研究者詳細 - 石田　穣治

論文 - 石田　穣治

分割表示 66 件中 1 - 20 件目／全件表示 >>

Identification of factors related to functional prognoses in craniopharyngiomas. 国際誌

Tsuyoshi Umeda, Yoshihiro Otani, Kentaro Fujii, Joji Ishida, Shuichiro Hirano, Yasuki Suruga, Naoya Kemmotsu, Ryoji Imoto, Yasuhito Kegoya, Ryo Mizuta, Yohei Inoue, Madoka Hokama, Seiichiro Makihara, Kosei Hasegawa, Kenichi Inagaki, Fumio Otsuka, Takao Yasuhara, Shota Tanaka

Journal of neuro-oncology 2025年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Craniopharyngiomas are histologically benign tumors, but their proximity to vital neurovascular structures can significantly deteriorate functional prognoses and severely restrict patients' social interaction and activity. We retrospectively identified risk factors related to the functional prognoses in patients with craniopharyngioma treated at our center. METHODS: A retrospective analysis was conducted on 40 patients who underwent surgery for craniopharyngioma and follow-up at our institution between 2003 and 2022. Functional prognoses were evaluated in terms of obesity (body mass index [BMI] ≥ 25 for adults, BMI-Z ≥ 1.65 for children), visual function, endocrine function, and social participation. We investigated whether patient characteristics, tumor size, tumor location, hypothalamic involvement, surgical hypothalamic damage, extent of resection, and recurrence rate correlated with these functional prognostic factors. RESULTS: The median age at diagnosis was 28.0 years, with a median follow-up of 80.5 months. Postoperative obesity was present in 22 patients, and those with postoperative obesity had a significantly higher preoperative BMI or BMI-Z (preoperative BMI for adults: p = 0.074; preoperative BMI-Z for children: p = 0.020) and were significantly correlated with preoperative hypothalamic involvement grade 2 (p = 0.012) and surgical hypothalamic damage grade II (p = 0.0001). Deterioration in social participation was significantly associated with a larger tumor size (p = 0.023) and tumor recurrence (p = 0.0047). CONCLUSIONS: Patients with higher preoperative BMI or BMI-Z and hypothalamic involvement have a greater risk of postoperative obesity, and larger tumor size and recurrence can significantly deteriorate the rate of patients' social participation.

DOI： 10.1007/s11060-024-04925-7

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Myeloid Cells Induce Infiltration and Activation of B Cells and CD4+ T Follicular Helper Cells to Sensitize Brain Metastases to Combination Immunotherapy. 国際誌

Toshifumi Ninomiya, Naoya Kemmotsu, Fumiaki Mukohara, Masaki Magari, Ai Miyamoto, Youki Ueda, Takamasa Ishino, Joji Nagasaki, Tomohiro Fujiwara, Hidetaka Yamamoto, Hidetoshi Hayashi, Kota Tachibana, Joji Ishida, Yoshihiro Otani, Shota Tanaka, Shinichi Toyooka, Isamu Okamoto, Yosuke Togashi

Cancer research 2025年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Brain metastasis (BM) is a poor prognostic factor in cancer patients. Despite showing efficacy in many extracranial tumors, immunotherapy with anti-PD-1 monoclonal antibody (mAb) or anti-CTLA-4 mAb appears to be less effective against intracranial tumors. Promisingly, recent clinical studies have reported that combination therapy with anti-PD-1 and anti-CTLA-4 mAbs has a potent antitumor effect on BM, highlighting the need to elucidate the detailed mechanisms controlling the intracranial tumor microenvironment (TME) to develop effective immunotherapeutic strategies. Here, we analyzed the tumor-infiltrating lymphocytes in murine models of BM that responded to anti-CTLA-4 mAb to anti-PD-1 mAb. Activated CD4+ T follicular helper (TFH) cells with high CTLA-4 expression characteristically infiltrated the intracranial TME, which were activated by the combination anti-CTLA-4 and anti-PD-1 treatment. Loss of TFH cells suppressed the additive effect of CTLA-4 blockade on anti-PD-1 mAb. B cell-activating factor belonging to the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) produced by abundant myeloid cells, particularly CD80hiCD206lo pro-inflammatory M1-like macrophages, in the intracranial TME, induced B cell and TFH cell infiltration and activation. Furthermore, the intracranial TME of patients with non-small cell lung cancer featured TFH and B cell infiltration as tertiary lymphoid structures. Together, these findings provide insights into the immune cell crosstalk in the intracranial TME that facilitates an additive anti-tumor effect of CTLA-4 blockade with anti-PD-1 treatment, supporting the potential of a combination immunotherapeutic strategy for BM.

DOI： 10.1158/0008-5472.CAN-24-2274

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Comparative analysis of intraoperative MRI and early postoperative MRI findings in glioma surgery patients. 国際誌

Yoshihiro Otani, Fumiyo Higaki, Kentaro Fujii, Joji Ishida, Yosuke Shimazu, Shuichiro Hirano, Naoya Kemmotsu, Yasuki Suruga, Ryoji Imoto, Ryo Mizuta, Yasuhito Kegoya, Yohei Inoue, Tsuyoshi Umeda, Madoka Hokama, Takao Yasuhara, Takao Hiraki, Kazuhiko Kurozumi, Tomotsugu Ichikawa, Shota Tanaka, Isao Date

Journal of neurosurgery 1 - 9 2024年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: The extent of resection (EOR) is an important prognostic factor for both low- and high-grade gliomas. Intraoperative MRI (iMRI) has been used to increase the EOR in glioma surgery. While a recent study reported differences between iMRI and early postoperative MRI (epMRI), their specific relationship to postoperative clinical symptoms remains unclear. This study aims to compare the differences between iMRI and epMRI in glioma surgery. METHODS: A retrospective assessment was conducted on 43 patients with glioma who underwent surgery with iMRI and for whom no additional resection was performed after iMRI. The study evaluated the discrepancies in EOR, surgically induced contrast enhancement (SICE), and diffusion-weighted imaging (DWI) abnormality between iMRI and epMRI. EOR was defined as gross-total resection (GTR), near-total resection, subtotal resection (STR), or partial resection (PR) for enhancing lesions, and GTR, STR, or PR for nonenhancing lesions. In addition, the relationship between postoperative neurological findings and iMRI findings was evaluated. RESULTS: Discrepancies in EOR were observed in 2 (11.1%) of 18 cases with nonenhanced lesions and 1 (4.0%) of 25 cases with enhanced lesions. The positive rate of SICE was 25.0% on iMRI and 67.9% on epMRI. Enhancement at the resection cavity was the most frequent pattern in both iMRI and epMRI. The positive rate of enhancement of the resection cavity was strongly increased on epMRI compared with iMRI, potentially mimicking residual tumor. The positive rate of DWI abnormality was 73% on iMRI and 89.2% on epMRI. Among the 10 patients who showed no DWI abnormality on iMRI, 6 exhibited DWI abnormality on epMRI (the late-developing group). Two patients developed new neurological deficits postoperatively, and both showed DWI abnormality on both iMRI and epMRI. No patient in the late-developing group developed postoperative neurological deficits. CONCLUSIONS: Overall, iMRI demonstrated more accurate EOR and less SICE compared with epMRI. Although the positive rate of DWI abnormality was lower on iMRI than on epMRI, the late-developing group showed no postoperative neurological deficits. Therefore, iMRI is more useful in assessing accurate EOR and detecting postoperative neurological deficits than epMRI.

DOI： 10.3171/2024.7.JNS24784

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EXTH-04. COMBINATION OF BEVACIZUMAB ENHANCES THE ANTI-TUMOR EFFICACY OF AD-SGE-REIC FOR GLIOMA

Yoshihiro Otani, Yasuhiko Hattori, Atsuhito Uneda, Nobushige Tsuboi, Keigo Makino, Shuichiro Hirano, Joji Ishida, Kentaro Fujii, Yusuke Tomita, Tetsuo Oka, Yuji Matsumoto, Yosuke Shimazu, Hiroyuki Michiue, Kazuhiko Kurozumi, Hiromu Kumon, Isao Date, Shota Tanaka

Neuro-Oncology 26 ( Supplement_8 ) viii236 - viii237 2024年11月

掲載種別：研究論文（学術雑誌）出版者・発行元：Oxford University Press (OUP)

Abstract

Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) is a tumor suppressor gene and its overexpression has been shown to exert anti-tumor effects as a therapeutic target gene in many human cancers. Recently, we revealed the anti-glioma effects of an adenoviral vector carrying REIC/Dkk-3 with the super gene expression system (Ad-SGE-REIC) and conducted the phase Ⅰ/Ⅱ a clinical trial for recurrent malignant glioma (jRCT2063190013). Anti-vascular endothelial growth factor treatments such as bevacizumab have demonstrated convincing therapeutic efficacy in patients with glioma. In this study, we examined the effects of Ad-SGE-REIC on glioma treated with bevacizumab in vitro and in vivo. Ad-SGE-REIC treatment resulted in a significant reduction in the number of invasion cells treated with bevacizumab. Western blot analyses revealed the increased expression of several endoplasmic reticulum stress markers in cells treated with both bevacizumab and Ad-SGE-REIC, as well as decreased β-catenin protein levels. In glioma-bearing mouse models, survival was extended in the combination therapy group. These results suggest that the combination therapy of Ad-SGE-REIC and bevacizumab showed anti-glioma effects by suppressing the angiogenesis and invasion of tumor cells. Combined Ad-SGE-REIC and bevacizumab might be a promising strategy for the treatment of malignant glioma.

DOI： 10.1093/neuonc/noae165.0935

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TMIC-31. MOLECULAR PROGNOSTIC FACTORS OF THE PROGRESSION OF VESTIBULAR SCHWANNOMA AFTER PRIMARY TUMOR RESECTION

Ryo Mizuta, Keigo Makino, Yoshihiro Otai, Kentaro Fujii, Joji Ishida, Atsuhito Uneda, Nobushige Tsuboi, Shuichiro Hirano, Naoya Kemmotsu, Yasuki Suruga, Ryoji Imoto, Yasuhito Kegoya, Madoka Hokama, Ryosuke Ikemachi, Yuji Matsumoto, Yusuke Tomita, Yosuke Shimazu, Hirofumi Inoue, Yuanqing Yan, Ziyi Wang, Mitsuaki Ono, Kazuhiko Kurozumi, Tomotsugu Ichikawa, Takao Yasuhara, Shota Tanaka

Neuro-Oncology 26 ( Supplement_8 ) viii304 - viii305 2024年11月

掲載種別：研究論文（学術雑誌）出版者・発行元：Oxford University Press (OUP)

Abstract

BACKGROUND

Although vestibular schwannoma is a benign tumor, 10% of the tumor regrow after primary tumor resection. The factors associated with tumor progression from several reports remain controversial, and the role of the tumor microenvironment in vestibular schwannoma is still unclear. In this study, we analyzed the prognostic factors associated with the tumor progression after primary resection.

METHODS

We retrospectively reviewed the medical records of patients who underwent surgical resection and were diagnosed with vestibular schwannoma between January 2005 and June 2020. We performed RNA sequencing to identify the prognostic factors and immunohistochemistry to assess the tumor microenvironment, including analysis of the CD80 and CD206 expression of macrophages. We compared the progressed group whose tumor size got larger than 2mm after primary resection or who underwent additional treatment because of regrowth with the stable group.

RESULTS

Fifty-five patients underwent surgical resection for newly diagnosed vestibular schwannoma, and 12 of them had tumor regrowth. RNA sequencing revealed that the significantly upregulated pathways in the stable group was related to immune systems, while that of the progressed group was related to cell cycle. In addition, there were more myeloid cells, especially M2 macrophage infiltration in the stable group. Immunohistochemistry also showed higher M2 macrophages in the stable group.

CONCLUSION

In this study, multiomic analysis revealed the upregulation of immune-related pathways in the stable group and the cell cycle pathway in the progressed group. Altering the tumor microenvironment may offer a therapeutic strategy in vestibular schwannoma after primary resection.

DOI： 10.1093/neuonc/noae165.1209

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Tectal glioma: clinical, radiological, and pathological features, and the importance of molecular analysis.

Ryoji Imoto, Yoshihiro Otani, Kentaro Fujii, Joji Ishida, Shuichiro Hirano, Naoya Kemmotsu, Yasuki Suruga, Ryo Mizuta, Yasuhito Kegoya, Yohei Inoue, Tsuyoshi Umeda, Madoka Hokama, Kana Washio, Hiroyuki Yanai, Shota Tanaka, Kaishi Satomi, Koichi Ichimura, Isao Date

Brain tumor pathology 2024年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Tectal glioma (TG) is a rare lower grade glioma (LrGG) that occurs in the tectum, mainly affecting children. TG shares pathological similarities with pilocytic astrocytoma (PA), but recent genetic analyses have revealed distinct features, such as alterations in KRAS and BRAF. We conducted a retrospective review of cases clinically diagnosed as TG and treated at our institute between January 2005 and March 2023. Six cases were identified and the median age was 30.5 years. Four patients underwent biopsy and two patients underwent tumor resection. Histological diagnoses included three cases of PA, one case of astrocytoma, and two cases of high-grade glioma. The integrated diagnosis, according to the fifth edition of the World Health Organization Classification of Tumours of the central nervous system, included two cases of PA and one case each of diffuse high-grade glioma; diffuse midline glioma H3 K27-altered; glioblastoma; and circumscribed astrocytic glioma. Among the three patients who underwent molecular evaluation, two had KRAS mutation and one had H3-3A K27M mutation. Our results demonstrate the diverse histological and molecular characteristics of TG distinct from other LrGGs. Given the heterogeneous pathological background and the risk of pathological progression in TG, we emphasize the importance of comprehensive diagnosis, including molecular evaluation.

DOI： 10.1007/s10014-024-00494-9

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New Anti-Angiogenic Therapy for Glioblastoma With the Anti-Depressant Sertraline. 国際誌

Nobushige Tsuboi, Yoshihiro Otani, Atsuhito Uneda, Joji Ishida, Yasuki Suruga, Yuji Matsumoto, Atsushi Fujimura, Kentaro Fujii, Hideki Matsui, Kazuhiko Kurozumi, Isao Date, Hiroyuki Michiue

Cancer medicine 13 ( 20 ) e70288 2024年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND AIMS: Anti-angiogenic therapies prolong patient survival in some malignancies but not glioblastoma. We focused on the relationship between the differentiation of glioma stem like cells (GSCs) into tumor derived endothelial cells (TDECs) and, anti-angiogenic therapy resistance. Especially we aimed to elucidate the mechanisms of drug resistance of TDECs to anti-angiogenic inhibitors and identify novel anti-angiogenic drugs with clinical applications. RESULTS: The mouse GSCs, 005, were differentiated into TDECs under hypoxic conditions, and TDECs had endothelial cell characteristics independent of the vascular endothelial growth factor (VEGF) pathway. In vivo, inhibition of the VEGF pathway had no anti-tumor effect and increased the percentage of TDECs in the 005 mouse model. Novel anti-angiogenic drugs for glioblastoma were evaluated using a tube formation assay and a drug repositioning strategy with existing blood-brain barrier permeable drugs. Drug screening revealed that the antidepressant sertraline inhibited tube formation of TDECs. Sertraline was administered to differentiated TDECs in vitro and 005 mouse models in vivo to evaluate genetic changes by RNA-Seq and tumor regression effects by immunohistochemistry and MRI. Sertraline reduced Lama4 and Ang2 expressions of TDEC, which play an important role in non-VEGF-mediated angiogenesis in tumors. The combination of a VEGF receptor inhibitor axitinib, and sertraline improved survival and reduced tumor growth in the 005 mouse model. CONCLUSION: Collectively, our findings showed the diversity of tumor vascular endothelial cells across VEGF and non-VEGF pathways led to anti-angiogenic resistance. The combination of axitinib and sertraline can represent an effective anti-angiogenic therapy for glioblastoma with safe, low cost, and fast availability.

DOI： 10.1002/cam4.70288

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中枢神経原発リンパ腫におけるplasmablastサブポピュレーションの分子学的特性について

小林宏紀, 千々松良太, 直井友亮, 大谷理浩, 水田亮, 藤井謙太郎, 石田穣治, 村上裕之, 氏家英貴, 池内一廣, 浦田知宏, 清家圭介, 藤原英晃, 淺田騰, 藤井伸治, 松岡賢市, 佐藤康晴, 前田嘉信, 遠西大輔

日本血液学会学術集会 86回 O3 - 2 2024年10月

脳腫瘍に対する全ゲノム解析(Whole-genome sequencing analysis of brain tumors)

鈴木啓道, 中島拓真, 舟越勇介, 金森政之, 柴原一陽, 鈴木智成, 木下学, 園田順彦, 荒川芳輝, 永根基雄, 田中將太, 石田穣治, 齋藤竜太, 花谷亮典, 吉本幸司, 成田善孝

日本癌学会総会記事 83回 S08 - 3 2024年9月

脳腫瘍の分子診断と治療2 NF1関連グリオーマにおける腫瘍微小環境の解析

駿河和城, 大谷理浩, 松本悠司, 平野秀一郎, 藤井謙太郎, 石田穣治, 柳井広之, 田中將太

Brain Tumor Pathology 41 ( Suppl. ) 100 - 100 2024年5月

【頭蓋頸椎移行部病変】Chiari奇形に対する治療

安原隆雄, 佐々田晋, 石田穣治, 金恭平

脊椎脊髄ジャーナル 37 ( 4 ) 267 - 273 2024年5月

記述言語：日本語出版者・発行元：(株)三輪書店

＜文献概要＞はじめに 2023年12月末日現在,'Chiari malformation'をPubMed検索すると,1938年のAringの報告を皮切りに,5,698件の論文がhitし,2010年以降が2,979件,2023年は314件と,いまだに議論が尽きない病態であることがわかる.Chiari奇形は4型に分類され,成人や小児期に発症することが多く脊髄空洞を半数以上で合併するI型が最も多い.次いで,乳幼児期に発症することが多く,水頭症や脊髄髄膜瘤を合併するII型がそれに続く.本稿では,臨床家が最も遭遇する可能性が高いChiari I型奇形をChiari奇形として以下表記し議論する.外科治療については,谷らが2008年に報告しているように,大孔部減圧術+C1椎弓切除が行われることが多いが,硬膜形成の方法や小脳扁桃切除に関しては,いまだ議論が分かれる部分もある.本稿では,最近の報告からChiari奇形の病態や治療について概説し,私たちの試みについて症例を交えて報告する.

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当院で経験したDiffuse midline glioma,H3K27-alteredの臨床的特徴

外間まどか, 大谷理浩, 石田穣治, 梅田剛志, 井上陽平, 水田亮, 井本良二, 駿河和城, 劒持直也, 家護谷泰仁, 平野秀一郎, 冨田祐介, 藤井謙太郎, 鷲尾佳奈, 田中將太

小児の脳神経 49 ( 2 ) 209 - 209 2024年4月

頭蓋咽頭腫の神経内分泌機能予後に関する因子の検討

梅田剛志, 大谷理浩, 井上陽平, 外間まどか, 水田亮, 井本良二, 駿河和城, 劒持直也, 家護谷泰仁, 平野秀一郎, 石田穣治, 藤井謙太郎, 安原隆雄, 長谷川高誠, 稲垣兼一, 伊達勲

日本内分泌学会雑誌 99 ( 5 ) 1422 - 1422 2024年4月

当院で経験したDiffuse midline glioma,H3K27-alteredの臨床的特徴

小児の脳神経 49 ( 2 ) 209 - 209 2024年4月

Combined simultaneous endoscopic endonasal and transcranial surgery using high-definition three-dimensional exoscope for malignant tumors of the anterior skull base. 査読国際誌

Seiichiro Makihara, Yoshihiro Otani, Kensuke Uraguchi, Aiko Shimizu, Aya Murai, Takaya Higaki, Naoki Akisada, Shohei Fujimoto, Takuma Makino, Joji Ishida, Kentaro Fujii, Takao Yasuhara, Tomoyuki Ota, Hiroshi Matsumoto, Mizuo Ando

Head & neck 2024年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Advanced surgical interventions are required to treat malignancies in the anterior skull base (ASB). This study investigates the utility of endoscopic endonasal and transcranial surgery (EETS) using a high-definition three-dimensional exoscope as an alternative to traditional microscopy. METHODS: Six patients with carcinomas of varying histopathologies underwent surgery employing the EETS maneuver, which synchronized three distinct surgical modalities: harvesting of the anterolateral thigh flap, initiation of the transnasal technique, and initiation of the transcranial procedure. RESULTS: The innovative strategy enabled successful tumor resection and skull base reconstruction without postoperative local neoplastic recurrence, cerebrospinal fluid leakage, or neurological deficits. CONCLUSION: The integration of the exoscope and EETS is a novel therapeutic approach for ASB malignancies. This strategy demonstrates the potential of the exoscope in augmenting surgical visualization, enhancing ergonomics, and achieving seamless alignment of multiple surgical interventions. This technique represents a progressive shift in the management of these complex oncological challenges.

DOI： 10.1002/hed.27724

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Midline invasion predicts poor prognosis in diffuse hemispheric glioma, H3 G34-mutant: an individual participant data review. 査読国際誌

Yasuhito Kegoya, Yoshihiro Otani, Yohei Inoue, Ryo Mizuta, Fumiyo Higaki, Kana Washio, Shinichiro Koizumi, Kazuhiko Kurozumi, Joji Ishida, Kentaro Fujii, Norio Yamamoto, Yoshihiro Tanaka, Isao Date

Journal of neuro-oncology 2024年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Diffuse hemispheric glioma, H3 G34-mutant (DHGs), is a newly categorized tumor in pediatric-type diffuse high-grade gliomas, World Health Organization grade 4, with a poor prognosis. Although prognostic factors associated with genetic abnormalities have been reported, few reports have examined the clinical presentation of DHGs, especially from the viewpoint of imaging findings. In this study, we investigated the relationship between clinical factors, including imaging findings, and prognosis in patients with DHGs. METHODS: We searched Medline through the PubMed database using two search terms: "G34" and "glioma", between 1 April 2012 and 1 July 2023. We retrieved articles that described imaging findings and overall survival (OS), and added one DHG case from our institution. We defined midline invasion (MI) as invasion to the contralateral cerebrum, brainstem, corpus callosum, thalamus, and basal ganglia on magnetic resonance imaging. The primary outcome was 12-month survival, estimated using Kaplan-Meier curves and logistic regression. RESULTS: A total of 96 patients were included in this study. The median age was 22 years, and the proportion of male patients was 48.4%. Lesions were most frequently located in the frontal lobe (52.6%). MI was positive in 39.6% of all patients. The median OS was 14.4 months. Univariate logistic regression analysis revealed that OS was significantly worse in the MI-positive group compared with the MI-negative group. Multivariate logistic regression analysis revealed that MI was an independent prognostic factor in DHGs. CONCLUSIONS: In this study, MI-positive cases had a worse prognosis compared with MI-negative cases. PREVIOUS PRESENTATIONS: No portion of this study has been presented or published previously.

DOI： 10.1007/s11060-024-04587-5

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Subtyping of Group 3/4 medulloblastoma as a potential prognostic biomarker among patients treated with reduced dose of craniospinal irradiation: a Japanese Pediatric Molecular Neuro-Oncology Group study. 査読国際誌

Kohei Fukuoka, Jun Kurihara, Tomoko Shofuda, Naoki Kagawa, Kai Yamasaki, Ryo Ando, Joji Ishida, Masayuki Kanamori, Atsufumi Kawamura, Young-Soo Park, Chikako Kiyotani, Takuya Akai, Dai Keino, Yosuke Miyairi, Atsushi Sasaki, Junko Hirato, Takeshi Inoue, Atsuko Nakazawa, Katsuyoshi Koh, Ryo Nishikawa, Isao Date, Motoo Nagane, Koichi Ichimura, Yonehiro Kanemura

Acta neuropathologica communications 11 ( 1 ) 153 - 153 2023年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: One of the most significant challenges in patients with medulloblastoma is reducing the dose of craniospinal irradiation (CSI) to minimize neurological sequelae in survivors. Molecular characterization of patients receiving lower than standard dose of CSI therapy is important to facilitate further reduction of treatment burden. METHODS: We conducted DNA methylation analysis using an Illumina Methylation EPIC array to investigate molecular prognostic markers in 38 patients with medulloblastoma who were registered in the Japan Pediatric Molecular Neuro-Oncology Group and treated with reduced-dose CSI. RESULTS: Among the patients, 23 were classified as having a standard-risk and 15 as high-risk according to the classic classification based on tumor resection rate and presence of metastasis, respectively. The median follow-up period was 71.5 months (12.0-231.0). The median CSI dose was 18 Gy (15.0-24.0) in both groups, and 5 patients in the high-risk group received a CSI dose of 18.0 Gy. Molecular subgrouping revealed that the standard-risk cohort included 5 WNT, 2 SHH, and 16 Group 3/4 cases; all 15 patients in the high-risk cohort had Group 3/4 medulloblastoma. Among the patients with Group 3/4 medulloblastoma, 9 of the 31 Group 3/4 cases were subclassified as subclass II, III, and V, which were known to an association with poor prognosis according to the novel subtyping among the subgroups. Patients with poor prognostic subtype showed worse prognosis than that of others (5-year progression survival rate 90.4% vs. 22.2%; p < 0.0001). The result was replicated in the multivariate analysis (hazard ratio12.77, 95% confidence interval for hazard ratio 2.38-99.21, p value 0.0026 for progression-free survival, hazard ratio 5.02, 95% confidence interval for hazard ratio 1.03-29.11, p value 0.044 for overall survival). CONCLUSION: Although these findings require validation in a larger cohort, the present findings suggest that novel subtyping of Group 3/4 medulloblastoma may be a promising prognostic biomarker even among patients treated with lower-dose CSI than standard treatment.

DOI： 10.1186/s40478-023-01652-4

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Utility of Comprehensive Genomic Profiling for Precise Diagnosis of Pediatric-Type Diffuse High-Grade Glioma.

Keigo Makino, Yoshihiro Otani, Kentaro Fujii, Joji Ishida, Shuichiro Hirano, Yasuki Suruga, Kana Washio, Kenji Nishida, Hiroyuki Yanai, Shuta Tomida, Daisuke Ennishi, Isao Date

Acta medica Okayama 77 ( 3 ) 323 - 330 2023年6月

記述言語：英語

In the current World Health Organization classification of central nervous system tumors, comprehensive genetic and epigenetic analyses are considered essential for precise diagnosis. A 14-year-old male patient who presented with a cerebellar tumor was initially diagnosed with glioblastoma and treated with radiation and concomitant temozolomide chemotherapy after resection. During maintenance temozolomide therapy, a new contrast-enhanced lesion developed in the bottom of the cavity formed by the resection. A second surgery was performed, but the histological findings in specimens from the second surgery were different from those of the first surgery. Although genome-wide DNA methylation profiling was conducted using frozen tissue for a precise diagnosis, the proportion of tumor cells was insufficient and only normal cerebellum was observed. We then performed comprehensive genetic analysis using formalin-fixed paraffin-embedded sections, which revealed MYCN amplification without alteration of IDH1, IDH2, or Histone H3. Finally, the patient was diagnosed with pediatric-type diffuse high-grade glioma, H3-wildtype and IDH-wildtype. In conclusion, comprehensive genetic and epigenetic analysis should be considered in pediatric brain tumor cases.

DOI： 10.18926/AMO/65502

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脳腫瘍のメチル化診断診断困難症例に対するゲノムワイドメチル化解析の検討

大谷理浩, 藤井謙太郎, 石田穣治, 駿河和城, 鷲尾佳奈, 柳井広之, 里見介史, 市村幸一, 伊達勲

Brain Tumor Pathology 40 ( Suppl. ) 062 - 062 2023年5月

Utility of genome-wide DNA methylation profiling for pediatric-type diffuse gliomas.

Yoshihiro Otani, Kaishi Satomi, Yasuki Suruga, Joji Ishida, Kentaro Fujii, Koichi Ichimura, Isao Date

Brain tumor pathology 40 ( 2 ) 56 - 65 2023年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Despite the current progress of treatment, pediatric-type diffuse glioma is one of the most lethal primary malignant tumors in the central nervous system (CNS). Since pediatric-type CNS tumors are rare disease entities and highly heterogeneous, the diagnosis is challenging. An accurate diagnosis is essential for the choice of optimal treatment, which leads to precision oncology and improvement of the patient's outcome. Genome-wide DNA methylation profiling recently emerged as one of the most important tools for the diagnosis of CNS tumors, and the utility of this novel assay has been reported in both pediatric and adult patients. In the current World Health Organization classification published in 2021, several new entities are recognized in pediatric-type diffuse gliomas, some of which require methylation profiling. In this review, we investigated the utility of genome-wide DNA methylation profiling in pediatric-type diffuse glioma, as well as issues in the clinical application of this assay. Furthermore, the combination of genome-wide DNA methylation profiling and other comprehensive genomic assays, which may improve diagnostic accuracy and detection of the actionable target, will be discussed.

DOI： 10.1007/s10014-023-00457-6

PubMed

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