug efficacy studies tailored to individual patients.

BACKGROUND: With the widespread use of MRI equipment and brain scans, opportunities to perform follow-up examinations for meningiomas have increased. On the other hand, an objective evaluation index for meningiomas characterized by slow changes on imaging has not been established. To establish a volume-based evaluation index for meningoceles, we are developing an application for automatic lesion extraction using artificial intelligence as a highly reproducible tumor volume measurement technique that enables large volume image data processing. METHODS: In this study, 195 patients with meningioma who underwent contrast-enhanced MRI imaging at Osaka University Hospital were included. The images were manually extracted by three neurosurgeons and used as supervised data. deeplabV3 was used as the learning network. All the supervised data were randomly divided into training (80%) and testing (20%) data, and the application was constructed by deep learning and validation with 5-fold cross-validation. The matching rate of the area of the region automatically extracted by the device against the test data and the mean square error rate of the calculated tumor volume were used as indices of the product measurement performance. RESULTS: The matching rate using the automatic extraction application for the correct data(Dice index) was 91.5% on average. The mean squared error rate of the tumor volume calculated from these extracted regions was 8.84%. CONCLUSION: We consider that this application using artificial intelligence has a certain degree of validity in terms of the accuracy of extracted lesions. In the future, it is necessary not only to improve the performance of the equipment but also to clarify the clinical significance of the new imaging biomarkers based on tumor volume that can be obtained from these lesion extraction techniques.

Aim To evaluate the toxicity and efficacy of re-irradiation with salvage stereotactic radiotherapy (SRT) for recurrent glioma using CyberKnife. Patients and methods This study retrospectively investigated 35 patients with 48 recurrent grade 2-4 gliomas who received SRT between 1998 and 2011. Six patients (17.1%) had grade 2 gliomas, nine (25.7%) had grade 3 gliomas, and 20 (57.1%) had glioblastomas; all initially underwent surgery and conventional radiotherapy. The median initial and subsequent radiotherapy doses were 60 and 26 Gy, respectively. Results After a median follow-up period of 9.0 months, the only toxicity of grade 2 or more was radiation-induced brain necrosis in four patients (11.4%). The median overall and progression-free survival periods following re-irradiation were 9.0 and 3.0 months, respectively. Univariate analysis revealed that performance status at salvage re-irradiation was a significant predictor of progression-free survival. Conclusion Salvage re-irradiation using CyberKnife is feasible, with an acceptable toxicity profile, for patients with recurrent glioma.

BACKGROUND Children with medulloblastoma cannot avoid chemoradiotherapy including craniospinal radiation, although prognosis of medulloblastoma has improved and previous studies have reported a significant risk of intellectual disturbance by these treatments. We retrospectively analysed neurocognitive functions, clinical MRI parameters of patients with posterior fossa tumors, especially medulloblastomas. MATERIALS AND METHODS Twenty-two patients (12 medulloblastomas, 5 ependymomas, 5 astrocytomas) treated in our institution were enrolled in this study. Mean age was 7.8 years and 6.5 years, percentage of hydrocephalus at onset was 66.7% and 60%, respectively in medulloblastoma group and in other tumor group (ependymoma and astrocytoma). Postoperative chemoradiotherapy including reduced-dose craniospinal irradiation (18Gy) was done for medulloblastoma group and local radiation or operation only was done for other group. Version 3 or 4 of Wechsler Intelligent Scale for Children (WISC) was used by neurocognitive function analysis. Ventricular size, white matter volume and other parameters were also was estimated based on MRI. Follow-up duration was 6–17 years (mean: 10.5 years). RESULTS Evaluations of neurocognitive functions based on WISC pointed out lower performance IQ than verbal IQ in long term survivor of both group, especially working memory (P=0.05). Both hydrocephalus and cranial nerve complications was influenced lower scores of WISC, but age at onset did not influence WISC scores. Comparison between both group showed there was no significant difference about cognitive function and white matter volume.

BACKGROUND Spontaneous regression in intracranial germ cell tumors has been reported in some literatures, but the mechanism has not been well known. We retrospectively measured the tumor volume before chemoradiotherapy and analyzed factors that influence reduction of tumor volume. PATIENTS AND METHODS Plural MRI scans were done before the first course of chemotherapy regimen in 27 patients with primary intracranial germinomas. Their age ranged from 8 to 31 years. 35 lesions from them were enrolled and included 13 pineal, 4 neurohypophyseal, 4 basal ganglia, 4 bifocal type, and 2 multiple lesions. All regions were verified as pure germinoma or HCG-producing germinoma by histopathological examination. Tumor volume of 35 lesions was analyzed by volumetric assessment based on MRI. Ratio of volumetric change between the first MRI and the scan immediately before chemotherapy was defined as shrinking rate (%). Period between disease onset and the first chemotherapy was 20 to 47 days. Diagnostic radiation dose was calculated in each case. RESULTS Initial tumor volume ranged from 0.962 to 72.356 cubic centimeters (mean: 8.27). Diagnostic radiation dose: 40.5 to 910.1 mGy. Shrinking rate ranged from -57.8 to 85.4% (mean: 30.8). In 10 regions, shrinking rate was within 30%. Shrinking rate was significant positively influenced by diagnostic radiation dose (p CONCLUSION This study shows that the volume of intracranial germ cell tumors is changing dynamically before chemoradiotherapy in many cases. Diagnostic exposure to low-dose radiation influences tumor shrinkage of intracranial germinomas.

Background: Although 11C-Methionine (MET) PET has widely used, 11C-MET tracer has not been approved in Japan. We conducted multi-center prospective clinical trials using MET for drug approval in diagnosis of brain tumors[Methods] Two trials using 11C-MET PET were performed in Hokkaido University, Osaka University and Fukushima Medical University; 1) Diagnostic accuracy in differentiating tumor recurrence from radiation injury after radiotherapy in brain tumors, 2) The diagnostic efficacy in newly-diagnosed gliomas. 1) The patients with suspected brain tumor recurrence underwent MET and 18F-Fluorodeoxyglucose (FDG) PET. When the target lesion showed MET and/or FDG uptake, the patients underwent target resection for pathological confirmation. Positive prediction values of each tracer uptake were assessed as primary outcome measure, and the sensitivities and specificities of each PET exams were also assessed. 2) The patients with suspected gliomas underwent MET PET. Tissue samplings were performed from MET uptake lesions without contrast-enhancement on MRI in each patient, and evaluated the existence of tumor cells. Diagnostic additional values of MET PET on contrast-enhanced MRI was also investigated. Safety of MET PET was also assessed in each trial.[Result] 1) 57 cases were investigated. 38 cases underwent surgery and 32 cases (84%) were confirmed tumor recurrence histopathologically. MET and FDG uptake in 32 recurrence cases were 100% and 50%, respectively. Sensitivities and specificities of tumor recurrence were 84% and 89% in MET, and 100% and 56% in FDG. 2) 53 glioma cases were enrolled. Viable tumor cells were proven in 98% in MET uptake lesion without contrast-enhancement. In 42 out of 53 cases (78%), MET PET depicted tumor area beyond the contrast-enhancement area on MRI. No severe adverse events were observed in both trials. [Conclusions] MET PET were effective in diagnosis of brain tumors, and safety of MET was demonstrated.

PURPOSE The current research tested the hypothesis that TI shorter than 2400 ms under 3T for FLAIR can improve the diagnostic accuracy of the T2-FLAIR mismatch sign for identifying IDHmt, non-CODEL astrocytomas. EXPERIMENTAL DESIGN We prepared three different cohorts; 94 MRI from 76 IDHmt, non-CODEL LrGGs, 33 MRI from 31 LrGG under the restriction of FLAIR being acquired with TI < 2400 ms for 3T or 2016 ms for 1.5T, and 103 MRI from 103 patients from the TCIA/TCGA dataset for LrGG. The presence or absence of the “T2-FLAIR mismatch sign” was evaluated, and we compared diagnostic accuracies according to TI used for FLAIR acquisition. RESULTS The T2-FLAIR mismatch sign was more frequently positive when TI was shorter than 2400 ms under 3T for FLAIR acquisition (p = 0.0009, Fisher’s exact test). The T2-FLAIR mismatch sign was positive only for IDHmt, non-CODEL astrocytomas even if we confined the cohort with FLAIR acquired with shorter TI (p = 0.0001, Fisher’s exact test). TCIA/TCGA dataset validated that the sensitivity, specificity, PPV, and NPV of the T2-FLAIR mismatch sign to identify IDHmt, non-CODEL astrocytomas improved from 31%, 90%, 79%, and 51% to 67%, 94%, 92%, and 74%, respectively if we acquired FLAIR with TI shorter than 2400 ms. CONCLUSIONS We revealed that TI for FLAIR impacts diagnostic accuracy of the T2-FLAIR mismatch sign and that FLAIR scanned with TI < 2400 ms in 3T is necessary for LrGG imaging.

Leptomeningeal metastasis from solid cancer is a devastating state for cancer patients. Leptomeningeal metastasis is diagnosed either by cerebrospinal fluid cytology and/or magnetic resonance imaging (MRI). However, it remains unclear as to whether tumor cells attached to leptomeninges are the same from floating tumor cells in cerebrospinal fluid (CSF). In this study, we aim to analyze the differences between tumor cells attached to leptomeninges and floating cells in CSF by xenograft models. We used breast cancer cell line, MDA-MB-231, labelled with green fluorescent protein (GFP) and luciferase. We injected those cells into right lateral ventricle of NOD/Shi-scid IL2Rγ KO mice. When the mice got any signs of tumor, we dissected spinal cord and got CSF from mice. We sorted tumor cells by flow cytometry and extracted RNA from the sorted tumor cells from spinal cord and CSF, respectively. We analyzed transcriptome differences between tumor cells from spinal cord and CSF by RNA sequencing. We found that extracellular matrix related proteins were highly upregulated while cell growth related proteins were downregulated in tumor cells from spinal cord compared with those from CSF. These results suggest that tumor cells attached to leptomeninges have different transcriptome profiles from floating tumor cells in CSF and extracellular matrix related proteins could be therapeutic targets for breast cancer leptomeningeal metastasis.

Primary motor cortex glioma is usually considered unresectable because of its high risk for motor deficit. However, recent reports suggest that surgical resection for primary motor cortex brain tumor is feasible for selected patients. In this study, we analyzed the neurological outcomes for 27 patients who underwent surgical resections for precentral gyrus glioma. Glioma grades for 27 patients were Grade II in 6 cases, Grade III in 7 cases, and Grade IV in 13 cases. 11 patients were recurrent glioma cases and glioma grade for those patients were Grade II in 4 cases, Grade III in 3 cases, and Grade IV in 4 cases. Extent of resection for 27 patients was biopsy in 2 cases, partial resection in 16 cases, and more than 90% of resections in 9 cases. 6 patients underwent awake surgery and glioma grade for those patients were Grade II in 3 cases, Grade III in 2 cases, and Grade IV in 1 case. Median extent of resection for patients who underwent awake surgery was 90%. Transient neurological worsening was observed in 5 patients, however, no patient exhibited permanent neurological deficit. Surgical resections for primary motor cortex glioma were feasible in selected patients without severe neurological complication. Careful intraoperative awake mapping is desirable to achieve maximum resections.

Objective: As childhood cancer survivors gradually increased, late complications of treatment have been at issue and risk of secondary neoplasm is increasing cumulatively. We retrospectively analyzed clinical outcome and problems of treatment for secondary intracranial neoplasm. Patients and Methods: 497 patients (children, adolescents and young adults) with malignant central nervous system neoplasm were treated in our institution from 1971 to 2015. 188 cases (37.8%) were enrolled in this follow-up study. Diagnosis of primary neoplasm included low grade glioma (29%), embryonal tumor (23.5%), germ cell tumor (24.5%), ependymoma (8%), other (15%). Results: Fourteen cases of them were diagnosed as secondary intracranial neoplasm. Twelve cases were operated and histopathological diagnosis included 6 glioblastomas, 1 anaplastic astrocytoma, 1 anaplastic ependymoma, 4 meningiomas. In all cases, histopathological finding and molecular profile of secondary intracranial neoplasm differed from that of primary malignant brain tumors. Duration from the first operation of primary tumors to diagnosis of secondary intracranial neoplasm ranged from 5 to 36 years (average: 29.3). In malignant glioma cases except meningioma cases, origin of them was contained in high irradiation field (>40Gy). In malignant glioma cases, Chemotherapies using temozolomide and bevacizumab were selected after tumor removal. In 3 cases of them, reirradiation was performed. Response for treatment was poor or transient in most cases, median survival time was 12 months. Of late complications, such as endocrinological problem needed replacement (55%), cerebrovascular event (15.9%), secondary neoplasm (7.4%), secondary neoplasm was importantly related with prognosis. Conclusion: It is difficult to plan therapeutic strategies against second malignant neoplasm because of lack of information in case of long-term survivors and restriction for first radiation. Clinical outcome of them is poor and new treatment targets should be developed. It is important to plan clinical trials to reduce treatment intensity and usable long-term follow-up system.

Introduction: Clinical application of survival prediction of primary glioblastoma (pGBM) using preoperative images remains challenging due to a lack of robustness and standardization of the method. This research focused on validating a machine learning-based texture analysis model for this purpose using internal and external cohorts. Method: We included all cases of IDH wild-type pGBM available of preoperative MRI (T1WI, T2WI, and Gd-T1WI) from the databases of Kansai Molecular Diagnosis Network for CNS tumors (KN) and The Cancer Genome Atlas (TCGA). Of 242 cases from KN, we assigned 137 cases as a training dataset (D1), and the remaining 105 cases as an internal validation dataset (D2). Furthermore, we extracted 96 cases from TCGA as an external validation dataset (D3). Preoperative MRI scans were semi-quantitatively analyzed, leading to the acquisition of 489 texture features as explanatory variables. Dichotomous overall survival (OS) with a 16.6 months cutoff was regarded as the response variable (short/long OS). We employed Lasso regression for feature selection, and a survival prediction model constructed for D1 via cross-validation (M1) was applied to D2 and D3 to ensure the model robustness. Results: The population of predicted short OS by M1 significantly showed poorer prognosis in D2 (median OS 11.1 vs. 19.4 months; log-rank test, p=0.03), while there was no significant difference in D3 (median OS 14.2 vs. 11.9 months; p=0.61). In the comparative analysis using t-SNE, there was little variation in the feature distribution among three datasets. Conclusion: We were able to validate the prediction model in the internal but not in the external cohort. The presented result supports the use of machine learning-based texture analysis for survival prediction of pGBM in a localized population or country. However, further consideration is required to achieve a universal prediction model for pGBM, irrespective of regional difference.

CD166/activated leukocyte cell adhesion molecule (CD166/ALCAM) is a transmembrane receptor, widely expressed in various tissues, and is involved in several functions such as cell adhesion, neurogenesis and angiogenesis. We have previously reported that CD166/ALCAM is expressed on glioblastoma progenitor cells and is involved in glioblastoma invasion. However, we only have analyzed the functional roles of ALCAM using glioblastoma cell lines, not using patient derived xenografts. In this study, we investigated the functional roles of CD166/ALCAM using patient derived xenografts. We established CD166/ALCAM knocked-down glioblastoma patient derived cell lines by shRNA. For in vitro analysis, we seeded control and CD166/ALCAM knocked-down glioblastoma cells on culture dishes and performed time lapse analysis to investigate cell motility. For in vivo analysis, we orthotopically injected control and CD166/ALCAM knocked-down glioblastoma cells into the immunodeficient mice. When the mice got sick due to the tumor, we dissected the mice and analyzed the difference in invasion by immunohistochemical analysis. We found that CD166/ALCAM knocked-down glioblastoma cells significantly decreased cell motility by time lapse analysis. In addition, CD166/ALCAM knocked-down glioblastoma cells suppressed cell invasion and leptomeningeal metastasis by immunohistochemical analysis from patient derived xenografts. Our results suggest that CD166/ALCAM is involved in glioblastoma invasion, thus future studies are necessary to investigate whether CD166/ALCAM could be a therapeutic target for glioblastoma.

BACKGROUND: Spontaneous regression in intracranial germ cell tumors has been reported in some literatures, but the mechanism has not been well known. We retrospectively measured the tumor volume before chemoradiotherapy and analyzed factors that influence shrinkage of tumor volume. PATIENTS AND METHODS: Thirty-nine cases with primary intracranial germinomas and HCG-producing germinomas were treated in our hospital from 1994 to 2017. In twenty-one of them, plural MRI scans were done before the first course of chemotherapy regimen. Their age ranged from 8 to 31 years. Three cases were bifocal type, one case had multiple lesions. Biopsies were performed in all regions. Tumor volume of twenty-four lesions was analyzed by volumetric assessment based on MRI. Ratio of volumetric change between the first MRI and the scan immediately before chemotherapy was defined as shrinking rate (%). Period between disease onset and the first chemotherapy was 20 to 47 days. Diagnostic radiation dose was calculated in each case. RESULTS: Initial tumor volume ranged from 0.962 to 72.356 cubic centimeters (mean: 9.67). Diagnostic radiation dose: 52.2 to 910.1 mGy. Shrinking rate ranged from -57.8 to 85.4% (mean: 28.7). In only 7 regions (29.1%), shrinking rate was within 30%. Shrinking rate was significant positively influenced by diagnostic radiation dose (p

Primary motor cortex glioma is usually considered unresectable because of its high risk for motor deficit. However recent reports suggest that surgical resections for primary motor cortex brain tumor is feasible for selected patients. In this case report, we report two cases we can successfully resected primary motor cortex glioma by awake surgery without neurological worsening. Case1 was 32 year-old woman with right primary motor cortex oligodendroglioma. We could only perform biopsy at initial surgery, however the patient got worsening of left hemiparesis which were gradually improved by rehabilitation. The patient underwent 50 Gy of radiation therapy and 6 courses of PCV chemotherapy. 60 months after the initial surgery, the tumor recurred and the she underwent 12 courses of temozolomide chemotherapy, but tumor continued to grow. She underwent second surgery 13 years after the initial biopsy. We resected primary motor cortex tumor by awake surgery without neurological complication. Case2 was 31 year-old woman with left primary motor cortex oligodendroglioma. We could only perform biopsy at initial surgery, however the patient got mild right hemiparesis which were improved by rehabilitation. The patient underwent 4 courses of PAV chemotherapy and 54 Gy of Intensity Modulated Radiation Therapy (IMRT). 21 months after IMRT, the tumor recurred and the she underwent second surgery. We resected primary motor cortex tumor by awake motor mapping without severe neurological complication. In conclusion, surgical resections for primary motor cortex glioma is feasible in selected patients without severe neurological complication. Neural plasticity is the reason for this, but careful intraoperative awake mapping is necessary to achieve maximum resections.

OBJECTIVEIn the present study the authors aimed to determine preferred locations of meningiomas by avoiding descriptive analysis and instead using voxel-based lesion mapping and 3D image-rendering techniques.METHODSMagnetic resonance images obtained in 248 treatment-naïve meningioma patients with 260 lesions were retrospectively and consecutively collected. All images were registered to a 1-mm isotropic, high-resolution, T1-weighted brain atlas provided by the Montreal Neurological Institute (the MNI152), and a lesion frequency map was created, followed by 3D volume rendering to visualize the preferred locations of meningiomas in 3D.RESULTSThe 3D lesion frequency map clearly showed that skull base structures such as parasellar, sphenoid wing, and petroclival regions were commonly affected by the tumor. The middle one-third of the superior sagittal sinus was most commonly affected in parasagittal tumors. Substantial lesion accumulation was observed around the leptomeninges covering the central sulcus and the sylvian fissure, with very few lesions observed at the frontal, parietal, and occipital convexities.CONCLUSIONSUsing an objective visualization method, meningiomas were shown to be located around the middle third of the superior sagittal sinus, the perisylvian convexity, and the skull base. These observations, which are in line with previous descriptive analyses, justify further use of voxel-based lesion mapping techniques to help understand the biological nature of this disease.

BACKGROUND: We have ever proven safety and effectiveness of Wilms tumor 1 peptide (WT1) vaccination for newly-diagnosed or recurrent glioblastomas (GBM) in adult. But pediatric GBM and diffuse intrinsic pontine glioma (DIPG) are known to differ from adult GBM biologically. A pilot study designed to investigate safety and effectiveness of Wilms tumor 1 peptide vaccination for recurrent GBM and DIPG in children was planned. PATIENTS AND METHODS: HLA-A*2402–positive five children with recurrent malignant glioma (three spratentorial GBMs and two DIPGs) were registered in this clinical study of WT1 immunotherapy. In all children, the tumors were resistant to standard therapy including radiation and temozolomide. Patients received intradermal injections of an HLA-A*2402–restricted, WT1 peptide every week for 12 weeks. Patients with an effective response continued to be vaccinated until tumor progression occurred or performance status deteriorated. Tumor responses were evaluated based on MRI data by RANO (Response Assessment in Neuro-Oncology) criteria. Progression-free survival and overall survival after initial WT1 treatment were analysed. RESULTS: In all patients, no severe adverse event was observed. The protocol was well tolerated in children. The 6-month progression-free survival rate was 40%. Progression-free survival and overall survival were significantly improved as compared with historical control in Osaka University Hospital. Two patients with supratentorial GBM are still alive more than three years. CONCLUSIONS: This study showed that WT1 vaccine therapy against recurrent GBM and DIPG in HLA-A*2402–positive children was safe and improved their prognosis. Based on these results, further clinical studies of WT1 immunotherapy in children suffering from newly diagnosed or recurrent malignant glioma should be authorized.

BACKGROUND The opportunity to follow up for asymptomatic meningiomas has increased. We have reported the risk of volume increase by individual continuous volume measurement of asymptomatic meningiomas. However, We have not reached fully understanding about natural history of meningiomas. Among cases are followed up over time, there are some cases that the volume increase rates slows down or almost stops are observed. METHODS We enrolled consecutive adult patients of asymptomatic meningiomas who follow-up for 2 years or more and 3 or more MRI scans. We performed sequential volumetric measurements on 95 patients (105 lesions) who met the criteria. We classified these transient volume curve of each lesion into three groups “Growing”, “Slowdown”, and “Growth arrest” for analysis. RESULTS The average age at the first visit was 62.8 years, the average follow-up period was 61.8 months, and the male-female ratio was 20:75 (male: female). There were 67 cases (73 lesions: 70.9%) that were in increasing trend, and 19 cases of those were received resection. Eleven cases (12 lesions: 11.7%) showed a tendency of “slow down” the increase rate, and one patient who became symptomatic led to surgical excision. In 18 cases (18 lesions: 17.4%) in which almost no volume change was observed during the observation period, no cases resulted in surgical treatment. CONCLUSIONS Among the meningiomas cases that have been followed for a long time, there are not a few those increase rate of tumor volume slows or does not change. Furthermore, most of these cases did not result in surgical treatment. The presence of these “Slowdown” and “Growth arrest” cases at a certain rate may have suggested the possibility of a Gompertz curve model as the natural course of meningiomas.

PURPOSE Our clinical trials shows the safety and clinical efficacy of Wilms’ tumor 1 (WT1) human leukocyte antigen (HLA) class I (Izumoto S et al. J Neurosurg. 2008) and class II (Tsuboi A et al. Cancer Immunol Immunother. 2019) peptide vaccination for recurrent malignant gliomas have been established. We have developed a cocktail vaccine (WT1 trio) containing two class I peptides (HLA-A*24:02 and HLA-A*02:01) and one II class peptide to improve more effective immunological response and improve patient’s prognosis. Clinical trial of a cocktail vaccination using WT1 HLA class I and II peptides for recurrent malignant gliomas is planned to verify its safety, clinical efficacy and usefulness of surrogate markers. PATIENTS AND METHODS Twenty-three patients with recurrent malignant gliomas, which showed WT1-positive in tumor samples and HLA-A*24:02 or HLA-A*02:01-positive in blood sample, were enrolled. These patients (age: 26–72 years old, average: 49.4) included 15 cases of glioblastomas and 8 of anaplastic astrocytomas. Patients received a WT1 trio vaccine intradermally, 7 times at 2-week intervals during 3 months.WT1-DTH and WT1-IgG antibody were regularly measured. Vaccine-related adverse events, best clinical response and the transfer rate of long-term administration of WT1 trio vaccination were estimated. RESULTS WT1-DTH positive cases were 12, WT1-IgG antibody positive were in 11. In most patients, WT1 -DTH positiveness coincided with that of WT1-IgG antibody. 9 of 11 cases showed stable disease at 3 months and transferred long-term administration of WT1 trio vaccination. Transfer rate in GBM and AA of long-term administration was 33% and 25%, respectively. Grade1 skin eruption was observed at the injection sites in 15 cases, but no significant adverse events related with vaccination were shown. CONCLUSION the safety and clinical efficacy of WT1 trio vaccination was verified for recurrent malignant gliomas. WT1-DTH and WT1-IgG antibody may be useful surrogate markers.

INTRODUCTION Preoperative magnetic resonance imaging (MRI) is a critical modality for the determination of glioblastoma (GBM) treatment strategy, as it is thought to reflect the biology of the tumor to some extent. The authors attempted to predict prognosis of newly diagnosed GBM (nGBM) using machine learning-based texture analysis of preoperative MRI in this study. METHOD A total of 160 nGBMs with determined overall survival were collected from Kansai Molecular Diagnosis Network for CNS tumors. Preoperative MRI scans (T1WI, T2WI, and Gd-T1WI) from all cases were semi-quantitatively analyzed leading to acquisition of 489 texture features as explanatory variables using Matlab-based in-house software. Dichotomous overall survival (OS) with a cutoff of 15 months was regarded as the response variable (short or long OS). Lasso regression was employed for feature selection to ensure robustness of the prediction model. One hundred patients were randomly assigned as training dataset (TR), followed by predictive model construction via 5-fold cross-validation. Subsequently, the constructed model was transferred to the remaining 60 patients, which was assigned as test dataset (TD). The survival distribution between populations with predicted short and long OS was compared using log-rank test. RESULTS Distributions of the analyzed data were as follows; 53 short OS cases in the TR (53.0%) and 27 cases in the TD (45.0%). As for the result of transfer analysis in TD, 38 cases out of 60 (63.3%) were predicted to be short OS (76.3 % of recall, 54.3% of precision, and 63.5% of F-measure). The population of predicted short OS significantly showed poorer prognosis (median OS 14.0 vs 19.1 months) (p=0.02, log-rank test). CONCLUSION Short OS was successfully identified from preoperative MRI with high recall rates with our algorithm. The presented result ensures the potential of machine learning-based texture analysis for prognostic stratification of nGBM.

Object Existing training methods for neuroendoscopic surgery have mainly emphasized the acquisition of anatomical knowledge and procedures for operating an endoscope and instruments. For laparoscopic surgery, various training systems have been developed to teach handling of an endoscope as well as the manipulation of instruments for speedy and precise endoscopic performance using both hands. In endoscopic endonasal surgery (EES), especially using a binostril approach to the skull base and intradural lesions, the learning of more meticulous manipulation of instruments is mandatory, and it may be necessary to develop another type of training method for acquiring psychomotor skills for EES. Authors of the present study developed an inexpensive, portable personal trainer using a webcam and objectively evaluated its utility. Methods Twenty-five neurosurgeons volunteered for this study and were divided into 2 groups, a novice group (19 neurosurgeons) and an experienced group (6 neurosurgeons). Before and after the exercises of set tasks with a webcam box trainer, the basic endoscopic skills of each participant were objectively assessed using the virtual reality simulator (LapSim) while executing 2 virtual tasks: grasping and instrument navigation. Scores for the following 11 performance variables were recorded: instrument time, instrument misses, instrument path length, and instrument angular path (all of which were measured in both hands), as well as tissue damage, max damage, and finally overall score. Instrument time was indicated as movement speed; instrument path length and instrument angular path as movement efficiency; and instrument misses, tissue damage, and max damage as movement precision. Results In the novice group, movement speed and efficiency were significantly improved after the training. In the experienced group, significant improvement was not shown in the majority of virtual tasks. Before the training, significantly greater movement speed and efficiency were demonstrated in the experienced group, but no difference in movement precision was shown between the 2 groups. After the training, no significant differences were shown between the 2 groups in the majority of the virtual tasks. Analysis revealed that the webcam trainer improved the basic skills of the novices, increasing movement speed and efficiency without sacrificing movement precision. Conclusions Novices using this unique webcam trainer showed improvement in psychomotor skills for EES. The authors believe that training in terms of basic endoscopic skills is meaningful and that the webcam training system can play a role in daily off-the-job training for EES.