Awake surgery for a deaf patient using sign language: A case report.

Background: Although awake surgery is the gold standard for resecting brain tumors in eloquent regions, patients with hearing impairment require special consideration during intraoperative tasks. Case Description: We present a case of awake surgery using sign language in a 45-year-old right-handed native male patient with hearing impairment and a neoplastic lesion in the left frontal lobe, pars triangularis (suspected to be a low-grade glioma). The patient primarily communicated through sign language and writing but was able to speak at a sufficiently audible level through childhood training. Although the patient remained asymptomatic, the tumors gradually grew in size. Awake surgery was performed for tumors resection. After the craniotomy, the patient was awake, and brain function mapping was performed using tasks such as counting, picture naming, and reading. A sign language-proficient nurse facilitated communication using sign language and the patient vocally responded. Intraoperative tasks proceeded smoothly without speech arrest or verbal comprehension difficulties during electrical stimulation of the tumor-adjacent areas. Gross total tumor resection was achieved, and the patient exhibited no apparent complications. Pathological examination revealed a World Health Organization grade II oligodendroglioma with an isocitrate dehydrogenase one mutant and 1p 19q codeletion. Conclusion: Since the patient in this case had no dysphonia due to training from childhood, the task was presented in sign language, and the patient responded vocally, which enabled a safe operation. Regarding awake surgery in patients with hearing impairment, safe tumor resection can be achieved by performing intraoperative tasks depending on the degree of hearing impairment and dysphonia.

Automated volumetry of meningiomas in contrast-enhanced T1-Weighted MRI using deep learning.

BACKGROUND: Meningiomas are among the most common intracranial tumors. In these tumors, volumetric assessment is not only important for planning therapeutic intervention but also for follow-up examination.However, a highly accurate automated volumetric method for meningiomas using single-modality magnetic resonance imaging (MRI) has not yet been reported. Here, we aimed to develop a deep learning-based automated volumetry method for meningiomas in MRI and investigate its accuracy and potential clinical applications. METHODS: For deep learning, we used MRI images of patients with meningioma who were referred to Osaka University Hospital between January 2007 and October 2020. Imaging data of eligible patients were divided into three non-overlapping groups: training, validation, and testing. The model was trained and tested using the leave-oneout cross-validation method. Dice index (DI) and root mean squared percentage error (RMSPE) were measured to evaluate the model accuracy. Result: A total of 178 patients (64.6 ± 12.3 years [standard deviation]; 147 women) were evaluated. Comparison of the deep learning model and manual segmentation revealed a mean DI of 0.923 ± 0.051 for tumor lesions. For total tumor volume, RMSPE was 9.5 ± 1.2%, and Mann-Whitney U test did not show a significant difference between manual and algorithm-based measurement of the tumor volume (p = 0.96). CONCLUSION: The automatic tumor volumetry algorithm developed in this study provides a potential volume-based imaging biomarker for tumor evaluation in the field of neuroradiological imaging, which will contribute to the optimization and personalization of treatment for central nervous system tumors in the near future.

Association of Plasma Claudin-5 with Age and Alzheimer Disease.

The blood-brain barrier (BBB) plays pivotal roles in synaptic and neuronal functioning by sealing the space between adjacent microvascular endothelial cells. BBB breakdown is present in patients with mild cognitive impairment (MCI) or Alzheimer disease (AD). Claudin-5 (CLDN-5) is a tetra-spanning protein essential for sealing the intercellular space between adjacent endothelial cells in the BBB. In this study, we developed a blood-based assay for CLDN-5 and investigated its diagnostic utility using 100 cognitively normal (control) subjects, 100 patients with MCI, and 100 patients with AD. Plasma CLDN-5 levels were increased in patients with AD (3.08 ng/mL) compared with controls (2.77 ng/mL). Plasma levels of phosphorylated tau (pTau181), a biomarker of pathological tau, were elevated in patients with MCI or AD (2.86 and 4.20 pg/mL, respectively) compared with control subjects (1.81 pg/mL). In patients with MCI or AD, plasma levels of CLDN-5-but not pTau181-decreased with age, suggesting some age-dependent BBB changes in MCI and AD. These findings suggest that plasma CLDN-5 may a potential biochemical marker for the diagnosis of AD.

Surgical resection of glioblastoma in basal ganglia and utility of exoscope: Technical case reports.

Background: Due to the presence of many perforating arteries and the deep location of basal ganglia tumors, dissection of the perforating arteries is critical during tumor resection. However, this is challenging as these arteries are deeply embedded in the cerebrum. Surgeons need to bend their heads for a long time using operative microscope and it is uncomfortable for the operating surgeon. A high-definition (4K-HD) 3D exoscope system can significantly improve the surgeon's posture during resection and widen the operating view field considerably by adjusting the camera angle. Methods: We report two cases of glioblastoma (GBM) involving basal ganglia. We used a 4K-HD 3D exoscope system for resecting the tumor and analyzed the intraoperative visualization of the operative fields. Results: We could approach the deeply located feeding arteries before successfully resecting the tumor using a 4K-HD 3D exoscope system which would have been difficult with the sole use of an operative microscope. The postoperative recoveries were uneventful in both cases. However, postoperative magnetic resonance imaging showed infarction around the caudate head and corona radiata in one of the cases. Conclusion: This study has highlighted using a 4K-HD 3D exoscope system in dissecting GBM involving basal ganglia. Although postoperative infarction is a risk, we could successfully visualize and dissect the tumors with minimal neurological deficits.

Identification of glioblastoma-specific antigens expressed in patient-derived tumor cells as candidate targets for chimeric antigen receptor T cell therapy.

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.

Growth risk classification and typical growth speed of convexity, parasagittal, and falx meningiomas: a retrospective cohort study.

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.

Cerebellopontine angle metastasis of a neuroendocrine tumor mimicking vestibular schwannoma: A case report.

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.

Modifying the blood-brain barrier by targeting claudin-5: Safety and risks.

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.

How Much Tumor Volume Is Responsible for Development of Clinical Symptoms in Patients With Convexity, Parasagittal, and Falx Meningiomas?

Purpose: Meningiomas are the most common primary intracranial neoplasms and clinical symptom appearance depends on their volume and location. This study aimed to identify factors that influence clinical symptoms and to determine a specific threshold tumor volume for the prediction of symptomatic progression in patients with convexity, parasagittal, and falx meningiomas. Materials and Methods: We retrospectively studied patients with radiologically suspected convexity, parasagittal, or falx meningiomas at our institution. Results: The data of three hundred thirty-three patients were analyzed. We further divided patients into two groups based on clinical symptoms: an asymptomatic group (250 cases) and a symptomatic group (83 cases). Univariate analysis revealed significant differences between the groups in terms of sex (p = 0.002), age at the time of volumetric analysis (p < 0.001), hyperintense lesions on T2-weighted images (p = 0.029), peritumoral edema (p < 0.001), maximum tumor diameter (p < 0.001), and tumor volume (p < 0.001). Further multivariate analysis revealed significant differences between the groups in terms of age at the time of volumetric analysis (p = 0.002), peritumoral edema (p < 0.001), and tumor volume (p < 0.001). The receiver operating characteristic curve revealed a threshold tumor volume of 21.1 ml for predicting whether a patient would develop symptoms (sensitivity 0.843, specificity 0.880, an area under the curve 0.919 [95% confidence interval: 0.887-0.951]). Conclusion: We identified factors predictive of clinical symptoms in patients with convexity, parasagittal, and falx meningiomas and determined the first-ever threshold tumor volume for predicting symptomatic progression in such patients.

Distinct difference in tumor-infiltrating immune cells between Wilms' tumor gene 1 peptide vaccine and anti-programmed cell death-1 antibody therapies.

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.

Safety and efficacy of an anti-claudin-5 monoclonal antibody to increase blood-brain barrier permeability for drug delivery to the brain in a non-human primate.

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.

Determination of brain tumor recurrence using 11 C-methionine positron emission tomography after radiotherapy.

We conducted a prospective multicenter trial to compare the usefulness of 11 C-methionine (MET) and 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for identifying tumor recurrence. Patients with clinically suspected tumor recurrence after radiotherapy underwent both 11 C-MET and 18 F-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 11 C-MET or 18 F-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 11 C-MET PET and 18 F-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 11 C-MET PET was significantly better than that of 18 F-FDG PET (87.5% vs. 69.6%, P = .033). No examination-related adverse events were observed. The results of the study demonstrated that 11 C-MET PET was superior to 18 F-FDG PET for discriminating between tumor recurrence and radiation-induced necrosis.

The Impact of 5-Year Tumor Doubling Time to Predict the Subsequent Long-Term Natural History of Asymptomatic Meningiomas.

OBJECTIVE: 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. METHODS: 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). RESULTS: 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 and <98.8 months (P < 0.001). 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. CONCLUSIONS: 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.

Successful neurosurgical separation of conjoined spinal cords in pygopagus twins: illustrative cases.

BACKGROUND: Conjoined 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. OBSERVATIONS: The 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. LESSONS: Pygopagus 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.

Overview of the Premarketing and Postmarketing Requirements for Drugs Granted Japanese Conditional Marketing Approval.

For drugs that are intended to fill unmet medical needs, such as the treatment of rare diseases or a subtype of cancer, it can take a long time to conduct confirmatory clinical trials due to limited patient availability. Delayed access to these drugs increases the risk of mortality of patients with these diseases. To address this issue, the Ministry of Health, Labour, and Welfare of Japan has decided to implement the Conditional Early Approval System with issuing the Ministry Notification in 2017. Drugs eligible for conditional early approval are those that are indicated for the treatment of a serious disease, have proven safety and efficacy, and cannot be examined easily by confirmatory clinical trials. When the benefit of immediate availability outweighs the risk of having less comprehensive data with which to confirm the clinical benefit of a product in the premarketing phase, products can be approved under the Conditional Early Approval System, accompanied by postmarketing regulatory requirements to manage postmarketing risks and, if needed, conduct postmarketing confirmatory clinical studies. Overview of the pre-approval and post-approval regulatory considerations will promote to more efficiently develop pharmaceutical products that fill unmet medical needs, leading to the prompt delivery of safe and effective drugs to patients who often have few therapeutic options available. As of March 2020, four drugs had been approved under the Conditional Early Approval System. In this review, we describe the premarketing and postmarketing requirements of these drugs and discuss the regulatory landscape around the Conditional Early Approval System.

The Roadmap to Approval under Japan's Two-Track Regulatory System: Comparing Six Regenerative Medical Products.

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.

Impact of Inversion Time for FLAIR Acquisition on the T2-FLAIR Mismatch Detectability for IDH-Mutant, Non-CODEL Astrocytomas.

The current research tested the hypothesis that inversion time (TI) shorter than 2,400 ms under 3T for FLAIR can improve the diagnostic accuracy of the T2-FLAIR mismatch sign for identifying IDHmt, non-CODEL astrocytomas. We prepared three different cohorts; 94 MRI from 76 IDHmt, non-CODEL Lower-grade gliomas (LrGGs), 33 MRI from 31 LrGG under the restriction of FLAIR being acquired with TI < 2,400 ms for 3T or 2,016 ms for 1.5T, and 112 MRI from 112 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. The T2-FLAIR mismatch sign was more frequently positive when TI was shorter than 2,400 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 and the area under the curve of ROC improved from 0.63 to 0.87 when FLAIR was acquired with shorter TI. We revealed that TI for FLAIR impacts the T2-FLAIR mismatch sign's diagnostic accuracy and that FLAIR scanned with TI < 2,400 ms in 3T is necessary for LrGG imaging.

Feasibility of Salvage Re-irradiation With Stereotactic Radiotherapy for Recurrent Glioma Using CyberKnife.

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.

Voxel-based lesion mapping of meningioma: a comprehensive lesion location mapping of 260 lesions.

OBJECTIVE In 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. METHODS Magnetic 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. RESULTS The 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. CONCLUSIONS Using 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.

Different spatial distributions of brain metastases from lung cancer by histological subtype and mutation status of epidermal growth factor receptor.

BACKGROUND: The purpose of this study was to test the hypothesis that the genetic backgrounds of lung cancers could affect the spatial distribution of brain metastases. METHODS: CT or MR images of 200 patients with a total of 1033 treatment-naive brain metastases from lung cancer were retrospectively reviewed (23 by CT and 177 by MRI). All images were standardized to the human brain MRI atlas provided by the Montreal Neurological Institute 152 database. Locations, depths from the brain surface, and sizes of the lesions after image standardization were analyzed. RESULTS: The posterior fossa, the anatomic "watershed areas," and the gray-white matter junction were confirmed to be more commonly affected by lung cancer brain metastases, and brain metastases with epidermal growth factor receptor (EGFR) L858R mutation occurred more often in the caudate, cerebellum, and temporal lobe than those with exon 19 deletion of EGFR. Median depths of the lesions from the brain surface were 13.7 mm (range, 8.6-21.9) for exon 19 deleted EGFR, 11.5 mm (6.6-16.8) for L858R mutated, and 15.0 mm (10.0-20.7) for wild-type EGFR. Lesions with L858R mutated EGFR were located significantly closer to the brain surface than lesions with exon 19 deleted or wild-type EGFR (P = .0032 and P < .0001, respectively). Furthermore, brain metastases of adenocarcinoma lung cancer patients with a history of chemotherapy but not molecular targeted therapy were located significantly deeper from the brain surface (P = .0002). CONCLUSION: This analysis is the first to reveal the relationship between EGFR mutation status and the spatial distribution of brain metastases of lung cancer.