bluuebunny/crossref_metadata_2025_split huggingface dataset:
COT-2 MALIGNANT BRAIN TUMOR DIAGNOSED AS SUBDURAL HEMATOMA DURING A BRAIN CHECKUP: CASE REPORT
Authors: Ogawa Takahiro , Kotani Saki , Doi Tomoyuki , Nagai Toshiki , Murakami Nobukuni 
Published: December 2022

Abstract

Case description
65-year-old female. One month before the checkup, she had a bruise on the parietal region of her head. The patient was referred to our department because a subdural hematoma was suspected on the MRI scan of the head taken at a brain checkup. However, a few months after the initial visit, headache localized around the bruised area began to appear. Since the headache symptoms did not improve, he returned to our department and contrast-enhanced MRI was performed again. Contrast-enhanced MRI showed a tumor lesion of more than 6 cm in size, which infiltrated subcutaneously, epidurally, intradurally, and contralaterally. Other mass lesions were also found in the left frontal region and left neck. The patient underwent subcutaneous mastectomy to remove the left parietal subcutaneous mass and confirm the diagnosis. The scalp tumor had a soft and elastic subcutaneous mass, which was easily detached from the scalp and bone, removed in one lump. The pathological diagnosis was malignant lymphoma. The patient was transferred to the Department of Hematology and started R-MPV therapy.

Conclusion
No case has been reported in the literature that led to the diagnosis of malignant lymphoma during a brain checkup. In the present case, a subdural hematoma was diagnosed at the brain checkup because of the origin of the tumor and the history of head injury at the same site. However, there is a report that it was a subcutaneous mass and an epidural mass caused by malignant lymphoma mimicking epidural hematoma. This should be kept in mind. Although the brain scan was not sufficient to screen the patient, the fact that the patient was symptomatic confirmed the diagnosis, and the patient had an outcome that led to subsequent treatment.
COT-8 DEVELOPMENT OF TARGETED GENE PANEL FOR RAPID MOLECULAR DIAGNOSIS OF BRAIN TUMORS
Authors: Nakashima Takuma , Funakoshi Yusuke , Uneda Atsuhito , Nambu Shohei , Kitahara Mai , Yanagisawa Shunsuke , Ohno Makoto , Takahashi Masamichi , Miyakita Yasuji , Narita Yoshitaka , Suzuki Hiromichi 
Published: December 2022

Abstract

Background
Brain tumors are diagnosed based on pathological and genetic features defined by WHO classification. Although targeted gene panels are clinically available, most of them do not cover all the necessary genes for the diagnosis of brain tumors. Moreover, broad copy number analysis, which the current WHO classification requires, usually lacks in the gene panel. Another problem is that those panels demand a high burden of time and cost, which disturbs rapid diagnosis and broad application. To overcome those problems, we developed a rapid and cost-effective workflow of molecular diagnosis for brain tumors.

Methods
Our panel contains 109 genes of which 68 are necessary for fundamental molecular diagnosis and 41 are other common driver genes. To detect copy number changes and structural variants, which generate a fused gene, additional probes are placed on common SNPs and introns containing common breakpoints. MGMT methylation status is examined at the same time using bisulfite-converted DNA amplification. Sequencing data is analyzed using a supercomputer.

Results
The analysis time is within 4 days: 2 days for library preparation, 1 day for sequencing, and 12 hours for analysis. Detected driver alterations were validated by whole genome sequencing data. MGMT methylation status was correlated between the results of our workflow and pyrosequencing.

Conclusions
We have developed a rapid comprehensive molecular analysis workflow that detects genetic alterations and MGMT methylation. Our method allows a cost-effective molecular diagnosis with high accuracy, which would improve molecular diagnosis for brain tumors.
COT-12 ANALYSIS OF 5-ALA STRONGLY POSITIVE FINDINGS USING IMAGE J FOR MALIGNANT BRAIN TUMOR
Authors: Kon Takashi , Kobayashi Yusuke , Sato Yosuke , Shimizu Katsuyoshi , Mizutani Tohru 
Published: December 2022

Abstract
For brain tumor surgery using 5-ALA during surgery, we analyze the brightness using image analysis software Image J, we report the results to date for strongly positive findings. Thirty-nine patients who were suspected of having malignant glioma before surgery and who were strongly positive for 5-ALA during surgery were included. (21 malignant glioma, 14 metastatic brain tumor, 3 meningioma, and 1 germ cell tumor.) Intraoperative 5-ALA-positive findings were analyzed with image analysis software Image J (Wayne Rasband: NIH), brightness was measured with histograms, and maximum brightness was compared. The average maximum brightness titer was 106.38 (50-225) in 21 cases of malignant glioma. The brightness titer was 84.5 (28-121) in 14 cases of metastatic brain tumor, 80 (59-97) in meningioma, and 43 in 1 case of germ cell tumor. No clear correlation was found between brightness, tumor grading, and MIB-1 LI. In addition, a clear difference in luminance was observed between the tumor and the ventricle in one case.By analyzing brightness with Image J, it will be possible to obtain informations about tumors from different perspectives.
COT-13 OUTCOMES OF MEDULLOBLASTOMA IN KOBE CHILDREN,S HOSPITAL OVER THE RECENT 11 YEARS
Authors: Kawamura Atsufumi , Koyama Junji , Akutsu Nobuyuki , Enami Haryka , Hayashi Hideya 
Published: December 2022

Abstract

Introduction
Medulloblastoma is the most frequent malignant brain tumor in children, which 5-year survival rate have improved to 70-85%. In this study, we retrospectively reviewed outcomes and late complications of 31 medulloblastoma cases treated at our institute from 2010 to 2021.

Cases
The mean age of the cases was 6.5 years. 22 cases were total resection and 17 were judged to be in the high-risk group. With respect to histopathological diagnosis, 23 cases were classified as classic type, 2 as desmoplastic/nodular type, 2 as with extensive nodularity type, and 4 as anaplastic/large cell type. As for molecular analysis, WNT was 2, SHH was 3 , Group 3 was 3, Group 4 was 8 cases. One case was lost due to relocation.

Results
21 patients have no recurrence of medulloblastoma, but two were victims of second cancers. The remaining 19 cases were all in the standard-risk group and survived with a complete reaction (CR). There were 9 cases of recurrence (including disseminated disease) and the survived case after retreatment was only one in the high-risk group which indicated CR.

Discussion
The 5-year survival rate for patients in standard-risk group at our institution was 92.3%, indicating improved outcomes. The poor prognosis group could be divided in group who developed recurrence or second cancers after 5 years or more and group who indicated insufficient reaction to multimodality treatment and died around 2 years after diagnosis. As late complications, there were 5 cases of higher functional impairment, who were 16.7% of whole cases and almost in the high-risk group. It is necessary to pursue further treatment for the high-risk group and to recognize that the number of survivors of medulloblastoma cases is increasing, and to support for the AYA generation.
COT-14 OUTCOMES OF MEDULLOBLASTOMA IN KOBE CHILDREN,S HOSPITAL OVER THE RECENT 11 YEARS
Authors: Kawamura Atsufumi , Koyama Junji , Akutsu Nobuyuki , Enami Haryka , Hayashi Hideya 
Published: December 2022

Abstract

Introduction
Medulloblastoma is the most frequent malignant brain tumor in children, which 5-year survival rate have improved to 70-85%. In this study, we retrospectively reviewed outcomes and late complications of 31 medulloblastoma cases treated at our institute from 2010 to 2021.

Cases
The mean age of the cases was 6.5 years. 22 cases were total resection and 17 were judged to be in the high-risk group. With respect to histopathological diagnosis, 23 cases were classified as Classic type, 2 as Desmoplastic/nodular type, 2 as With extensive nodularity type, and 4 as Anaplastic/Large cell type. As for molecular analysis, WNT was 2, SHH was 3 , Group 3 was 3, Group 4 was 8 cases. One case was lost due to relocation.

Results
21 patients have no recurrence of medulloblastoma, but two were victims of second cancers. The remaining 19 cases were all in the standard-risk group and survived with a complete reaction (CR). There were 9 cases of recurrence (including disseminated disease) and the survived case after retreatment was only one in the high-risk group which indicated CR.

Discussion
The 5-year survival rate for patients in standard-risk group at our institution was 92.3%, indicating improved outcomes. The poor prognosis group could be divided in group who developed recurrence or second cancers after 5 years or more and group who indicated insufficient reaction to multimodality treatment and died around 2 years after diagnosis. As late complications, there were 5 cases of higher functional impairment, who were 16.7% of whole cases and almost in the high-risk group. It is necessary to pursue further treatment for the high-risk group and to recognize that the number of survivors of medulloblastoma cases is increasing, and to support for the AYA generation.
COT-15 PATHOLOGICAL ANALYSIS OF MALIGNANT GLIOMA IN THE END STAGE
Authors: Hirai Nozomi , Saito Norihiko , Sato Sho , Kushida Naoki , Hiramoto Yu , Fujita Satoshi , Nakayama Haruo , Hayashi Morito , Ito Keisuke , Sakurai Takatoshi , Oharazeki Toshiaki , Iwabuchi Satoshi 
Published: December 2022

Abstract

Background
Malignant gliomas have an extremely high rate of recurrence and brain invasion despite standard treatment, ultimately leading to tumor death. Tumor death is generally thought to be caused by brain herniation due to mass effect, as confirmed by studies of malignant glioma brain autopsies performed in the 1960s and 1980s. However, there have been few studies of brain autopsies of malignant gliomas after the introduction of chemotherapy with temozolomide, and the pathological characteristics of the end stage of the disease have not been clarified in recent years. In this study, we report the clinical and pathological characteristics of the end stages of malignant glioma cases treated at our hospital from the initial treatment to the confirmation of death.

Methods
10 cases of malignant glioma that were treated from initial treatment to pathological autopsy at our hospital from 2007 to 2018 were included in this study. We analyzed the pathology, neuroradiological changes, and clinical course of these cases at the end stage.

Results
The mean age of the 10 patients was 59 (15-77) years, and the median overall survival was 16.5 months. The primary tumor sites were 2 frontal lobes, 3 parietal lobes, 3 temporal lobes, 1 cerebellum, and 1 multiple lesions. The direct cause of death in all cases was neurological death due to tumor progression. Gross findings of pathological autopsy specimens showed that tumor excision sites were cavitated or recurrent, but mass effect was poor and there were few cases of brain herniation. On the other hand, microscopic findings showed infiltration of tumor cells into the brain stem through the brain parenchyma.

Conclusion
This study suggests that tumor invasion into the brainstem is involved as a cause of tumor death. It is possible that the new treatment may change the recurrence pattern or alter the morphology of glioma cells.
COT-16 NATION-WIDE LANDSCAPE OF GENOMIC ANALYSIS OF ADULT CENTRAL NERVOUS SYSTEM TUMORS IN JAPAN
Authors: Takahashi Masamichi , Watanabe Yuko , Koyama Takafumi , Sunami Kuniko , Kubo Takashi , Cho Hourin , Hirata Makoto , Tao Kayoko , Sudo Kazuki , Kohsaka Shinji , Yanagisawa Shunsuke , Ohno Makoto , Miyakita Yasuji , Yamamoto Noboru , Narita Yoshitaka 
Published: December 2022

Abstract

Background
Comprehensive genomic profiling (CGP) testing has been covered by public health insurance and its clinical application has started in Japan since June 2019. All the results of CGP testing are sent to the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) and shared with clinicians after discussion at the Expert Panel (EP). Here we report the results of analysis of adult central nervous system (CNS) tumors registered in Japan.

Methods
C-CAT registry data as of April 2022 (ver. 20220406) was used. Patient background, diagnosis, type of CGP testing, genetic alterations and treatment status after EP were analyzed.

Results
1042 patients with CNS tumors were enrolled, 338 (32.4%) were younger than 20 years old and 704 (67.6%) were older. Among 704 adult patients, mean age was 47.6 years and median ECOG PS was 1. Top tumor diagnosis included glioblastoma (42.8%), anaplastic astrocytoma (11.8%) and anaplastic oligodendroglioma (5.0%), and 634 (90.0%) were tested with FoundationOne CDx(R). Regarding genomic alterations, 278 had TP53 mutation, 242 had CDKN2A deletion, 221 had TERT mutation, 218 had CDKN2B deletion, 136 had IDH1 mutation, and 39 had TMB high (&gt;10Mb) and no NTRK gene fusion was observed. EP recommended treatment options in 187 cases (26.6%) and 60 cases (8.5%) reached therapeutic agents, including 25 Patient-Proposed Healthcare Services, 16 approved drugs, 8 pharmaceutical clinical trials, 7 investigator-initiated clinical trials and 4 others.

Conclusion
This is the first report of nation-wide results of CNS tumors analyzed by CGP in Japan. Although some patients were able to reach therapeutic agents under the Patient-Proposed Healthcare Services system, little number of patients reached clinical trial. Development of new drugs is urgently warranted.
LW-1 MY LIFE WORK : MY RESEARCH WORK FOCUSING ON TUMOR-ASSOCIATED ENDOTHELIAL CELLS ALONG WITH VEGF FOR 30 YEARS
Authors: Tanaka Toshihide 
Published: December 2022

Abstract
When I was a medical student, I happened to see the typical histopathology of glioblatoma (GBM) containing expanding necrosis surrounded by enormous glomerulous microvasculature with endothelial proliferation resembling glomeruli in the kidney. It looks like tumor cells starving out due to lack of blood supply with accelerating growth. Since then, I have been fascinated by tumor angiogenesis that might be an attractive therapeutic target.In 1989, vascular endothelial growth factor (VEGF) and vascular permeability factor (VPF) turned out to be identical. In 1992, VEGF expression was distributed surrounding necrosis area in GBM. In 1993, anti-tumor effect of monoclonal antibody for VEGF via inhibition of angiogenesis on various tumor models including glioma was verified in vivo. In 1996, VEGF was found to inhibit the functional maturation of dendritic cells, suggesting that therapeutic blockade of VEGF may improve prospect for immunotherapy as well as inhibition of angiogenesis. Those findings made me excited with visionary idea that combination therapy of anti-VEGF therapy and dendritic cell-based immunotherapy might be a potential therapeutic approach for GBM. Currently, I am dedicated in clinical study of dendritic cell-based immunotherapy and bevacizumab for GBM.Since graduating from medical school and discovery of VEGF in the same era, my clinic and research have been supported by serendipity of a vast of experiences and many people. I would give take-home message to next generation that originality and creativity were cultivated in real-world, and that serendipity and integration were precious for development of basic and clinical research.
LW-5 DENDRITIC CELL IMMUNOTHERAPY FOR MALIGNANT GLIOMA: RESEARCH HISTORY FOR 25 YEARS AND THE FUTURE PROSPECTS
Authors: Akasaki Yasuharu , Kikuchi Tetsuro , Tnaka Toshihide , Murayama Yuichi 
Published: December 2022

Abstract
We started a research of dendritic cell (DC) immunotherapy for malignant glioma in late 1997, and were continuing the clinical study for more than 20 years with making several improvements of methods. The presenter has been participating in this research from its inception, and has continued to conduct research as the life's work. We will present research history and the future prospects. Autologous cultured tumor cells were established from tumor tissue obtained from a surgery of patient with malignant glioma in our hospital. Mature DCs were induced from autologous peripheral blood mononuclear cells (PBMC), and were fused with the established tumor cells. Cell manufacturing performed at a cell processing facility (CPF) maintained and managed by our university. Before 2004, the tumor-fused DCs (TFDC) were co-administrated with rIL-12. Since 2014, TFDCs were stimulated with Poly(I:C) and IL-10-siRNA in order to increase IL-12 secretion levels of them. Since 2014, PBMCs were collected by the apheresis method. Since 2006, the TFDC immunotherapy was combined with temozolomide (TMZ) chemotherapy. 111 cases were enrolled in the clinical study. The TFDC-immunotherapy was combined with the TMZ chemotherapy in 88 cases enrolled after 2006. No serious problem was confirmed in the cell manufacturing. The therapeutic effect in this study will be compared with a historical control that were the cases of malignant glioma treated with a standard therapy at the other affiliated hospitals at the same period. The results will be reported in the presentation. The safety and efficacy of this treatment were confirmed in the previous study. We would like to establish a provision system of the TFDCs by use of our CPF by preparing product uniformity, transport safety, preservation methods, etc., and aim to expand the hospitals that can perform this immunotherapy.
LW-6 OKAYAMA ROSAI HOSPITAL GLIOMA SUPPORT CENTER INITIATIVES
Authors: Adachi Yoshiaki 
Published: December 2022

Abstract
For glioblastoma, which is a rare and intractable disease, it is necessary to speed up the development and verification of new treatment methods through nationwide clinical trials by consolidating cases in the High Volume Center. Okayama University-related facilities have consolidated glioblastoma cases at Okayama University Hospital and are actively conducting high-precision surgery, genetic analysis, and clinical trials. On the other hand, there are cases where it is difficult to continue treatment at university hospitals, such as dissemination cases and poor Performance Status cases. In order to respond to this need with One Stop, we established the Okayama Rosai Hospital Glioma Support Center. We provide seamless support for postoperative radiation chemotherapy, rehabilitation, maintenance chemotherapy, alternating current electric field therapy, best supportive care, and end-of-life support including backward coordination. The goal is not to make glioblastoma patients and their families “cancer refugees” but to provide QOL-oriented treatment until the end within the comprehensive regional care system. We will report on the results of 29 cases of glioblastoma intervention from May 2013 to August 2022 and future issues.
LW-8 TREATMENT STRATEGY FOR OLIGODENDROGLIOMAS WITH NEOADJUVANT STRATEGY AND STAGED RESECTION UTILIZING THEIR CHEMOTHERAPEUTIC RESPONSIVENESS
Authors: Sasaki Hikaru , Kanazawa Tokunori , Kitamura Yohei , Nakaya Masato , Fujiwara Hirokazu , Kimura Tokuhiro , Nakae Shunsuke , Ohba Shigeo , Nishiyama Yuya , Toda Masahiro , Yoshida Kazunari , Hirose Yuichi 
Published: December 2022

Abstract

Background
In glioma surgery, both of functional preservation and maximal safe resection are critical, however, neoadjuvant strategy has never been used because of difficulty of tissue sampling without craniotomy.

Method
In Keio University Hospital, oligodendrogliomas, i.e., diffuse gliomas with IDH mutation and 1p/19q codeletion, with incomplete initial resection have been treated by upfront chemotherapy and subsequent resection after tumor volume decrease (second look resection, SLR) since 2006 (J Neurooncol 124:127-35, 2015). At first, initial radiotherapy was prescribed immediately after chemotherapy or SLR only for the cases with aggressive clinical course or subarachnoid infiltration, however, cases with residual FLAIR abnormality after upfront chemotherapy or SLR were also subjected to initial radiotherapy since 2018. Cases 1) with IDH mutation and 1p/19q codeletion, and 2) without history of either chemotherapy or radiotherapy, and 3) treated with upfront chemotherapy and subsequent resection strategy, were included.

Results
Thirty nine cases of oligodendroglioma have been treated with the above strategy since 2006. Tumor volume decrease following upfront chemotherapy was 30-35% (median), and 19 tumors underwent SLR. Among the total 39 cases, PFS and OS after initiation of upfront chemotherapy were 81 months and not reached, respectively, and were 64 months and not reached, respectively, among the 32 cases with deferred radiotherapy. Importantly, the majority of tumor recurrence occurred at the residual FLAIR abnormality following upfront chemotherapy.

Conclusions
Treatment of oligodendrogliomas utilizing neoadjuvant strategy enables 1) decrease of resection volume as compared with initial maximal safe resection, 2) more precise resection, 3) confirmation of the necessity of initial radiotherapy based on the observed efficacy of chemotherapy. Moreover, the study also suggested that 4) invasion front of oligodendroglioma likely withdraw by alkylating agents, and 5) cases with residual FLAIR abnormality following chemotherapy may be appropriate subjects for initial radiotherapy.
LW-10 PRECLINICAL THERAPEUTIC TESTING FOR BRAIN TUMOR USING PATIENT-DERIVED XENOGRAFT (PDX) MODEL
Authors: Hashizume Rintaro 
Published: December 2022

Abstract
I have been working on the brain tumor research about 20 years in the United State. My primary research interests in understanding of the mechanisms of genetic and epigenetic regulation that promote tumor development and progression, and identify novel therapeutic targets for the treatment of human brain cancer. For these purposes, I have developed many unique patient-derived xenograft (PDX) models for human brain tumors in the brains of immunocompromised mice. This animal model system has been shown to better preserve tumor characteristics, as manifested in patients, than tumor cell propagation in cell culture. In association with the development of these models, my laboratory utilizes numerous techniques to investigate brain tumor growth and response to novel agents that are administered singularly or in combinations, including with radiation. My laboratory employs the latest genomic/epigenomic technologies to identify novel genetic and epigenetics alteration that would reveal rational therapeutic targets, and test the anti-tumor activity of the therapeutics using PDX mouse model including diffuse intrinsic pontine glioma (DIPG) harboring histone H3 gene mutation (H3K27M). We have investigated the role of H3K27M mutations and histone modifications, and preclinical therapeutic testing in DIPG PDX models. In addition to the molecular targeted therapy, we recently implement AI machine learning approach and emerging patient genomic data to discover more effective and less toxic candidates from billions of compounds for brain tumor therapy. Moreover, we investigate new drug delivery systems to bypass the blood-brain barrier using convection-enhanced delivery and intranasal delivery. My long-term goal of my work further tests the efficacy of my approach preclinically and, if validated, move this therapeutic approach to clinical trial. In the meeting, I will present current advances in experimental therapeutics in my laboratory.