bluuebunny/crossref_metadata_2025_split huggingface dataset:
10211- GEN-12 IDENTIFICATION OF PROGNOSIS-RELATED METHYLATION PROFILES AND METHYLATION BIOMARKERS IN IDH-WILD-TYPE GLIOBLASTOMA
Authors: Saito Kuniaki , Satomi Kaishi , Shimizu Saki , Kugasawa Kazuha , Sasaki Nobuyoshi , Kobayashi Keiichi , Shibahara Junji , Ichimura Koichi , Nakotmi Hirofumi , Nagane Motoo 
Published: November 2024

Abstract

BACKGROUND
Genome-wide DNA methylation analysis is currently available and is used to diagnose brain tumors. Although MGMT promoter hypermethylation is a strong biomarker in glioblastoma (GBM), there are few reports of DNA methylation profiles associated with prognosis or other DNA methylation biomarkers. In this study, we examined DNA methylation profiles correlated with prognosis and DNA methylation biomarkers.

METHODS
We selected 20 long-term survivors (LS) and 20 short-term survivors (SS) from 407 patients with newly diagnosed IDH-wild-type GBM treated at our institution, divided by MGMT methylation status (methylated; M/unmethylated; U), and adjusted for age. DNA methylation analysis was performed by EPIC array, and DKFZ classifier, tSNE analysis, and copy number analysis were performed. DNA methylation data and DNA methylation profiles were compared between LS and SS groups.

RESULTS
There were no significant differences in age and sex between the LS and SS groups in the M and U groups, respectively. Median OS (months) in the M group was 62.1/17.3 in LS/SS and 28.1/6.8 in the U group. Differentially methylated genes in the promoter region between LS/SS groups in the M group were HOXD13 and HAGH (methylated in LS), KCTD14 and ALPK3 (methylated in SS). Those in the U group were KLF14 and HOXB4 (methylated in LS), ZMYND10 and SLFN13 (methylated in SS). Gene Ontology analysis revealed that the genes with a hypermethylated promoter in the LS are enriched in G protein-coupled receptor signaling pathway and plasma membrane in the M group and Homeobox antennapedia and sequence-specific double-stranded DNA binding in the U group.

CONCLUSION
We identified DNA methylation biomarkers and key pathways involved in the prognosis of GBM with methylated and unmethylated MGMT promoter. Multi-omics analysis is necessary to validate the mechanism related to the prognosis of GBM.
10022- ET-2 DEVELOPMENT OF MICROSURGICAL FORCEPS EQUIPPED WITH HAPTICS TECHNOLOGY FOR IN SITU DIFFERENTIATION OF BRAIN TUMORS DURING MICROSURGERY
Authors: Ezaki Taketo , Kishima Kohki , Shibao Shunsuke , Matsunaga Takuya , Pareira Eriel Sandika , Nakayama Yuji , Tsuda Noboru , Kitamura Yohei , Takahara Kento , Iwama Takashi , Sampetrean Oltea , Ohnishi Kouhei , Shimono Tomoyuki , Sasaki Hikaru 
Published: November 2024

Abstract
The stiffness of human cancers may be corelated with their pathology, and can be used as a biomarker for diagnosis, malignancy prediction, molecular expression, and postoperative complications. Neurosurgeons perform tumor resection based on tactile sensations. However, it takes years of surgical experience to appropriately distinguish brain tumors from surrounding parenchymal tissue. Haptics is a technology related to the touch sensation. Haptic technology can amplify, transmit, record, and reproduce real sensations, and the physical properties (e.g., stiffness) of an object can be quantified. In the present study, glioblastoma (SF126-firefly luciferase-mCherry [FmC], U87-FmC, U251-FmC) and malignant meningioma (IOMM-Lee-FmC, HKBMM-FmC) cell lines were transplanted into nude mice, and the stiffness of tumors and normal brain tissues were measured using our newly developed surgical forceps equipped with haptic technology. We found that all five brain tumor tissues were stiffer than normal brain tissue (p&lt;0.001), and that brain tumor pathology (three types of glioblastomas, two types of malignant meningioma) was significantly stiffer than normal brain tissue (p&lt;0.001 for all). While glioblastomas showed no significant stiffness differences (p=0.468), IOMM-Lee-FmC was stiffer than HKBMM-FmC among meningiomas (p=0.032). Histologically, compared with IOMM-Lee-FmC, HKBMM-FmC showed abundant necrotic foci (i.e., similar to glioblastoma), which may explain the differences in stiffness.
10025- ET-3 IDENTIFICATION OF A NEW MOLECULAR TARGET FOR MESENCHYMAL GLIOBLASTOMA AND ITS FUNCTION
Authors: Miyazono Kohei , Tanabe Ryo , Matsumoto Takehisa 
Published: November 2024

Abstract
In order to identify molecular target(s) for treatment of glioblastoma multiforme (GBM), we searched for genes characteristically expressed in mesenchymal (MES)-type GBM and identified HVEM (herpes virus entry mediator, also known as TNF receptor superfamily 14), whose expression is higher in brain tumor tissue than in normal brain, especially in MES-type GBM. Furthermore, a significant correlation between HVEM expression and prognosis of GBM patients was found. Using GBM cells from HGCC (human glioblastoma cell culture) bank, the effect of HVEM was analyzed. Knockdown of HVEM expression in MES-type GBM cells resulted in a significant reduction in proliferative and sphere-forming capacity in vitro and loss of stem cell-like characteristics was observed. In an intracranial transplantation study in nude mice, tumor-forming capacity was also inhibited in MES-type GBM cells in which HVEM expression was knocked down, and mouse survival was significantly prolonged. For targeting HVEM, we generated alpaca-derived anti-human HVEM VHH (variable domain of heavy chain of heavy chain antibody) antibody, and analyzed the effects of the VHH antibody on MES-type GBM cells in vitro and in vivo. Currently, we are conducting preclinical studies using the VHH antibody targeting human HVEM and promoting research for future clinical application of human HVEM antibodies to MES-type GBM (This work has been conducted in collaboration with Drs. Carl-Henrik Heldin and Bengt Westermark, Uppsala University, Sweden).
10309- ACT-18 A PHASE 1, RANDOMIZED, PERIOPERATIVE TRIAL OF VORASIDENIB AND IVOSIDENIB IN DIFFUSE GLIOMA WITH AN IDH1 MUTATION: UPDATED RESULTS
Authors: Cloughesy Timothy F , Mellinghoff Ingo K , Wen Patrick Y , Taylor Jennie W , Maher Elizabeth A , Arrillaga-Romany Isabel , Ellingson Benjamin M , Mahboub-Johnson Paria , Baron Eric , Hassan Islam , Steelman Lori , Clarke Jennifer L 
Published: November 2024

Abstract

INTRODUCTION
Vorasidenib (VOR) and ivosidenib (IVO) showed clinical activity in patients with isocitrate dehydrogenase mutant (mIDH) gliomas. We evaluated both agents in a Phase 1, randomized, open-label perioperative trial (NCT03343197). Pharmacodynamics, pharmacokinetics and preliminary objective response rate (ORR) data as of April-29, 2020 were previously reported (Mellinghoff et al. Nat Med 2023). Progression-free survival (PFS) data were not mature at publication time. Herein, we report longer-term follow-up results, including mature PFS.

METHODS
Patients with grade 2/3 non-enhancing mIDH1 R132H mutant gliomas were randomized to VOR (50 or 10 mg QD), IVO (500 or 250 mg BID), or no treatment (control) for 4 weeks prior to planned surgery, with the option to continue treatment with VOR or IVO postsurgery. Secondary objectives included PFS, ORR assessed by investigator in the postsurgery period, and safety profile of VOR and IVO.

RESULTS
Enrollment completed in April-2019. Of the 49 patients randomized, 46 (24 oligodendroglioma, 20 astrocytoma, one anaplastic oligodendroglioma, one anaplastic oligoastrocytoma) received treatment with either VOR (n=24) or IVO (n=22) after surgery. As of data cutoff (September-23, 2023), 11 (46%) and five (20%) patients remained on treatment for VOR and IVO, respectively. Median (range) post-operative treatment duration was 44.7 months (0.9–62.7) for VOR, 23.9 months (0–62.7) for IVO. Median (95% CI) PFS was 41.4 months (9.3–NE) for VOR, 38.6 months (18.3–NE) for IVO. ORR per Response Assessment in Neuro-Oncology in low-grade gliomas was 46% for VOR and 27% for IVO. Longer safety follow-up will also be presented.

CONCLUSIONS
These results provide further evidence of prolonged response using IVO and VOR immediately following surgery in predominantly non-enhancing gliomas. This longer-term follow-up is consistent with Phase 3 INDIGO study results in which VOR demonstrated PFS benefit with manageable safety, compared with placebo, in patients with non-enhancing mIDH gliomas.
10100- NQPC-4 ACTIVITIES OF OITA UNIVERSITY NEUROSURGICAL UNIT TO ESTABLISH ACP SUPPORT FRAMEWORK FOR BRAIN TUMOR PATIENTS
Authors: Fudaba Hirotaka , Satou Chizuru , Abe Kayo , Momii Yasutomo , Kawasaki Yukari , Takao Kunpei , Yanagida Masayuki , Anan Mitsuhiro , Hata Nobuhiro , Inoue Ryo , Fujiki Minoru 
Published: November 2024

Abstract

BACKGROUND
Advance care planning (ACP) involves thinking ahead about desired medical treatment and care at the end of life and discussing and sharing this information with the medical and care team. Our facility in Oita Prefecture, which performs surgery and induction chemoradiotherapy for malignant brain tumors, has been providing ACP support for brain tumor patients since 2019. We report on our multidisciplinary collaboration activities and evaluation, including creating a brain tumor-specific ACP leaflet in July 2022.

METHODS
We organized an “ACP Support Team for Brain Tumor Patients” and began bi-weekly ACP conferences. We analyzed 79 patients using the achievement rate of each ACP step and the number of times the process was repeated during hospitalization. Additionally, a questionnaire survey was conducted to assess changes in “nursing practice regarding decision support” for patients with malignant brain tumors and their families due to ACP conferences.

RESULTS
Forty-eight patients were supported by the leaflet, and 31 were not. Both groups mostly achieved confirmation of their priorities and selection of a decision-making representative. However, the achievement rate of discussion and documentation steps in ACP significantly improved after the leaflet’s introduction. The questionnaire survey revealed changes in nursing practices, including “intentional information gathering based on the progress of the brain tumor,” “reflection on nursing practice,” “sharing the patient’s intention with the whole team,” and a “positive attitude toward ACP practice.”

CONCLUSION
The brain tumor-specific ACP leaflet was effective in supporting ACP for brain tumor patients. Additionally, the ACP conference raised awareness of the importance of ACP in nursing practice from the early stages of the disease. Multidisciplinary cooperation played a crucial role in decision-making support.
10116- NQPC-6 USEFULNESS OF THE NEUROPSYCHOLOGICAL QUICK ASSESSMENT IN THE EVALUATION OF NEUROPSYCHOLOGICAL COMPLICATIONS IN PATIENTS WITH PEDIATRIC BRAIN TUMORS
Authors: Tabata Ami , Ueda Keita , Nukui Megumi , Komaki Misa , Arakawa Yoshiki 
Published: November 2024

Abstract

BACKGROUND
Neuropsychological complications impair the qualitative prognosis of patients with pediatric brain tumors. However, multifaceted evaluation cannot be conducted for all patients owing to various issues, such as time constraints or burden on patients. The Neuropsychological Quick Assessment (NQA) was devised by the Japan Children’s Cancer Group as a screening assessment tool for neuropsychological complications, but without reliability and validity. In this study, we examined the usefulness of NQA in the assessment of neuropsychological complications in patients with pediatric brain tumors.

METHODS
Patients with pediatric brain tumors treated at Kyoto University Hospital were enrolled. The NQA and functional outcomes (neurocognitive outcome; WISC-IV/WAIS-IV, motor coordination outcome; BOT-2, fatigue; CFS, social behavior outcome; CBCL/ABCL) were assessed (approved by the Kyoto University Graduate School and Faculty of Medicine, Ethics Committee; R1580). We categorized the NQA into five subscales according to the content of the assessments: Neurocognitive, Directional Attention, Coordination, Fatigue, and Social Behavior. The correlations between each subscale score (except Directional Attention) of the NQA and functional outcomes were calculated using Spearman rank correlations.

RESULTS
This study included 17 patients with pediatric brain tumors with a median age of 14.0 years. The FSIQ (WISC-IV/WAIS-IV) and the Total Motor Composite (BOT-2) strongly negatively correlated with the Neurocognitive score and the Coordination score (ρ=-0.7851, -0.7746; p=0.0002, 0.0007, respectively). Moreover, the score of CFS and the Total T-score (CBCL/ABCL) positively correlated with the Fatigue score and the Social Behavior score (ρ=0.5127, 0.5488; p=0.0353, 0.0225, respectively).

CONCLUSIONS
Each subscale score of the NQA showed a strong correlation with each functional outcome. Therefore, we believe that the NQA is a simple and clinically useful method for assessing neuropsychological complications in patients with pediatric brain tumors. One limitation of this study is its small sample size; therefore, further investigation is required.
10153- NQPC-7 ADVANCING COGNITIVE ASSESSMENT IN GLIOBLASTOMA TREATMENT WITH MOLECULAR IMAGING (THK5351 PET)
Authors: Miyake Keisuke , Tatano Masaki , Kanda Takahiro , Suzuki Kenta , Fujimori Takeshi , Ogawa Daisuke , Hatakeyama Tetsuhiro , Okauchi Masanobu , Kawanishi Masahiko 
Published: November 2024

Abstract

INTRODUCTION
Cancer treatment-related higher brain dysfunction significantly impacts quality of life (QOL) and social life. This study investigates the relationship between PET accumulation areas and advancing cognitive assessment in glioblastoma IDH-wild type (GBM) patients using the PET tracer THK5351, developed to detect tau protein.

METHODS
Twenty-four GBM patients who underwent changes in tumor to normal ratio (TNR) and metabolic tumor volume (MTV) for THK5351 evaluation before and after temozolomide (TMZ), bevacizumab (Bev), and radiation therapy from February 2020 to March 2024 were included. Cognitive assessments included the Mini-Mental State Examination (MMSE), Trail Making Test (TMT), Frontal Assessment Battery (FAB), Raven’s Coloured Progressive Matrices (RCPM), and Kohs block-design test (Kohs), administered at admission and discharge.

RESULTS
The mean age of the patients was 70.5 years (14 males, 10 females). All patients were diagnosed with GBM and received TMZ, Bev, and radiation therapy. In 11 patients, a reduction in THK5351 MTV correlated with MMSE improvement. However, 5 patients showed TMT deterioration, with a significant increase in THK5351 TNR change. FAB scores increased in 3 patients, while RCPM and Kohs scores deteriorated in 1 patient, alongside an increase in THK5351 TNR change. Among the 13 patients with enlarged THK5351 MTV, 5 showed decreased MMSE scores, and 3 showed decreased TMT and FAB scores. These cases exhibited an increased THK5351 TNR change, with accumulation expanding from the medial thalamus to the anterior nuclei of the thalamus, hypothalamus, caudate nucleus, hippocampus, and corpus callosum. Patients with reduced THK5351 TNR but enlarged THK5351 MTV had improved MMSE scores but decreased motivation and cognitive function.

CONCLUSION
Improving the GBM removal rate and preserving function requires attention to THK5351 accumulation in the corpus callosum, hippocampus, and hypothalamus for advancing cognitive assessment.
10003- MET-1 NEOADJUVANT STEREOTACTIC RADIOTHERAPY FOLLOWED BY SURGICAL RESECTION FOR BRAIN METASTASES: EFFICACY AND SAFETY STUDY (NEO-TACTICS TRIAL)
Authors: Mitsuya Koichi , Motimura Kazuya , Kibe Yuji , Otake Takumi 
Published: November 2024

Abstract

BACKGROUND
Postoperative stereotactic radiosurgery (SRS) for resected brain metastases (BM) improves local control compared to observation, while also preserving neurocognitive function in comparison to whole brain radiation therapy. However, even with surgery and SRS, rates of local recurrence at 1 year may be as high as 40%, especially for larger cavities, and there is also a known risk of leptomeningeal disease after surgery. The safety and effectiveness of neoadjuvant fractionated stereotactic radiotherapy (SRT) before piecemeal resection of large BM remains unknown.

METHODS
We retrospectively reviewed 20 consecutive patients with BM who underwent neoadjuvant fractionated SRT followed by piecemeal resection between July 2019 and March 2021. The prescribed dose regimens were as follows: 30 Gy or 35 Gy in five fractions.

RESULTS
The mean follow-up duration was 7.8 months. The median age was 67 years. Fourteen patients were male. All patients were symptomatic. All tumors were located in the supratentorial compartment. The median maximum diameter and volume were 3.7 cm and 17.6 cm3 respectively. The median time from the end of SRT to resection was 4 days. Nausea (CTCAE Grade 2) occurred in one patient and simple partial seizures (Grade 2) in two patients during radiation therapy. Gross total removal was performed in seventeen patients and sub-total removal in three patients. Postoperative complications were deterioration of paresis in two patients. Local recurrence was found in one patient (5%) who underwent sub-total resection at 2 months after craniotomy. Distant recurrence was found in six patients (30%) at a median of 6.9 months. Leptomeningeal disease recurrence was found in one patient (5%) at 3 months. No radiation necrosis developed.

CONCLUSIONS
Neoadjuvant SRT appears to be a safe and effective approach for patients with BM requiring piecemeal resection. Now, a multi-institutional prospective trial (NEO-TACTICS trial) is ongoing. (jRCT s042220014)
10213- MET-17 A CASE OF METASTATIC BRAIN TUMOR FROM HER2-POSITIVE PAROTID CARCINOMA WITH LOCALIZED MENINGEAL DISSEMINATION
Authors: Tabei Yusuke , Ishikawa Hisashi , Suma Takeshi , Ooyama Kenichi , Matsuno Akira , Nomura Ryutarou 
Published: November 2024

Abstract
A 30s-year-old man was undergoing chemotherapy with intravenous trastuzumab for recurrent HER2-positive parotid carcinoma. Gamma knife therapy was given to a metastatic brain tumor of left frontal lobe in February X. The lesion was temporarily reduced in size, but in November X, local re-growth and a new lesion in the right frontal lobe were observed. He underwent ZAP-X fractionated stereotactic radiotherapy 24 Gray per 3 fractions for the left frontal lobe lesion and 20 Gray for the right temporal lobe lesion. In February X+1, he received ZAP-X stereotactic radiotherapy for a new lesion near the Sylvian fissure. He was admitted to the hospital with a diagnosis of meningeal carcinomatosis due to contrast findings in the cerebral gyrus from the left Sylvian fissure. Whole brain irradiation was avoided, and intrathecal methotrexate was administered. MRI scan in June X+1 showed multiple intraparenchymal brain metastases with surrounding brain edema and recurrent headaches, so steroids were prescribed and palliative care was continued. The number of cases of localized meningeal dissemination is expected to increase with advances in chemotherapy and the widespread use of stereotactic radiotherapy. The indication of Trastuzumab deruxtecan has been expanded to HER2-positive metastatic solid tumors abroad. It is expected to be available in Japan as soon as possible.
10080- COT-9 HIGH EXPRESSION OF COX-2 PREDICTS IMPROVED OVERALL SURVIVAL OUTCOME IN BEVACIZUMAB-TREATED HIGH-GRADE GLIOMA PATIENTS
Authors: Kesumayadi Irfan , Kambe Atsushi , Kanda Haruto , Hosoya Tomohiro , Sakamoto Makoto , Kurosaki Masamichi 
Published: November 2024

Abstract

INTRODUCTION
Studies have shown that bevacizumab (BEV) improves progression-free survival (PFS) but not overall survival (OS) in high-grade glioma (HGG) patients. Here we evaluate the potential of cyclooxygenase-2 (COX-2), a rate-limiting enzyme involved in inflammation and tumor progression by producing prostaglandin E2, as a differentiating factor for the subset of participants who benefit from BEV treatment.

METHODS
We performed a retrospective study on newly diagnosed HGG patients who received Temozolomide (TMZ) alone or TMZ+BEV chemotherapy. We assessed the expression of COX-2 using immunohistochemistry staining prior to receiving chemotherapy. An immunoreactivity score &gt; 3 is considered high. We performed survival analysis on PFS and OS among patients with high vs. low expression.

RESULTS
A total of 60 patients were enrolled in our study, with 28 treated with TMZ only and 32 treated with TMZ+BEV. We found 36 patients with low expression and 24 patients with high expression. High expression of COX-2 is known to be associated with poor prognosis for HGG patients. Here we found no significant differences in median PFS and OS between low and high expression of COX-2 among those receiving TMZ+BEV (PFS: 22 vs. 18 months, p=0.95; OS: 25 vs. 25 months, p=0.53). Interestingly, among patients with high expression of COX-2, those receiving TMZ+BEV showed significantly higher median PFS and OS than the TMZ only group (PFS: 18 vs. 8 months, p=0.001; OS: 25 vs. 14 months, p=0.022). This difference was not identified in patients with low expression of COX-2 between the TMZ+BEV vs. TMZ only groups (PFS: 22 vs. 10 months, p=0.16; OS: 25 vs. 20 months, p=0.09).

CONCLUSION
Our data demonstrate the benefit of BEV chemotherapy for HGG patients with high expression of COX-2, thus supporting the use of COX-2 as a predictive biomarker for determining which HGG patients are likely to benefit from BEV chemotherapy.
10110- COT-11 EVALUATING SHORT-TERM SURVIVORS OF GLIOBLASTOMA: A PROPOSAL BASED ON SEER REGISTRY DATA
Authors: Tomita Yusuke , Otani Yoshihiro , Omae Ryo , Mizuta Ryo , Ishida Joji , Hirotsune Nobuyuki , Tanaka Shota 
Published: November 2024

Abstract

BACKGROUND
Glioblastomas (GBMs) are central nervous system tumors with a poor prognosis and limited treatment options. Although small subsets of GBM patients survive longer than 3 years, there is little evidence regarding the prognostic factors of GBM. Therefore, we conducted a thorough characterization of GBM in the United States.

METHODS
We queried the Surveillance, Epidemiology and End Results database (SEER) between 2000 and 2021 to extract age-adjusted incidence rates (AAIR), age-adjusted mortality rates (AAMR), and survival data for GBM. Age group comparisons for each measure varied depending on the available SEER data. We compared trends in AAIR, AAMR, and survival time across age groups 0-14, 15-39, 40-69, and 70+ years. Also, we employed the Fine-Gray competing risk model among short-term survivors (STSs), defined as those with a survival time of 6 months or less, and long-term survivors (LTSs), defined as those with a survival time of 3 years or more.

RESULTS
This study included 16,625 STSs and 4,197 LTSs between 2000 and 2021. The mortality-to-incidence ratio was constant among STSs, whereas it increased with age among LTSs. Higher age and male sex were significantly associated with GBM-specific death among LTSs, whereas non-Hispanic White, subtotal resection/biopsy, no radiation therapy, and no chemotherapy were associated with GBM-specific death among STSs. Interestingly, higher age was significantly associated with other causes of death among STSs.

CONCLUSIONS
STSs partially consist of populations who died from causes other than GBM. It is important to include only GBM-specific deaths in STS groups to conduct reproducible research comparing STSs and LTSs.