bluuebunny/crossref_metadata_2025_split huggingface dataset:
MPC-11 IDH1/2 MUTATIONS ARE ASSOCIATED WITH SEIZURE ONSET AND VETRY IMAGING IN PATIENTS WITH DIFFUSE GLIOMA VISUALIZING 2-HYDROXYGLUTARATE BY MASS SPECTRUM
Authors: Ohno Makoto , Hayashi Mitsuhiro , Aikawa Hiroaki , Matsushita Yuko , Miyakita Yasuji , Takahashi Masamichi , Ichimura Koichi , Hamada Akinobu , Narita Yoshitaka 
Published: December 2019

Abstract

BACKGROUND
Mutations in isocitrate dehydrogenase 1 or 2 genes (IDH1/2) frequently occur in lower-grade gliomas. Mutant IDH1/2 proteins gain a new ability to produce 2-hydroxyglutarate (2HG). IDH1/2 mutations have shown to be related with seizure through the structural similarity of 2HG to glutamate. We, therefore, sought to investigate the relationship between seizure and IDH1/2 mutations and to visualize tissue 2HG distribution in patients with diffuse gliomas.

METHODS
We assessed 149 patients with diffuse glioma, and measured tissue 2HG concentrations in 104 patients by using liquid chromatography-tandem mass spectrometry. The matrix-assisted laser desorption/ionization high resolution mass spectrometry imaging (MALDI-HR-MSI) was used to visualize tissue 2HG distribution for 12 tissue samples.

RESULTS
Seizure onset was observed in 34 among 56 (60.7%) patients with IDH1/2 mutant tumor, whereas in 18 among 93 (19.4%) patients with IDH1/2 wild-type tumor (p&lt;0.0001). The tissue 2HG concentration was significantly higher in IDH1/2 mutant tumor than in IDH1/2 wild-type tumor (median: 4862 ng/mg vs 75 ng/mg) (p&lt;0.0001). Multivariate analysis, including tissue 2HG concentration, IDH1/2 status, histology, grade, and location, showed that IDH1/2 mutations was significantly correlated with seizure onset. The MALDI-HR-MSI showed that 2HG spread in various concentration independent of cellularity and also in extracellular space in IDH1/2 mutant tumor tissue.

CONCLUSIONS
We demonstrated the association between IDH1/2 mutations and seizure, and the heterogeneous 2HG distribution not only in cellular area but also in extracellular space. These findings suggest the potential role of 2HG as an intercellular mediator to tumor environment, resulting in epileptogenesis formation.
MPC-14 BRAF V600E MUTANT OLIGODENDROGLIOMA-LIKE TUMORS WITH CHROMOSOMAL INSTABILITY IN ADOLESCENTS AND YOUNG ADULTS
Authors: Fukuoka Kohei , Tabori Uri , Hawkins Cynthia 
Published: December 2019

Abstract
We performed genome-wide methylation analysis on 136 pediatric low grade gliomas, identifying a unique cluster consisting of oligodendroglioma-like BRAF V600E mutant tumors with Recurrent gain of Chromosome 7 and loss of Chromosome 10 (OLIVER). Hierarchical clustering and t-stochastic neighbor embedding analyses cluster them with previously described pediatric-type low grade gliomas, separate from adult gliomas. OLIVERS exhibit distinct clinical behavior as temporal lobe lesions in adolescents and young adults, prolonged history of seizures and all are alive with no recurrence (follow-up 3.2 to 13.2 years). Morphogically, all showed oligodendroglioma-like features, including round nuclei with perinuclear halos, a chicken-wire pattern of branching capillaries and microcalcification. None showed astrocytic features or characteristics suggestive of high-grade tumors including necrosis or mitotic figures. All tumors harbored multiple chromosomal copy number abnormalities (more than 10 chromosomes per OLIVER), but none showed 1p/19q co-deletion or IDH1 mutation. Interestingly, one tumor showed a TERT promoter mutation. Although the series is small, OLIVER may represent a new category of IDH wild-type low grade gliomas which may be confused with molecular GBM. Further, they highlight the heterogeneity of IDH wild-type gliomas and the relatively indolent behavior of pediatric-type gliomas.
NI-14 EVALUATION OF PREOPERATIVE APPARENT DIFFUSION COEFFICIENT (ADC) OF PERITUMORAL LESION FOR PREDICTING SITE PRONE TO RECURRENCE IN PATIENTS WITH GLIOBLASTOMA
Authors: Matsuda Kenichiro , Sakurada Kaori , Kayama Takamasa , Sonoda Yukihiko 
Published: December 2019

Abstract

PURPOSE
In the surgery of glioblastoma (GBM), the maximum safe resection is desired in order to prevent recurrence. The purpose of this study is to make it possible to evaluate the site in which the recurrence after resection of the tumor occur, according to the findings in preoperative MRI, and to avoid the recurrence.

METHOD
The 26 initial cases with GBM treated in our department was investigated. Preoperative MRI, postoperative MRI, and follow-up MRI during the course were analyzed in a retrospective view. In the FLAIR high-signal area around the contrast-enhanced tumor body in preoperative MRI, we investigated the relationship between the site and the ADC value, from the standpoint of whether a recurrence occurred or not.

RESULTS
For preoperative MRI of 26 patients, the FLAIR high-signal region was set to a total of 54 ROI, and several values, such as the ADC values, were measured. In the preoperative images, ADC were higher in the site where the no recurrence occurred during the postoperative course and lower in the site where the recurrence occurred.

CONCLUSION
In the FLAIR high-signal area around the tumor in preoperative images, ADC value is useful in evaluating whether it has tendency to develop the recurrence in the future course or not. It was suggested that significant recurrence occurs at part with low-ADC value. It is considered useful for the planning of the extent of resection in the surgery and the irradiation range in radiation treatment.
NQPC-07 IMMEDIATE POSTOPERATIVE REHABILITATION FOR PATIENTS WITH NEWLY-DIAGNOSED GLIOMA
Authors: Ikeda Mitsuyo , Yamada Shin , Okajima Yasutomo , Saito Kuniaki , Kobayashi Keiichi , Shiokawa Yoshiaki , Nagane Motoo 
Published: December 2019

Abstract

BACKGROUNDS
Importance of early intensive rehabilitation is recently emphasized not only for Stroke Unit but for Intensive Care Unit. We have started such early comprehensive rehabilitation for patients after brain tumor surgery. Rehabilitation therapists were specially assigned to our brain surgery unit as members of the ward staffers. The purpose of this study is to show how this rehabilitation trial works for post-surgery patients with glioma.

METHODS
Thirty-two patients with glioma (20 males and 12 females) who were admitted to our institution in the year of 2018 were included. Mean age was 61.8±13.3 years; glioblastoma was the major tumor type (24 patients). We retrospectively analyzed rehabilitation outcome focusing on improvement of the Functional Independence Measure (FIM) scores during hospitalization.

RESULTS
Mean duration from surgery to the first rehabilitation intervention was 2.4±1.2 days, and mean hospital stay was 74.4±31.4days. Twenty patients were discharged to home (62 %) and 12 were transferred to other hospitals for convalescence. Motor, cognitive and total FIM scores were 41.0±22.2, 18.0±7.5, and 59.1±27.3 before surgery, whereas they were 61.4±28.6, 21.8±9.4, and 83.2±36.9, respectively, at discharge. Motor FIM items revealed more remarkable improvement than those of cognitive ones. Since starting the early intensive rehabilitation trial, patients with brain tumor have been systematically rehabilitated with an organized manner before and after surgery.

CONCLUSION
Early intensive rehabilitation for patients with brain tumor is recommended to be done by on-ward therapists who are assigned to work specially as members of the ward. Both motor and cognitive improvement is expected during hospitalization even in patients with malignant brain tumor.
NQPC-10 END-OF-LIFE PHASE OF GLIOBLASTOMA
Authors: Omura Tomoko , Miyakita Yasuji , Omura Takaki , Ohno Makoto , Takahashi Masamichi , Satomi Natsuko , Fujimoto Kenji , Narita Yoshitaka 
Published: December 2019

Abstract

BACKGROUND
Despite aggressive treatment with surgery and chemo-radiation therapy, it is difficult to cure patients with glioblastoma (GBM). The end-of-life (EOL) phase of patients with GBM, and related problems, have not yet been adequately studied. Most cancer patients died in the hospital (84%) in 2017, but the Japanese government has recommended palliative home-care and the number of deaths at home has recently been increasing. This study explores the current situation of EOL care for GBM patients in our hospital.

METHODS
We retrospectively examined the clinical course and EOL phase of 166 consecutive patients who were treated in our hospital between 2010 and 2017.

RESULT
In total, 107 patients died; 28 (26%) at home, 25 (23%) in hospice care, 9(9%) in nursing homes, 21(20%) in long-term care hospitals (LTCH), 13(12%) in our hospital, and 11(10%) in other neurosurgical hospitals. The median survival time and length of EOL phase for patients who died at home were 596 and 77 days; 469 and 103 days in hospice care; 528 days and 149 days in LTCH; 388 days and 52 days in our hospital; 802 and 91 days in other neurosurgical hospital; and 565 days and 55 days in nursing homes, respectively. The KPS of patients who transferred to LTCH or was started palliative care in other neurological hospital was 60. That of other patients was 50.The patients who died at home entered deep coma in the last 3.5 days (n=24) of life and could not take oral feeds for 7 days (n=26).

CONCLUSION
According to cancer patient study, the home-based palliative time of longer prognosis group were 59 days. EOL phase of GBM may be longer than other cancer. We must consider the problems of the EOL phase and improve the quality of EOL care.
ML-02 MULTIAGENT IMMUNOCHEMOTHERAPY, R-MPV-A, FOR PATIENTS WITH SECONDARY CENTRAL NERVOUS SYSTEM LYMPHOMA
Authors: Nagane Motoo , Kobayashi Keiichi , Saito Kuniaki , Shimada Daisuke , Matsumoto Yoshie , Iijima Shohei , Sasaki Nobuyoshi , Yamagishi Yuki , Takayama Nobuyuki , Shiokawa Yoshiaki 
Published: December 2019

Abstract

BACKGROUNDS
Standard of care (SOC) for primary central nervous system lymphoma (PCNSL) has been induction therapy with high-dose methotrexate (MTX)-based multiagent immunochemotherapies followed by consolidation, and we have shown that one such regimen, R-MPV-A have superior efficacy over HD-MTX alone with whole brain radiotherapy (WBRT). While SOC for secondary CNS involvement of systemic diffuse large B-cell lymphoma (DLBCL)(SCNSL) has not been established. Here we report the outcome of R-MPV-A for patients with SCNSL.

PATIENTS AND METHODS
Fifteen patients with SCNSL treated with R-MPV-A from January 2014 to January 2019 in Kyorin University Hospital were eligible. Prior treatment for systemic DLBCL was mostly R-CHOP. Response and survival outcomes were evaluated.

RESULTS
Median age was 68.0 y (55–84), male/female 6/9, median KPS 70 (40–90), histopathological confirmation was achieved in 12 patients (80%; biopsy 11). RMPV (rituximab+MTX+procarbazine+vincristine) 3 cycles in 3, 4–7 cycles in 6, 8 cycles in 5. WBRT and cytarabine were delivered in 6 and 9 patients, respectively. R-MPV resulted in 6 CRs/CRus, 5 PRs, 1 SD, and 2 PDs (Response rate 73%). R-MPV-A including consolidation led to 9 CRs/CRus, 2 PRs, 1 SD, and 2 PDs (complete response rate 60%). With median F/U period of 11.2 m (0.1–51.5), 1y-PFS and 2y-PFS of R-MPV-A were 66.0% and 56.6%, 1y-OS and 2y-OS were 72.2% and 72.2%, respectively. Median PFS/OS were not reached. Consolidation cytarabine was associated with better outcome. Three deaths occurred during the treatment (20%; two during R-MPV with aged 70s, KPS 40 and 50; one presented MTX clearance delay). No other serious adverse events were observed.

CONCLUSIONS
These results suggest the certain efficacy of R-MPV-A for SCNSL. Being heavily pretreated frequently, precautions should be taken to identify high risk cases.
ML-05 A CASE OF NEUROLYMPHOMATOSIS ARISED SECONDARILY FROM PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA
Authors: Horiguchi Keishi , Asano Hirofumi , Osawa Tadashi , Tosaka Masahiko , Yoshimoto Yuhei 
Published: December 2019

Abstract
A woman in her 40s. A biopsy of multiple intracranial lesions was performed, and the patient was diagnosed with DLBCL. As an initial treatment, 6 courses of high dose MTX therapy were performed and CR was achieved. Radiation therapy was not desired by the patient. On the 19th month after initial treatment, tumor recurrence was confirmed by MRI and added 2 courses of HD-MTX. On the 23rd month, second recurrence around the left basal ganglia were observed. One additional course of HD-MTX was performed, but due to the appearance of renal damage that was thought to be acute tubular necrosis, additional HD-MTX was not performed and whole brain irradiation was performed. She began complaining of pain in the trunk and extremities during radiation. When MRI and FDG-PET were performed in the 25th month, multiple lesions were found in the ganglia, plexus, and peripheral nerves from the cervical spinal cord to the sacral spinal cord. Cerebrospinal fluid cytology revealed atypical lymphocytes and lymphoma dissemination in the spinal cord. When intrathecal administration of the anticancer agent was performed nine times weekly, the CSF cytology was negative. Imaging findings showed that the lesions relapsed, although the lesions were temporarily reduced. After confirming that the renal function had recovered, two additional courses of HD-MTX were performed. Accumulation of FDG-PET in the lesion disappeared in the 29th month. However, peripheral neuropathic pain and paraplegia remained. Discussion: Neurolymphomatosis is considered to be a clinically rare disease that presents invasion of lymphoma into peripheral nerves including the cranial nerves, nerve roots or plexus. Diagnosis of NL has been required to be proved by nerve biopsy or autopsy, but noninvasive FDG-PET has been reported to be effective. In this case, CR was not obtained with anticancer drug intrathecal injection, and HD-MTX therapy was successful.
ML-09 DIAGNOSIS AND TREATMENT OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA IN HIV POSITIVE PATIENTS
Authors: Takano Koji , Nishimoto Keisuke , Yamazaki Hiroki , Murakami Koki , Tachi Tetsuro , Kidani Tomoki , Kanemura Yonehiro , Nakajima Shin , Masuda Tomohito , Kurusu Tomomi , Hirota Kazuyuki , Uechi Takashi , Watanabe Dai , Nishida Yasuharu , Uehira Tomoko , Fujinaka Toshiyuki 
Published: December 2019

Abstract

INTRODUCTION
HIV infection is known to cause a variety of central nervous system complications, such as malignant lymphoma (ML), toxoplasma encephalopathy, cryptococcal encephalopathy, progressive multifocal leukoencephalopathy (PML), brain tuberculosis and HIV encephalopathy. In our hospital, we performed brain biopsy for HIV-positive patients with central nervous system lesions suspected malignant lymphoma, or cases difficult to diagnose with blood, cerebrospinal fluid, and imaging alone. In this study, we retrospectively examined HIV-positive patients who underwent brain biopsy at our hospital, and analyzed diagnosis and treatment of patients with ML.
Methods HIV-positive patients who underwent brain biopsy in our hospital from January 2010 to April 2019 were examined in this study. We analyzed background factors, preoperative examination results, pathological diagnosis, treatment and prognosis.

RESULTS
There were 1,894 HIV-positive patients who were treated at our hospital during the period, of which 16 cases underwent a total of 18 brain biopsies. The final diagnosis was 7 ML (6 PCNSL, 1 brain metastasis), 3 toxoplasma encephalopathy, 1 PML, 1 brain tuberculosis, 1 immune reconstitution syndrome, 1 Penicillium marneffei infection, 1 hematoma and one case that could not be diagnosed. In patients with ML, preoperative sIL-2 receptor was higher and EBV positive cases in cerebrospinal fluid tended to be more common (p=0.051, p=0.086, respectively). Five of the six patients with PCNSL were treated at our hospital, four of which were treated with highly active antiretroviral treatment (HAART) and whole-brain irradiation and one with HAARA alone, resulting four with CR and one with SD. Four patients, except one who had sudden death of unknown cause, were still alive without recurrence (median observation period 44.5 months).

CONCLUSION
At the moment, it is difficult to diagnose ML without brain biopsy. HIV-positive status has been regarded as a poor prognosis factor in PCNSL patients, but the prognosis seems to have improved with HAART.
MET-01 INDICATION AND OUTCOME OF SALVAGE SURGERY FOR LOCAL PROGRESSION OF BRAIN METASTASIS PREVIOUSLY TREATED WITH STEREOTACTIC IRRADIATION
Authors: Mitsuya Koichi , Deguchi Shoichi , Nakasu Yoko , Hayashi Nakamasa 
Published: December 2019

Abstract

PURPOSE
To determine treatment outcome following salvage surgery (SS) for local progression of brain metastasis treated by stereotactic irradiation (STI).

METHODS
The clinical records of patients who underwent SS of local progression of brain metastases after STI at our institute between October 2002 and July 2019 were retrospectively reviewed. Kaplan-Meier curves were used for the assessment of overall survival (OS). The decision to perform SS was based on findings of magnetic resonance imaging and/or clinical evidence of local progression of the brain metastases and status of systemic disease. Prognostic factors for survival were analyzed; age, sex, primary cancer, RPA classification at surgery, extent of resection, radiotherapy after salvage surgery, and pre-surgical neutrophil-to-lymphocyte ratio (NLR).

RESULTS
Fifty-four SS of 48 patients were performed. The median age of the patients was 63 years (range 36–79). The median interval from STI to SS was 12 months. The median overall survival was 20.2 months from SS. Primary cancer were lung 34, breast 10, and other 10. Fourteen of 54 lesions (26%) developed local recurrence. Leptomeningeal dissemination occurred after the SS in 3 patients (5.7%). RPA classification (1 vs 3, HR:0.16, 95%CI: 0.03–0.59) (2 vs 3, HR:0.44, 95%CI:0.19–0.97) and primary cancer (breast vs lung, HR:0.21, 95%CI:0.05–0.64) (breast vs others, HR:0.08, 95%CI:0.015–0.32) (lung vs others, HR:0.38, 95%CI:0.16–0.94)) were identified as good prognostic factors of overall survival in multivariate analysis. The optimum NLR threshold value was identified as 3.65 for 1-year survival from SS (AUC0.62, sensitivity:71%).

CONCLUSIONS
Salvage surgery for local progression of brain metastases after STI in selected cases leads to a meaningful improvement in survival.
CS-04 INTEGRATED CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR DATA ANALYSIS OF 190 CENTRAL NERVOUS SYSTEM GERM CELL TUMORS FROM THE IGCT CONSORTIUM
Authors: Takami Hirokazu , Fukuoka Kohei , Mukasa Akitake , Saito Nobuhito , Shibui Soichiro , Nakazato Yoichi , Nishikawa Ryo , Matsutani Masao , Ichimura Koichi 
Published: December 2019

Abstract

BACKGROUND
We integrated clinical, histopathological, and molecular data of central nervous system germ cell tumors to provide insights into their management.

METHODS
Data from the Intracranial Germ Cell Tumor Genome Analysis Consortium were reviewed. A total of 190 cases were classified as primary GCTs based on central pathological reviews.

RESULTS
All but one of the cases that were bifocal (neurohypophysis and pineal glands) and cases with multiple lesions including neurohypophysis or pineal gland were germinomas (34 of 35). Age was significantly higher in patients with germinoma than other histologies. Comparison between tumor marker and histopathological diagnoses showed that 18.2% of histopathologically diagnosed germinomas were marker-positive and 6.1% of non-germinomatous GCTs were marker-negative, suggesting a limitation in the utility of markers or histopathology alone using small specimens for diagnosis. Comparison between local and central histopathological diagnoses revealed a discordance of 12.7%. Discordance was significantly less frequent in biopsy cases, implying difficulty in detecting all histopathological components of heterogeneous GCTs. Germinomas at the typical sites (neurohypophysis or pineal gland) showed a better PFS than those at atypical sites (p=0.03). A molecular-clinical association study revealed frequent MAPK pathway mutations in males (51.4 vs 14.3 %, p=0.007), and PI3K/mTOR pathway mutations in basal ganglia cases (p=0.004). Basal ganglia cases also had frequent chromosomal losses. Some chromosomal aberrations (2q, 8q gain, 5q, 9p/q, 13q, 15q loss) showed potential prognostic significance.

CONCLUSIONS
These in-depth findings of this study regarding the clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.
CS-12 IDH-1 MUTANT GLIOMA IN BROTHER AND SISTER, ONSET AT AGE OF 30s
Authors: Kitai Ryuhei , Yamauchi Takahiro , Neishi Hiroyuki , Isozaki Makoto , Tsunetoshi Kenzo , Matsuda Ken , Arishima Hidetaka , Kodera Toshiaki , Kikuta Ken-ichiro 
Published: December 2019

Abstract
A 38-year-old man consulted with our neurosurgery group at University of Fukui hospital, due to tonic-clonic seizures. An MRI revealed a non-enhanced intra-axial tumor at the left frontal lobe. CT showed no calcification in the tumor. The tumor was removed by awake brain surgery. The pathological specimen was diagnosed as a diffuse astrocytoma with IDH-mutant. Immunohistochemical staining and DNA sequencing confirmed a R132H mutation at IDH-1. Telomerase Reverse Transcriptase (TERT) promoter mutation and 1p 19q codeletion was not evident. Four years later, his sister, a 40-year-old woman, had an MRI as a routine medical check that found a right frontal tumor at the mirror site of her brother’s tumor, and with identical radiological findings. The tumor was completely removed. The specimen revealed oligodendrocytoma, with mutant IDH and 1p/19q co-deleted. DNA sequencing showed also R132H at IDH-1. TERT promoter mutation was evident at C228T, which is a surrogate marker for oligodendroglioma. IDH-mutant astrocytoma and oligodendroglioma in siblings; and germline mutation of IDH have not been reported. However, the respective incidences of astrocytoma and oligodendroglioma are 0.55/100,000/year and 0.26/100,000/year according to United State statistics, which indicates that merely coincidental occurrence of these tumors is extremely unlikely. A trigger for IDH mutation that runs in rare families could warrant whole-genome sequencing.
CS-14 A CASE OF CIC-REARRANGED INTRACRANIAL SARCOMA
Authors: Tanaka Shota , Sato Daisuke , Ikemura Masako , Takayanagi Shunsaku , Tsutsumi Kazuo , Saito Nobuhito 
Published: December 2019

Abstract

INTRODUCTION
Intracranial sarcoma is extremely rare among primary brain tumors and often misdiagnosed. Its standard treatment is yet to be established, and treatment options are discussed on a case-by-case basis. Here we report our recent case of intracranial sarcoma review the relevant literature.

CASE ILLUSTRATION
A 57-year-old right-handed man presented with headache and was found to have a 5cm mass in the right frontal lobe. Gross total resection was achieved without complications. Given the local pathological diagnosis being glioblastoma, adjuvant radiotherapy with concurrent temozolomide was administered. Further pathological examination revealed Capicua (CIC) rearrangement on FISH, which lead to the diagnosis of sarcoma. No further treatment was pursued at that time. However, he noticed rapid decline in the right visual acuity 7 months from the initial diagnosis. MRI demonstrated a rapidly-growing mass in the right optic nerve sized 1.5cm, which was depicted as a high uptake area on FDG-PET, suggestive of recurrence. Two cycles of chemotherapy with vincristine, ifosfamide, doxorubicin, and etoposide as well as GammaKnife stereotactic radiosurgery were performed with partial response. Sustained myelosuppression and debilitating constitutional symptoms precluded additional chemotherapy. No further recurrence was noted 1 year after diagnosis.

CONCLUSION
We have recently experienced a case of CIC-rearranged intracranial sarcoma. FISH was useful in detecting CIC rearrangement and reaching the correct pathological diagnosis. Rapid recurrence of the tumor was noted, but well controlled with radiochemotherapy.