Faculty Profiles - Tanaka Shota

Papers - Tanaka Shota

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Development of a New Image-Guided Neuronavigation System: Mixed-Reality Projection Mapping Is Accurate and Feasible. International journal

Tsukasa Koike, Taichi Kin, Shota Tanaka, Katsuya Sato, Tatsuya Uchida, Yasuhiro Takeda, Hiroki Uchikawa, Satoshi Kiyofuji, Toki Saito, Hirokazu Takami, Shunsaku Takayanagi, Akitake Mukasa, Hiroshi Oyama, Nobuhito Saito

Operative neurosurgery (Hagerstown, Md.) 21 ( 6 ) 549 - 557 2021.11

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Image-guided systems improve the safety, functional outcome, and overall survival of neurosurgery but require extensive equipment. OBJECTIVE: To develop an image-guided surgery system that combines the brain surface photographic texture (BSP-T) captured during surgery with 3-dimensional computer graphics (3DCG) using projection mapping. METHODS: Patients who underwent initial surgery with brain tumors were prospectively enrolled. The texture of the 3DCG (3DCG-T) was obtained from 3DCG under similar conditions as those when capturing the brain surface photographs. The position and orientation at the time of 3DCG-T acquisition were used as the reference. The correct position and orientation of the BSP-T were obtained by aligning the BSP-T with the 3DCG-T using normalized mutual information. The BSP-T was combined with and displayed on the 3DCG using projection mapping. This mixed-reality projection mapping (MRPM) was used prospectively in 15 patients (mean age 46.6 yr, 6 males). The difference between the centerlines of surface blood vessels on the BSP-T and 3DCG constituted the target registration error (TRE) and was measured in 16 fields of the craniotomy area. We also measured the time required for image processing. RESULTS: The TRE was measured at 158 locations in the 15 patients, with an average of 1.19 ± 0.14 mm (mean ± standard error). The average image processing time was 16.58 min. CONCLUSION: Our MRPM method does not require extensive equipment while presenting information of patients' anatomy together with medical images in the same coordinate system. It has the potential to improve patient safety.

DOI： 10.1093/ons/opab353

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Gene expression profiling of 19q-loss astrocytomas suggest a specific pattern associated with the better prognosis. International journal

Ryohei Otani, Akitake Mukasa, Takeo Uzuka, Fumi Higuchi, Hadzki Matsuda, Masashi Nomura, Shota Tanaka, Phyo Kim, Keisuke Ueki

Journal of neuro-oncology 154 ( 2 ) 221 - 228 2021.9

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: We previously reported that there was a subgroup of IDH-mutated astrocytomas harboring only 19q-loss showing oligodendroglioma-like morphology and significantly longer overall survival (OS) compared with 19q-intact astrocytomas. The aim of this study was to further explore the biological characteristics of this possible subgroup and obtain insight into the mechanism of their relatively benign clinical behavior. METHODS: We compared gene expression pattern between five 19q-loss and five 19q-intact IDH-mutated astrocytomas by microarray analysis. RESULTS: By comparing expression levels of genes of 19q-loss astrocytomas to those of 19q-intact astrocytomas, 102 up-regulated genes and 162 down-regulated genes were extracted. The down-regulated genes clustered heavily to 19q and 4p while the up-regulated genes clustered to 4q. It was noteworthy that fibroblast growth factor 1 associated with stem cell maintenance and multiple genes associated with glioma progression were down-regulated in 19q-loss astrocytomas, and these results were validated with the independent TCGA data set. On t-SNE analysis of the 19q-loss astrocytomas with other IDH-mutant glioma subgroups from the TCGA datasets, the expression pattern of the 19q-loss astrocytomas showed no shift toward oligodendrogliomas with 1p/19q codeletion but rather constituted a subgroup of astrocytoma. CONCLUSIONS: These findings suggested that 19q-loss in astrocytomas is more likely acquired event rather than an early event in oncogenesis like the 1p/19q-codeletion in oligodendrogliomas, and that the biological features of 19q-loss astrocytomas are possibly related to differentially expressed genes associated with stem cell maintenance and glioma progression.

DOI： 10.1007/s11060-021-03816-5

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Clinical Features and Prognostic Factors for Primary Anaplastic Large Cell Lymphoma of the Central Nervous System: A Systematic Review. International journal

Yudai Hirano, Satoru Miyawaki, Shota Tanaka, Kazuki Taoka, Hiroki Hongo, Yu Teranishi, Hirokazu Takami, Shunsaku Takayanagi, Mineo Kurokawa, Nobuhito Saito

Cancers 13 ( 17 ) 2021.8

Language：English Publishing type：Research paper (scientific journal)

Primary anaplastic large cell lymphoma (ALCL) of the central nervous system (CNS) is a subtype of primary CNS lymphoma (PCNSL). There are very few comprehensive reports on this extremely rare tumor. Therefore, it is necessary to investigate the clinical features and prognostic factors for primary ALCL of the CNS. We performed a systematic review of the published literature. Past cases were comprehensively searched using PubMed, Cochrane Library, and Web of Science. Clinical information, such as age, sex, anaplastic lymphoma kinase (ALK) status, lesion sites, treatment methods, and survivorship were extracted. Thirty-nine cases with information on ALK status and treatment course were identified. The average observation period was 13 months, and the overall 2-year survival rate was 58%. Univariate analyses showed a statistically significantly better prognosis among patients < 40 years of age (p = 0.039, HR 0.32 (0.11-0.95)) and in relation to ALK positivity (p = 0.010, HR 0.24 (0.08-0.71) and methotrexate treatment (p = 0.003, HR 0.17 (0.05-0.56)). Because of the sparsity of cases, it is necessary to accumulate cases in order to perform more detailed analyses.

DOI： 10.3390/cancers13174358

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TERT promoter mutation status is necessary and sufficient to diagnose IDH-wildtype diffuse astrocytic glioma with molecular features of glioblastoma. International journal

Kenji Fujimoto, Hideyuki Arita, Kaishi Satomi, Kai Yamasaki, Yuko Matsushita, Taishi Nakamura, Yasuji Miyakita, Toru Umehara, Keiichi Kobayashi, Kaoru Tamura, Shota Tanaka, Fumi Higuchi, Yoshiko Okita, Yonehiro Kanemura, Junya Fukai, Daisuke Sakamoto, Takehiro Uda, Ryunosuke Machida, Aya Kuchiba, Taketoshi Maehara, Motoo Nagane, Ryo Nishikawa, Hiroyoshi Suzuki, Makoto Shibuya, Takashi Komori, Yoshitaka Narita, Koichi Ichimura

Acta neuropathologica 142 ( 2 ) 323 - 338 2021.8

Language：English Publishing type：Research paper (scientific journal)

The Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) update 3 recommends that histologic grade II and III IDH-wildtype diffuse astrocytic gliomas that harbor EGFR amplification, the combination of whole chromosome 7 gain and whole chromosome 10 loss (7 + /10 -), or TERT promoter (pTERT) mutations should be considered as glioblastomas (GBM), World Health Organization grade IV. In this retrospective study, we examined the utility of molecular classification based on pTERT status and copy-number alterations (CNAs) in IDH-wildtype lower grade gliomas (LGGs, grade II, and III). The impact on survival was evaluated for the pTERT mutation and CNAs, including EGFR gain/amplification, PTEN loss, CDKN2A homozygous deletion, and PDGFRA gain/amplification. We analyzed 46 patients with IDH-wildtype/pTERT-mutant (mut) LGGs and 85 with IDH-wildtype/pTERT-wildtype LGGs. EGFR amplification and a combination of EGFR gain and PTEN loss (EGFR + /PTEN -) were significantly more frequent in pTERT-mut patients (p < 0.0001). Cox regression analysis showed that the pTERT mutation was a significant predictor of poor prognosis (hazard ratio [HR] 2.79, 95% confidence interval [CI] 1.55-4.89, p = 0.0008), but neither EGFR amplification nor EGFR + /PTEN - was an independent prognostic factor in IDH-wildtype LGGs. PDGFRA gain/amplification was a significant poor prognostic factor in IDH-wildtype/pTERT-wildtype LGGs (HR 2.44, 95% CI 1.09-5.27, p = 0.03, Cox regression analysis). The IDH-wildtype LGGs with either pTERT-mut or PDGFRA amplification were mostly clustered with GBM by DNA methylation analysis. Thus, our study suggests that analysis of pTERT mutation status is necessary and sufficient to diagnose IDH-wildtype diffuse astrocytic gliomas with molecular features of glioblastoma. The PDGFRA status may help further delineate IDH-wildtype/pTERT-wildtype LGGs. Methylation profiling showed that IDH-wildtype LGGs without molecular features of GBM were a heterogeneous group of tumors. Some of them did not fall into existing categories and had significantly better prognoses than those clustered with GBM.

DOI： 10.1007/s00401-021-02337-9

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polymorphous low-grade neuroepithelial tumor of the young(PLNTY)が考えられた側頭葉腫瘍の一例

畑野颯佑, 雨宮史織, 鈴木文夫, 中井雄大, 池村雅子, 田中將太, 國井尚人, 阿部修

日本医学放射線学会秋季臨床大会抄録集 57回 S389 - S389 2021.8

A Novel Topical Fluorescent Probe for Detection of Glioblastoma. International journal

Yosuke Kitagawa, Shota Tanaka, Mako Kamiya, Yugo Kuriki, Kyoko Yamamoto, Takenori Shimizu, Takahide Nejo, Taijun Hana, Reiko Matsuura, Tsukasa Koike, Erika Yamazawa, Yoshihiro Kushihara, Satoshi Takahashi, Masashi Nomura, Hirokazu Takami, Shunsaku Takayanagi, Akitake Mukasa, Yasuteru Urano, Nobuhito Saito

Clinical cancer research : an official journal of the American Association for Cancer Research 27 ( 14 ) 3936 - 3947 2021.7

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Five-aminolevulinic acid (5-ALA) is widely used as an intraoperative fluorescent probe for radical resection of high-grade glioma, and thus aids in extending progression-free survival of patients. However, there exist some cases where 5-ALA fails to fluoresce. In some other cases, it may undergo fluorescence quenching but cannot be orally readministered during surgery. This study aimed to develop a novel hydroxymethyl rhodamine green (HMRG)-based fluorescence labeling system that can be repeatedly administered as a topical spray during surgery for the detection of glioblastoma. EXPERIMENTAL DESIGN: We performed a three-stage probe screening using tumor lysates and fresh tumor tissues with our probe library consisting of a variety of HMRG probes with different dipeptides. We then performed proteome and transcript expression analyses to detect candidate enzymes responsible for cleaving the probe. Moreover, in vitro and ex vivo studies using U87 glioblastoma cell line were conducted to validate the findings. RESULTS: The probe screening identified proline-arginine-HMRG (PR-HMRG) as the optimal probe that distinguished tumors from peritumoral tissues. Proteome analysis identified calpain-1 (CAPN1) to be responsible for cleaving the probe. CAPN1 was highly expressed in tumor tissues which reacted to the PR-HMRG probe. Knockdown of this enzyme suppressed fluorescence intensity in U87 glioblastoma cells. In situ assay using a mouse U87 xenograft model demonstrated marked contrast of fluorescence with the probe between the tumor and peritumoral tissues. CONCLUSIONS: The novel fluorescent probe PR-HMRG is effective in detecting glioblastoma when applied topically. Further investigations are warranted to assess the efficacy and safety of its clinical use.

DOI： 10.1158/1078-0432.CCR-20-4518

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Development of Innovative Neurosurgical Operation Support Method Using Mixed-Reality Computer Graphics. International journal

Tsukasa Koike, Taichi Kin, Shota Tanaka, Yasuhiro Takeda, Hiroki Uchikawa, Taketo Shiode, Toki Saito, Hirokazu Takami, Shunsaku Takayanagi, Akitake Mukasa, Hiroshi Oyama, Nobuhito Saito

World neurosurgery: X 11 100102 - 100102 2021.7

Language：English Publishing type：Research paper (scientific journal)

Background: In neurosurgery, it is important to inspect the spatial correspondence between the preoperative medical image (virtual space), and the intraoperative findings (real space) to improve the safety of the surgery. Navigation systems and related modalities have been reported as methods for matching this correspondence. However, because of the influence of the brain shift accompanying craniotomy, registration accuracy is reduced. In the present study, to overcome these issues, we developed a spatially accurate registration method of medical fusion 3-dimensional computer graphics and the intraoperative brain surface photograph, and its registration accuracy was measured. Methods: The subjects included 16 patients with glioma. Nonrigid registration using the landmarks and thin-plate spline methods was performed for the fusion 3-dimensional computer graphics and the intraoperative brain surface photograph, termed mixed-reality computer graphics. Regarding the registration accuracy measurement, the target registration error was measured by two neurosurgeons, with 10 points for each case at the midpoint of the landmarks. Results: The number of target registration error measurement points was 160 in the 16 cases. The target registration error was 0.72 ± 0.04 mm. Aligning the intraoperative brain surface photograph and the fusion 3-dimensional computer graphics required ∼10 minutes on average. The average number of landmarks used for alignment was 24.6. Conclusions: Mixed-reality computer graphics enabled highly precise spatial alignment between the real space and virtual space. Mixed-reality computer graphics have the potential to improve the safety of the surgery by allowing complementary observation of brain surface photographs and fusion 3-dimensional computer graphics.

DOI： 10.1016/j.wnsx.2021.100102

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[Glioblastoma].

Shota Tanaka

No shinkei geka. Neurological surgery 49 ( 3 ) 623 - 631 2021.5

Language：Japanese Publishing type：Research paper (scientific journal)

Glioblastoma, the most malignant and most common form of glioma, is known to portend very poor prognosis with the median overall survival of approximately 1.5 years. Its treatment requires a multidisciplinary approach, which consists of maximal safe resection followed by radiotherapy and chemotherapy with temozolomide. Bevacizumab is approved for newly diagnosed as well as recurrent malignant glioma in Japan. NovoTTF is a novel medical device that emits alternating electric fields; it inhibits the proliferation and growth of the tumor by interfering with tumor cell mitosis at anaphase. A photodynamic therapy with talaporfin sodium has been approved for primary malignant brain tumor including glioblastoma in Japan. For epilepsy secondary to glioblastoma, a novel class of antiepileptics such as levetiracetam and lacosamide is preferred given the lack of drug-drug interactions. Perampanel is a selective antagonist of AMPA receptors, the major subtype of ionotropic glutamate receptors; it may be a preferred antiepileptics for glioblastoma, given the in vitro and in vivo analyses suggesting that it decreases the proliferation and invasion of tumor cells. In this chapter, I describe the overview of the multidisciplinary treatments of glioblastoma. I also describe the future perspectives.

DOI： 10.11477/mf.1436204436

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成人移行期に当院へ紹介された結節性硬化症症例の特徴

佐藤敦志, 高柳俊作, 辛正廣, 田中將太, 國井尚人, 嶋田勢二郎, 佐藤悠佑, 管析, 坊木ひかり, 澤村裕正, 漆山博和, 水口雅

脳と発達 53 ( Suppl. ) S303 - S303 2021.5

癌ゲノム医療 TodaiOncoPanelなどのがん遺伝子パネル検査と脳腫瘍病理の今後の展望

高柳俊作, 田中將太, 高見浩数, 宮脇哲, 辛正廣, 池村雅子, 牛久哲男, 牛久綾, 織田克利, 齊藤延人

Brain Tumor Pathology 38 ( Suppl. ) 068 - 068 2021.5

癌ゲノム医療 TodaiOncoPanelなどのがん遺伝子パネル検査と脳腫瘍病理の今後の展望

高柳俊作, 田中將太, 高見浩数, 宮脇哲, 辛正廣, 池村雅子, 牛久哲男, 牛久綾, 織田克利, 齊藤延人

Brain Tumor Pathology 38 ( Suppl. ) 068 - 068 2021.5

A New Era of Neuro-Oncology Research Pioneered by Multi-Omics Analysis and Machine Learning. International journal

Satoshi Takahashi, Masamichi Takahashi, Shota Tanaka, Shunsaku Takayanagi, Hirokazu Takami, Erika Yamazawa, Shohei Nambu, Mototaka Miyake, Kaishi Satomi, Koichi Ichimura, Yoshitaka Narita, Ryuji Hamamoto

Biomolecules 11 ( 4 ) 2021.4

Language：English Publishing type：Research paper (scientific journal)

Although the incidence of central nervous system (CNS) cancers is not high, it significantly reduces a patient's quality of life and results in high mortality rates. A low incidence also means a low number of cases, which in turn means a low amount of information. To compensate, researchers have tried to increase the amount of information available from a single test using high-throughput technologies. This approach, referred to as single-omics analysis, has only been partially successful as one type of data may not be able to appropriately describe all the characteristics of a tumor. It is presently unclear what type of data can describe a particular clinical situation. One way to solve this problem is to use multi-omics data. When using many types of data, a selected data type or a combination of them may effectively resolve a clinical question. Hence, we conducted a comprehensive survey of papers in the field of neuro-oncology that used multi-omics data for analysis and found that most of the papers utilized machine learning techniques. This fact shows that it is useful to utilize machine learning techniques in multi-omics analysis. In this review, we discuss the current status of multi-omics analysis in the field of neuro-oncology and the importance of using machine learning techniques.

DOI： 10.3390/biom11040565

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Fine-Tuning Approach for Segmentation of Gliomas in Brain Magnetic Resonance Images with a Machine Learning Method to Normalize Image Differences among Facilities. International journal

Satoshi Takahashi, Masamichi Takahashi, Manabu Kinoshita, Mototaka Miyake, Risa Kawaguchi, Naoki Shinojima, Akitake Mukasa, Kuniaki Saito, Motoo Nagane, Ryohei Otani, Fumi Higuchi, Shota Tanaka, Nobuhiro Hata, Kaoru Tamura, Kensuke Tateishi, Ryo Nishikawa, Hideyuki Arita, Masahiro Nonaka, Takehiro Uda, Junya Fukai, Yoshiko Okita, Naohiro Tsuyuguchi, Yonehiro Kanemura, Kazuma Kobayashi, Jun Sese, Koichi Ichimura, Yoshitaka Narita, Ryuji Hamamoto

Cancers 13 ( 6 ) 2021.3

Language：English Publishing type：Research paper (scientific journal)

Machine learning models for automated magnetic resonance image segmentation may be useful in aiding glioma detection. However, the image differences among facilities cause performance degradation and impede detection. This study proposes a method to solve this issue. We used the data from the Multimodal Brain Tumor Image Segmentation Benchmark (BraTS) and the Japanese cohort (JC) datasets. Three models for tumor segmentation are developed. In our methodology, the BraTS and JC models are trained on the BraTS and JC datasets, respectively, whereas the fine-tuning models are developed from the BraTS model and fine-tuned using the JC dataset. Our results show that the Dice coefficient score of the JC model for the test portion of the JC dataset was 0.779 ± 0.137, whereas that of the BraTS model was lower (0.717 ± 0.207). The mean Dice coefficient score of the fine-tuning model was 0.769 ± 0.138. There was a significant difference between the BraTS and JC models (p < 0.0001) and the BraTS and fine-tuning models (p = 0.002); however, no significant difference between the JC and fine-tuning models (p = 0.673). As our fine-tuning method requires fewer than 20 cases, this method is useful even in a facility where the number of glioma cases is small.

DOI： 10.3390/cancers13061415

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So-called bifocal tumors with diabetes insipidus and negative tumor markers: are they all germinoma? International journal

Masayuki Kanamori, Hirokazu Takami, Shigeru Yamaguchi, Takashi Sasayama, Koji Yoshimoto, Teiji Tominaga, Akihiro Inoue, Naokado Ikeda, Atsushi Kambe, Toshihiro Kumabe, Masahide Matsuda, Shota Tanaka, Manabu Natsumeda, Ken-Ichiro Matsuda, Masahiro Nonaka, Jun Kurihara, Masayoshi Yamaoka, Naoki Kagawa, Naoki Shinojima, Tetsuya Negoto, Yukiko Nakahara, Yoshiki Arakawa, Seiji Hatazaki, Hiroaki Shimizu, Atsuo Yoshino, Hiroshi Abe, Jiro Akimoto, Yu Kawanishi, Tomonari Suzuki, Atsushi Natsume, Motoo Nagane, Yukinori Akiyama, Dai Keino, Tadateru Fukami, Takahiro Tomita, Kohei Kanaya, Tsutomu Tokuyama, Shuichi Izumoto, Mitsutoshi Nakada, Daisuke Kuga, Shohei Yamamoto, Ryogo Anei, Takeo Uzuka, Junya Fukai, Noriyuki Kijima, Keita Terashima, Koichi Ichimura, Ryo Nishikawa

Neuro-oncology 23 ( 2 ) 295 - 303 2021.2

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The Delphi consensus statements on the management of germ cell tumors (GCTs) failed to reach agreements on the statement that the cases with (i) pineal and neurohypophyseal bifocal lesion, (ii) with diabetes insipidus, and (iii) with negative tumor markers can be diagnosed as germinoma without histological verification. To answer this, multicenter retrospective analysis was performed. METHODS: A questionnaire on clinical findings, histological diagnosis, and details of surgical procedures was sent to 86 neurosurgical and 35 pediatrics departments in Japan. RESULTS: Fifty-one institutes reported 132 cases that fulfilled the 3 criteria. Tissue sampling was performed in 91 cases from pineal (n = 44), neurohypophyseal (n = 32), both (n = 6), and distant (n = 9) lesions. Histological diagnosis was established in 89 cases: pure germinoma or germinoma with syncytiotrophoblastic giant cells in 82 (92.1%) cases, germinoma and mature teratoma in 2 cases, and granulomatous inflammation in 2 cases. Histological diagnosis was not established in 2 cases. Although no tumors other than GCTs were identified, 3 (3.4%) patients had non-germinomatous GCTs (NGGCTs). None of the patients developed permanent complications after endoscopic or stereotactic biopsy. Thirty-nine patients underwent simultaneous procedure for acute hydrocephalus without permanent complications, and hydrocephalus was controlled in 94.9% of them. CONCLUSION: All patients who fulfilled the 3 criteria had GCTs or granulomatous inflammation, but not other types of tumors. However, no fewer than 3.4% of the patients had NGGCTs. Considering the safety and the effects of simultaneous procedures for acute hydrocephalus, biopsy was recommended in such patients.

DOI： 10.1093/neuonc/noaa199

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Necessity for craniospinal irradiation of germinoma with positive cytology without spinal lesion on MR imaging—A controversy

Masayuki Kanamori, Hirokazu Takami, Tomonari Suzuki, Teiji Tominaga, Jun Kurihara, Shota Tanaka, Seiji Hatazaki, Motoo Nagane, Masahide Matsuda, Atsuo Yoshino, Manabu Natsumeda, Masayoshi Yamaoka, Naoki Kagawa, Yukinori Akiyama, Junya Fukai, Tetsuya Negoto, Ichiyo Shibahara, Kazuhiro Tanaka, Akihiro Inoue, Mitsuhiro Mase, Takahiro Tomita, Daisuke Kuga, Noriyuki Kijima, Tadateru Fukami, Yukiko Nakahara, Atsushi Natsume, Koji Yoshimoto, Dai Keino, Tsutomu Tokuyama, Kenichiro Asano, Kenta Ujifuku, Hiroshi Abe, Mitsutoshi Nakada, Ken-ichiro Matsuda, Yoshiki Arakawa, Naokado Ikeda, Yoshitaka Narita, Naoki Shinojima, Atsushi Kambe, Masahiko Nonaka, Shuichi Izumoto, Yu Kawanishi, Kohei Kanaya, Sadahiro Nomura, Kohei Nakajima, Shohei Yamamoto, Keita Terashima, Koichi Ichimura, Ryo Nishikawa

Neuro-Oncology Advances 3 ( 1 ) 2021.1

Publishing type：Research paper (scientific journal) Publisher：Oxford University Press (OUP)

<title>Abstract</title>
<sec>
<title>Background</title>
Cerebrospinal fluid (CSF) cytology and spinal MR imaging are routinely performed for staging before treatment of intracranial germinoma. However, the interpretation of the results of CSF cytology poses 2 unresolved clinical questions: (1) Does positive CSF cytology correlate with the presence of spinal lesion before treatment? and (2) Is craniospinal irradiation (CSI) necessary for patients with positive CSF cytology in the absence of spinal lesion?

</sec>
<sec>
<title>Methods</title>
Multicenter retrospective analyses were performed based on a questionnaire on clinical features, spinal MR imaging finding, results of CSF cytology, treatments, and outcomes which was sent to 86 neurosurgical and 35 pediatrics departments in Japan. Pretreatment frequencies of spinal lesion on MR imaging were compared between the patients with positive and negative cytology. Progression-free survival (PFS) rates were compared between patients with positive CSF cytology without spinal lesion on MR imaging treated with CSI and with whole brain or whole ventricular irradiation (non-CSI).

</sec>
<sec>
<title>Results</title>
A total of 92 germinoma patients from 45 institutes were evaluated by both CSF cytology and spinal MR images, but 26 patients were excluded because of tumor markers, the timing of CSF sampling or incomplete estimation of spinal lesion. Of the remaining 66 germinoma patients, spinal lesions were equally identified in patients with negative CSF cytology and positive cytology (4.9% and 8.0%, respectively). Eleven patients treated with non-CSI had excellent PFS comparable to 11 patients treated with CSI.

</sec>
<sec>
<title>Conclusion</title>
CSI is unnecessary for germinoma patients with positive CSF cytology without spinal lesions on MR imaging.

</sec>

DOI： 10.1093/noajnl/vdab086

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Other Link： http://academic.oup.com/noa/article-pdf/3/1/vdab086/39555495/vdab086.pdf

Low tumor cell content predicts favorable prognosis in germinoma patients

Hirokazu Takami, Kaishi Satomi, Kohei Fukuoka, Shintaro Fukushima, Yuko Matsushita, Kai Yamasaki, Taishi Nakamura, Shota Tanaka, Akitake Mukasa, Nobuhito Saito, Tomonari Suzuki, Takaaki Yanagisawa, Hideo Nakamura, Kazuhiko Sugiyama, Kaoru Tamura, Taketoshi Maehara, Mitsutoshi Nakada, Masahiro Nonaka, Akio Asai, Kiyotaka Yokogami, Hideo Takeshima, Toshihiko Iuchi, Yonehiro Kanemura, Keiichi Kobayashi, Motoo Nagane, Kazuhiko Kurozumi, Koji Yoshimoto, Masahide Matsuda, Akira Matsumura, Yuichi Hirose, Tsutomu Tokuyama, Toshihiro Kumabe, Yoshitaka Narita, Soichiro Shibui, Yoichi Nakazato, Ryo Nishikawa, Masao Matsutani, Koichi Ichimura

Neuro-Oncology Advances 3 ( 1 ) 2021.1

Publishing type：Research paper (scientific journal) Publisher：Oxford University Press (OUP)

<title>Abstract</title>
<sec>
<title>Background</title>
Germinoma preferentially occurs in pediatric and young adult age groups. Although they are responsive to treatment with chemotherapy and radiation, the treatment may cause long-term sequelae in their later lives. Here, we searched for clinical and histopathological features to predict the prognosis of germinoma and affect treatment response.

</sec>
<sec>
<title>Methods</title>
A total of 114 germinoma cases were included in the analysis. We investigated the association between clinical factors, tumor cell content, and progression-free survival (PFS).

</sec>
<sec>
<title>Results</title>
The tumor cell content was widely distributed from &lt;5% to 90% in the specimens, with a median value of 50%. Female patients showed higher tumor cell content in the specimens (P = .002). Cases with lesions at atypical sites showed shorter PFS than those with lesions at other sites (P = .03). Patients with a higher tumor cell content (≥50%) showed shorter PFS than those with a lower tumor cell content (&lt;50%) (P = .03). In multivariate analysis, tumor cell content was the only statistically significant prognostic factor (P = .04). Among the 7 cases treated with local radiation and chemotherapy, all 3 cases that recurred (2 outside of the radiation field, 1 unknown) had tumor cell content of ≥50% in the original specimen, whereas all 4 cases without recurrence had tumor cell contents of &lt;50%.

</sec>
<sec>
<title>Conclusions</title>
We found that tumor cell content significantly affected the prognosis of germinomas. Although validation of these results using an independent and larger cohort is necessary, this potentially opens the possibility of leveraging this pathological factor in future clinical trials when stratifying the treatment intensity.

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DOI： 10.1093/noajnl/vdab110

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Other Link： http://academic.oup.com/noa/article-pdf/3/1/vdab110/40404167/vdab110.pdf

検査からみる神経疾患オンコパネル検査と脳腫瘍

高柳俊作, 田中將太, 齊藤延人

Clinical Neuroscience 39 ( 1 ) 120 - 122 2021.1

A Case of Myxoid Glioneuronal Tumor carrying a PDGFRA p.K385‒ mutant at the Septum Pellucidum

Fujii, G., Tanaka, S., Shin, M., Kikuchi, M., Takami, H., Takayanagi, S., Saito, N.

Japanese Journal of Neurosurgery 30 ( 12 ) 2021

MPC-11 Comprehensive gene expression analysis of IDH-mutated astrocytomas with 19q-loss

Ryohei Otani, Akitake Mukasa, Takeo Uzuka, Fumi Higuchi, Hadzki Matsuda, Shota Tanaka, Phyo Kim, Keisuke Ueki

Neuro-Oncology Advances 2 ( Supplement_3 ) ii12 - ii12 2020.11

Publishing type：Research paper (scientific journal) Publisher：Oxford University Press (OUP)

Abstract

We previously reported that there was a subgroup of IDH-mutated astrocytomas harboring only 19q-loss showing oligodendroglioma-like morphology and significantly longer overall survival (OS) compared with 19q-intact astrocytomas. To further explore the biological characteristics of this possible subgroup and obtain insight into the mechanism of their relatively benign clinical behavior, we compared gene expression pattern between five 19q-loss and five 19q-intact IDH-mutated astrocytomas by microarray analysis. By comparing expression levels of genes of 19q-loss astrocytomas to those of 19q-intact astrocytomas,136 up-regulated genes and 203 down-regulated genes were extracted. Down-regulated genes in the 19q-loss astrocytomas were heavily clustered to 19q and 4p, and up-regulated genes to 4q. It was noted that fibroblast growth factor 1 associated with stem cell maintenance was down-regulated in 19q-loss astrocytomas and genes associated with glioma progression were differentially expressed, these results were validated with the independent TCGA data set. On t-SNE analysis of the 19q-loss astrocytomas with other IDH-mutant glioma subgroups from the TCGA datasets, 19q-loss astrocytomas did not shift to oligodendrogliomas with 1p/19q codeletion but were a subgroup in astrocytomas. These results indicated that 19q-loss in astrocytomas is more likely to be an acquired event rather than early event in oncogenesis like 1p/19q codeletion in oligodendrogliomas, and the biological and morphological features of 19q-loss astrocytomas were possibly related to differentially expressed genes associated with stem cell maintenance and glioma progression.

DOI： 10.1093/noajnl/vdaa143.053

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TERT promoter mutation confers favorable prognosis regardless of 1p/19q status in adult diffuse gliomas with IDH1/2 mutations. International journal

Hideyuki Arita, Yuko Matsushita, Ryunosuke Machida, Kai Yamasaki, Nobuhiro Hata, Makoto Ohno, Shigeru Yamaguchi, Takashi Sasayama, Shota Tanaka, Fumi Higuchi, Toshihiko Iuchi, Kuniaki Saito, Masayuki Kanamori, Ken-Ichiro Matsuda, Yohei Miyake, Kaoru Tamura, Sho Tamai, Taishi Nakamura, Takehiro Uda, Yoshiko Okita, Junya Fukai, Daisuke Sakamoto, Yasuhiko Hattori, Eriel Sandika Pareira, Ryusuke Hatae, Yukitomo Ishi, Yasuji Miyakita, Kazuhiro Tanaka, Shunsaku Takayanagi, Ryohei Otani, Tsukasa Sakaida, Keiichi Kobayashi, Ryuta Saito, Kazuhiko Kurozumi, Tomoko Shofuda, Masahiro Nonaka, Hiroyoshi Suzuki, Makoto Shibuya, Takashi Komori, Hikaru Sasaki, Masahiro Mizoguchi, Haruhiko Kishima, Mitsutoshi Nakada, Yukihiko Sonoda, Teiji Tominaga, Motoo Nagane, Ryo Nishikawa, Yonehiro Kanemura, Aya Kuchiba, Yoshitaka Narita, Koichi Ichimura

Acta neuropathologica communications 8 ( 1 ) 201 - 201 2020.11

Language：English Publishing type：Research paper (scientific journal)

TERT promoter mutations are commonly associated with 1p/19q codeletion in IDH-mutated gliomas. However, whether these mutations have an impact on patient survival independent of 1p/19q codeletion is unknown. In this study, we investigated the impact of TERT promoter mutations on survival in IDH-mutated glioma cases. Detailed clinical information and molecular status data were collected for a cohort of 560 adult patients with IDH-mutated gliomas. Among these patients, 279 had both TERT promoter mutation and 1p/19q codeletion, while 30 had either TERT promoter mutation (n = 24) or 1p/19q codeletion (n = 6) alone. A univariable Cox proportional hazard analysis for survival using clinical and genetic factors indicated that a Karnofsky performance status score (KPS) of 90 or 100, WHO grade II or III, TERT promoter mutation, 1p/19q codeletion, radiation therapy, and extent of resection (90-100%) were associated with favorable prognosis (p < 0.05). A multivariable Cox regression model revealed that TERT promoter mutation had a significantly favorable prognostic impact (hazard ratio = 0.421, p = 0.049), while 1p/19q codeletion did not have a significant impact (hazard ratio = 0.648, p = 0.349). Analyses incorporating patient clinical and genetic information were further conducted to identify subgroups showing the favorable prognostic impact of TERT promoter mutation. Among the grade II-III glioma patients with a KPS score of 90 or 100, those with IDH-TERT co-mutation and intact 1p/19q (n = 17) showed significantly longer survival than those with IDH mutation, wild-type TERT, and intact 1p/19q (n = 185) (5-year overall survival, 94% and 77%, respectively; p = 0.032). Our results demonstrate that TERT promoter mutation predicts favorable prognosis independent of 1p/19q codeletion in IDH-mutated gliomas. Combined with its adverse effect on survival among IDH-wild glioma cases, the bivalent prognostic impact of TERT promoter mutation may help further refine the molecular diagnosis and prognostication of diffuse gliomas.

DOI： 10.1186/s40478-020-01078-2

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