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Background An open‐label single‐arm phase 2 study was conducted to evaluate the role of levetiracetam as a sensitizer of concurrent chemoradiotherapy (CCRT) for patients with newly diagnosed glioblastoma. This study aimed to determine the survival benefit of levetiracetam in conjunction with the standard treatment for glioblastoma. Methods Major eligibility requirements included histologically proven glioblastoma in the supratentorial region, patients 18 years or older, and Eastern Cooperative Oncology Group (ECOG) performance status of 0–2. Levetiracetam was given at 1,000–2,000 mg daily in two divided doses during CCRT and adjuvant chemotherapy thereafter. The primary and the secondary endpoints were 6‐month progression‐free survival (6mo‐PFS) and 24‐month overall survival (24mo‐OS), respectively. Outcomes of the study group were compared to those of an external control group. Results Between July 2016 and January 2019, 76 patients were enrolled, and 73 patients were included in the final analysis. The primary and secondary outcomes were improved in the study population compared to the external control (6mo‐PFS, 84.9% vs. 72.3%, p = 0.038; 24mo‐OS, 58.0% vs. 39.9%, p = 0.018), but the differences were less prominent in a propensity score‐matched analysis (6mo‐PFS, 88.0% vs. 76.9%, p = 0.071; 24mo‐OS, 57.1% vs. 38.8%, p = 0.054). In exploratory subgroup analyses, some results suggested that patients with ages under 65 years or unmethylated MGMT promoter might have a greater survival benefit from the use of levetiracetam. Conclusions The use of levetiracetam during CCRT in patients with newly diagnosed glioblastoma may result in improved outcomes, but further investigations are warranted., Patients aged less than 65 years exhibited better outcomes with levetiracetam. Patients with unmethylated MGMT promoter possibly have greater benefits from levetiracetam.

Rationale: Aberrant androgen receptor (AR) signaling via full-length AR (AR-FL) and constitutively active AR variant 7 (AR-V7) plays a key role in the development of castration-resistant prostate cancer (CRPC) and resistance to hormone therapies. Simultaneous targeting of AR-FL and AR-V7 may be a promising strategy to overcome resistance to hormone therapy. This study aimed to identify novel drug candidates co-targeting AR-FL and AR-V7 activities and elucidate their molecular mechanism of anti-CRPC activities. Methods: Using a CRPC cell-based reporter assay system, we screened a small library of antimalarial agents to explore the possibility of repositioning them for CRPC treatment and identified bruceantin (BCT) as a potent anti-CRPC drug candidate. A series of cell-based, molecular, biochemical, and in vivo approaches were performed to evaluate the therapeutic potential and molecular mechanism of BCT in CRPC. These approaches include reporter gene assays, cell proliferation, RNA-seq, qRT-PCR, mouse xenografts, co-immunoprecipitation, GST pull-down, immobilized BCT pull-down, molecular modeling, and bioinformatic analyses. Results: We identified BCT as a highly potent inhibitor co-targeting AR-FL and AR-V7 activity. BCT inhibits the transcriptional activity of AR-FL/AR-V7 and downregulates their target genes in CRPC cells. In addition, BCT efficiently suppresses tumor growth and metastasis of CRPC cells. Mechanistically, BCT disrupts the interaction of HSP90 with AR-FL/AR-V7 by directly binding to HSP90 and inhibits HSP90 chaperone function, leading to degradation of AR-FL/AR-V7 through the ubiquitin-proteasome system. Clinically, HSP90 expression is upregulated and correlated with AR/AR-V7 levels in CRPC. Conclusion: Our findings suggest that BCT could serve as a promising therapeutic candidate against CRPC and highlight the potential benefit of targeting AR-FL/AR-V7-HSP90 axis to overcome resistance caused by aberrant AR-FL/AR-V7 signaling.

Optogenetics is a powerful technique that allows target-specific spatiotemporal manipulation of neuronal activity for dissection of neural circuits and therapeutic interventions. Recent advances in wireless optogenetics technologies have enabled investigation of brain circuits in more natural conditions by releasing animals from tethered optical fibers. However, current wireless implants, which are largely based on battery-powered or battery-free designs, still limit the full potential of in vivo optogenetics in freely moving animals by requiring intermittent battery replacement or a special, bulky wireless power transfer system for continuous device operation, respectively. To address these limitations, here we present a wirelessly rechargeable, fully implantable, soft optoelectronic system that can be remotely and selectively controlled using a smartphone. Combining advantageous features of both battery-powered and battery-free designs, this device system enables seamless full implantation into animals, reliable ubiquitous operation, and intervention-free wireless charging, all of which are desired for chronic in vivo optogenetics. Successful demonstration of the unique capabilities of this device in freely behaving rats forecasts its broad and practical utilities in various neuroscience research and clinical applications., Although wireless optogenetic technologies enable brain circuit investigation in freely moving animals, existing devices have limited their full potential, requiring special power setups. Here, the authors report fully implantable optogenetic systems that allow intervention-free wireless charging and controls for operation in any environment.

OBJECTIVE. The existing literature lacks research into the benefits of initial screening imaging for patients with cerebellar hemangioblastoma. We aimed to evaluate the diagnostic yield of initial screening imaging using abdominal CT and whole-spine MRI in patients with cerebellar hemangioblastoma. MATERIALS AND METHODS. This retrospective study included 117 consecutive patients with histopathologically confirmed, newly diagnosed cerebellar hemangioblastomas at a single tertiary hospital between January 2006 and October 2018. Patients underwent contrast-enhanced abdominal CT, whole-spine MRI, or both to detect abdominal and spinal lesions of von Hippel-Lindau disease. Diagnostic yields and false referral rates for initial screening imaging were determined. RESULTS. After exclusion of six patients who forewent any initial imaging, 111 patients were included (53 men [mean age ± SD, 51 ± 13 years] and 58 women [mean age, 43 ± 16 years]). The diagnostic yield of abdominal CT was 3.8% (4 of 105; 95% CI, 1.1-9.3%), whereas the false referral rate was 1.0% (1 of 105; 95% CI, 0.0-5.2%). For whole-spine MRI, the corresponding values were 5.6% (4 of 71; 95% CI, 1.6-13.8%) and 2.8% (2 of 71; 95% CI, 0.3-9.8%), respectively. The respective diagnostic yields in patients with a single cerebellar hemangioblastoma were both 0% (0 of 98 and 66, respectively). CONCLUSION. For patients with a single cerebellar hemangioblastoma, screening examinations with abdominal CT and whole-spine MRI are unnecessary before the results of genetic testing are available.

Background Amide proton transfer (APT) MRI has the potential to demonstrate antitumor effects by reflecting biologically active tumor portion, providing different information from diffusion-weighted imaging (DWI) or dynamic susceptibility contrast (DSC) imaging. Purpose To evaluate whether a change in APT signal intensity after antiangiogenic treatment is predictive of early treatment response in recurrent glioblastoma. Materials and Methods In this retrospective study, APT MRI, DWI, and DSC imaging were performed in patients with recurrent glioblastoma from July 2015 to April 2019, both before treatment and 4-6 weeks after initiation of bevacizumab (follow-up). Progression was based on pathologic confirmation or clinical-radiologic assessment, and progression patterns were defined as local enhancing or diffuse nonenhancing. Changes in mean and histogram parameters (fifth and 95th percentiles) of APT signal intensity, apparent diffusion coefficient, and normalized cerebral blood volume (CBV) between imaging time points were calculated. Predictors of 12-month progression and progression-free survival (PFS) were determined by using logistic regression and Cox proportional hazard modeling and according to progression type. Results A total of 54 patients were included (median age, 56 years [interquartile range, 49-64 years]; 24 men). Mean APT signal intensity change after bevacizumab treatment indicated a low 12-month progression rate (odds ratio [OR], 0.36; 95% confidence interval [CI]: 0.13, 0.90

PurposeWe investigated the efficacy of temozolomide during and after radiotherapy in Korean adults with anaplastic gliomas without 1p/19q co-deletion.Materials and MethodsThis was a randomized, open-label, phase 2 study and notably the first multicenter trial for Korean grade III glioma patients. Eligible patients were aged 18 years or older and had newly diagnosed non-co-deleted anaplastic glioma with an Eastern Cooperative Oncology Group performance status of 0-2. Patients were randomized 1:1 to receive radiotherapy alone (60 Gy in 30 fractions of 2 Gy) (control group, n=44) or to receive radiotherapy with concurrent temozolomide (75 mg/m2/day) followed by adjuvant temozolomide (150-200 mg/m2/day for 5 days during six 28-day cycles) (treatment group, n=40). The primary end-point was 2-year progression-free survival (PFS). Seventy patients (83.3%) were available for the analysis of the isocitrate dehydrogenase 1 gene (IDH1) mutation status.ResultsThe two-year PFS was 42.2% in the treatment group and 37.2% in the control group. Overall survival (OS) did not reach to significant difference between the groups. In multivariable analysis, age was a significant risk factor for PFS (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.04 to 4.16). The IDH1 mutation was the only significant prognostic factor for PFS (HR, 0.28; 95% CI, 0.13 to 0.59) and OS (HR, 0.19; 95% CI, 0.07 to 0.50). Adverse events over grade 3 were seen in 16 patients (40.0%) in the treatment group and were reversible.ConclusionConcurrent and adjuvant temozolomide in Korean adults with newly diagnosed non-co- deleted anaplastic gliomas showed improved 2-year PFS. The survival benefit of this regimen needs further analysis with long-term follow-up at least more than 10 years.

We aimed to develop and validate a multiparametric MR radiomics model using conventional, diffusion-, and perfusion-weighted MR imaging for better prognostication in patients with newly diagnosed glioblastoma. A total of 216 patients with newly diagnosed glioblastoma were enrolled from two tertiary medical centers and divided into training (n = 158) and external validation sets (n = 58). Radiomic features were extracted from contrast-enhanced T1-weighted imaging, fluid-attenuated inversion recovery, diffusion-weighted imaging, and dynamic susceptibility contrast imaging. After radiomic feature selection using LASSO regression, an individualized radiomic score was calculated. A multiparametric MR prognostic model was built using the radiomic score and clinical predictors. The results showed that the multiparametric MR prognostic model (radiomics score + clinical predictors) exhibited good discrimination (C-index, 0.74) and performed better than a conventional MR radiomics model (C-index, 0.65, P P

Background: To analysis the role of gamma knife radiosurgery (GKRS) in treatment of the recurrent or residual World Health Organization (WHO) grade II and III meningiomas.Methods: Between 1995 and ...

Tumor treating fields (TTFields) are anti-mitotic, non-invasive loco-regional cancer therapy comprising low intensity, intermediate frequency alternating electric fields. TTFields plus Temozolomide (TTFields/TMZ) extended survival versus TMZ alone in newly diagnosed glioblastoma (GBM) patients in the EF-14 trial. We report on Korean newly diagnosed GBM patients who participated in the EF-14 trial. Thirty-nine participants of the EF-14 trial were enrolled at 8 sites in South Korea. Patients (24 TTFields/TMZ; 14 TMZ alone) received: TTFields (200 kHz) for > 18 h/day; TMZ at 120–150 mg for 5 days per a 28 day cycle. Safety and efficacy were assessed. Patient baseline characteristics were balanced in the 2 arms and the mean age was 52.1 years, 66.7% were male with a mean KPS of 90. Safety incidence was comparable between the 2 arms. In the TTFields/TMZ arm, 30% suffered from skin irritation versus 52% in the entire study population. No TTFields-related serious adverse events were reported. The median progression-free survival (PFS) in the TTFields/TMZ arm was 6.2 months (95% CI 4.2–12.2) versus 4.2 (95% CI 1.9–11.2) with TMZ alone (p = 0.67). Median overall survival was 27.2 months (95% CI 21-NA) with TTFields/TMZ versus 15.2 months (95% CI 7.5–24.1; HR 0.27, p = 0.01) with TMZ alone. Median OS and 1- and 2-year survival rates were higher with TTFields/TMZ and similar to the entire EF-14 population. About 30% of patients reported skin irritation, a lower rate than seen in the entire EF-14 population. These results demonstrate the efficacy and safety of TTFields in Korean newly diagnosed glioblastoma patients. Clinicaltrials.gov Identifier: NCT00916409.

The fate of residual tumor after salvage surgery for recurrent vestibular schwannoma (VS) after radiosurgery has not been elucidated so far. We reviewed our surgical series of salvage surgery for recurrent VS, with focus on the natural history of the residual tumor after salvage surgery.This study enrolled 14 patients who underwent salvage surgical resection in our institute and were followed up for12 months.The study included 3 men and 11 women with a median age of 55 years (range: 16-70 years). The median pre-stereotactic radiosurgery tumor volume was 6591 mmThe behavior of residual tumors after salvage surgery for irradiated VS was stable. Adjuvant treatment for these residual tumors may not be necessary.

Background A rosette-forming glioneuronal tumor (RGNT), a rare brain tumor, presents as a benign feature with a favorable outcome. To date, a few cases with aggressive behaviors, such as recurrence or dissemination, but none with malignant transformation, have been reported. We describe 1 case that recurred as glioblastoma after complete resection of the benign RGNT. Case Description A man aged 58 years presented with headache and dizziness without neurologic symptoms. Magnetic resonance imaging showed a 4 × 2.5 cm, well-demarcated mass in the left cerebellar hemisphere. The patient underwent gross total resection of the tumor and a diagnosis of RGNT was made. There was no evidence of recurrence on serial follow-up. However, a recurrent heterogeneous enhancing mass in the previous surgical cavity was observed on a 7-year postoperative magnetic resonance imaging scan. Reoperation was performed and a histopathological study revealed a glioblastoma. Conclusions To the best of our knowledge, this is the first case of spontaneous malignant transformation of an RGNT. Our case may be helpful in better understanding the biological behavior and clinical outcome of RGNT. We emphasize the malignant potential of this rare tumor and the necessity of future large-scaled research for most appropriate therapeutic strategies.

Objective The association of primary brain tumors with coexisting unruptured intracranial aneurysms (UIAs) has been debated, and treatment strategies have not yet been established. We evaluated the flow association between brain tumors and coexisting UIAs and the outcomes of patients with brain tumor who did not receive treatment of coexisting UIAs. Methods The medical records of patients with coexisting UIAs and brain tumors who had undergone surgical tumor resection were retrospectively analyzed to evaluate the incidence of UIAs according to tumor type, association of arterial feeder vessels and coexisting UIAs, and the occurrence of subarachnoid hemorrhage during the follow-up period for patients who had not receive treatment for the UIAs. Results Of the 55 patients, 21 (38.9%) had undergone treatment of UIAs and 33 (61.1%) had received regular follow-up examinations without UIA treatment. Two patients (6.1%) developed subarachnoid hemorrhage. Of the 33 patients with astrocytic or oligodendroglial tumors who had not undergone treatment of UIAs, 2 had experienced an interval increase. Flow-related UIAs were found to be significantly more common in patients with astrocytic or oligodendroglial tumors than in those with tumors of other histological types (P = 0.01). Conclusions The incidence of UIAs among patients with primary brain tumors appears to be greater than that in the general population. An interval increase in aneurysm size and aneurysmal rupture was observed in 2 patients with astrocytic or oligodendroglial tumors. We would recommend perioperative treatment of flow-related UIAs in patients with astrocytic or oligodendroglial tumors and noninvasive evaluations such as magnetic resonance angiography if coexisting UIAs remain untreated.

The growth rate and natural history of untreated hemangioblastomas remain unclear. This study investigated the natural history of untreated intracranial hemangioblastomas and predictors of tumor growth using volumetric assessment. This study retrospectively enrolled 31 patients with untreated hemangioblastomas between 2004 and 2017 who were followed up for at least 12 months. The 31 patients had a total of 52 hemangioblastomas. The 31 patients included 11 (35.5%) men and 20 (64.5%) women, of mean age 42.5 years. Seventeen (54.8%) patients were genetically diagnosed with Von Hippel-Lindau (VHL) disease. Of the 52 lesions, 33 (63.5%) grew during the follow-up period, whereas 19 (36.5%) remained stable. Overall mean actual growth rate (AGR) was 1.94 cm3/year, 2.38 cm3/year in the VHL and 1.79 cm3/year in the non-VHL group (p = 0.31). Overall mean relative growth rate (RGR) was 21%/year, 26%/year in the VHL and 19%/year in the non-VHL group. Time to 50% treatment probability was 34 months. The 1, 3, 5, and 7-year treatment probabilities were 11.5%, 50.1%, 52.7%, and 73%, respectively. The presence of only symptomatic lesions was significantly predictive of the growth of intracranial hemangioblastoma (odds ratio: 5.0, p = 0.02). The overall growth rate of intracranial hemangioblastoma was faster than that of other benign intracranial tumors, with symptomatic lesions being the only meaningful predictor of tumor growth. Because of their rapid growth rate and high probability of treatment, a wait and scan management strategy should be carefully applied to intracranial hemangioblastomas.

Primary central nervous system lymphoma (PCNSL) is a rare extranodal non-Hodgkin lymphoma for which standard treatment has yet to be established. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a suitable consolidation strategy for patients who respond to induction chemotherapy. The purpose of this study was to compare the outcome and toxicity profile of the combination of busulfan, cyclophosphamide, and etoposide (BuCyE) with that of the combination of thiotepa, busulfan, and cyclophosphamide (TBC) as conditioning regimens of upfront ASCT for consolidation therapy in PCNSL. The PCNSL registry data set, prospectively collected from March 1993 to May 2017 at Asan Medical Center, was reviewed retrospectively. Patients with objective response to induction chemotherapy who received BuCyE or TBC as conditioning regimen for ASCT were included in the analysis. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Among 241 patients with a diagnosis of PCNSL, 53 received ASCT as upfront consolidation therapy with TBC (28 patients) or BuCyE (25 patients) as conditioning regimen. No median OS or PFS was reached in the TBC group, while the BuCyE group reached a median OS of 4.9 years (p = 0.02) and median PFS of 1.1 years (p = 0.007). The incidence of oral mucositis, nausea, and vomiting was higher with TBC than BuCyE. The median admission duration and days to engraftment were similar between the two groups. Despite the greater incidence of adverse events, TBC showed better outcomes than BuCyE in terms of survival.

A novel psychoactive substance, α-pyrrolidinopentiothiophenone (α-PVT), is a structural analog to amphetamine. Recently, it has been shown that α-PVT has an abuse potential similar to psychomotor stimulants like cocaine or amphetamine. However, it has not been performed yet to determine whether α-PVT develops behavioral sensitization, a well-known phenomenon for psychomotor stimulants. In the present study, rats were first pre-exposed to either saline or α-PVT (20 mg/kg, IP) with a total of four injections in every 2–3 days of interval. Then, 2-weeks after withdrawal, locomotor activity was measured with a challenge dose (10 mg/kg, IP) of α-PVT and the nucleus accumbens core region was taken out. Similar to psychomotor stimulants, repeated administration of α-PVT produced locomotor sensitization. Further, the phosphorylation levels of GSK3β in the nucleus accumbens core were found to be decreased only in rats with sensitization developed, but not in those with acute or non-sensitized. Correlation analysis revealed that the phosphorylation levels of GSK3β have a strong negative correlation with locomotor activity only in rats with α-PVT pre-exposed, but not in those with its acute injection. These results suggest that a certain level of change in the phosphorylation levels of GSK3β in the nucleus accumbens core may involve in mediating the expression of locomotor sensitization by repeated injection of α-PVT in rats.

Gross total resection for glioblastoma (GBM) has been associated with better prognosis. However, it is not always feasible, and the threshold for the extent of resection required for better prognosis has been controversial. Therefore, we compared the survival and clinical outcomes of patients with GBM who had undergone partial resection (PR) or biopsy.Of the 110 patients, 32 and 78, who had undergone PR and biopsy, respectively, were enrolled to identify any differences in clinical outcomes. No differences were found in patient demographics between the 2 groups, except for tumor location and mean tumor volume (P = 0.02 and P0.01, respectively). Propensity score matching between the PR and biopsy groups was performed, in which 20 patients each in the PR and biopsy groups were matched.The overall survival (OS) and progression-free survival (PFS) did not differ significantly between the PR and biopsy groups (P = 0.84 and P = 0.48, respectively). After propensity score matching, the differences in OS and PFS between the 2 groups were still not statistically significant (P = 0.51 and P = 0.75, respectively). The hazard ratios for OS and PFS for the PR group compared with biopsy were 0.98 and 0.73, respectively; however, the difference was not statistically significant (P = 0.96 and P = 0.39, respectively). The surgical complication rate was greater in the PR group (14 of 32; 43.7%) than in the biopsy group (9 of 78; 11.5%; P0.01).PR failed to improve survival compared with biopsy for patients with GBM. Moreover, the surgical complication rate in the PR group was greater than that in the biopsy group.

Many cognitive processes require communication between the neocortex and the hippocampus. However, coordination between large-scale cortical dynamics and hippocampal activity is not well understood, partially due to the difficulty in simultaneously recording from those regions. In the present study, we developed a flexible, insertable and transparent microelectrode array (Neuro-FITM) that enables investigation of cortical-hippocampal coordinations during hippocampal sharp-wave ripples (SWRs). Flexibility and transparency of Neuro-FITM allow simultaneous recordings of local field potentials and neural spiking from the hippocampus during wide-field calcium imaging. These experiments revealed that diverse cortical activity patterns accompanied SWRs and, in most cases, cortical activation preceded hippocampal SWRs. We demonstrated that, during SWRs, different hippocampal neural population activity was associated with distinct cortical activity patterns. These results suggest that hippocampus and large-scale cortical activity interact in a selective and diverse manner during SWRs underlying various cognitive functions. Our technology can be broadly applied to comprehensive investigations of interactions between the cortex and other subcortical structures.

Background Updated response assessment in neuro-oncology (RANO) does not consider peritumoral non-enhancing lesion (NEL) and baseline (residual) contrast enhancement (CE) volume. The objective of this study is to explore helpful imaging characteristics to refine RANO for assessing early treatment response (pseudoprogression and time-to-progression [TTP]) in patients with IDH wild-type glioblastoma. Methods This retrospective study enrolled 86 patients with IDH wild-type glioblastoma who underwent consecutive MRI examinations before and after concurrent chemoradiotherapy (CCRT). NEL was classified as edema- or tumor-dominant type on pre-CCRT MRI. CE evolution was categorized into 4 patterns based on post-operative residual CE (measurable vs. non-measurable) and CE volume change (same criteria with RANO) during CCRT. Multivariable logistic regression, including clinical parameters, NEL type, and CE evolution pattern, was used to analyze pseudoprogression rate. TTP and OS according to NEL type and CE evolution pattern was analyzed by the Kaplan–Meier method. Results Pseudoprogression rate was significantly lower (chi-square test, P = .047) and TTP was significantly shorter (hazard ratio [HR] = 2.03, P = .005) for tumor-dominant type than edema-dominant type of NEL. NEL type was the only predictive marker of pseudoprogression on multivariate analysis (odds ratio = 0.26, P = .046). Among CE evolution patterns, TTP and OS was shortest in patients with residual CE compared with those exhibiting new CE (HR = 4.33, P P = .009, respectively). In edema-dominant NEL type, both TTP and OS was stratified by CE evolution pattern (log-rank, P = .001), whereas it was not in tumor-dominant NEL. Conclusions NEL type improves prediction of pseudoprogression and, together with CE evolution pattern, further stratifies TTP and OS in patients with IDH wild-type glioblastoma and may become a helpful biomarker for refining RANO.

Histologic grade has important implications for the management in meningioma. It is important to understand the risk of high-grade meningioma (grades II and III). In this article, we systematically reviewed the histologic grade of meningioma depending on the location and sex and its relationship with recurrence.The PubMed and Embase databases were systematically searched until February 4, 2020. We included studies that were not restricted to specific anatomic locations, histologic grade, or the sizes of the tumors. The proportion of high-grade meningiomas depending on the location and sex and the odds ratio (OR) of recurrence were pooled using a random-effects model.Outcome data were analyzed for 20,336 tumors from 34 studies. We found different proportions of high-grade meningiomas in the brain (12.8%) (95% confidence interval [CI], 10.5%-15.1%) versus the spine (2.4%) (95% CI, 1.0%-3.7%) (P0.01). Skull base meningiomas (8.7%) (95% CI, 5.8%-11.6%) had a lower proportion of high-grade meningiomas than non-skull base meningiomas (16.5%) (95% CI, 11.9%-21.1%) (P0.01). In addition, high-grade meningiomas were more likely to occur in male patients (18.0%) (95% CI, 10.1%-25.9%) than female patients (7.0%) (95% CI, 3.5%-10.6%) (P = 0.01). Higher rates of recurrence (OR = 13.83) were confirmed for high-grade meningiomas than grade I meningiomas (95% CI, 4.10-46.65) (P0.01).This meta-analysis found that intracranial, nonskull base, and male sex are risk factors for high-grade meningioma, and high-grade meningioma had a much higher recurrence rate as compared with grade I meningioma.

As per the 2016 World Health Organization (WHO) guidelines on the classification of central nervous system tumors, solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) constitute a single disease entity, known as SFT/HPC. This study provides a clinical analysis of these tumors and describes the treatment outcomes of SFT/HPCs. This retrospective study included 76 patients with histopathologically proven SFT/HPC. Reclassification according to the 2016 WHO guideline was done for patients who were diagnosed with SFT or HPC based on the 2007 WHO classification. Recurrence-free survival (RFS) and overall survival (OS) were evaluated for all patients and subgroups. The median follow-up period was 77.9 months. The median RFS and OS were 126.5 and 136.8 months, respectively. The 1-, 5-, 10-, and 15-year RFS rates were 93%, 72%, 40%, and 40%, respectively. The 1-, 5-, 10- and 15-year OS rates were 97%, 89%, 54%, and 35%, respectively. In multivariable analyses, stereotactic radiosurgery (SRS; p = 0.009, hazard ratio [HR] 6.986), female sex (p = 0.023, HR 1.76), and age over 45 (p = 0.037, HR 2.74) were associated with shorter RFS. Patients who underwent SRS as initial treatment had a shorter OS than that of patients who underwent primary resection (p

We aimed to develop multiparametric physiologic MRI-based spatial habitats and to evaluate whether temporal changes in these habitats help to distinguish tumor progression from treatment-related change in post-treatment glioblastoma. This retrospective, single-institution study included patients with glioblastoma treated by concurrent chemoradiotherapy who had newly developed or enlarging, measurable contrast-enhancing mass. Contrast-enhancing mass was divided into three spatial habitats by K-means clustering of voxel-wise ADC and CBV values. Temporal changes of these habitats between two consecutive examinations prior to the diagnosis of tumor progression or treatment-related change were assessed. Predictors were selected using logistic regression and the performance was measured with an area under the receiver operating characteristics curve (AUC). Spatiotemporal habitats were further analyzed for correlation with the site of tumor progression. There were 75 patients (mean, 58 years; range, 26−81 years; 43 men) with 48 cases of tumor progression and 39 cases of treatment-related change including 12 patient overlaps at different time points. Three spatial habitats of hypervascular cellular, hypovascular cellular, and nonviable tissue were identified. Increase in the hypervascular cellular (OR 4.55, p = .002) and hypovascular cellular habitat (OR 1.22, p < .001) was predictive of tumor progression. Combination of spatiotemporal habitats yielded a high diagnostic performance with an AUC of 0.89 (95% CI, 0.87–0.92). An increase in hypovascular cellular habitat predicted the site of tumor progression in 84% [21/25] of cases with tumor progression. Temporal changes in spatial habitats derived from multiparametric physiologic MRI provided diagnostic value in distinguishing tumor progression from treatment-related change and predicted site of tumor progression in post-treatment glioblastoma. • In post-treatment glioblastoma, three spatial habitats of hypervascular cellular, hypovascular cellular, and nonviable tissue were identified, and an increase in the hypervascular cellular (OR 4.55, p = .002) and hypovascular cellular habitat (OR 1.22, p < .001) was predictive of tumor progression. • Combination of spatiotemporal habitats yielded a high diagnostic performance with an AUC of 0.89 (95% CI, 0.87–0.92). • An increase in hypovascular cellular habitat predicted the site of tumor progression in 84% (21/25) of cases with tumor progression.

The aim of this study was to evaluate prognostic factors including surgical, radiographic, and histopathologic analyses in anaplastic oligodendroglioma (AO) patients. We reviewed the electronic records of 95 patients who underwent surgery and were diagnosed with AO for 20 years. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Univariate and multivariable analyses included clinical, histopathological, and radiographic prognostic factors. Subgroup analysis was performed in isocitrate dehydrogenase (IDH1/2)-mutant and 1p/19q-codeleted patients. The median PFS and OS were 24.7 months and 50.8 months, respectively. The 1-, 3-, 5-, and 10-year PFS were 75.8%, 42.9%, 32.4%, and 16.4%, respectively. Furthermore, the 1-, 3-, 5-, and 10-year OS were 98.9%, 76.9%, 42.9%, and 29.7%, respectively. The median PFS and OS of the IDH1/2-mutant and 1p/19q-codeleted patients were 54.2 and 57.8 months, respectively. In univariate analyses, young age, frontal lobe, weak enhancement, gross total resection (GTR), low Ki-67 index, 1p/19q codeletion, and IDH1/2 mutations were associated with a favorable outcome. In multivariable analyses, IDH1/2 mutation was related to better PFS and OS. In subgroup analysis, GTR was associated with favorable outcomes.

Purpose: Heterogeneity in glioblastomas is associated with poorer outcomes, and physiologic heterogeneity can be quantified with noninvasive imaging. We developed spatial habitats based on multiparametric physiologic MRI and evaluated associations between temporal changes in these habitats and progression-free survival (PFS) after concurrent chemoradiotherapy (CCRT) in patients with glioblastoma. Experimental Design: Ninety-seven patients with isocitrate dehydrogenase (IDH)-wildtype glioblastoma were enrolled and two serial MRI examinations after CCRT were analyzed. Cerebral blood volumes and apparent diffusion coefficients were grouped using k-means clustering into three spatial habitats. Associations between temporal changes in spatial habitats and PFS were investigated using Cox proportional hazard modeling. The performance of significant predictors for PFS and overall survival (OS) was measured using a discrete increase of habitat (habitat risk score) in a temporal validation set from a prospective registry (n = 53, ClinicalTrials.gov NCT02619890). The site of progression was matched with the spatiotemporal habitats. Results: Three spatial habitats of hypervascular cellular, hypovascular cellular, and nonviable tissue were identified. A short-term increase in the hypervascular cellular habitat (HR, 40.0; P = 0.001) and hypovascular cellular habitat was significantly associated with shorter PFS (HR, 3.78; P < 0.001) after CCRT. Combined with clinical predictors, the habitat risk score showed a C-index of 0.79 for PFS and 0.74 for OS and stratified patients with short, intermediate, and long PFS (P = 0.016). An increase in the hypovascular cellular habitat predicted tumor progression sites. Conclusions: Hypovascular cellular habitats derived from multiparametric physiologic MRIs may be useful predictors of clinical outcomes in patients with posttreatment glioblastoma.

Proteolysis-targeting chimera (PROTAC)-mediated protein degradation is a rapidly emerging therapeutic intervention that induces the degradation of targeted proteins. Herein, we report the design and biological evaluation of a series of androgen receptor (AR) PROTAC degraders for the treatment of metastatic castration-resistant prostate cancer. Predominantly, instead of thalidomide, we utilized the TD-106 scaffold, a novel cereblon (CRBN) binder that was identified in our previous study. Our results suggest that the linker position in the TD-106 CRBN binder is critical for the efficiency of AR degradation. The compounds attached to the 6-position of TD-106 promoted better degradation of AR than those at the 5- and 7-positions. Among the synthesized AR PROTACs, the representative degrader 33c (TD-802) effectively induced AR protein degradation, with a degradation concentration 50% of 12.5 nM and a maximum degradation of 93% in LNCaP prostate cancer cells. Additionally, most AR PROTAC degraders, including TD-802, displayed good liver microsomal stability and in vivo pharmacokinetic properties. Finally, we showed that TD-802 effectively inhibited tumor growth in an in vivo xenograft study.

Although stereotactic radiosurgery (SRS) has been proven to be effective and safe for treating intracranial meningiomas, concerns have been raised about the use of SRS for large-sized tumors involving the skull base that frequently encroach onto adjacent critical neural structures. The purpose of this study was to investigate the role of hypofractionated SRS as a therapeutic option for large-sized skull base meningiomas. Thirty-one consecutive patients (median age: 55 years, 9 men and 22 women) who had been treated with hypofractionated SRS using CyberKnife for large-sized skull base meningiomas (> 10 cm3 in volume, median of 18.9 cm3, range 11.6–58.2 cm3) were enrolled. All patients harbored middle or posterior skull base tumors, most frequently of cavernous sinus (n = 7, 22.6%), petroclival (n = 6, 19.4%), or tentorial edge (n = 6, 19.4%) locations. SRS was delivered in five daily fractions (range 3–5 fractions) with a median cumulative dose of 27.8 Gy (range 22.6–27.8 Gy). With a median follow-up of 57 months (range 9–98 months), tumor control was achieved for 28 (90.3%) of 31 patients. Treatment response on MRI included partial response (volume decrease > 20%) in 17 (54.8%) patients, stable in 11 (35.5%), and progression (volume increase > 20%) in 3 (9.7%). Of 21 patients with cranial neuropathy, 20 (95.2%) showed improved neurological status. Our current results suggest a promising role of hypofractionated SRS for large-sized skull base megningiomas in terms of tumor control and neurological outcomes. It is a reasonable therapeutic option for select patients.

Objective Although they are generally slow-growing benign tumors, meningiomas may recur after surgery with transformation into atypical meningiomas. The purpose of this study was to investigate the radiological and histopathological factors that predict the risk of tumor progression from a benign to an atypical meningioma. Patients and Methods All patients treated for recurrent meningiomas in whom the tumor showed histopathologically confirmed high-grade transformation (HGT) from a benign to an atypical meningioma between 2001 and 2017 were included. To evaluate the predictors of transformation, patient medical records documenting the diagnosis of a benign meningioma at the first surgery prior to second surgery with HGT were reviewed. Each patient was matched with four age- and sex-matched controls who were treated for a benign meningioma. The control group comprised all patients without any recurrence for at least 60 months. Results Fourteen patients with benign meningioma underwent HGT and were included. The median time interval of transformation was 63 months (range, 19–132 months). Multivariate analysis indicated that an increased mitotic index (odds ratio [OR], 10.409; 95 % confidence interval [CI], 1.297–83.549; P = 0.027) was a significant predictor of transformation. Prominent peritumoral edema (OR, 33.822; 95 % CI, 0.935–223.688; P = 0.054) did not reach the statistical significance. Conclusion An increased mitotic index may be used as the predictor for HGT of benign meningiomas. Although these tumors with a high risk for transformation do not meet the diagnostic criteria for atypical meningiomas, they may require more attentive observation and management than other benign meningiomas.

Ependymomas are biologically and clinically heterogeneous tumors of the central nervous system that have variable clinical outcomes. The status of the tumor immune microenvironment in ependymoma remains unclear. Immune cell subsets and programmed death ligand 1 (PD-L1) expression were measured in 178 classical ependymoma cases by immunohistochemistry using monoclonal antibodies that recognized tumor-infiltrating lymphocyte subsets (TILs; CD3, CD4, CD8, FOXP3, and CD20), tumor-associated macrophages (TAMs; CD68, CD163, AIF1), indoleamine 2,3-dioxygenase (IDO)+ cells and PD-L1-expressing tumor cells. Increases in CD3+ and CD8+ cell numbers were associated with a prolonged PFS. In contrast, increased numbers of FOXP3+ and CD68+ cells and a ratio of CD163/AIF1+ cells were significantly associated with a shorter PFS. An increase in the IDO+ cell number was associated with a significantly longer PFS. To consider the quantities of TILs, TAMs, and IDO+ cells together, the cases were clustered into 2 immune cell subgroups using a k-means clustering analysis. Immune cell subgroup A, which was defined by high CD3+, low CD68+ and high IDO+ cell counts, predicted a favorable PFS compared to subgroup B by univariate and multivariate analyses. We found six ependymoma cases expressing PD-L1. All these cases were supratentorial ependymoma, RELA fusion-positive (ST-RELA). PD-L1 expression showed no prognostic significance. This study showed that the analysis of tumor-infiltrating immune cells could aid in predicting the prognosis of ependymoma patients and in determining therapeutic strategies to target the tumor microenvironment. PD-L1 expression in the ST-RELA subgroup suggests that this marker has a potential added value for future immunotherapy treatments.

Background. Chronic low back pain (CLBP) arising from degenerative disc disease continues to be a challenging clinical and diagnostic problem whether treated with nonsurgical, pain intervention, or motion-preserving stabilization and arthrodesis. Methods. Fourteen patients with CLBP, greater than 6 months, unresponsive to at least 4 months of conservative care were enrolled. All patients were treated successfully following screening using MRI findings of Modic type I or II changes and positive confirmatory provocative discography to determine the affected levels. All patients underwent ablation of the basivertebral nerve (BVN) using 1414 nm Nd:YAG laser-assisted energy guided in a transforaminal epiduroscopic approach. Macnab’s criteria and visual analog scale (VAS) score were collected retrospectively at each follow-up interval. Results. The mean age was 46 ± 9.95 years. The mean symptoms duration was 21.21 ± 21.87 months. The mean follow-up was 15.3 ± 2.67 months. The preoperative VAS score of 7.79 ± 0.97 changed to 1.92 ± 1.38, postoperatively (P<0.01). As per Macnab’s criteria, seven patients (50%) had excellent, six patients (42.85%) had good, and one patient (7.14%) had fair outcomes. Conclusion. The transforaminal epiduroscopic basivertebral nerve laser ablation (TEBLA) appears to be a promising option in carefully selected patients with CLBP associated with the Modic changes.

BACKGROUND: Pseudoprogression is a diagnostic challenge in early posttreatment glioblastoma. We therefore developed and validated a radiomics model using multiparametric MRI to differentiate pseudoprogression from early tumor progression in patients with glioblastoma. METHODS: The model was developed from the enlarging contrast-enhancing portions of 61 glioblastomas within 3 months after standard treatment with 6472 radiomic features being obtained from contrast-enhanced T1-weighted imaging, fluid-attenuated inversion recovery imaging, and apparent diffusion coefficient (ADC) and cerebral blood volume (CBV) maps. Imaging features were selected using a LASSO (least absolute shrinkage and selection operator) logistic regression model with 10-fold cross-validation. Diagnostic performance for pseudoprogression was compared with that for single parameters (mean and minimum ADC and mean and maximum CBV) and single imaging radiomics models using the area under the receiver operating characteristics curve (AUC). The model was validated with an external cohort (n = 34) imaged on a different scanner and internal prospective registry data (n = 23). RESULTS: Twelve significant radiomic features (3 from conventional, 2 from diffusion, and 7 from perfusion MRI) were selected for model construction. The multiparametric radiomics model (AUC, 0.90) showed significantly better performance than any single ADC or CBV parameter (AUC, 0.57–0.79, P < 0.05), and better than a single radiomics model using conventional MRI (AUC, 0.76, P = 0.012), ADC (AUC, 0.78, P = 0.014), or CBV (AUC, 0.80, P = 0.43). The multiparametric radiomics showed higher performance in the external validation (AUC, 0.85) and internal validation (AUC, 0.96) than any single approach, thus demonstrating robustness. CONCLUSIONS: Incorporating diffusion- and perfusion-weighted MRI into a radiomics model improved diagnostic performance for identifying pseudoprogression and showed robustness in a multicenter setting.

Background Pleomorphic xanthoastrocytoma (PXA) is a very rare glial neoplasm. The clinical behavior of PXA is not uniform, and the purpose of this study was to investigate the clinical characteristics of adult PXA and identify prognostic factors. Methods Twenty-five patients aged 18 years or older who were diagnosed with PXA between 2002 and 2016 were analyzed. Results Twenty-one patients (84%) had PXA World Health Organization (WHO) grade II and 4 patients (16%) had anaplastic PXA (WHO grade III). The median overall survival of PXA WHO grade II and III was 97 and 56 months, respectively. The 3-year progression-free survival of PXA WHO grade II and III was 65.1% and 50%, respectively (P = 0.37 and 0.21). Diffusion-weighted imaging, perfusion-weighted imaging, and positron emission tomography findings failed to predict the histologic grade of PXA and recurrence of PXA WHO grade II. Tumor size >40 mm and presence of evident peritumoral edema (ePTE) were prognostic factors for poor progression-free survival (hazard ratios, 4.4 and 15.2, respectively; P = 0.03 and 0.01) according to a univariate analysis. In the recurrent and silent PXA grade II groups, ePTE was present in 87.5% and 23.1% of cases, respectively (P Conclusions The clinical and radiologic features of PXA are not uniform. Tumor size and ePTE are possible prognostic factors for adult PXA. Also, peritumoral edema may be associated with recurrence in PXA WHO grade II. PXA showed a high recurrence rate, and thus close follow-up is needed.

Objective Pituitary apoplexy can cause severe neuro-ophthalmologic or endocrinologic sequelae, requiring timely treatment. The present study was performed to evaluate postoperative neurologic outcomes and to identify their risk factors in patients who underwent transsphenoidal surgery for pituitary apoplexy. Methods Forty-one consecutive patients with pituitary apoplexy who underwent transsphenoidal surgery were reviewed retrospectively. The initial rates of visual acuity (VA) decrease, visual field (VF) defect, and ocular palsy were 34.1%, 46.3%, and 68.3%, respectively. The median maximal diameter and tumoral volume was 2.6 cm (range, 2.0–4.6 cm) and 5.3 cm3 (range, 2.4–38.8 cm3), respectively. Seventeen patients (41.5%) underwent surgery within 7 days. The median follow-up duration was 45 months (range, 12–196 months). Results At the last follow-up, 62.9% (22/35) of patients had made a full recovery from preoperative neurologic deficits, with partial recovery observed in the remaining patients. The rates of improvement and full recovery from VA decrease were 92.9% and 57.1%, respectively; those from VF defect were 94.7% and 36.8%, respectively; and those from ocular palsy were 100.0% and 96.4%, respectively. On multivariate analysis, initial visual impairment score (≥20) was the only significant risk factor for postoperative neurologic sequelae (P Conclusions Ocular palsy was fully recovered in 96.4% patients with pituitary apoplexy after transsphenoidal surgery. Initial visual impairment status was found to be more strongly associated with postoperative neurologic recovery than surgical timing.

BACKGROUND: Radiomics is a rapidly growing field in neuro-oncology, but studies have been limited to conventional MRI, and external validation is critically lacking. We evaluated technical feasibility, diagnostic performance, and generalizability of a diffusion radiomics model for identifying atypical primary central nervous system lymphoma (PCNSL) mimicking glioblastoma. METHODS: A total of 1618 radiomics features were extracted from diffusion and conventional MRI from 112 patients (training set, 70 glioblastomas and 42 PCNSLs). Feature selection and classification were optimized using a machine-learning algorithm. The diagnostic performance was tested in 42 patients of internal and external validation sets. The performance was compared with that of human readers (2 neuroimaging experts), cerebral blood volume (90% histogram cutoff, CBV90), and apparent diffusion coefficient (10% histogram, ADC10) using the area under the receiver operating characteristic curve (AUC). RESULTS: The diffusion radiomics was optimized with the combination of recursive feature elimination and a random forest classifier (AUC 0.983, stability 2.52%). In internal validation, the diffusion model (AUC 0.984) showed similar performance with conventional (AUC 0.968) or combined diffusion and conventional radiomics (AUC 0.984) and better than human readers (AUC 0.825–0.908), CBV90 (AUC 0.905), or ADC10 (AUC 0.787) in atypical PCNSL diagnosis. In external validation, the diffusion radiomics showed robustness (AUC 0.944) and performed better than conventional radiomics (AUC 0.819) and similar to combined radiomics (AUC 0.946) or human readers (AUC 0.896–0.930). CONCLUSION: The diffusion radiomics model had good generalizability and yielded a better diagnostic performance than conventional radiomics or single advanced MRI in identifying atypical PCNSL mimicking glioblastoma.

Community-acquired brain abscesses are still encountered in clinical practice and cause considerable complications, despite improvements in hygiene in modernized societies. This study aimed to identify potential risk factors pertaining to predisposing infections and microorganisms to facilitate the effective treatment of brain abscesses. Of 121 surgically treated patients with brain abscesses, the most frequent predisposing condition was odontogenic infections (49/121 patients, 40.5%) followed by sinusitis (14/121, 11.6%). Of 121 patients, 51 (42.1%) had no identifiable predisposing infection. Viridans group streptococci (VGS) were the most frequently identified (47%) bacteria in all patients, and anaerobes were more frequently isolated in patients with odontogenic infections (36.7%, p=0.001) than aerobes. Among the patients with no identifiable predisposing infection, the most commonly isolated pathogen was VGS (38.3%); anaerobes occurred significantly less frequently (p=0.045), and old pulmonary tuberculosis was significantly more common (p=0.001) than in the group with identified predisposing infections. There was only one case of staphylococcal infection in 121 patients. The present study indicates that VGS should be the first target for antibiotic treatment when predisposing infections are not identifiable in patients with brain abscesses. Additionally, the association of old tuberculosis with community-acquired brain abscesses is common in these patients.

To analyze factors affecting observation failure (Ob-F) of untreated intracranial meningiomas (IMs) and to develop a "wait-and-see" strategy for newly diagnosed IMs based on risk.Factors affecting Ob-F (i.e., development of neurologic symptoms, significant growth, loss of opportunity to do radiosurgery, and tumor invasion into the adjacent sinus) were examined using a multivariate Cox proportional hazard model. The utility of the Asan Intracranial Meningiomas Scoring System (AIMSS) for screening out patients at risk for Ob-F was also analyzed. The "wait-and-see" strategy was based on the growth rate affecting the 5-year observation success (Ob-S) rate.Over 46.9 months, 77 of 232 patients (33.2%) experienced Ob-F. Larger tumors, preexisting neurologic symptoms, absence of calcification, and isointense/hyperintense signal were predictors of Ob-F. An AIMSS score of 4 for tumors2.5 cm in diameter (P = 0.0002) and a score of 6 for tumors ≥2.5 to4.0 cm in diameter screened out tumors at risk for Ob-F (P = 0.0023). Initial growth rates of ≥20%/year for tumors2.5 cm (P0.0001) and ≥1 cmThe AIMSS is helpful for screening out IMs at risk for Ob-F at the time of diagnosis. The initial growth rate after follow-up predicts the risk of future Ob-F in small- to medium- sized IMs.

Two well-known appetite-regulatory peptides, leptin and cocaine- and amphetamine-regulated transcript (CART), are known to be involved in the brain rewarding pathway. However, it is not yet known how they interact in the nucleus accumbens, an important region mediating the rewarding effects of drugs of abuse. Using the immunoassay method, we found that a microinjection of leptin into the nucleus accumbens core induces an immediate and transient increase of the CART peptide in this site, whereas these effects were inhibited by cocaine. These results expand the role of accumbal leptin to the regulation of the CART peptide and further suggest that possible interaction of these appetite-regulating peptides may be involved in cocaine-mediated rewarding effects.

Background Hypophysitis is a rare disease entity mimicking a pituitary adenoma. Despite crucial disease involving a pituitary gland which is a main component of the hormonal axis, there have been minimal researches regarding the hypophysitis. In this study, we described the constellation of the preoperative findings including clinical, radiologic, and endocrinologic features, as well as postoperative outcomes of the hypophysitis. Methods The authors reviewed the data retrospectively of a total of 2814 patients who underwent microsurgery at our institution to treat a pituitary mass lesion. Among them, the patients proven as hypophysitis in histologic examination were enrolled, followed by stratification into tumor-associated hypophysitis and isolated hypophysitis depending on the existence of associated tumor lesion. As a result, a total 21 cases were enrolled consisting of the 13 cases of tumor-associated and the 8 cases of isolated hypophysitis. In this study, the isolated hypophysitis was focused on the analysis. All patients with isolated hypophysitis were evaluated the clinical, radiologic, and endocrinologic tests preoperatively. After microsurgery, all patients had a minimum follow up of 6 months (6∼72 months). The clinical symptoms, endocrinologic tests, and brain MRI were checked at every 6 months during first 2 year, since then, at every 12 months. Results Among 2814 cases of pituitary mass lesion underwent microsurgery, the hypophysitis were found 21 cases (0.74 %). The 13 cases were the tumor-associated hypophysitis, consisting of rathke's cleft cyst (7 cases), craniopharyngioma (3 cases), pituitary adenoma (2 cases), and germinoma (1 case). The 8 cases were the isolated hypophysitis including lymphocytic (4 cases), granulomatous (3 cases), and IgG4-related (1 case) hypophysitis. The patients presented a wide range of clinical symptoms from general weakness to panhypopituitarism. In addition, the most remarkable radiologic features of the isolated hypophysitis were infundibular thickening and the low signal intensity in T1WI and T2WI. All 8 patients with isolated hypophysitis presented endocrinologic deficiency with various extent in a preoperative biochemistry. After surgery, the hormonal status were not changed in 4 patients (50%), however, aggravated in 4 patients (50%). The 3 patients (37.5%) complained visual field defects in preoperative ophthalmologic test, but improved all after surgery. Conclusion In this study, the preoperative clinical manifestations, radiologic and endocrinologic features of hypophysitis were described comprehensively. In addition, we also revealed the long-term outcomes of hypophysitis in the aspect of visual function and endocrinologic outcomes. Preexisting visual field defects were improved in all patients (3 cases). However, all patients presented endocrinologic deficiency in preoperative biochemistry, among them, the 4 patients (50 %) were unchanged and the 4 patients (50 %) were exacerbated after surgery. In conclusion, the visual outcomes were satisfactory, however, the endocrinologic outcomes were vice versa, because the preoperative endocrinologic deterioration was unchanged or even aggravated after surgery in some cases.

Objective Objectives of this study were to identify and compare symptom clusters in patients with meningioma and glioma and to assess and compare predictors of quality of life (QoL) in both patient groups. Methods Data were collected using the MD Anderson Symptom Inventory–Brain Tumor Module, Functional Assessment of Cancer Therapy–General, and Karnofsky Performance Sale. Of 158 participating patients, 77 had meningioma, and 81 had glioma. Results In patients with meningioma, 4 symptom clusters were identified with 55.4% total variance: 1) physical, 2) cognitive, 3) elimination-appearance, and 4) motor-sensory symptoms. In patients with glioma, 4 clusters with 67.3% total variance were identified: 1) treatment-related, 2) cognitive, 3) appearance-elimination, and 4) gastrointestinal symptoms. Predictors of QoL in patients with meningioma were Karnofsky Performance Scale score (β = 0.41, P < 0.001), cognitive symptom cluster (β = −0.36, P < 0.001), and physical symptom cluster (β = −0.32, P = 0.001), whereas treatment-related symptom cluster (β = −0.55, P < 0.001) was identified as a predictor of QoL in patients with glioma. Conclusions In this study, the type and composition of symptom clusters differed between patients with meningioma and glioma. Our data also provide evidence that even when participants reported mild symptoms, these clusters could be used to predict QoL in patients with meningioma and glioma.

Background Next-generation sequencing (NGS) enables highly sensitive cancer genomics analysis, but its clinical implications for therapeutic options from imaging-based prediction have been limited. Purpose To predict core signaling pathways in isocitrate dehydrogenase (IDH) wild-type glioblastoma by using diffusion and perfusion MRI radiomics and NGS. Materials and Methods The radiogenomics model was developed by using retrospective patients with glioma who underwent NGS and anatomic, diffusion-, and perfusion-weighted imaging between March 2017 and February 2019. For testing model performance in predicting core signaling pathway, patients with IDH wild-type glioblastoma from a retrospective analysis from a registry (

Primary central nervous system lymphoma (PCNSL) involving the hypothalamic–pituitary axis (H–P axis) is a rare intracranial neoplasm. We aimed to determine the unique characteristics and treatment outcomes of patients with PCNSL at the H–P axis and review the literature. We retrospectively reviewed the electronic medical records of patients with PCNSL in our institute from 2000 to 2017. We analyzed patient characteristics, clinicopathologic features, imaging results, and treatment outcomes. Furthermore, we searched the PubMed database and gathered more cases from published studies to analyze patient treatment outcomes. A total of 488 patients were diagnosed with central nervous system lymphoma at our institute. Seven (1.4%) patients had H–P axis involvement, five had diffuse large B-cell lymphoma, and two had mucosa-associated lymphoid tissue lymphoma. All patients had anterior pituitary lobe dysfunction, and two had posterior lobe dysfunction. The median progression-free survival (PFS) for seven patients was 29.0 (range: 0.9–48.1) months, and the 3-year survival rate was 42.9%. Pooled analysis included 45 patients. The median PFS for these patients was 7.0 months (0.9–52.0), and the 2-year survival rate was 20%. Univariate and multivariate analyses revealed that the patients with visual field defects had better prognosis (p = 0.0153 and 0.043, respectively). PCNSL at the H–P axis is associated with a higher rate of pituitary dysfunction than other parasellar pathologies. PCNSL at the H–P axis has a worse treatment outcome than PCNSL at other sites. However, visual field defect is related to a favorable prognosis in these patients.

To determine whether diffusion- and perfusion-weighted MRI–based radiomics features can improve prediction of isocitrate dehydrogenase (IDH) mutation and tumor aggressiveness in lower grade gliomas (LGGs) Radiomics features (n = 6472) were extracted from multiparametric MRI including conventional MRI, apparent diffusion coefficient (ADC), and normalized cerebral blood volume, acquired on 127 LGG patients with determined IDH mutation status and grade (WHO II or III). Radiomics models were constructed using machine learning–based feature selection and generalized linear model classifiers. Segmentation stability was calculated between two readers using concordance correlation coefficients (CCCs). Diagnostic performance to predict IDH mutation and tumor grade was compared between the multiparametric and conventional MRI radiomics models using the area under the receiver operating characteristics curve (AUC). The models were tested using a temporally independent validation set (n = 28). The multiparametric MRI radiomics model was optimized with a random forest feature selector, with segmentation stability of a CCC threshold of 0.8. For IDH mutation, multiparametric MR radiomics showed similar performance (AUC 0.795) to the conventional radiomics model (AUC 0.729). In tumor grading, multiparametric model with ADC features showed higher performance (AUC 0.932) than the conventional model (AUC 0.555). The independent validation set showed the same trend with AUCs of 0.747 for IDH prediction and 0.819 for tumor grading with multiparametric MRI radiomics model. Multiparametric MRI radiomics model showed improved diagnostic performance in tumor grading and comparable diagnostic performance in IDH mutation status, with ADC features playing a significant role. • The multiparametric MRI radiomics model was comparable with conventional MRI radiomics model in predicting IDH mutation. • The multiparametric MRI radiomics model outperformed conventional MRI in glioma grading. • Apparent diffusion coefficient played an important role in glioma grading and predicting IDH mutation status using radiomics.

Repeated exposure to classical psychomotor stimulants, like amphetamine (AMPH), produces locomotor sensitization and accompanied structural plasticity of dendritic spines in the nucleus accumbens (NAcc). Following our previous report that repeated administration of methiopropamine (MPA), a structural analog to meth-AMPH, produces locomotor sensitization, it was examined in the present study whether this behavioral change also accompanies with structural plasticity in the NAcc in a similar way to AMPH. A week after adeno-associated viral vectors containing enhanced green fluorescent protein (eGFP) were microinjected into the NAcc core, rats were repeatedly injected with saline, AMPH (1 mg/kg, IP), or MPA (5 mg/kg, IP) once every 2–3 days for a total of 4 times. Two weeks after last injection, all rats were perfused and their brains were processed for immunohistochemical staining. The image stacks for dendrite segments of medium spiny neuronal cells in the NAcc core were obtained and dendritic spines were quantitatively analyzed. Interestingly, it was found that the number of total spine density, with thin spine as a major contributor, was significantly increased in MPA compared to saline pre-exposed group, in a similar way to AMPH. These results indicate that MPA, a novel psychoactive substance, has similar characteristics with AMPH in that they both produce structural as well as behavioral changes, further supporting MPA's dependence and abuse potential.

The importance of sleep has been gaining more and more attention nowadays. It has been widely studied that some major health issues, such as cardiovascular diseases or mortality, are closely related to the extreme ends of sleep durations. Anemia is one of the health problems in modern society. In this study, we aimed to find a relationship between anemia occurrence and sleep duration. Data of 11,131 Korean adults aged 19 years or older were recruited from the 2016–2017 Korea National Health and Nutrition Examination Survey and analyzed in this cross-sectional study. ‘Anemia’ was defined in this study by hemoglobin level of &lt, 13 g/dL in men and &lt, 12 g/dL in women. Selected data were sorted into five groups by sleep duration: &lt, 5 h, 5 h ~ &lt, 6 h, 6 h ~ &lt, 8 h, 8 h ~ &lt, 9 h, and ≥9 h per day. We performed multivariate logistic regression analysis to assess the relationship between sleep duration and risk of anemia after adjusting for covariates including age, gender, family income level, education level, physical activity, cigarette smoking, and alcohol usage. Other factors were assessed in the analysis, such as depression, hypertension, diabetes, dyslipidemia, stroke, coronary artery disease, malignancy, stress level, and body mass index (BMI). We found that sleep duration of &lt, 5 h was related to high risk of anemia (odds ratio = 1.87, 95% confidence interval = 1.01–3.49, sleep duration of 6 h ~ &lt, 8 h as the reference group). Also, sleep duration of ≥9 h was related to lower risk of anemia in most premenopausal women after adjusting for covariates (odds ratio = 0.61, 95% confidence interval = 0.38–0.96, sleep duration of 6 h ~ &lt, 8 h as the reference group). Male individuals with sleep durations of &lt, 5 h (odds ratio = 2.01, 95% confidence interval =1.05–3.84) and of ≥9 h (odds ratio = 2.48, 95% confidence interval =1.63–3.81) had a significantly higher risk of anemia without covariate adjustment. Postmenopausal women with sleep durations of ≥9 h had a significantly higher risk of anemia (odds ratio =2.02, 95% confidence interval =1.33–3.08) without adjusting for covariates. However, the associations became statistically insignificant after adjusting for age and covariates in both men and postmenopausal women. In conclusion, we found significant associations between extreme ends of sleep duration and risk of anemia in premenopausal Korean women. However, we did not observe strong associations between self-reported sleep duration and anemia risk in men or postmenopausal women.

We aimed to evaluate ERG and SOX9 as potential biomarkers of docetaxel response in metastatic castration-resistant prostate cancer (mCRPC) patients. Seventy-one mCRPC patients were evaluated. Tissue microarrays were constructed and immunohistochemistry was performed. Treatment response was assessed by prostate specific antigen (PSA) response rate, PSA progression-free survival (PSA-PFS), clinical/radiologic PFS (C/R-PFS) and overall survival (OS). ERG and SOX9 were found in 13 (18.3%) and 62 (87.3%) patients, respectively. ERG-positive had lower PSA response rates than negative (15.4% vs 62.1%, p = 0.004), and SOX9 showed a same trend (46.8% vs 100.0%, p = 0.003). ERG positivity correlated with a lower PSA-PFS (3.2 mos vs 7.4 mos, p < 0.001), C/R-PFS (3.8 mos vs 9.0 mos, p < 0.001) and OS (10.8 mos vs 21.4 mos, p < 0.001). SOX9 positivity also showed a lower PSA-PFS, C/R-PFS and OS (p =0.006, p =0.012 and p =0.023, respectively). On multivariate analysis, ERG positivity was a significant risk factor for a lower PSA-PFS, C/R-PFS and OS (p < 0.001, p < 0.001 and p =0.001, respectively). SOX9 expression was also a risk factor for a lower PSA-PFS, C/R-PFS and OS (p = 0.018, p = 0.025 and p =0.047, respectively). These findings indicate that ERG and SOX9 is potential biomarkers for prediction to docetaxel treatment in mCRPC patients.

// Doo-Sik Kong 1,* , Do-Hyun Nam 1,* , Shin-Hyuk Kang 2 , Jae Won Lee 3 , Jong-Hee Chang 4 , Jeong-Hoon Kim 5 , Young-Jin Lim 6 , Young-Cho Koh 7 , Yong-Gu Chung 2 , Jae-Min Kim 8 and Choong-Hyun Kim 8 1 Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 2 Department of Neurosurgery, College of Medicine, Korea University, Seoul, Korea 3 Department of Statistics, Korea University, Seoul, Korea 4 Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea 5 Department of Neurosurgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea 6 Department of Neurosurgery, Kyunghee University Hospital, Seoul, Korea 7 Department of Neurosurgery, Konkuk University Medical Center, Seoul, Korea 8 Department of Neurosurgery, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea * These authors have contributed equally to this work Correspondence to: Choong Hyun Kim, email: // Keywords : immunotherapy, autologous cytokine-induced killer cell, glioblastoma Received : August 05, 2016 Accepted : September 23, 2016 Published : September 27, 2016 Abstract Purpose: Adoptive cell immunotherapy involves an ex vivo expansion of autologous cytokine-induced killer (CIK) cells before their reinfusion into the host. We evaluated the efficacy and safety of CIK cell immunotherapy with radiotherapy-temozolomide (TMZ) for the treatment of newly diagnosed glioblastomas. Experimental design: In this multi-center, open-label, phase 3 study, we randomly assigned patients with newly diagnosed glioblastoma to receive CIK cell immunotherapy combined with standard TMZ chemoradiotherapy (CIK immunotherapy group) or standard TMZ chemoradiotherapy alone (control group). The efficacy endpoints were analyzed in the intention-to-treat set and in the per protocol set. Results: Between December 2008 and October 2012, a total of 180 patients were randomly assigned to the CIK immunotherapy ( n = 91) or control group ( n = 89 ). In the intention-to-treat analysis set, median PFS was 8.1 months (95% confidence interval (CI), 5.8 to 8.5 months) in the CIK immunotherapy group, as compared to 5.4 months (95% CI, 3.3 to 7.9 months) in the control group (one-sided log-rank, p = 0.0401). Overall survival did not differ significantly between two groups. Grade 3 or higher adverse events, health-related quality of life and performance status between two groups did not show a significant difference. Conclusions: The addition of CIK cells immunotherapy to standard chemoradiotherapy with TMZ improved PFS. However, the CIK immunotherapy group did not show evidence of a beneficial effect on overall survival.

Methiopropamine (MPA) is a structural analog to methamphetamine and is categorized as a novel psychoactive substance that needs to be controlled. However, no study has been performed to determine whether MPA actually develops an addiction-like behavior similar to those arising from other psychomotor stimulants. Thus, we attempted to determine whether MPA produces locomotor sensitization in a manner similar to amphetamine. In the first experiment, rats were pre-exposed to either saline or one of three different doses of MPA (0.2, 1.0, or 5.0mg/kg, IP) with a total of four injections, respectively. After a 2-week withdrawal period, when they were challenged with the same dose of MPA, only the group that was pre-exposed to high dose of MPA (5.0mg/kg) showed sensitized locomotor activity. In the second experiment, all rats were pre-exposed to MPA (5.0mg/kg) only. Interestingly, the expression of MPA-induced locomotor sensitization was inhibited by a pre-injection of a dopamine D2 receptor antagonist, eticlopride (0.05mg/kg, IP), though not by a dopamine D1 receptor antagonist, SCH23390 (0.01mg/kg, IP). These results suggest that repeated injection of MPA in the rat provokes certain neuronal changes involving specific, likely D2, dopamine receptor-mediated pathways that contribute to the expression of MPA-induced locomotor sensitization.

PURPOSE The purpose of this study was to investigate the feasibility and survival benefits of combined treatment with radiotherapy and adjuvant temozolomide (TMZ) in a Korean sample. MATERIALS AND METHODS A total of 750 Korean patients with histologically confirmed glioblastoma multiforme, who received concurrent chemoradiotherapy with TMZ (CCRT) and adjuvant TMZ from January 2006 until June 2011, were analyzed retrospectively. RESULTS After the first operation, a gross total resection (GTR), subtotal resection (STR), partial resection (PR), biopsy alone were achieved in 388 (51.7%), 159 (21.2%), 96 (12.8%), and 107 (14.3%) patients, respectively. The methylation status of O6-methylguanine-DNA methyltransferase (MGMT) was reviewed retrospectively in 217 patients. The median follow-up period was 16.3 months and the median overall survival (OS) was 17.5 months. The actuarial survival rates at the 1-, 3-, and 5-year OS were 72.1%, 21.0%, and 9.0%, respectively. The median progression-free survival (PFS) was 10.1 months, and the actuarial PFS at 1-, 3-, and 5-year PFS were 42.2%, 13.0%, and 7.8%, respectively. The patients who received GTR showed a significantly longer OS and PFS than those who received STR, PR, or biopsy alone, regardless of the methylation status of the MGMT promoter. Patients with a methylated MGMT promoter also showed a significantly longer OS and PFS than those with an unmethylated MGMT promoter. Patients who received more than six cycles of adjuvant TMZ had a longer OS and PFS than those who received six or fewer cycles. Hematologic toxicity of grade 3 or 4 was observed in 8.4% of patients during the CCRT period and in 10.2% during the adjuvant TMZ period. CONCLUSION Patients treated with CCRT followed by adjuvant TMZ had more favorable survival rates and tolerable toxicity than those who did not undergo this treatment.

The aim of this study was to determine whether diffusion and perfusion imaging parameters demonstrate different diagnostic values for predicting pseudoprogression between glioblastoma subgroups stratified by O6-mythylguanine-DNA methyltransferase (MGMT) promoter methylation status. We enrolled seventy-five glioblastoma patients that had presented with enlarged contrast-enhanced lesions on magnetic resonance imaging (MRI) one month after completing concurrent chemoradiotherapy and undergoing MGMT promoter methylation testing. The imaging parameters included 10 or 90 % histogram cutoffs of apparent diffusion coefficient (ADC10), normalized cerebral blood volume (nCBV90), and initial area under the time signal-intensity curve (IAUC90). The results of the areas under the receiver operating characteristic curve (AUCs) with cross-validation were compared between MGMT methylation and unmethylation groups. MR imaging parameters demonstrated a trend toward higher accuracy in the MGMT promoter methylation group than in the unmethylation group (cross-validated AUCs = 0.70–0.95 and 0.56–0.87, respectively). The combination of MGMT methylation status with imaging parameters improved the AUCs from 0.70 to 0.75–0.90 for both readers in comparison with MGMT methylation status alone. The probability of pseudoprogression was highest (95.7 %) when nCBV90 was below 4.02 in the MGMT promoter methylation group. MR imaging parameters could be stronger predictors of pseudoprogression in glioblastoma patients with the methylated MGMT promoter than in patients with the unmethylated MGMT promoter. • The glioblastoma subgroup was stratified according to MGMT promoter methylation status. • Diagnostic values of diffusion and perfusion parameters for predicting pseudoprogression were compared. • Imaging parameters showed higher diagnostic accuracy in the MGMT promoter methylation group. • Imaging parameters were independent to MGMT promoter methylation status for predicting pseudoprogression. • Imaging biomarkers might demonstrate different diagnostic values according to MGMT promoter methylation.

Background Despite advances in skull base surgery, achieving effective surgical management of jugular foramen schwannomas (JFSs) that avoids postoperative cranial nerve (CN) deficits remains a challenge. Subtotal resection followed by radiosurgery (rather than radical resection) is increasingly being viewed as a better treatment strategy. Here, an institutional database was retrospectively analyzed for outcomes after surgical treatment of JFSs to evaluate the optimal strategy for managing JFSs. Methods Twenty-two patients with JFSs were operated on by either radical resection ( n = 13) or conservative resection plus radiosurgery ( n = 9). These 2 different groups were compared in terms of early (≤4 weeks after surgery) and late postoperative functional outcome and oncologic control. Results No deaths occurred in either group, but there were 3 surgery-related complications in the radical resection group. Postoperative CN deficits and additional procedures related to CN morbidity were generally higher in the radical resection group, but the differences were not statistically significant. The conservative surgery group showed a statistically significant improvement in the level of dysphagia and dysphagia-related functional state in the late postoperative period. There was 1 case of recurrence after radical resection over a mean follow-up period of 73 months. All tumors in the conservative surgery group were controlled over a mean period of 34 months. Conclusions Our results suggest that conservative resection of JFSs via a familiar intracranial approach plus radiosurgery may be an effective surgical alternative for improving functional outcome with adequate oncologic control.

To correlate and compare diagnostic performance with amide proton transfer (APT) imaging as a tumor proliferation index with that with magnetic resonance (MR) spectroscopy in subgroups of patients with pre- and posttreatment glioma.This retrospective study was approved by the institutional review board. In 40 patients with pretreatment glioma and 25 patients with posttreatment glioma, correlation between APT asymmetry and the choline-to-creatine and choline-to-N-acetylaspartate ratios in corresponding voxels of interest was determined, and the 90% histogram cutoff of APT asymmetry values (APT90) for the entire solid portion of gliomas was calculated for diagnostic performance. Area under the receiver operating characteristic curve (AUC), leave-one-out cross validation, and intraclass correlation coefficients were analyzed.The APT asymmetry values showed a moderate correlation (r = 0.49, P.001) with the choline-to-creatine ratios and a mild correlation with the choline-to-N-acetyl-aspartate ratios (r = 0.32, P = .011) in the corresponding lesions. The APT90 showed comparable diagnostic accuracy for grading of gliomas (AUC, 0.81-0.84 vs 0.86; P = .582-.864) and superior accuracy for differentiation of tumor progression from treatment-related change (AUC, 0.89-0.90 vs 0.60; P = .031-.046) compared with those with MR spectroscopy. The cross-validated area under the curve and accuracy of the APT90 in posttreatment gliomas were 0.89-0.90 and 72%, respectively. The interreader agreement for APT90 was excellent in both pretreatment and posttreatment gliomas (intraclass correlation coefficient, 0.95 and 0.96, respectively).APT imaging used as a tumor proliferation index showed moderate correlation with MR spectroscopic values and is a superior imaging method to MR spectroscopy, particularly for assessment of posttreatment gliomas.

Primary central nervous system lymphoma (PCNSL) typically shows a strong uptake of 18F-fludeoxyglucose (FDG) imaged by positron emission tomography (PET). Uncommonly, PCNSL demonstrates a low uptake on FDG PET. We investigated the clinicopathological characteristics of the unusual cases of PCNSL with low FDG uptake. We retrospectively enrolled 104 consecutive patients with newly diagnosed PCNSL who underwent baseline brain FDG PET. The degree of FDG uptake of PCNSL was visually scored by 4 grades (0, ≤contralateral white matter; 1, >contralateral white matter and contralateral gray matter). Grades 0–2 were considered as PCNSL with low uptake. We investigated association of low uptake of PCNSL with the following clinicopathological factors: age, sex, steroid treatment, lactate dehydrogenase level, cerebrospinal fluid protein level, condition of PET scanning, immunohistochemical markers (cluster of differentiation 10 [CD10], B-cell lymphoma 6 [BCL-6], B-cell lymphoma 2 [BCL-2], multiple myeloma oncogene 1 [MUM1], Epstein-Barr virus [EBV] protein, and Ki67), location of lesions, tumor size, multiplicity of lesions, involvement of deep brain structures, and cystic or necrotic appearance of lesions. Of the 104 patients with PCNSL, 14 patients (13.5%) showed PCNSL with low FDG uptake on PET. Among various clinicopathological factors, MUM1 negativity was the only factor associated with low FDG uptake PCNSL by univariate (P = .002) and multivariate analysis (P = .007). This study suggests that the different clinicopathological characteristics between patients with high uptake and low uptake of PCNSL on FDG PET is closely associated with lack of MUM1, a protein known to be a crucial regulator of B-cell development and tumorigenesis.