bluuebunny/crossref_metadata_2025_split huggingface dataset:
10035-GMC-1 PTPN11 VARIANT MAY BE A PROGNOSTIC INDICATOR OF IDH-WILDTYPE GLIOBLASTOMA IN A COMPREHENSIVE GENOMIC PROFILING COHORT
Authors: Otani Ryohei , Ikegami Masachika , Yamada Ryoji , Yajima Hirohisa , Kawamura Shinji , Shimizu Sakura , Tanaka Shota , Takayanagi Shunsaku , Takami Hirokazu , Yamaguchi Tatsuro 
Published: December 2023

Abstract
Glioblastoma (GBM) is the most common type of primary malignant brain tumor and has a poor prognosis. Identifying novel targets and stratification strategies is urgently needed to improve patient survival. The present study aimed to identify clinically relevant genomic alterations in IDH-wildtype GBM using data from comprehensive genomic profiling (CGP) assays performed nationwide in Japan. The CGP assay results of 392 IDH-wildtype GBM cases performed between October 2019 and February 2023 obtained from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) were retrospectively analyzed. The median patient age was 52.5 years, and 207 patients (53%) were male. In the 286 patients for whom survival information was available, a protein-tyrosine phosphatase non-receptor type 11 (PTPN11) variant detected in 20 patients (6.8%) was extracted as the gene associated with significantly shorter overall survival (OS) (p = 0.002). Multivariate analysis demonstrated that the PTPN11 variant and poor PS were independent prognostic indicators. In contrast, no prognostic impact was observed in the cohort in The Cancer Genome Atlas data. The discrepancy in the prognostic impact of the PTPN11 variant from these two pools might have resulted from differences in the biases affecting the survival of patients who underwent a CGP assay, including left-truncation and right-censored bias. However, survival simulation done to adjust for these biases showed that the prognostic impact of the PTPN11 variant was also significant, suggesting that the PTPN11 variant was a negative prognostic indicator of IDH-wildtype GBM in the patient cohort with the CGP assay.
10036-IM-3 SPATIAL AND GENOMIC ANALYSES FOR THE CONSTRUCTION OF TERTIARY LYMPHOID STRUCTURE IN GLIOBLASTOMA
Authors: Mizuta Ryo , Muraoka Daisuke , Okamura Ayako , Okamoto Takanari , Nohira Shota , Otani Yoshihiro , Ishida Joji , Fujii Kentaro , Date Isao , Matsushita Hirokazu 
Published: December 2023

Abstract

BACKGROUND
Recently, the presence of tertiary lymphoid structure (TLS), composed mainly of intratumoral B cells, has been reported as a favorable prognostic factor in various types of cancer. However, in glioblastoma, TLS has not been well studied though increased B-cell infiltration was likely to be related to improved prognosis. In this study, we performed spatial and genomic analyses in human glioblastoma, focusing on TLS.

METHODS
We evaluated lymphocytic infiltration by immunostaining in 54 cases. Flow cytometry was conducted on 12 prospective samples. RNA-sequencing (RNA-seq) was performed in 43 cases to compare those with and without TLS by differential gene expression (DGE) analysis and Gene Set Enrichment Analysis (GSEA).

RESULTS
TLS was detected in 5 (9.3%) of the 54 cases. Flow cytometry showed that 3 cases with TLS by immunostaining had higher numbers of T and B cells than those without TLS. DGE analysis showed increased gene expression related to the T cell activation marker (TNFRSF9), chemokine (CCL5), etc., in patients with TLS. GSEA also confirmed the activation of immune responses such as adaptive immune response and B cell receptor signaling pathway. We are currently validating these data with spatial transcriptome analysis and investigating the TLS formation in detail.

DISCUSSION
Although several TLS signatures and TLS components have been reported so far, the formation mechanism of TLS is still unknown. In addition, to our knowledge, there are no reports yet on spatial transcriptome analysis in multiple cases of glioblastoma focusing on the presence of TLS.

CONCLUSION
We analyzed a total of 54 glioblastoma cases by immunostaining. RNA-seq and spatial transcriptome analysis were performed to assess TLS in glioblastoma comprehensively.
10048-CO-2 CAN NATURAL LANGUAGE PROCESSING AI BE AN APPROPRIATE “ADVISER” FOR BRAIN TUMOR PATIENTS? CLINICAL APPLICATION AND ISSUES ON CHATGPT
Authors: Hana Taijun , Takahashi Satoshi , Kawaguchi Yuki , Oya Soichi 
Published: December 2023

Abstract

INTRODUCTION
Brain tumors affect approximately 20,000 individuals annually in Japan, with some cases requiring urgent treatment. However, the medical knowledge of non-medical individuals (the general public) is often limited, resulting in delays in seeking treatment even when neurological symptoms are evident. Having appropriate advisors who can encourage medical consultations could potentially improve this situation. While Natural Language Processing AI (NLP-AI) is widely used, its full integration into healthcare remains a work in progress. ChatGPT, a prominent NLP-AI, possesses extensive knowledge and is accessible 24/7 online. We explored the potential of leveraging its advanced capabilities and accessibility in the field of brain tumor management.

METHODS
To evaluate its ability to guide hospital visits effectively, we simulated various symptoms associated with primary brain tumors and consulted ChatGPT(GPT3.5) as patients. We also assessed how ChatGPT handled unnecessary noise information (unrelated symptoms) during symptom consultations.

RESULTS
ChatGPT consistently recommended hospital visits for all simulated brain tumor patients and provided appropriate advice regarding the urgency and relevant medical department. Notably, even when patients expressed hesitation and refusal hospital visits, ChatGPT persistently persuaded them to visit the hospital despite the user(patient)'s intention. Despite the introduction of noise information, ChatGPT accurately identified and emphasized the importance of relevant symptoms, prompting appropriate medical attention. However, accuracy declined when excessive noise was present. Additionally, ChatGPT generated concise summaries of medical histories for presentation during hospital visits.

DISCUSSION
While AI is widely utilized in medical imaging, the comprehensive integration of conversational AI in healthcare is still in progress. ChatGPT, despite not being a healthcare professional, holds potential as an "advisor" with extensive medical knowledge, accessible for consultations at any time, to support brain tumor patients. However, challenges related to accountability and expanding knowledge capabilities remain to be addressed.
10053-MNG-1 STRATIFICATION OF TUMOR VOLUME GROWTH RATE USING RISK FACTORS IN SUPRATENTORIAL MENINGIOMAS
Authors: Hirayama Ryuichi , Yamada Shuhei , Iwata Takamitsu , Kawamoto Yuki , Nakagawa Kanji , Murakami Kouki , Utsugi Reina , Tachi Tetsuro , Kuroda Hideki , Kijima Noriyuki , Okita Yoshiko , Kagawa Naoki , Kishima Haruhiko 
Published: December 2023

Abstract

BACKGROUND
The natural history of meningiomas is still unclear, and no guidelines have been established based on objective indices regarding the necessity and timing of therapeutic intervention. Objective: We attempted to provide statistics on the characteristics of tumor volume change, stratify tumor growth by risk factors, and generate a predictive tumor volume curve based on the statistics, with the aim of describing the natural history of meningiomas.

METHODS
313 cases were included in the study, with the origin of meningioma being the circumflex and parasagittal sinus areas and the cerebral sickle region, and with multiple MRI scans performed at intervals of at least 3 months. Relative growth rate (RGR) and annual volume change (AVC) were calculated by tumor volume, and the patients were classified into three groups according to the combination of gender, age, and MRI T2WI signal intensity, and compared.

RESULTS
The median RGR and AVC of the entire cohort were 6.1% and 0.20 cm3/year, respectively, and there were significant differences between groups in gender (p=0.018) and MRI T2WI (p &lt; 0.001) for RGR and tumor location (p=0.025) and initial tumor volume (p &lt; 0.001)for AVC. The median RGR and AVC in the classification were 17.5% and 1.05 cm3/year for the very high growth group, 8.2% and 0.33 cm3/year for the high growth group, and 3.4% and 0.04 cm3/year for the low growth group, showing significant differences between the groups (p &lt; 0.001). The predicted tumor volume curve showed an average 2.24-fold or 5.24 cm3 increase in volume over 5 years in the very high-growth group, while little tumor volume change was observed in the low-growth group.

CONCLUSION
The combination of growth risk factors allowed stratification of tumor growth and provided a predictive tumor volume curve for each county. The results may assist in the treatment of supratentorial meningiomas.
10054-STMO-1 5-ALA INTENSITY ANALYSIS OF NON-NEOPLASTIC LESIONS BY IMAGE J
Authors: Kon Takashi , Kobayashi Yusuke , Shimizu Katsuyoshi , Mizutani Tohru , Sato Yosuke 
Published: December 2023

Abstract

PURPOSE
We used 5-ALA during surgery for malignant brain tumors, and analyzed the brightness using Image J for positive findings during surgery. We report on three cases that were positive for intraoperative 5-ALA and had high brightness but were diagnosed as non-tumor, including the results of brightness analysis by Image J.

METHODS
5-ALA was administered according to the protocol, and intraoperative 5-ALA-positive findings were analyzed with Image J (Wayne Rasband: NIH), brightness was measured with histograms, and maximum brightness was compared.

RESULTS
Case 1 was suspected malignant tumor before surgery, but the diagnosis was inflammation, different from lymphoma. The intraoperative maximum brightness was as high as 239, but there was no finding of' blazing fire' characteristic of malignant tumors, and the lesion and its surroundings were uniformly red. Case 2 required differentiation between metastatic brain tumor and radiation necrosis, and case 3 required differentiation between recurrent anaplastic astrocytoma and radiation necrosis, both of which had high intraoperative brightness (113,166).

CONCLUSION
Measuring the brightness of 5-ALA-positive findings during surgery can help in the rapid pathological diagnosis of tumors and the determination of peripheral edema.
10060-MET-5 LEPTOMENINGEAL METASTASES FROM HER2 POSITIVE SALIVARY GLAND CARCINOMATREATED WITH CRANIOSPINAL IRRADIATION FOLLOWED BY INTRATHECAL TRASTUZUMAB
Authors: Tabei Yusuke , Tada Yuichiro , Oyama Kenichi , Matsuno Akira 
Published: December 2023

Abstract
We report our experience with a case of intrathecal trastuzumab (Tmab) after craniospinal irradiation for leptomeningeal metastases (LM) of HER2-positive salivary gland carcinoma. The patient was a 46-year-old male with postoperative extensive cervical recurrence of left parotid carcinoma (salivary gland conduit carcinoma, HER2 positive) treated with intravenous Tmab and docetaxel. He was hospitalized for headache and nausea, and diagnosed as LM by MRI and CSF cytology. He received whole brain irradiation of 30Gy/10Fr and whole spinal cord irradiation of 30Gy/10Fr. Because of HER2 positive cancer, we applied to the ethics committee and started Tmab intrathecal treatment(IT) . The initial dose was 20 mg, which was administered intrathecally once every 3 weeks, and the dose was increased by 20 mg in 20 mg increments up to 60 mg while checking for post-dose side effects. The side effect was discomfort in the extremities during IT, which resolved by slowing down the administration rate. The time from diagnosis of LM to CNS deterioration was 9 months. Tmab IT may be effective in treating LM in HER2-positive salivary gland carcinoma. Further clinical studies are needed to evaluate efficacy and safety.
10073-CBMS-6 CURCUMIN ANALOG B EXHIBIT ANTI-TUMOR ACTIVITY AGAINST GLIOBLASTOMAAT LOWER CONCENTRATIONS THAN CURCUMIN
Authors: Inai Kyoko , Hamabe-Horiike Toshihide , Ono Masaya , Iwashimizu Sonoka , Ito Ryo , Sunagawa Yoichi , Katanasaka Yasufumi , Arakawa Yoshiki , Hasegawa Koji , Morimoto Tatsuya 
Published: December 2023

Abstract

PURPOSE
Glioblastoma (GBM) has a high risk of recurrence and a poor prognosis due to the difficulty of surgical resection and resistance to the standard treatment, temozolomide. Therefore, the development of noble therapeutic agents against GBM is required. This study investigated the anti-tumor activity of the curcumin (Cur) analog Compound B (ComB) against GBM.

METHODS AND RESULTS
To evaluate anti-tumor activity against GBM, we performed an MTT assay. The human glioblastoma cell lines U87-MG and U251 were pre-treated with Cur or ComB, and then cell viability was examined using a cell counting kit, and IC50 values were calculated. The IC50 value for U87-MG of Cur was 9.78 μM, and that of ComB was1.28 μM. The IC50 value for U251 of Cur was 9.50 μM, and that of ComB was 0.64 μM. To examine the effects of ComB on normal cells, the same MTT assay was performed on primary cultured astrocytes prepared from neonatal rats. ComB did not reduce cell viability in astrocytes at concentrations that had an anti-tumor effect on GBM cells. Next, a cell cycle analysis was performed with Propidium Iodide (PI) staining and an apoptosis assay with Annexin V/PI staining using flow cytometry. ComB induced cell cycle G2/M arrest and apoptosis at lower concentrations than Cur. qPCR showed that mRNA expression levels of CDK1 and CyclinB1, which play an essential role in the progression from the G2 phase to the M phase, decreased by ComB at lower concentrations than Cur.

DISCUSSION
These results suggest that ComB, at lower concentrations than Cur, has an anti-tumor effect without affecting normal cells by inducing cell cycle arrest and apoptosis against GBM. Further detailed analysis and in vivo studies are expected to lead to the development of novel therapeutic agents for GBM.
10074-COT-10 A NEW PREOPERATIVE PREDICTIVE SCORING SYSTEM FOR SUPRATENTORIAL NEWLY DIAGNOSED ISOCITRATE DEHYDROGENASE-WILD TYPE GLIOBLASTOMA TREATED WITH RADIOTHERAPY PLUS CONCOMITANT AND ADJUVANT TEMOZOLOMIDE
Authors: Mtsuda Ryosuke , Maeoka Ryosuke , Morisaki Yudai , Yokoyama Shohei , Park Young-Soo , Nakagawa Ichiro 
Published: December 2023

Abstract
We aimed to evaluate the usefulness of a preoperative predictive score for assessing overall survival in patients with supratentorial newly diagnosed isocitrate dehydrogenase (IDH)-wild type glioblastoma (GBM) treated with radiotherapy plus concomitant and adjuvant temozolomide. In this study, 104 patients with newly diagnosed supratentorial IDH-wild type GBM were enrolled between May 2007 and April 2021. Four prognostic factors were evaluated preoperatively: age, initial symptoms, neutrophil/lymphocyte ratio (NLR), and contact of the tumor with the ventricles on magnetic resonance imaging (MRI). A scoring system of 0-6 points was created, with 2, 1, 2, and 1 points assigned to age &gt; 75 years, no seizure onset, NLR &gt; 2.23, and ventricular c ontact. The median follow-up period after surgery was 15 months (range: 1-146 months). The total score was 0, 1, 2, 3, 4, 5, and 6 points for 6, 6, 18, 15, 43, 6, and 10 patients respectively. Patients with 0-2, 3-4, and 5-6 points were assigned to groups 1, 2, and 3, respectively. The median survival time from surgery was 20 months in the entire cohort and 34, 19, and 10 months in groups 1, 2, and 3, respectively. The three groups showed significant differences in the median survival time (p&lt; 0.001), with lower scores corresponding to longer survival times. We propose a new preoperative prognostic scoring system for newly diagnosed patients with supratentorial IDH-wild GBM. The prognostic information obtained using this system can help determine the intensity of treatment for the patient.
10075-CO-3 PREDICTION OF KPS DETERIORATION IN GLIOBLASTOMA USING MULTIMODAL LEARNING WITH PRE- AND POST-OPERATIVE MRI IMAGES AND CLINICAL INFORMATION
Authors: Mineharu Yohei , Sasagasako Tomoki , Ueda Akihiko , Mochizuki Yusuke , Numa Arisa , Doi Soichiro , Arakawa Yoshiki , Okuno Yasushi 
Published: December 2023

Abstract

BACKGROUND
Previous AI studies on glioblastoma have mostly focused on predicting genetic subtypes or survival outcomes using preoperative imaging alone. We aimed to investigate the feasibility of utilizing postoperative imaging in combination with clinical chart data for multimodal learning, to evaluate systemic functional outcome.

METHODS
We included 77 glioblastoma cases that received treatment at Kyoto University between December 2001 and January 2022. These cases had both pre- and postoperative MRI images, including T1WI, CE-T1WI, FLAIR, ADC, and DWI. Molecular diagnoses were confirmed for all cases. First, using external data (BRaTS2020), we constructed models for tumor segmentation prediction from MRI images followed by an image feature extraction model using an autoencoder (VAE), extracting 192 image feature variables from preoperative and postoperative images. These variables were combined with 24 clinical variables, and 6 variables of radiologists' findings. We built a CNN model to predict a decrease of 30% or more KPS at 6 months and evaluated its accuracy using the AUC. Feature importance was calculated using PermutationImportance.

RESULTS
When predicting KPS deterioration using only clinical data, the AUC was 0.79. When combined with radiologists' findings, the AUC increased to 0.84. Combination with preoperative image features resulted in an AUC of 0.78. On the other hand, when combined with both pre- and postoperative image features, the AUC increased to 0.94. Both pre- and post-operative images were identified as important features.

DISCUSSION
Our findings demonstrate the utility of incorporating postoperative imaging into multimodal learning for predicting systemic functional outcomes in glioblastoma patients. Further validation in independent cases from different medical facilities is warranted to confirm these results.
10077-NI-4 POSTOPERATIVE DISAPPEARANCE OF LEPTOMENINGEAL ENHANCEMENT AROUND THE BRAINSTEM IN GLIOBLASTOMA
Authors: Inoue Hirotaka , Kuroda Jun-ichiro , Uetani Hiroyuki , Matsuyama Tomohiko , Kaku Yasuyuki , Shinojima Naoki , Hirai Toshinori , Mukasa Akitake 
Published: December 2023

Abstract

BACKGROUND AND PURPOSE
Leptomeningeal enhancement (LME) suggests leptomeningeal dissemination (LMD) of tumor cells, which is an end-stage glioblastoma complication associated with a poor prognosis. However, magnetic resonance imaging (MRI) occasionally indicates the disappearance of peri-brainstem LME after surgical resection of glioblastoma. Since preoperative LMD may affect treatment indication, we aimed to analyze the clinical significance of preoperative LME of the brainstem on glioblastoma, focusing on imaging examinations and patient outcomes.

METHODS
We retrospectively collected clinical and radiological data obtained from consecutive patients with glioblastoma and preoperative LME of the brainstem, who were treated at our hospital between 2017 and 2020.

RESULTS AND CONCLUSIONS
Among 112 patients with glioblastoma, nine (8%) showed preoperative LME of the brainstem. Tumors with LME were relatively large (median size, 59 cm; range, 47-83 cm) and frequently located in the temporal lobe (temporal lobe: n = 4, 44%; frontal lobe: n = 1; parietal lobe: n = 2; corpus callosum: n = 2). Notably, among six patients who underwent surgical resection for glioblastoma with peri-brainstem LME, four showed significant radiological disappearance of the LME on postoperative MRI. This suggests that the LME did not result from LMD in these cases. Moreover, these four patients lived longer than would be expected from the presence of LMD. This LME disappearance was not observed after biopsy or chemoradiotherapy. These findings suggest that preoperative LME does not necessarily indicate the presence of untreatable LMD; moreover, LME may disappear after surgical tumor resection. Thus, transient preoperative LME could be attributed to other mechanisms, including impaired venous flow due to intratumoral arteriovenous shunts, which can be resolved by reducing the tumor burden.
10079-MPC-6 RADIOLOGICAL AND MOLECULAR ANALYSIS OF WHO GRADE 4 BUTTERFLY GLIOMAS WITH A TAILORED SURGICAL APPROACH
Authors: Shibahara Ichiyo , Shigeeda Ryota , Tanihata Yoko , Fujitani Kazuko , Handa Hajime , Hyakutake Yuri , Toyoda Mariko , Uemasu Kouhei , Shinoda Mitsuhiro , Inukai Madoka , Komai Hideto , Sato Sumito , Hide Takuichiro , Kumabe Toshihiro 
Published: December 2023

Abstract

OBJECT
Surgical resection for butterfly gliomas (bG) are still under debate, but recent findings have shown that surgery prolongs survival. However, clinical and molecular background of bG still remains unknown and surgical strategies based on such findings are scarce.

OBJECTS AND METHODS
We treated 39 bG patients between 2005 and 2023, including 32 cases of glioblastoma and 5 cases of astrocytoma, WHO grade 4, IDH-mutant. For the validation, we reviewed 968 MRI obtained from the public datasets (UPENN-GBM, n=611; TCGA-GBM, n=255; CPTAC-GBM, n=61; IvyGAP, n=41).

RESULTS
Molecular analyses revealed that 51.3% of TERT promoter mutations, 59.0% of EGFR amplification/gain, 38.5% of PTEN hemi/homozygous, and 51.3% of CDKN2A hemi/homozygous deletion. Sequential radiological imaging before typical bG diagnosis demonstrated that bG harbors two subtypes which are corpus callosum (CC)-type and hemispheric (H)-type. The multisampling of H-type showed that accumulating alterations in the CC lesions than hemisphere, indicating an invasive trajectory from the hemisphere to the CC region. Survival analysis presented that CC-type was significantly poorer overall survival (OS) than H-type (263 days and 691 days, respectively, P = 0.018). The validation cohort also supported the poor survival of CC-type.

CONCLUSION
Our detail analyses demonstrated the possibility of two subtypes in bG. Unilateral trans-cortical approach from the larger tumor size with CC removal is favored in the H-type. On the other hand, bilateral trans-sulcal and interhemispheric approaches preserving the intact cortex and cingulate gyrus is an alternative for CC-type.
10084-TB-2 IN VITRO CHARACTERIZATION OF COMBINATION THERAPY IN GENETICALLY-ENGINEERED MURINE DIFFUSE MIDLINE GLIOMA MODELS
Authors: Tomita Yusuke , Takata Nozomu , Becher Oren 
Published: December 2023

Abstract

BACKGROUND
Diffuse midline glioma (DMG) is an incurable pediatric brain cancer without a FDA-approved drug that prolongs survival. Recent molecular analyses have suggested the potential efficacy of CDK4/6 inhibitors and MEK inhibitors. We recently established a genetically engineered murine DMG model that could capitulate the characteristics of human DMG. Here, we evaluated the features of DMG cells and the efficacy of the CDK4/6 inhibitor ribociclib and the MEK inhibitor trametinib in vitro.

METHODS
We used the RCAS/Tv-a avian retroviral system to generate DMG in Nestin-expressing progenitors in the neonatal mouse brainstem. We dissociated the DMG tissue to single cells and conducted the spheroid culture. We incubated the DMG cells with a hindbrain organoid to evaluate invasiveness. We treated the DMG cells with CDK4/6 inhibitor ribociclib and MEK inhibitor trametinib to evaluate the synergistic effect.

RESULTS
Induction of PDGF-A overexpression, H3.3K27M mutation, and p53 deletion resulted in gliomas in murine brainstem. Median survival of the murine DMG model was 62.5 days. From the DMG tissue, we successfully established the DMG cell line with spheroid culture. By incubating with the organoid, DMG cells could invade into the organoid. There was a mild synergistic effect with ribociclib and trametinib both in the cytotoxicity assay and the TUNEL apoptosis assay.

CONCLUSIONS
We could establish the DMG cell line that maintained the proliferative capability and invasiveness.