bluuebunny/crossref_metadata_2025_split huggingface dataset:
MPC-16 CHARACTERISTICS AND PROGNOSTIC FACTORS OF H3K27M-MUTANT DIFFUSE MIDLINE GLIOMA
Authors: Tanaka Kazuhiro , Nagashima Hiroaki , Yamanishi Shunsuke , Iwahashi Hirofumi , Itoh Tomoo , Sasayama Takashi 
Published: December 2022

Abstract
H3 K27M-mutant diffuse midline gliomas (DMG) is a still challenging disease with no effective medical therapies. We analyzed the characteristics and prognostic factors of 64 patients with midline gliomas including 18 patients with H3 K27M-mutant DMG treated in Kobe University Hospital from 2006 to 2021. The median age at diagnosis in midline gliomas was 50.1 years (range: 14-82 y). All tumors were located in thalamus n=25, corpus callosum n=8, brainstem n=8, spinal cord n=6, cerebellum n=15, and pineal region n=2. Isocitrate dehydrogenase 1 (IDH1) and H3 K27 mutation was recognized in 6 and 18 patients, respectively, which was mutually exclusive. In all midline gliomas, the identification of an H3 K27M mutation was significantly a poor prognosis factor (median 19.8 months vs 27.9 months, p=0.042). Compared to midline gliomas without histone H3 and IDH1 mutations (IDH1/H3 wild type), however, H3 K27M-mutant DMG had no worse overall survival (median 19.8 months vs 15.9 months, p=0.51). H3 K27M-mutant DMG is considered as a distinct WHO Grade 4 regardless of histological features, but the biological properties of H3 K27M mutation is not yet defined in IDH1 wild-type midline gliomas.
MPC-19 DIAGNOSTIC APPROACH IN HISTOPATHOLOGICALLY CHALLENGING CASES IN KYOTO UNIVERSITY HOSPITAL
Authors: Takeuchi Yasuhide , Arakawa Yoshiki 
Published: December 2022

Abstract
In 2021, the WHO classification of tumors of the central nervous system (CNS) was published, which drastically changed the diagnostic approach to tumors in the CNS. In the diagnosis of most subtypes of CNS tumors, especially in gliomas, the genetic test became critical in the latest version of the classification, meanwhile analyzing genetic alterations in routine practice is still quite difficult in most of the hospitals in Japan because of the accessibility of the genetic analysis. In Kyoto University Hospital (KUHP), around 80 tumors in CNS are newly diagnosed every year, half of which are gliomas with a few challenging cases on the histopathological diagnosis. The diagnostic approach to CNS tumors in KUHP can be divided into two steps: the clinical phase and the academic phase. The clinical phase includes a pre-operative conference with neurosurgeons, radiologists, and pathologists, and classical histopathological analysis on formalin-fixed and paraffin-embedded tissues with H&E staining, immunohistochemistry on p53, IDH1 R132H, and ATRX, fluorescence in situ hybridization on 1p/19q co-deletion, and consultation to the experts of the CNS tumors. Some cases are further analyzed by clinical cancer genome sequencing. When the tumors are expected to be glioma during the pre-operative conference, after the surgery, the tumor tissue gets frozen to be submitted to the academic phase. The academic phase includes analysis of genetic alterations with Sanger sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) assay on the representative glioma-associated genes. In some cases, the tumors are further analyzed by methylome assay and/or mRNA sequencing (PMID: 35900258), to identify novel genetic alterations. Most of the neuropathologists in Japan today are suffering in diagnosing gliomas because of the novel, sophisticated, and complicated WHO classification. In this presentation, we want to share our diagnostic approach to the diagnosis of CNS tumors and shed light on it.
NI-1 METHYLTHIOADENOSINE PHOSPHOLYLASE STATUS CORRELATES WITH PROGNOSIS AND METHIONINE UPTAKE IN IDH MUTANT ASTROCYTOMA
Authors: Yamamura Toshihiro , Tamura Kaoru , Kobayashi Daisuke , Inaji Motoki , Toyama Yuka , Hara Shoko , Tanaka Yoji , Nariai Tadashi , Ishii Kenji , Maehara Taketoshi 
Published: December 2022

Abstract

Purpose
Methylthioadenosine phosphorylase (MTAP) immunohistochemistry staining has been proposed as a surrogate of Cyclin-dependent kinase inhibitor 2A homozygous deletion (CDKN2A HD) in various type of tumors. This study was designed to determine whether MTAP status correlates with clinical outcome and uptake of 11C-methionine in astrocytoma with IDH mutations.

Methods
We conducted a MTAP immunohistochemistry staining of 30 IDH-mutant astrocytoma patients who underwent 11C-methionine positron emission tomography scans prior to surgical resection from 2000 to 2020. The tumor-to-normal ratio (T/N) of 11C-methionine uptake was calculated by dividing the mean standardized uptake value (SUV) for the tumor by the mean SUV of the normal brain.

Results
Eight of the thirty astrocytomas harboring IDH mutations exhibited loss of cytoplasmic MTAP expression, which is accompanied with a poor prognosis. The median progression free survival (PFS) in IDH-mutant astrocytoma patients with loss of MTAP was 1.88 years, significantly shorter than that of those with MTAP retention (6.80 years, p=0.003). The median Overall survival (OS) in IDH-mutant astrocytoma patients with loss of MTAP was 5.23 years, again significantly shorter than that of those with MTAP retention (p=0.0191). Multivariate analysis revealed MTAP status to be an independent prognostic marker for PFS in IDH-mutant astrocytoma patients. The median T/N ratio in tumors with loss of cytoplasmic MTAP expression was 2.12 (IQR 1.92-2.50), i.e., significantly higher than that of tumors with MTAP retention (1.65, IQR 1.23-1.94, p=0.0116, U test).

Conclusion
Our study showed MTAP status to correlate with clinical outcome and T/N ratio of astrocytoma patients with IDH mutations.
NI-2 DUAL-ISOTOPE 123I-IMP/201TL SPECT FOR THE DIFFERENTIAL DIAGNOSIS OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA AND GLIOBLASTOMA
Authors: Osawa Sho , Tosaka Masahiko , Horiguchi Keishi , Tokue Azusa , Higuchi Tetsuya , Tsushima Yoshito , Yoshimoto Yuhei 
Published: December 2022

Abstract

Background
Preoperative differential diagnosis between primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) is important because these tumors require different surgical strategies. This study investigated the usefulness of dual isotope, iodine-123-labeled N-isopropyl-p-iodoamphetamine (123I-IMP) and thallium-201 chloride single photon emission computed tomography (201Tl SPECT) for the differential diagnosis.

Methods
Sixteen PCNSL patients and 20 GBM patients who underwent dual isotope imaging, 123I-IMP and 201Tl SPECT, are included. Early and delayed SPECT images were obtained after 30 minutes and 4 hours, respectively. Tumor to normal (T/N) ratio was calculated from the ratio of maximum tracer counts in the lesion to the mean counts in the contralateral cerebral cortex. The mean and minimum apparent diffusion coefficient values (ADCmean and ADCmin, respectively) on magnetic resonance imaging were also analyzed for comparison of diagnostic accuracy.

Results
Delayed phase 123I-IMP SPECT was the most useful imaging examination for the differentiation between PCNSL and GBM compared with early phase 123I-IMP SPECT, early and delayed phase 201Tl SPECT, ADCmean and ADCmin. However, the median T/N ratios of PCNSL and GBM were 1.29 and 0.84, respectively, in the delayed phase 123I-IMP SPECT, and the tumor detection was inadequate. On the other hand, the median T/N ratios of PCNSL and GBM were 3.23 and 2.34, respectively, in the delayed phase 201Tl SPECT, with excellent tumor detection. Thirty-five of 36 patients (97.2%) showed a tracer retention rate of 201Tl SPECT 0.7 or higher, which indicates malignant property of brain tumors.

Conclusion
Delayed phase 123I-IMP SPECT could differentiate between PCNSL and GBM with high accuracy, but T/N ratio was low and tumor detection was poor. 201Tl SPECT was useful for estimation of the localization and the malignant property of the tumors. The combination of these isotopes was useful for the diagnosis of PCNSL and GBM.
NI-3 FEASIBILITY OF MRI PERFUSION IN DISCRIMINATING BETWEEN EDEMA AND INFILTRATIVE AREAS IN THE PERI-GBM NON-CONTRAST T2 WEIGHTED HIGH AREA
Authors: Kuroda Hideki , Okita Yoshiko , Arisawa Atsuko , Utugi Rena , Tachi Tetsuro , Hirayama Ryuichi , Kijima Noriyuki , Nakamura Hajime , Kagawa Naoki , Kishima Haruhiko 
Published: December 2022

Abstract

Background
Glioblastomas are highly infiltrative tumors, and differentiating between infiltrating tumors and vasogenic edema occurring in the non-enhancing T2-weighted hyperintense area is challenging. Here, we differentiated between infiltrating tumors and edemas in glioblastomas using dynamic perfusion-weighted MR imaging.

Methods
Data were collected from 33 patients with glioblastomas and 15 with meningioma as controls, who underwent resection at our institution between January 2019 and March 2022. The MRI data included T2 weighted images and contrast-enhanced T1 weighted images, and dynamic perfusion-weighted MR imaging. Two neurosurgeons manually assigned regions of interest (ROIs) to infiltrating tumors and vasogenic edema based on a previous report using conventional MRI features. The ratio of cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) in the ROIs to that contralateral normal regions were calculated. We also histological analysis using histological specimens obtained by stereotactic biopsy in each ROI.

Results
CBF and MTT ratios of infiltrating tumors and edemas differed significantly (p&lt;0.01), while CBF and MTT ratios of edemas and controls showed similarities. MTT values of controls and infiltrating tumors differed significantly (p=0.02). Receiver operating characteristic curve analysis revealed that CBF (area under the curve [AUC]=0.81) and MTT(AUC=0.95) were effective in distinguishing between infiltrating tumors and edemas. Pathological analysis revealed that cell density, MIB1-index, and microvessel density were higher in infiltrating tumors than in edemas.

Conclusions
Using dynamic perfusion-weighted MR imaging may prove useful in differentiating infiltrating tumors from edemas in the non-contrast T2 hyperintensity region of glioblastomas.
NI-8 LATE-DELAYED MRI FINDINGS AFTER RADIOTHERAPY: DOT-LIKE ENHANCED LESION
Authors: Asano Kenichiro , Kakuta Kiyohide , Fujiwara Nozomi , Saito Atsushi , Kakeda Shingo 
Published: December 2022

Abstract

Introduction
Late-delayed radiation reactions after radiotherapy include brain atrophy, leukoencephalopathy, radiation necrosis, and cerebrovascular disease. We will discuss the contrast-enhanced SPGR to detect dot-like enhanced lesions that are considered to be late late-delayed radiation reactions.

Material and Methods
One hundred eleven patients (62 males and 49 females; median age at irradiation: 49 years) who had received radiotherapy since 1994 and were alive since 2010, had dot-like lesions by contrast-enhanced SPGR, and had a PFS OS of at least 24 months were included in the study. Of these, 64 had high-grade glioma, 4 had low-grade glioma, 15 had PCNSL, 7 had metastatic brain tumors, 9 had germ cell tumors, 5 had medulloblastoma, and 7 had other tumors, with a mean follow-up of 89.

Results
Contrast-enhanced SPGR showed dot-like or rod-like findings in 23/111 patients (20.7%). Contrast-enhanced FIESTA and Flair-Cube were also detectable in some cases. However, it was difficult to detect by contrast SE-T1WI, SE-T2WI, or contrast SE-Flair. The lesions appeared a median of 49 months after irradiation (IQR 34, 103. Range 25-298). There were no lesions that increased in size, and multiple lesions appeared during the course of the study in 8/23 (34.8%) of the patients. All lesions occurred within the irradiated field and were seen in patients receiving a total dose of 50 Gy or more, but not in patients receiving whole-brain irradiation alone or whole-brain irradiation plus boost at 50 Gy or less.

Discussion and Conclusion
It is difficult to elucidate the pathogenesis without pathological evidence, but it is one of the late-delayed radiation reactions that occur more than 2 years later, and it is presumed to be vasculopathy or granulation reaction in the Virchow-Robin space. It tends to increase over time and is not considered to be a condition that causes sudden clinical manifestations.
NI-10 CLINICAL BENEFITS FROM ONE-SHOT BEVACIZUMAB BEFORE A RESECTION OF GLIOBLASTOMA
Authors: Beppu Takaaki , Sato Yuichi , Nomura Jyun-ichi , Fujiwara Shunrou , Ogasawara Kuniaki 
Published: December 2022

Abstract

Purpose
We aimed to clarify of clinical impacts from preoperative administration of bevacizumab (BEV) in patients with newly diagnosed glioblastoma.

Methods
Subjects were 17 patients who met the entry criteria, and were administered with BEV (10 mg/kg) one time before surgery. Between phases before and after BEV administration, we compared KPS and volumes of hyperintense areas on FLAIR and enhanced areas on T1-weighted imaging with contrast media (Gd-T1WI). Tumor resection was carried out at least three weeks after BEV. Also between phases immediately before and after operation, volumes of hyperintense areas on FLAIR and enhanced areas on Gd-T1WI (= tumor removal rate) were compared. These were compared with those in the control group of patients who received tumor resection without BEV.

Results
One-shot BEV led to significant improvement of KPS and significant volume reductions of hyperintense areas on FLAIR (43.8±26.3%) and enhanced areas on Gd-T1WI (34.6±18.2%). No patients showed any adverse effects around surgery. On MRI after surgery, volume-reduction rates of hyperintense areas on FLAIR and enhanced areas on Gd-T1WI were 44.7±24.7% and 96.2±5.4%, respectively. Compared with control group, a significant difference was identified in the reduction rate of hyperintense areas, but not in that of enhanced areas.

Conclusions
One-shot administration with BEV reduced both volumes of hyperintense areas on FLAIR and enhanced areas on Gd-T1WI, thereby improved KPS before surgery. Preoperative BEV was safe for tumor resections but did not affect to tumor removal rate. We speculated a significant volume reduction of hyperintense areas on FLAIR might have been led by continuous effect from BEV rather than an increase of resected volume.
NI-11 USEFULNESS OF MRI ARTERIAL SPIN LABELING METHOD FOR DIAGNOSING BRAIN TUMOR
Authors: Hiu Takeshi , Shiozaki Eri , Ishikawa Ayano , Morikawa Minoru , Matsuo Ayaka , Yoshida Michiharu , Baba Shiro , Ujifuku Kenta , Yoshida Koichi , Morofuji Yoichi , Izumo Tsuyoshi , Matsuo Takayuki 
Published: December 2022

Abstract

Background
Diagnosis of hemangioblastoma by magnetic resonance imaging (MRI) can sometimes be difficult when the tumor is a solid mass in the posterior fossa. We therefore evaluated perfusion images and diffusion-weighted images as brain function images to diagnose hemangioblastoma in order to obtain the most useful quantitative features.

Methods
Forty-five posterior fossa tumors whose pathological diagnosis was confirmed by surgery were included in groups A (18 hemangioblastomas) and B (non-hemangioblastoma 27 cases: metastatic brain tumor 8 cases, pilocytic astrocytoma 6 cases, and other 13 cases). All cases were imaged by 3.0-Tesla MRI, with arterial spin labeling (ASL) as the relative value from the CBF map to the region of interest (ROI) in the contralateral hemisphere as perfusion image. Among 45 cases, 27 cases were evaluated with both ASL and dynamic susceptibility contrast (DSC) as rCBF, rCBV, corrected CBV, and K2. The ROI was set to match the contrast-enhanced part, and the two groups were compared and examined.

Results
The relative ASL value of group A and the corrected CBV in DSC were significantly higher than group B (p &lt; 0.001). In contrast, the ADC showed no marked difference between the two groups. In the distinction between the two groups, the receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) of the relative ASL value was significantly higher than the other parameters (AUC 0.995, cut-off value 2.34, sensitivity 100%, specificity 99.5%).

Conclusions
The non-contrast ASL method was extremely useful for diagnosing hemangioblastoma in posterior fossa tumors. Non contrast ASL can be used instead of contrast-enhanced DSC in diagnosing posterior fossa hemangioblastoma.
NI-13 THE RATIO OF T1-WEIGHTED TO T2-WEIGHTED SIGNAL INTENSITY AND IDH MUTATION IN GLIOMA
Authors: Sanada Takahiro , Yamamoto Shota , Sakai Mio , Umehara Toru , Sato Hirotaka , Saito Masato , Mitsui Nobuyuki , Hiroshima Satoru , Anei Ryogo , Kanemura Yonehiro , Tanino Mishie , Nakanishi Katsuyuki , Kishima Haruhiko , Kinoshita Manabu 
Published: December 2022

Abstract

Purpose
The current study aims to test the hypothesis that the ratio of T1-weighted image to T2-weighted image signal intensity (T1w/T2w-Ratio: rT1/T2), an imaging surrogate developed for myelin integrity, is predictive of histologically lower-grade glioma's IDH mutation status.

Materials and Methods
25 histologically and molecularly confirmed lower-grade glioma patients with eight IDH-wildtype (IDHwt) and 17 IDH-mutant (IDHmt) tumors at Asahikawa Medical University Hospital (AMUH) were used as a test cohort. Twenty-nine patients (IDHwt: 13, IDHmt: 16) from Osaka International Cancer Institute (OICI) and 101 patients from the Cancer Imaging Archive (TCIA) / Cancer Genome Atlas (TCGA) dataset (IDHwt: 19, IDHmt: 82) were used as external cohorts. rT1/T2 images were calculated from T1- and T2-weighted images using a recommended signal correction. The relationship between the mean rT1/T2 (mrT1/T2) and the IDH mutation status was investigated. Moreover, t-Distributed Stochastic Neighbor Embedding (t-SNE) investigated the difference in MRI qualities and characteristics between the three cohorts.

Results
The test cohort at AMUH revealed that mrT1/T2 of IDHwt tumors was significantly higher than that of IDHmt tumors (p &lt; 0.05) and that the optimal cut-off of mrT1/T2 for discriminating IDHmt was 0.666-0.677, (AUC = 0.75, p &lt; 0.05), which finding was validated by the external domestic cohort at OICI (AUC = 0.75, p = 0.02). However, the external international cohort deriving from TCIA/TCGA could not validate this (AUC = 0.63, p = 0.08). t-SNE analysis revealed that the difference in image characteristics within the cohort was more diverse for the TCIA/TCGA than for the two domestic cohorts.

Conclusion
The current study revealed that mrT1/T2 was able to discriminate IDHwt and IDHmt tumors in two domestic cohorts significantly. This was not validated by the TCIA/TCGA cohort due to the wide variety in the original imaging characteristics of the TCIA/TCGA cohort.
NI-16 RESPONSE ASSESSMENT OF BEVACIZUMAB THERAPY FOR GLIOBLASTOMA BY USING MULTIPLE PET TRACERS
Authors: Miyake Keisuke , Fuke Tomono , Tatano Masaki , Kawai Nobuhiko , Ishikawa Momo , Mino Satoshi , Kanda Takahiro , Suzuki Kenta , Fujimori Takeshi , Toyota Yasunori , Ogawa Daisuke , Hatakeyama Tetsuhiro , Okauchi Masanobu , Kawanishi Masahiko 
Published: December 2022

Abstract

Objective
PET scans are useful for the diagnosis and treatment planning of glioma. Introduced in 2013, bevacizumab (Bev) treatment efficacy can be difficult to determine using MRI imaging. We instead performed PET scans to determine the efficacy of Bev-based glioblastoma treatment.

Methods
Eighty glioblastoma patients treated with Bev from July 2013 to December 2021 were included. The patients were divided into the following three groups: the first group received Bev added to the Stupp regimen after biopsy or subtotal resection (first-dose group), the second group received Bev added to the Stupp regimen after biopsy followed by tumor resection (neoadjuvant group), and the third group received the Stupp regimen after tumor resection followed by TMZ + Bev at recurrence (recurrent group). PET scans (FDG, MET, FLT, and FMISO) were performed before and 4 weeks after the start of the Bev treatment. FDG, MET, and FLT measured tumor-to-normal ratio (TNR), and FMISO measured tumor-to-blood ratio (TBR), as well as the percent change in SUVmax, TNR, TBR, and MTV before and after Bev treatment. Using the Cox proportional hazards model, we examined which of these rates of change were the prognostic factors.

Results
The median PFS (months) and median OS from Bev treatment were 8.87, 16.53, and 4.0 and 12.53, 22.13, and 8.0, respectively. Significant differences in the percent change in MTV for MET, FLT, and FMISO in the first-line group, the percent change in MTV for FDG and MET, the percent change in FDG TNR and FMISO TBR in the recurrent group, and the percent change in MTV for MET and FLT in the neoadjuvant group were shown in the Cox proportional hazards model.

Conclusion
Neoadjuvant treatment with Bev prolonged PFS and OS. The decrease in MET MTV change rate and FMISO TBR.
NI-17 NEW ASSESSMENT FOR FLAIR ABNORMALITY AREA OF GLIOMA USING APT IMAGING
Authors: Yamauchi Takahiro , Maatta Yuki , Kanamoto Masayuki , Tai Katsuhide , Tsukinowa Yu , Kawajiri Satoshi , Yomo Munetaka , Kidoguchi Masamune , Akazawa Ayumi , Higashino Yoshifumi , Isozkai Makoto , Arishima Hidetaka , Kimura Hirohiko , Okazawa Hidehiko , Kikuta Ken-Ichiro 
Published: December 2022

Abstract

Background
In glioma, decision of infiltrating margin in extensive FLAIR hyperintensity area around enhanced area and only FLAIR hyperintensity without enhanced is difficult. For deciding this margin, there are some useful reports using perfusion imaging, diffusion-weighted imaging and PET. Recently, there are some reports that amide proton transfer (APT) imaging is useful for assessment for tumor invasion. In this study, we assessed FLAIR hyperintensity area in gliomas using APT imaging and discussed about pattern of APT signal intensity (SI).

Methods
For patients with glioblastoma (GBM) and oligodendroglioma (OL: IDH-mutant and 1p/19q-codeleted), APT imaging was performed. Gadolinium T1WI, FLAIR and apparent diffusion coefficient (ADC) were performed for tumor invasion and edema. Areas of these sequences were compared with APT hyperintensity and APT and ADC were determined the quantity by SI.

Results
37 sections from 10 GBM and 5 OL patients were assessed. Areas of differences between FLAIR and APT hyperintensity was significantly different between GBM and OL (p = 0.0142). SIs of the hyperintensity area between GBM and OL were different on ADC and APT SIs (ADC: p = 0.0267 / APT: p = 0.055). On GBM, hyperintensity area of APT imaging showed a correlation with hyperintensity area of FLAIR (R2 = 0.600, p &lt; 0.0001). On OL, hyperintensity area of APT imaging showed a strong correlation with hyperintensity area of FLAIR (R2 = 0.806, p &lt; 0.0001), and ADC SI showed correlation with APT SI (R2 = 0.675, p = 0.0019).

Conclusions
FLAIR hyperintensity area of GBM and OL, APT imaging showed different distribution. In FLAIR hyperintensity area of GBM with various phenomenon, APT imaging may indicate increasing area of tumor cell and reactive cells. Furthermore, mismatch between FLAIR and APT hyperintensity area may be useful for differentiation for glioma subtypes.