bluuebunny/crossref_metadata_2025_split huggingface dataset:
ET-04 Enhancing drug delivery with MRI-guided focused ultrasound for diffuse intrinsic pontine glioma model
Authors: Ishida Joji , Alli Saira , Bondoc Andrew , Fujita Naohide , Kullervo Hynynen , James Rutka 
Published: November 2020

Abstract
Diffuse intrinsic pontine glioma (DIPG) is surgically unresectable and one of the most devasting tumours in children. To date, there have been no effective chemotherapeutics against DIPG, despite a myriad of clinical trials. The intact blood-brain barrier (BBB) is partly responsible for the limited clinical response to chemotherapy. MRI-guided focused ultrasound (MRgFUS) is a promising non-invasive tissue ablation method for treating CNS tumours. Moreover, MRgFUS allows for temporary and repeatable BBB disruption. Our first objective was to determine the feasibility and safety of temporary BBB disruption within the brainstem using MRgFUS following intravenous administration of microbubbles in vivo. Our second objective was to select effective chemotherapeutics against DIPG cell lines, and to examine their therapeutic effects with MRgFUS in a murine model of DIPG which exhibits an intact BBB. Non-invasive opening of the BBB was determined in the brainstem of normal rodents using physiological monitoring and histological analysis. Doxorubicin was selected from a drug screen consisting of conventional chemotherapeutics tested against DIPG cell lines. We established SU-DIPG17 orthotopic xenografts which demonstrated diffusely infiltrative tumour growth. By LC-MS/MS analysis, MRgFUS led to a 4-fold increase in doxorubicin concentrations within the brainstem tumours as compared to controls. Moreover, the volumetric tumour growth rate was significantly suppressed in MRgFUS-treated animals, which also exhibited decreased Ki-67 expression. We demonstrated the feasibility and safety of MRgFUS in the rodent brainstem and have shown that MRgFUS increases doxorubicin uptake in the brainstem of a rodent model of DIPG. This preclinical data provides critical support for clinical trials investigating MRgFUS-mediated BBB opening, which may greatly improve chemotherapeutic efficacy against DIPG in children.
CO-01 Prediction of pathological and radiological nature of glioma by mass spectrometry combined with machine learning
Authors: Kawataki Tomoyuki , Hanihara Mitsuto , Suzuki Keiko , Yoshimura Kentaro , Takeda Sen , Kinouchi Hiroyuki 
Published: November 2020

Abstract
BACKGROUND: We have previously developed a medical diagnostic pipeline that employs mass spectrometry and machine learning. It does not annotate molecular markers that are specific to cancer but uses entire mass spectra for predicting the properties of glioma. OBJECT: To validate the power of our diagnostic method in predicting the pathological and radiological properties of glioma with a simple sample preparation procedure. METHODS: Ten patients with glioma and 4 non-glioma patients who went through surgical resection were enrolled in our hospital. A total of 1020 mass spectra were acquired from 88 specimens. In order to examine the prediction power of the diagnostic pipeline that we have developed, we performed ten-fold cross-validation for pathological and radiological findings and calculated agreement rates with the conventional methods such as pathological diagnosis (WHO grading, MIB-1 labeling index (LI), mutations in the isocitrate dehydrogenase (IDH)-1 gene and positive 5-ALA fluorescence) and radiological information (gadolinium (Gd)-enhanced area, high-intensity area on fluid-attenuated inversion recovery (FLAIR) imaging,). RESULTS: Prediction accuracy for WHO malignant grade was 91.37%. Those for MIB-1 LI more than 10% and IDH-1 mutation-positive were 82.84% and 87.75%, respectively. Our method achieved an accurate prediction of 95.00% for the 5-ALA-positive lesion. The present method displayed an accuracy of 82.36% in predicting the area of FLAIR hyperintensity and 81.27% for the Gd enhanced area. CONCLUSION: Our methodology achieved a higher rate of prediction of glioma in terms of pathology and radiology. Research is ongoing to develop a validation cohort to verify the biological profiles of glioma specimens.
TB-02 Comprehensive analysis of expandable benign pituitary adenomas without genetic manipulations
Authors: Yokogami Kiyotaka , Watanabe Takashi , Takeishi Go , Yamashita Shinji , Mizuguchi Asako , Takeshima Hideo 
Published: November 2020

Abstract
Background: Since most pituitary adenomas are benign, there is no model of pituitary adenomas that can be continuously cultured without genetic manipulation. In this study, we analyzed the genetic characteristics of the established cell lines by continuous culture of benign pituitary adenomas without genetic manipulation. Method: The pituitary adenoma was continuously cultured by modifying the conditional reprogramming (CR) method, and the morphology was observed and fluorescent immunostaining (IF) was performed. In addition, genetic characteristics were comprehensively analyzed, differences from the surgical samples were analyzed by enrichment analysis using GSEA, and network analysis was performed using cytoscape based on the protein-protein interaction database. (Results) 1) Of the 14 cases of pituitary adenoma that had undergone primary culture (median MIB-1 labeling index 1.5%), 12 cases were capable of continuous culture for more than 2 months. (6 months or more: 5 cases) 2) After 2 weeks of culturing, the cell morphology changed dramatically. These cultured cells were positive for follicular cell marker s100, ectodermal nervous system markers Nestin, Notch1, and mesodermal marker Vimentin. In these cells, synaptophysin, which was strongly positive in the surgical specimen collected at the same time as the culture, disappeared. 3) Enrichment analysis revealed that gene expression such as epithelial mesenchymal transition(EMT), angiogenesis, IL6 signaling via NFkB, extracellular degradation, integrin cell surface interaction increased in cultured cells, and gene expression such as neurotransmitter including synaptophysin decreased significantly.(Conclusion) 1) The modified CR method allowed continuous culture of pituitary adenoma cells. 2) The cultured cells showed characteristic change of EMT, which was seen in invasive pituitary adenoma.
TB-06 Eribulin prolongs survival in an orthotopic xenograft mouse model of malignant meningioma
Authors: Nakano Tomoyuki , Fujimoto Kenji , Achiha Takamune , Arita Hideyuki , Yasukawa Mami , Masutomi Kenkichi , Takahashi Masamichi , Tomiyama Arata , Maehara Taketoshi , Ichimura Koichi 
Published: November 2020

Abstract
Meningioma is the most common intracranial tumor, and its prognosis is typically favorable. However, patients of malignant meningioma (WHO grade III) most often experience recurrence, undergo multiple surgical treatments, and have poor prognosis. No effective therapy for malignant meningioma has been established yet. We recently reported an efficacy of eribulin (Haraven®) for glioblastoma. Eribulin is considered to target TERT, which is frequently mutated in its promoter. Since TERT promoter mutation is also found in malignant meningioma, this study aims at investigating the anti-tumor effect of eribulin against TERT promoter mutation-harboring human malignant meningioma cell lines in vitro and in vivo.
Two meningioma cell lines IOMM-Lee and HKBMM were used in this study. In the viability assay and the flow cytometry, eribulin strongly inhibited cell proliferation by cell cycle arrest. Apoptotic cell death in malignant meningioma cell lines was confirmed by vital dye assay and immunoblotting. Moreover, wound healing assay revealed the suppression of tumor cell migration after eribulin exposure. To assess the effect of eribulin in vivo, orthotopic xenograft mouse models of both malignant meningioma cell lines were constructed. The intraperitoneal administration of eribulin significantly prolonged the survival of meningioma cell lines implanted in the brain (p&lt;0.0001). Furthermore, apoptosis was histologically observed in brain tumor tissue by immunohistochemistry.
Thus, this study suggests that eribulin is a potential therapeutic agent for treating malignant meningioma.
STMO-01 Cerebral edema and perioperative epilepsy due to placement of BCNU wafer for malignant glioma
Authors: Fujii Yu , Ogiwara Toshihiro , Agata Masahiro , Hanaoka Yoshiki , Horiuchi Tetsuyoshi 
Published: November 2020

Abstract
Introduction: Cerebral edema is the most frequent adverse event of BCNU wafer, which is used as local chemotherapy of malignant glioma. However, predictive factor of this event is unknown. Moreover, there is no consensus about cerebral edema and perioperative seizure, which is often observed in glioma. Here, we report risk factor of cerebral edema with BCNU placement and relationship with perioperative seizure in malignant glioma cases.
Material and Method: Thirty-one case of adult malignant glioma who underwent BCNU placement in our institute between March 2013 to March 2019 were investigated. The patients were dichotomized to two groups; patient with postoperative transient cerebral edema (CE+ group) and patient without postoperative transient cerebral edema (CE- group).
Result: Postoperative cerebral edema associated with placement of BCNU was observed in 9 out of 31 patients (29%). Tumor malignancy was significant parameter for postoperative cerebral edema (p=0.003). Other factors such as, age, gender, laterality, tumor location, primary or recurrent, number of BCNU wafers, duration of recurrence were not significant for postoperative cerebral edema. Seizure was seen in 14 patients (45%), and cerebral edema was not significant parameter for seizure. Tumor malignancy was significant parameters for postoperative cerebral edema. Tumor malignancy was significant parameters for seizure (p=0.0004). Although postoperative seizure was observed in 4 patients (44%) with CE+ group, neither maximum volume (mean 61.1 ml) nor change ratio (mean 354%) of FLAIR-high-intensity region were not related with postoperative seizure.
Conclusions: Tumor malignancy was important factor for patients who underwent placement of BCNU wafer with postoperative cerebral edema and seizure. On the other hand, there were no relationship between postoperative cerebral edema and perioperative seizure in patients treated with BCNU wafer.
STMO-02 Efficacy of preoperative embolization for hemangioblastoma
Authors: Hiu Takeshi , Hirayama Kousuke , Baba Shiro , Ujifuku Kenta , Yoshida Koichi , Matsuo Takayuki 
Published: November 2020

Abstract
Introduction: Preoperative transarterial embolization (TAE) for hemangioblastoma carries a risk of cerebral infarction and hemorrhagic complications, and its safety and efficacy are controversial.
Method: Twenty-two cases of hemangioblastoma (cerebellar: 18 cases, medulla oblongata: 3 cases, spinal cord: 1 case) treated via direct surgery in our hospital from 2007 to 2020 were enrolled.
Results: Preoperative TAE was performed in 6 cases of cerebellar hemangioblastoma (1 bilateral case) and 1 case of spinal hemangioblastoma. The cerebellar hemangioblastoma feeders were only superior cerebellar artery (SCA) in 3 cases, SCA/anterior inferior cerebellar artery (AICA)/posterior inferior cerebellar artery (PICA) in 2 cases, AICA/PICA in 1 case, and single drainer in 5 cases. Tumors were ≥30 mm in all cases (25 mm on 1 side in bilateral cases), and solid or nodular lesions were located on the upper surface of the cerebellum. Cerebellar edema was severe in five cases with hydrocephalus. TAE was performed under local anesthesia in all cases, using a coil alone in two cases and liquid or particle embolization material in five cases. The day before direct surgery, TAE was performed in four cases, one of which underwent emergency decompression due to severe cerebellar edema. Three cases were intentionally embolized on the day of direct surgery. The median blood loss during direct surgery was 100 ml. Although cerebral infarction was observed in all cases, there were no cases of brain stem infarction or hemorrhagic complications. The Modified Rankin Scale at discharge was 0 in 2 cases, 1 in 3 cases, 3 in 1 case, and 4 in 1 case.
Discussion/Conclusion: Preoperative TAE for hemangioblastoma reduced the blood loss for direct surgery. Same-day TAE avoided neurological deficit due to cerebral infarction and cerebellar edema. To prevent severe infarction, guiding the microcatheter to the vicinity of the tumor bed is important.
STMO-07 Adverse events related to the glioblastoma surgery and their perioperative management in our hospital
Authors: Kashiwagi Hideki , Kawabata Shinji , Kimura Seigo , Yagi Ryokichi , Ikeda Naokado , Nonoguchi Naosuke , Furuse Motomasa , Wanibuchi Masahiko 
Published: November 2020

Abstract
Background: The standard treatment for glioblastoma is surgical resection following chemoradiation therapy. The rate of removal or the amount of residual tumor has some impact on the prognosis of patients with glioblastoma, but the highly invasive nature of this tumor makes complete removal limited to the contrast-enhanced lesions difficult due to its localization. Furthermore, when postoperative seizures and venous thrombosis are included in surgery-related complications, these perioperative adverse events can cause delays in the initiation of chemoradiotherapy and delay the return to work and home, such as prolonged hospitalization and rehabilitation time.
Methods: We retrospectively reviewed the perioperative status of the recent 50 consecutive cases with histologically confirmed as glioblastoma at our hospital, the patient background, tumor localization, and perioperative treatment, and so on. Results: The major perioperative complications were ischemic or hemorrhagic complications, epileptic seizures, venous thrombosis, and pneumonia; CTCAE grade 2 or higher, grade 3 or higher, and grade 4 occurred in about 40%, 20%, and 10%, respectively, with some patients having multiple complications. Discussion: Although there was a tendency for ischemic changes around the cavity of the resection as the resection rate increased, most cases were asymptomatic and it seemed to be acceptable if residual brain function could be preserved. Residual tumors tended to show hemorrhagic changes and epileptic seizures because this is thought to be that the tumor was deliberately left in place to preserve function, based on the localization of the tumor. Postoperative FDP levels were useful in predicting the development of deep vein thrombosis and pulmonary artery thromboembolism. Conclusion: Because glioblastoma has short survival time and patient PS before and after surgery varies greatly depending on tumor localization, it is important to consider risk-benefit strategies for each case and to establish a scheme for a seamless transition from perioperative management to the introduction of postoperative therapy and maintenance therapy.
RT-01 Treatment results of salvage gamma knife and bevacizumab (AVAgamma therapy) for recurrent glioblastoma
Authors: Sato Kenichi , Asanome Taku , Ishida Yuuki , Sugio Hironori , Ozaki Yoshimaru , Takanashi Masami , Nakamura Hirohiko 
Published: November 2020

Abstract
Purpose: We report the treatment results of AVAgamma therapy combining gamma knife (GK) and bevacizumab for recurrent glioblastoma. Subjects: From August 2013 to April 2020, 44 patients (88 lesions) with recurrent glioblastoma treated with AVAgamma therapy as salvage therapy at the time of relapse after initial treatment. The average age is 61.5 years, with 26 men and 18 women. The tumor volume is 150 ml or less, and KPS is 40% or more as the indication of AVAgamma therapy. When the irradiation volume of GK is 15 ml or less, a single irradiation with a boundary dose of 20 to 26 Gy was performed, and when the irradiation volume was 15 ml or more, a single irradiation boundary dose was divided into two divided irradiations of 12 to 15 Gy. The mean therapeutic borderline dose was 24 Gy. Bevacizumab was administered 10 mg / kg or 15 mg / kg 1 to 10 times after GK. Methods: Median progression-free survival (mPFS), 6-month progression-free survival (PFS-6m), 6-month survival (OS-6m), median survival (mOS) from treatment with AVAgamma Considered mOS from initial treatment. Results: The mPFS from AVAgamma therapy was 5 months, PFS-6m was 37%, OS-6m was 79%, and mOS was 9 months. The mOS from initial treatment were 25 months. In relapsing glioma RPA classification, NABTT CNC class 5 mOS is 5.6 months, class 6 mOS is 6.4 months, but mOS from AVAgamma therapy is 9 months in class 5, 9 months in class 6. The survival time has been extended. Discussion: By AVAgamma therapy, it was thought that recurrent lesions were locally controlled and life prognosis was prolonged. Conclusion: AVAgamma therapy is thought to prolong the survival of recurrent glioblastoma and play an important role as salvage treatment.
RT-04 Stereotactic irradiation for 2 - 3 cm brain metastases: A multicenter retrospective cohort study
Authors: Hirata Takero , Harada Ken , Shimamoto Shigetoshi , Kawaguchi Hiroki , Igaki Hiroshi , Ito Yusuke , Yamada Kazunari , Kakuhara Hisao , Maebayashi Katsuya , Aoyama Hidefumi 
Published: November 2020

Abstract
Purpose: We retrospectively analyzed the treatment outcomes of Stereotactic irradiation (STI) for large size (2–3 cm) brain metastasis. Materials and methods: One hundred and sixty-nine lesions with 156 patients who underwent STI from January 1, 2013 to December 31, 2015 at 21 institutions participating in the Japanese Radiation Oncology Study Group were included in the study. Patients who had a history of whole-brain irradiation in the past and those who received whole-brain irradiation sequentially with STI were excluded. RANO-BM was used to evaluate the effect on each lesion, and the survival time or time to occurrence of local failure was defined as the number of months from the initial day of STI to the day of the events. Results: The median age was 66 (33–87) years. The median follow-up time was 14 (1–52) months. Male/female = 95/61 cases. The number of brain metastases was 1/2/3/4 or more = 93/35/14/14 cases. The median doses and fraction size were 30 Gy in 3 fractions. The primary site was lung/breast/colon or rectum/others = 95/14/14/33 cases. The median survival time was 16 months. A 1-year overall survival rate was 62% and a 1-year local control rate was 77%. Comparing the 1-year local control rate by the fraction size, single/3 or 4 /5 or more = 66/86/75%, the rate was better in the 3–4 fractions group (Log-rank test, p = 0.069). Cerebral necrosis (Grade 1/2/3/unknown = 9/10/8/3 cases) was observed in 30 lesions (18%), and the median time to diagnosis of brain necrosis was 9 (1–41) months. The incidence of necrosis in the single fraction cases was 29%, which was significantly higher than that in the fractionated irradiation cases (15%) (p = 0.039). Conclusion: Fractionated STI seems to be more favorable than single fraction STI for large brain metastases.
NI-04 Evaluation of post boron neutron capture therapy for recurrent meningioma using fluoride-labeled boronophenylalanine PET
Authors: Takai Satoshi , Matsushita Yoko , Kawabata Shinji , Ono Koji , Isohashi Kayako , Wanibuchi Masahiko , Miyatake Shinichi 
Published: November 2020

Abstract
We have applied boron neutron capture therapy (BNCT) for 46 recurrent high grade meningiomas (HGM). Twelve cases among them, fluoride-labeled boronophenylalanine positron emission tomography (18F-BPA-PET) were utilized before and after BNCT to evaluate the tumor activity. The lesion to normal brain (L/N) ratios of 14 lesions of these 11 cases were investigated. In all cases L/N ratio decreased after BNCT. The L/N ratio of recurrent (HGM) was 3.2±1.5 (mean±SD) before BNCT and 2.1±0.6 after that. In contrast enhanced MRI, 13 out of 14 lesions shrank or unchanged at least 3 months after BNCT, while one lesion transiently increased and then decreased within 3 months, showing pseudoprogression. In addition, 6 of 12 lesions which could be followed on MRI for more than 3 months progressed after 8 months. 4 of them were performed PET at the time of progressing. The L/N ratio of 2 progressing lesion which were diagnosed as recurrence due to continuously increasing were showed increasing. The L/N ratio of the other 2 lesions which were diagnosed radiation necrosis due to unchanged or shrinkage showed decreasing. Moreover, some systemic metastasis detected in PET image. F-BPA-PET seems to be useful for the evaluation of tumor activity.
NI-08 Utility of multiple positron emission tomography tracers in the diagnosis of brain tumors according to the 2016 World Health Organization classification
Authors: Miyake Keisuke , Fujimori Takeshi , Toyota Yasunori , Ogawa Daisuke , Hatakeyama Tetsuhiro , Okauchi Masanobu , Kawanishi Masahiko , Tamiya Takashi 
Published: November 2020

Abstract
Objective: Magnetic resonance imaging alone is not sufficient for the diagnosis and therapy outcomes in brain tumors. We herein examined the utility of positron emission tomography (PET) studies for diagnosis in brain tumors. Methods: Between April 2009 and June 2020, 320 patients with central nervous diseases, including 140, 65, 52, 52, and 11 patients with glioma, metastatic brain tumor, malignant lymphoma, meningioma, and demyelinating disease, respectively, underwent PET studies (FDG, MET, FLT, and FMISO) in our department. Lesion/normal (L/N) ratios for FDG, MET, and FLT and lesion/blood ratio (L/B ratio) for FMISO were compared. The glioma subtypes were compared based on the 2016 World Health Organization classification (IDH-mut, Codel, IDH-wt, GBM), and metastatic brain tumors, malignant lymphomas, meningiomas, and demyelinating diseases were compared with GBM. Results: In glioma, the cutoff MET L/N ratios to distinguish between IDH-mut and Codel, IDH-mut and GBM, Codel and GBM, and IDH-wt and GBM were 3.61, 4.42, 4.92, and 4.33, respectively, and the cutoff FLT L/N ratios to distinguish between IDH-mut and IDH-wt, IDH-mut and GBM, Codel and GBM, and IDH-wt and GBM were 3.43, 6.46, 3.39, and 7.56, respectively. The cutoff FDG and MET L/N ratios between metastatic brain tumors and GBM were 2.27 and 4.89; the cutoff FDG L/N and FMISO L/B ratios between malignant lymphoma and GBM were 4.68 and 2.13; and the cutoff FDG and MET L/N ratios between meningioma and GBM were 1.58 and 4.36. Demyelinating disease and GBM were distinguishable by FDG, MET, and FLT L/N ratios of 2.29, 3.32, and 5.85, and FMISO L/B ratio of 1.68. Conclusion: Four PET tracers were required to differentiate glioma subtypes. FDG and MET are useful for distinguishing GBM from metastatic brain tumor, malignant lymphoma, and meningioma, whereas accumulation was lower for all four PET tracers in demyelinating diseases than in GBM.