bluuebunny/crossref_metadata_2025_split huggingface dataset:
PEDT-18 PHASE I/II TRIAL OF OP-10 (ONC201) IN JAPANESE PATIENTS WITH RELAPSED OR REFRACTORY DIFFUSE MIDLINE GLIOMA
Authors: Okada Keiko , Narita Yoshitaka , Koga Yuhki , Nishikawa Ryo , Koh Katsuyoshi , Manabe Atsushi , Terashima Keita , Miyairi Kazunari , Taguchi Fumi , Hara Junichi 
Published: December 2022

Abstract

Background
Diffuse midline glioma (DMG) occurs mainly in the brain stem and most of patients have the mutation of histone (H3K27M). The prognosis is poor, and median overall survival (OS) is less than 12 months. OP-10 (ONC201) have antagonistic activity against dopamine D2 ha and to activate ClpP, a mitochondrial protease, leading tumor cells to apoptosis. We conducted a multicenter, single-arm, open-label phase I/II study of OP-10 in Japan.

Methods
A 3 + 3 design was used to determine the recommended dose of OP-10 for nine patients with recurrent or refractory glioma in the phase-I trial. Patients with recurrent or refractory DMG in the phase-II trial orally received OP-10 once weekly until discontinuation because of progression or adverse events. The efficacy and safety of OP-10 were evaluated in the phase-II part. The tumor objective response rate (ORR), the primary endpoint of the phase-II trial, was assessed through a blinded, independent central review according to RANO-LGG criteria.

Results
A total of 9 (age: 24-72 years) and 31 (age: 4-39 years) patients were administered in the phase-I and phase-II trials, respectively. Although the lower limit of the 90% confidence interval for ORR did not exceed the pre-specified threshold (5%), nine of 31 patients showed tumor regression on T2/FLAIR images. In the phase-II trial, the median OS was 28.4 weeks, and the OS rate at 6 months was 54.8%. Adverse events of grade ≥ 3 were reported in five of 31 (16.1%) patients in the phase-II part, with death of disease, hyperuricemia, malaise, pyrexia, alanine transaminase elevation, and aspartate transaminase elevation.

Conclusion
The results of this study suggested that OP-10 might be efficacious in some patients with recurrent or refractory DMG, without major safety concerns.
PEDT-19 RECENT PROGRESS IN CHILDHOOD BRAIN TUMORS RESEARCH
Authors: Terashima Keita 
Published: December 2022

Abstract
The multidisciplinary standard of care for medulloblastoma, a typical pediatric malignant brain tumor of cerebellar primary origin, has been established by large RCTs in the United States. The results of the Phase III RCTs sponsored by Children's Oncology Group's for newly-diagnosed medulloblastoma in children 3 years of age and older, ACNS0331, which attempted radiotherapy reduction for the average-risk group, and ACNS0332, which attempted intensified treatment with carboplatin as a radiosensitizer and isotretinoin as an apoptosis inducer for high-risk group are discussed.It has recently been reported that some infantile glioma cells have activating fusion genes with tyrosine kinase receptor genes, including NTRK, and that TRK inhibitors are effective against these tumors, and two TRK inhibitors have been used with cancer genome panel tests as companion diagnostics, Two TRK inhibitors can now be available for glioma treatment in Japanese practice. The results of clinical trials on the efficacy of these targeting agents in brain tumors with NTRK mutations will be presented.CAR-T cell therapy was developed for GD2 following HER2, which had attracted attention as an immunotherapeutic target for pediatric glioma, and its efficacy was demonstrated in clinical trials. We will examine the results of clinical trials of this immunotherapy, a promising treatment for DMS/DIPG, the disease with absolutely poor prognosis with no effective drug therapy, although it is used in a small number of cases.
IMT-1 PROS AND CONS OF SURGICAL INTERVENTION FOR DIFFUSE MIDLINE GLIOMA AIMED AT DENDRITIC CELL IMMUNOTHERAPY
Authors: Akasaki Yasuharu , Suzuki Tomoya , Takei Jun , Tanak Toshihide , Mori Ryosuke , Koseki Hirokazu , Yamamoto Yohei , Teshigawara Akihiko , Kamata Yuko , Yanagisawa Takaaki , Murayama Yuichi 
Published: December 2022

Abstract
Since a diffuse midline glioma (DMG) has no effective therapy, it is an urgent need to develop new therapeutic strategy. We performed immunotherapy using fusions of autologous dendritic cells (DC) with tumor cells in DMG cases in which tumor tissue was collected by surgery aimed at biopsy, and evaluate the effectiveness and examine the pros and cons of surgical intervention against DMG. Among the patients with basal ganglia or brain stem tumors received surgery at our hospital, 5 adult cases of DMG with H3K27M gene mutation were registered. All patients received radiation therapy and temozolomide chemotherapy. 4 cases received bevacizumab chemotherapy when the patients had recurrence or progression of the disease. The tumor-fused DCs (TFDC) were made by DCs induced from autologous peripheral blood mononuclear cells and tumor cells established from surgical specimens. They were injected subcutaneously into the neck 3 ~ 6 times in a 14 ~ 28 day cycle as the immunotherapy. The adverse events, PFS, and OS were evaluated. A transient complication of facial numbness was observed in one case on right after surgery. Although two patients had CR in those therapies, both of them died of disease (OS at 18 and 32 months, respectively). Since the remaining three cases were registered very recently, adverse event or treatment efficacy judgment have not been determined at the time of submission of the abstract. Serious surgical complications have not been observed in the presented cases. Surgery may be acceptable for DMG as long as the surgery is performed by sufficiently experienced surgeon in an appropriate environment. The TFDC immunotherapy, which can be performed only by collecting a small amount of tumor tissue, expects to be a novel treatment for MDG. In this presentation, the pros and cons of surgical intervention aimed at TFDC immunotherapy for DMG will be examined.
STMO-4 INITIAL EXPERIENCE WITH BRAIN TUMOR SURGERY USING STEALTH AUTOGUIDE
Authors: Kobayashi Yusuke , Satou Yosuke , Kon Takashi , Tanioka Daisuke , Shimizu Katsuyoshi , Mizutani Tohru 
Published: December 2022

Abstract
Tissue sampling of brain tumors is generally performed by biopsy with large or small craniotomy and stereotaxic brain biopsy. Recently, Stealth Autoguide, a robotic system for stereotactic deep electrode implantation and brain tumor biopsy in epilepsy, has become available. We report the initial experience of brain tumor surgery using stealth Autoguide in our hospital.Case: A man in his 70s. Left paralysis occurred during chemotherapy for esophageal cancer. Magnetic resonance imaging (MRI) revealed a ring-enhanced lesion from the right basal ganglia to the coronal radiatum. Because he was under steroid administration, he was diagnosed with metastatic brain tumor, malignant lymphoma, malignant glioma, or demyelinating disease. Since paralysis was progressing and MRS was suspected to be a malignant tumor, a stereotactic biopsy using a stealth autoguide was performed. Biopsies were performed with skin incisions of 1 cm or less from two locations that were automatically positioned based on the preoperative planning, and a sufficient amount of tissue was collected from the lesions. No complications such as bleeding were observed. Since the histological diagnosis was glioblastoma, chemotherapy with temozolomide and radiotherapy were promptly started.Brain tumor biopsy using stealth Autoguide allows accurate tissue sampling in a short period of time, and is a very useful tool for brain tumor diagnosis in the future.
STMO-13 PATHOLOGICAL EVALUATION AND ONCOLOGICAL OUTCOME OF FLAIRECTOMY IN PATIENTS WITH IDH1 WILD-TYPE GLIOBLASTOMA
Authors: Hirono Seiichiro , Kouchi Yusuke , Kishimoto Takashi , Kobayashi Masayoshi , Matsutani Tomoo , Iwadate Yasuo 
Published: December 2022

Abstract

Purpose
The pathological significance as well as oncological outcome of FLAIRectomy in patients with IDH1 wild-type Glioblastoma are unknown.

Methods
We conducted a retrospective review in newly-diagnosed, IDH1 wild-type glioblastoma who achieved gross total resection (GTR) of enhancing tumor. Pre- and post-operative volume of FLAIR abnormal area were also calculated. All patients underwent standard radiotherapy and temozolomide treatment, and monitored for tumor recurrence and overall survival (OS).

Results
A total of 25 GTR patients were included in the study, and the median FLAIRectomy and residual FLAIR volume were 51.5% and 19.6cc respectively. More than 80% of GTR patients unintentionally achieved 20% and more of FLAIRectomy. The pathological specimen of FLAIR abnormal area without gadolinium enhancement was obtained in 6 out of 25, and the typical features of GBM was found in only one. Following FLAIRectomy &gt;20%, majority of recurrence was local. The progression-free and overall survival of those 25 patients were 14.9 months and 30.5 months respectively.

Conclusion
Although this study confirmed the unintentional FLAIRectomy &gt;20% in most of GTR patients, the improvement of local control and survival was not clarified, necessitating prospective study with pathological and neurofunctional evaluation.
STMO-14 VALIDATION OF SURGICAL METHODS FOR GLIOMA AROUND THE MOTOR CORTEX
Authors: Nakahara Yukiko , Ito Hiroshi , Yoshioka Fumitaka , Masuoka Jun , Abe Tatsuya 
Published: December 2022

Abstract
Surgery for glioma around the primary motor area (primary MA) including premotor area (PA) and supplementary motor area (SMA) is performed by general anesthesia with motor evoked potential, called asleep surgery (Asleep S) or awake surgery (Awake S). The literature has shown that there is no difference in tumor removal rate and preservation of neurological function between the two methods. We retrospectively studied 14 patients who underwent craniotomy for glioma of the frontal lobe at our hospital, and 19 surgeries with contrast-enhancing lesions or T2 high-signal areas in the motor area. Tumor primary location was PMA: 6, PMA/ primary MA: 5, primary MA: 2, SMA 6 surgeries. All surgeries identified central sulcus by SEP and monitored transcranial and transcortical MEP. 11 surgeries were Asleep S and 8 were Awake S. Of the 11 Asleep S surgeries, 10 were high grade glioma with contrast on preoperative imaging. Of the 8 Awake S surgeries, 7 were lower grade gliomas, and most of these surgeries were performed for multiple recurrences. In Awake S, difficulties of assessment of motor function arose when the PMA and SMA were removed early in the surgery. In the case of Asleep S, to clarify the criteria for MEP warning signs is necessary, while in Awake S, the knowledge that how much motor decline is tolerated in voluntary movements need. In the case of Asleep S, to clarify the criteria for MEP warning signs is necessary, while in Awake S, the knowledge that how much motor decline is tolerated in voluntary movements need. In addition, the order of resection to avoid SMA syndrome and to evaluate motor function is important. We summarize the literatures and discuss these points for surgical strategy in glioma around motor area.
STMO-15 THE CLINICAL IMPACT OF VENTRICULAR OPENING IN THE IMPLANTATION OF BCNU WAFERS FOR MALIGNANT GLIOMA
Authors: Matsuda Ryosuke , Maeoka Ryosuke , Morimoto Takayuki , Yamada Shuichi , Nishimura Fumihiko , Nakagawa Ichiro , Park Young-Su , Nakase Hiroyuki 
Published: December 2022

Abstract

Objective
To evaluate the safety profile of bis-chloroethyl-nitrosourea (BCNU) wafer implantation after malignant glioma resection with or without ventricular opening (VO).

Methods
This single-center retrospective study included 61 consecutive patients with BCNU wafer implantation after malignant glioma resection between March 2013 and April 2021. The patients were categorized into two groups based on whether VO occurred during the malignant glioma resection. Fifty-three patients had glioblastoma, and eight had anaplastic astrocytoma or oligodendroglioma. Forty-five patients underwent an initial treatment, and 16 underwent recurrent surgeries. Symptomatic edema, newly occurring seizures within one month of the surgery, wound infection, brain abscess, hydrocephalus, cerebrospinal fluid leak, postoperative hemorrhage, and cyst formation were defined as adverse events (AEs).

Results
Twenty-nine patients underwent resection with VO, and 32 without. The median survival time was 28 months in the initial treatment group and 11.5 months in the recurrent treatment group. The with and without VO groups had similar median survival times. Postoperative AEs occurred in 7/29 patients (24.1%) with VO and 11/32 (34.4%) without VO, with no difference between them (p = 0.414).

Conclusions
This study showed that VO during surgery with BCNU wafer implantation might not influence the occurrence of postoperative AEs. If VO happens, BCNU wafer implantation can be performed safely with accurate closing of the ventricle.
STMO-17 USEFULNESS OF INTEGRATION OF PREOPERATIVE FUNCTIONAL IMAGING AND INTRAOPERATIVE MRI NAVIGATION SYSTEM IN GLIOMA SURGERY
Authors: Tamura Manabu , Sato Ikuma , Sito Taiichi , Nitta Masayuki , Tsuzuki Shunsuke , Koriyama Shunichi , Kuwano Atsushi , Masamune Ken , Kawamata Takakazu , Muragaki Yoshihiro 
Published: December 2022

Abstract

Purpose
Intraoperative magnetic resonance imaging (MRI) update navigation is performed in all cases to preserve neurological function and remove the tumor as much as possible, and to prevent recurrence and improve prognosis. And under awake craniotomy, we supported operators by integrating preoperative functional images with intraoperative MRI. We report our usefulness of image superimposition between medium magnetic field intraoperative MRI and preoperative position emission tomography (PET) and preoperative diffusion tensor imaging (DTI) color-map.

Method
Of more than 2,200 cases using intraoperative MRI since 2000, 58 preoperative PET (57 methionine and 1 FDG nuclides) superimposed cases (32 left-sided, 35 males, 15 under awake craniotomy, mean 44.8 y.o.) were evaluated. The tumor was located to 34 frontal-, 12 temporal-, 10 parietal lobes, 1 insular gyrus, 1 thalamus. Color-map image superimposition of preoperative DTI (3T, 6-axis application) anisotropic indices in 12 cases (localized in 8 frontal-, 2 insular-, 2 parietal lobes, 7 left-sided, 7 females, mean 35 y.o.). Neurophysiological monitoring was combined (5 under general, 7 awake anesthesia).

Results
The preoperative TN ratio was 3.8 (in 57 methionine-PET cases), and pathological results (Grade 3-4 in 15-31 cases respectively, out of 54 cases) were used for reliable and preferential removal of sites with higher malignancy and recurrence-prone sites. Recurrent cases (41/58) had altered brain structures that were too difficult to identify without the navigation. In the DTI cases, intraoperative MRI, DTI color-map, and microscopic surgical images were displayed on one screen, and white matter tracts information as a reference is quickly conveyed to operators, and helped to reduce perioperative neurological complications.

Conclusion
Co-registering an effective superimposition of medium magnetic field intraoperative MRI with high positional accuracy, and preoperative PET- and DTI- images according to the patient's characteristics is currently the most practical navigation application method for intraoperative prediction of important functional information.
RT-6 POTENTIAL AND PROSPECTS OF BORON NEUTRON CAPTURE THERAPY USING A COMBINATION OF MULTIPLE BORON AGENTS
Authors: Kawabata Shinji , Tsujino Kohei , Kashiwagi Hideki , Yoshimura Kohei , Hiramatsu Ryo , Nonoguchi Naosuke , Furuse Motomasa , Takami Toshihiro , Hu Naonori , Ono Koji , Miyatake Shin-Ichi , Wanibuchi Masahiko 
Published: December 2022

Abstract
Boron neutron capture therapy (BNCT) is a particle therapy that can target tumors at the cellular level. BNCT has been developed for the treatment of malignant gliomas with widely infiltrated tumors, but as the indication for BNCT was expanded to include the whole body, the focus shifted to borophalan-10B (BPA), which is based on the essential amino acid phenylalanine, as a candidate agent. We started BNCT for brain tumors in 2002 with a protocol combining two compounds (BPA, BSH) that had been clinically used, but later, with the development of an accelerator-based system, we conducted a clinical study of a single agent of BPA with a modified administration protocol in a nuclear reactor. In this report, we analyze the clinical studies of BNCT for recurrent malignant glioma using the reactor as a neutron source, and discuss the possibility of BNCT using multiple drugs in combination. The median survival with BSH+BPA was 11.0 months (n=29) overall, and the MST with BPA alone was 11.1 months (n=24), with similar results for BPA alone. The blood boron levels at the time of irradiation were 46.3 and 27.3 μg/ml, respectively, which were higher with the addition of BSH. The irradiation doses converted to X-rays (Gy) equivalent were calculated to be 69 and 76 Gy-Eq for the maximum tumor, 37 and 40 Gy-Eq for the minimum, and 10.9 and 10.5 Gy-Eq for the normal brain, respectively. The biological effectiveness ratios for tumor and normal tissue from neutron capture reactions with boron compounds and tissue boron concentrations were factored into these calculations, and since BPA and BSH have different target systems (BPA in the infiltration zone and BSH in the contrast zone, respectively), we believe that their combined use may improve therapeutic efficacy and attenuate adverse events.
MPC-8 CLINICAL CHARACTERISTICS OF H3 K27-MUTATED GLIOMAS AT MIDLINE AND NEAR MIDLINE
Authors: Hayashi Nobuhide , Fukai Junya , Nakatogawa Hirokazu , Kawaji Hiroshi , Okita Yoshiko , Kijima Noriyuki , Shofuda Tomoko , Yoshioka Ema , Kanemastu Daisuke , Katsuma Asako , Sumida Miho , Nakao Naoyuki , Mori Kanji , Kanemura Yonehiro 
Published: December 2022

Abstract

Background and Purpose
Diffuse midline glioma(DMG),H3K27 alterd (WHO 2021, CNS grade 4) is a type of tumor that mainly develops in the CNS's median. However, owing to its rarity, few comprehensive reports have been published. This report conducted a retrospective study on H3p.K27M mutation cases via the Kansai Molecular Diagnosis Network for CNS tumors.

Materials and Methods
H3p.K27M mutation cases were analyzed out of 4128 total gene analysis specimens submitted for suspected glioma during the case accumulation period from May 2007 to July 2022.

Results
There were 109 cases with the H3p.K27M mutation, of which 107 had the H3F3A mutation, and 2 had the HIST1H3B mutation. Of the 93cases that developed a tumor on or around the lateral ventricles of the brain along the midline of the CNS, affected sites included the thalamus (37 cases), brainstem (19 cases), spinal cord (11 cases), and other areas (15 cases), while 7 cases were of multifocal origin and 4 cases were unclassifiable. The patients' ages ranged from 4 to 76 years, with a mean and median age of 32.8 and 30 years, respectively (n = 88). The male to female ratio was 52:36. All cases had IDH-wild type with pMGMT methylation (9.6%), pTERT mutation (3.2%), TP53 mutation (56.5%), BRAF V600E mutation (1.1%), FGFR1 mutation (14.3%), or EGFR mutation (3.3%). Histopathological examination revealed the existence of WHO CNS grade 2, 3, and 4 tumors. Overall survival (OS) was confirmed in 38 cases, with a mean and median age of 15.0 and 11.9 months, respectively. The results of 51 cases in which prognosis was followed up on, suggested that the factors that contributed to the prolongation of OS were female sex (p = 0.0335), thalamus location (p = 0.0366), and irradiation of 50 Gy or more (p = 0.0237).

Discussion/Conclusion
Based on a literature review, we report on the clinical characteristics of DMG in our cases, including the category of midline in DMG.
MPC-10 RECURRENT ASTROCYTOMA WITH SOMATIC IDH MOSAICISM: A CASE REPORT AND WARRANT FOR MOLECULAR DIAGNOSTICS
Authors: Masui Kenta , Onizuka Hiromi , Nitta Masayuki , Muragaki Yoshihiro , Kawamata Takakazu , Komori Takashi 
Published: December 2022

Abstract

Introduction
Acquisition of somatic mutations is essential for the development of malignant tumors such as diffuse gliomas. Recent single-cell analyses have pointed out the importance of somatic mosaicism in the pathogenesis of cancer. Here we report a case of IDH (isocitrate dehydrogenase)-mutant astrocytoma that has relapsed after intensive chemoradiation with somatic mosaicism for the IDH1 R132H mutation.

Clinical and Pathological Findings
A 36-year-old male presented with epileptic symptoms and a mass lesion in the right frontal lobe. A needle biopsy demonstrated IDH-mutant astrocytoma (grade 2). At the age of 41, relapsed tumor was completely resected, and the tumor cells were diffusely positive for IDH1 R132H with grade 4 morphology. Chemoradiotherapy (PAV + IMRT 60Gy/30fr) was added, but contrast-enhanced lesions reappeared 5 months after the initial surgery. The re-excised specimen was grade 4 astrocytoma, and the number of IDH1 R132H-positive tumor cells was very small compared to the total number of tumor cells, suggesting somatic mosaicism for IDH mutations.

Conclusion
It is imperative to clarify the induction mechanism and significance of somatic cell mosaicism in cancer, and molecular genetic assessment with sequencing and digital PCR would be necessary in addition to immunostaining for accurate molecular diagnoses of the brain tumors.
MPC-15 CLINICAL FEATURE OF NON-MIDLINE GLIOMA WITH H3F3A GENE MUTATION
Authors: Nakatogawa Hirokazu , Kawaji Hiroshi , Hayashi Nobuhide , Fukai Junya , Kijima Noriyuki , Shofuda Tomoko , Yoshioka Ema , Kanematsu Daisuke , Katsuma Asako , Sumida Miho , Inenaga Chikanori , Mori Kanji , Kanemura Yonehiro 
Published: December 2022

Abstract

Introduction
Diffuse midline glioma (DMG), H3K27-altered, is a CNS WHO grade 4 glioma that usually occurs mainly in the brainstem region in children and also in the thalamus and spinal cord in older children and adults. On the other hand, glioma with histone H3 p. G34R/V mutations in the cerebral hemispheres are defined in a new classification of Diffuse hemispheric glioma, H3G34-mutant (DHG), in the WHO 2021 classification. However, there are some reports of H3K27-altered non-midline gliomas (NDMG) that are not located in the midline, but the differences between these hemispheric tumors with mutations in different regions of histone H3 are unknown. In this study, we report a comparative study of the clinical characteristics between two groups of glioma, H3K27-altered NDMGs and H3G34-mutant DHGs.

Methods
Among 4128 brain tumor specimens collected in the Kansai Network for Molecular Diagnosis of Central Nervous System Tumors, 25 NDMG cases, excluding 93 cases defined as DMG, were included out of 118 cases with mutations in the H3F3A gene. Both 16 H3K27-altered NDMG cases and 9 H3G34-mutant DHG cases were examined for comparison of clinical characteristics.

Results
There were no differences in gender, tumor location, or pathology between NDMG and DHG. The median age was 47.3 years in NDMG and 26.2 years in DHG, and NDMG was significantly older than DHG (p=0.003). The rate of MGMT promoter methylation is no significant difference between 4 cases (25%) in NDMG and 6 cases (66.7%) in DHG (p=0.087). The Kaplan-Meier survival curve showed no significant difference, with a median survival of 495 days for NDMG and 587 days for DHG (p=0.765).

Discussion and Conclusion
We reported on gliomas with H3F3A mutations that occur in the cerebral hemispheres. We compared the clinical characteristics of NDMG with H3K27-altered and DHG with H3G34-mutant, which have similar tumor locations of occurrence.