Faculty Profiles - SAITO Ryuta

Papers - SAITO Ryuta

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視床高悪性度神経膠腫におけるヒストン変異と予後についての検討

長田佳整, 齋藤竜太, 庄司拓大, 長南雅志, 柴原一陽, 金森政之, 園田順彦, 隈部俊宏, 渡邉みか, 冨永悌二

Brain Tumor Pathology Vol. 37 ( Suppl. ) page： 130 - 130 2020.8

IDH変異型膠芽腫自験連続9例の検討

齋藤竜太, 長田佳整, 柴原一陽, 金森政之, 園田順彦, 隈部俊宏, 渡辺みか, 冨永悌二

Brain Tumor Pathology Vol. 37 ( Suppl. ) page： 092 - 092 2020.8

Frequent Clinical and Radiological Progression of Optic Pathway/Hypothalamic Pilocytic Astrocytoma in Adolescents and Young Adults. Reviewed

Takuhiro Shoji, Masayuki Kanamori, Ryuta Saito, Yuko Watanabe, Mika Watanabe, Miki Fujimura, Yoshikazu Ogawa, Yukihiko Sonoda, Toshihiro Kumabe, Shigeo Kure, Teiji Tominaga

Neurologia medico-chirurgica Vol. 60 ( 6 ) page： 277 - 285 2020.5

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

Most cases of optic hypothalamic pilocytic astrocytoma (OHPA) develop during childhood, so few cases of histologically verified OHPA have been described in adolescents and young adults (AYA). To elucidate the clinical features of OHPA with histological verification in AYA, we reviewed the clinical and radiological finding of OHPA treated at our institute from January 1997 and July 2017. AYA are aged between 15 and 39 years. The clinical courses of 11 AYA patients with optic hypothalamic glioma (OHG) without neurofibromatosis type 1 were retrospectively reviewed. About six patients were diagnosed in childhood and followed up after 15 years of age, and five patients developed OHPA during AYA. Histological diagnosis, verified at initial presentation or recurrence, was pilocytic astrocytoma in 10 and pilomyxoid astrocytoma in one. After initial treatment including debulking surgery and/or chemotherapy, tumor progression occurred 16 times in seven patients as cyst formation, tumor growth, and intratumoral hemorrhage. Five of 10 patients suffered deterioration of visual function during AYA. One of 10 cases had endocrinopathies requiring hormone replacement at last follow-up examination. In conclusion, histological diagnoses of OHG before and in AYA were pilocytic astrocytoma or pilomyxoid astrocytoma. Both pediatric and AYA-onset OHPA demonstrate high incidences of tumor progression and visual dysfunctions in AYA, so that long-term follow up is essential after the completion of treatment for pediatric and AYA-onset OHPA. The optimal timing of debulking surgery and radiation therapy should be established to achieve the long-term tumor control and to preserve the visual function.

DOI： 10.2176/nmc.oa.2019-0208

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Regression of Recurrent Spinal Cord High-Grade Glioma After Convection-Enhanced Delivery of Nimustine Hydrochloride: Case Reports and Literature Review. International journal

Toshiki Endo, Tomoo Inoue, Shinichiro Sugiyama, Ryuta Saito, Teiji Tominaga

Operative neurosurgery (Hagerstown, Md.) Vol. 18 ( 4 ) page： 451 - 459 2020.4

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

BACKGROUND: Spinal cord high-grade glioma has poor prognosis. Especially, no treatment protocols have been established for recurrent cases. OBJECTIVE: To apply a novel treatment method, convection-enhanced delivery (CED), for recurrent high-grade glioma. CED can deliver chemotherapeutic agents directly into the intramedullary lesion and possibly lead to remarkable regression of enlarging tumors that are, otherwise, difficult to control. METHODS: Two patients developed high-grade glioma in the thoracic spinal cord. Partial resection and chemotherapy and radiotherapy induced remission of the disease. However, following the initial treatment, recurrence was noted in the spinal cord at 6 and 12 mo, respectively. No effective treatment was available for these recurrent lesions. Therefore, the authors decided to use CED to infuse nimustine hydrochloride (ACNU) directly into the spinal cord. During the procedure, the infusion cannula was inserted into the spinal cord lesion under intraoperative computed tomography scan. RESULTS: After ACNU CED, successive magnetic resonance imaging confirmed remarkable shrinkages of the tumors in both cases. However, the patient's preinfusion symptoms, including bilateral lower extremity weakness, did not change after the treatment. Importantly, overall survivals of the 2 patients were as long as 67 and 33 mo. CONCLUSION: The authors report the first 2 cases of recurrent spinal cord high-grade glioma. ACNU CED dramatically regressed enhanced mass lesions and provided local tumor controls in the spinal cord.

DOI： 10.1093/ons/opz172

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髄芽腫の放射線療法中に合併した難治性ITPに対し,rituximabが奏功した一例

戒能明, 新妻秀剛, 入江正寛, 片山紗乙莉, 森谷邦彦, 力石健, 齋藤竜太, 金森政之, 笹原洋二, 呉繁夫

日本小児科学会雑誌 Vol. 124 ( 2 ) page： 321 - 321 2020.2

髄芽腫の放射線療法中に合併した難治性ITPに対し,rituximabが奏功した一例

戒能明, 新妻秀剛, 入江正寛, 片山紗乙莉, 森谷邦彦, 力石健, 齋藤竜太, 金森政之, 笹原洋二, 呉繁夫

日本小児科学会雑誌 Vol. 124 ( 2 ) page： 321 - 321 2020.2

Phase I trial of convection-enhanced delivery of nimustine hydrochloride (ACNU) for brainstem recurrent glioma International journal

Ryuta Saito, Masayuki Kanamori, Yukihiko Sonoda, Yoji Yamashita, Kenichi Nagamatsu, Takaki Murata, Shunji Mugikura, Toshihiro Kumabe, Eva Wembacher-Schröder, Rowena Thomson, Teiji Tominaga

Neuro-Oncology Advances Vol. 2 ( 1 ) page： vdaa033 2020.1

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

<title>Abstract</title>
<sec>
<title>Background</title>
Treatment options for patients suffering brainstem gliomas are quite limited as surgery is not an option against intrinsic tumors at brainstem and chemotherapy generally failed to demonstrate its efficacy. Intracerebral convection-enhanced delivery (CED) is a novel approach for administering chemotherapy to patients with brain tumors. We present the results of phase I trial of CED of nimustine hydrochloride (ACNU), designed to determine the maximum tolerable concentration of ACNU, for patients with recurrent brainstem gliomas.

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<title>Methods</title>
Sixteen patients, aged 3–81 years old, suffering from recurrent brainstem gliomas, including diffuse intrinsic pontine glioma patients as well as patients with recurrent gliomas that originated from non-brainstem sites, were enrolled in this trial between February 2011 and April 2016. The dose/concentration escalation trial included 3 dose/concentration groups (0.25, 0.5, and 0.75 mg/mL, all at 7 mL) to determine the safety and tolerability of CED of ACNU. Real-time monitoring of drug distribution was performed by mixing gadolinium-tetraazacyclododecanetetraacetic acid (Gd-DOTA) in the infusion solution. CED of ACNU was given in combination with oral or intravenous temozolomide chemotherapy.

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<sec>
<title>Results</title>
CED of ACNU demonstrated antitumor activity, as assessed by radiographic changes and prolonged overall survival. The recommended dosage was 0.75 mg/mL. Drug-associated toxicity was minimal.

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<title>Conclusions</title>
Intracerebral CED of ACNU under real-time monitoring of drug distribution, in combination with systemic temozolomide, was well tolerated among patients with recurrent brainstem gliomas. The safety and efficacy observed suggest the clinical benefits of this strategy against this devastating disease. Based on this phase I study, further clinical development of ACNU is warranted.

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DOI： 10.1093/noajnl/vdaa033

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Other Link： http://academic.oup.com/noa/article-pdf/2/1/vdaa033/33171642/vdaa033.pdf

TERT promoter mutation associated with multifocal phenotype and poor prognosis in patients with IDH wild-type glioblastoma International journal

Zensho Kikuchi, Ichiyo Shibahara, Tetsu Yamaki, Ema Yoshioka, Tomoko Shofuda, Rintaro Ohe, Ken-ichiro Matsuda, Ryuta Saito, Masayuki Kanamori, Yonehiro Kanemura, Toshihiro Kumabe, Teiji Tominaga, Yukihiko Sonoda

Neuro-Oncology Advances Vol. 2 ( 1 ) page： vdaa114 2020.1

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

<title>Abstract</title>
<sec>
<title>Background</title>
Although mutations in the promoter region of the telomerase reverse transcriptase (TERTp) gene are the most common alterations in glioblastoma (GBM), their clinical significance remains unclear. Therefore, we investigated the impact of TERTp status on patient outcome and clinicopathological features in patients with GBM over a long period of follow-up.

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<sec>
<title>Methods</title>
We retrospectively analyzed 153 cases of GBM. Six patients with isocitrate dehydrogenase 1 (IDH1) or H3F3A gene mutations were excluded from this study. Among the 147 cases of IDH wild-type GBM, 92 (62.6%) had the TERTp mutation. Clinical, immunohistochemical, and genetic factors (BRAF, TP53 gene mutation, CD133, ATRX expression, O6-methylguanine-DNA methyltransferase [MGMT] promoter methylation) and copy number alterations (CNAs) were investigated.

</sec>
<sec>
<title>Results</title>
GBM patients with the TERTp mutation were older at first diagnosis versus those with TERTp wild type (66.0 vs. 60.0 years, respectively, P = .034), and had shorter progression-free survival (7 vs. 10 months, respectively, P = .015) and overall survival (16 vs. 24 months, respectively, P = .017). Notably, magnetic resonance imaging performed showed that TERTp-mutant GBM was strongly associated with multifocal/distant lesions (P = .004). According to the CNA analysis, TERTp mutations were positively correlated with EGFR amp/gain, CDKN2A deletion, and PTEN deletion; however, these mutations were negatively correlated with PDGFR amp/gain, CDK4 gain, and TP53 deletion.

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<sec>
<title>Conclusions</title>
TERTp mutations were strongly correlated with multifocal/distant lesions and poor prognosis in patients with IDH wild-type GBM. Less aggressive GBM with TERTp wild type may be a distinct clinical and molecular subtype of IDH wild-type GBM.

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DOI： 10.1093/noajnl/vdaa114

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Other Link： http://academic.oup.com/noa/article-pdf/2/1/vdaa114/35106481/vdaa114.pdf

Cystic Glioblastoma Rupturing into the Ventricle.

Yoshimichi Sato, Ryuta Saito, Masayuki Kanamori, Teiji Tominaga

NMC case report journal Vol. 7 ( 1 ) page： 39 - 41 2020.1

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

Cystic tumors, such as craniopharyngiomas and Rathke's cleft cysts, as well as arachnoid cysts have been reported to rupture occasionally. Approximately 8-10% of glioblastomas (GBMs) are known to have a significant cystic component; however, to the best of our knowledge, no studies have reported cystic rupturing of GBMs. Here, we describe a unique case of cystic GBM rupturing and penetrating into the cerebral ventricle. A 77-year-old man with a right frontal lobe lesion suspected as GBM with a large cyst was referred to our hospital. At admission, disorientation and left facial weakness were detected. Consciousness disturbance worsened on the 8th day of hospitalization. Computed tomography (CT) revealed prominent shrinkage of the tumor and intratumoral cyst. Signs of meningeal irritation were observed, and chemical meningitis due to cystic tumor rupture and leakage of necrotic components into the ventricle was highly suspected. Surgical resection of the right frontal lobe tumor was performed on the 10th day of hospitalization. During the surgery, clear and colorless cerebrospinal fluid was obtained upon penetration of the tumoral cyst, suggesting traffic of tumor cysts and cerebral ventricle. Adjuvant chemoradiation therapy was initiated postoperatively. Local recurrence was noted at the corpus callosum 7 months postoperatively and was treated with a gamma knife. Further therapy was performed after this recurrence. However, his condition gradually deteriorated 15 months postoperatively, and he was subjected to terminal care. To the best of our knowledge, this is the first report on a cystic GBM rupture.

DOI： 10.2176/nmccrj.cr.2019-0043

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Functional outcomes of germ cell tumors

Kanamori, M, Saito, R, Tominaga, T

Japanese Journal of Neurosurgery Vol. 29 ( 4 ) 2020

A multicenter randomized phase III study for newly diagnosed maximally resected glioblastoma comparing carmustine wafer implantation followed by chemoradiotherapy with temozolomide with chemoradiotherapy alone; Japan Clinical Oncology Group Study JCOG1703 (MACS study). International journal

Tomohiro Kadota, Ryuta Saito, Toshihiro Kumabe, Junki Mizusawa, Hiroshi Katayama, Minako Sumi, Hiroshi Igaki, Manabu Kinoshita, Takashi Komori, Koichi Ichimura, Yoshitaka Narita, Ryo Nishikawa

Japanese journal of clinical oncology Vol. 49 ( 12 ) page： 1172 - 1175 2019.12

Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS

A randomized phase III trial in Japan commenced in June 2019. The present standard treatment for newly diagnosed glioblastoma is maximal resection followed by chemoradiotherapy with temozolomide. The purpose of this study is to confirm the superiority of maximal resection with carmustine wafer implantation followed by chemoradiotherapy with temozolomide over the standard maximal resection followed by chemoradiotherapy with temozolomide in terms of overall survival for newly diagnosed glioblastoma. A total of 250 patients will be accrued from 35 Japanese institutions in 5.5 years. Patients with >90% surgical resection will be registered and randomly assigned to each group with 1:1 allocation. The primary endpoint is overall survival and the secondary endpoints are progression-free survival, loco-regional progression-free survival and incidence of adverse events. This trial has been registered in the Japan Registry of Clinical Trial, as jRCT1031190035 [https://jrct.niph.go.jp/en-latest-detail/jRCT1031190035].

DOI： 10.1093/jjco/hyz169

Web of Science

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Experience of Low Dose Perampanel to Add-on in Glioma Patients with Levetiracetam-uncontrollable Epilepsy. Reviewed

Chonan M, Saito R, Kanamori M, Osawa SI, Watanabe M, Suzuki H, Nakasato N, Tominaga T

Neurologia medico-chirurgica Vol. 60 ( 1 ) page： 37 - 44 2019.11

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

After introduction of levetiracetam (LEV), treatment of seizures in patients with malignant brain tumors has prominently improved. On the other hand, we still experience some cases with LEV-uncontrollable epilepsy. Perampanel (PER) is a noncompetitive a-amino-3-hydroxy-5-methyl-4-isoaxazolepropionate acid receptor antagonist that has recently been approved for treating focal epilepsy as a secondary drug of choice. Available literature reporting PER medication in patients with gliomas is still sparse. Here, we report our initial experience with glioma patients and report efficacy of adding low dose 2–4 mg PER to LEV in patients whose seizure were uncontrollable with LEV monotherapy. Clinical outcome data of 18 consecutive patients were reviewed. This included nine males and nine females aged 24–76 years (median, 48.5 years), treated for glioma between June 2009 to December 2018. We added PER to patients with LEV-uncontrollable epilepsy. Adverse effects, irritability occurred in two patients, but continuous administration was possible in all cases. Though epileptic seizures occurred in four cases receiving 2 mg PER, 17 cases achieved seizure freedom by dose increments; final dose, 2–4 mg PER added to LEV 500–3000 mg. Our study revealed anti-epileptic efficacy of low dose PER 2–4 mg as first add-on therapy to LEV in glioma patients who have failed or intolerable to LEV monotherapy. Low dose PER added on to LEV may have favorable efficacy with tolerable adverse effects in glioma patients with LEV-uncontrollable epilepsy.

DOI： 10.2176/nmc.oa.2018-0245

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超選択的Wada testによる血管解剖と機能解剖のハイブリッド評価 Reviewed

大沢伸一郎, 鈴木匡子, 新妻邦泰, 浮城一司, 柿沼一雄, 上利大, 神一敬, 斎藤竜太, 金森政之, 中里信和, 冨永悌二

脳血管内治療 Vol. 4 ( Suppl. ) page： S383 - S383 2019.11

Unilateral chronic subdural hematoma due to spontaneous intracranial hypotension: a report of four cases. Reviewed International journal

Osada Y, Shibahara I, Nakagawa A, Sakata H, Niizuma K, Saito R, Kanamori M, Fujimura M, Suzuki S, Tominaga T

British journal of neurosurgery Vol. 34 ( 6 ) page： 1 - 6 2019.9

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

Background: Chronic subdural hematoma (CSDH) is a common neurosurgical disease. A subset of patients with CSDH may exhibit underlying spontaneous intracranial hypotension (SIH). Bilateral CSDH has a causal relationship with SIH, but there is no known causal relationship between unilateral CSDH and SIH.Case description: We encountered four cases of unilateral CSDH due to SIH. The patients' age ranged between 44 and 64 years; there were three males and one female. All patients presented with headache as their initial symptom, and then became comatose. Computed tomography demonstrated unilateral CSDH and transtentorial herniation in all patients. Treatments were emergency epidural blood patch (EBP) and evacuation of CSDH. The site of cerebrospinal fluid leak could not be identified in three patients; therefore, EBP was performed at upper and lower spine. All patients recovered from SIH; however, one patient experienced poor outcome due to Duret hemorrhage and ischemic complications of transtentorial herniation. Cranial asymmetry was present in all four patients, and unilateral CSDH was located on the side of the most curved cranial convexity.Conclusions: Unilateral CSDH, asymmetric cranial morphology, and transtentorial herniation in relatively young patients may indicate underlying SIH.

DOI： 10.1080/02688697.2019.1667482

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Coexistence of Intracranial Germ Cell Tumor with Growing Arteriovenous Fistula.

Ishida T, Endo H, Saito R, Kanamori M, Sato K, Matsumoto Y, Endo T, Fujimura M, Tominaga T

World neurosurgery Vol. 127 page： 126 - 130 2019.7

Phase I study of a brain penetrant mutant IDH1 inhibitor DS-1001b in patients with recurrent or progressive IDH1 mutant gliomas. Reviewed

Atsushi Natsume, Toshihiko Wakabayashi, Yasuji Miyakita, Yoshitaka Narita, Yohei Mineharu, Yoshiki Arakawa, Fumiyuki Yamasaki, Kazuhiko Sugiyama, Nobuhiro Hata, Yoshihiro Muragaki, Ryo Nishikawa, Naoki Shinojima, Toshihiro Kumabe, Ryuta Saito, Kazumi Ito, Masaya Tachibana, Yasuyuki Kakurai, Soichiro Nishijima, Hiroshi Tsubouchi

JOURNAL OF CLINICAL ONCOLOGY Vol. 37 ( 15 ) page： . 2019.5

脳幹部神経膠腫診断におけるメチオニンPET検査の有用性

齋藤竜太, 金森政之, 高浪健太郎, 園田順彦, 冨永悌二

Brain Tumor Pathology Vol. 36 ( Suppl. ) page： 090 - 090 2019.5

IDH遺伝子変異型星細胞腫の予後因子

金森政之, 渡辺みか, 斎藤竜太, 長田佳整, 柴原一陽, 園田順彦, 隈部俊宏, 冨永悌二

Brain Tumor Pathology Vol. 36 ( Suppl. ) page： 102 - 102 2019.5

Coexistence of an intracranial germ cell tumor with a growing arteriovenous fistula: a case report. Reviewed

Ishida T, Endo H, Saito R, Kanamori M, Sato K, Matsumoto Y, Endo T, Fujimura M, Tominaga T

2019.4

Incidence of initial spinal metastasis in glioblastoma patients and the importance of spinal screening using MRI. Reviewed International journal

Ichiyo Shibahara, Ryuta Saito, Yoshinari Osada, Masayuki Kanamori, Yukihiko Sonoda, Toshihiro Kumabe, Shunji Mugikura, Mika Watanabe, Teiji Tominaga

Journal of neuro-oncology Vol. 141 ( 2 ) page： 337 - 345 2019.1

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

PURPOSE: Intracranial glioblastomas with simultaneous spinal lesions prior to chemoradiation therapy or craniotomy, defined as initial spinal metastasis, are not well understood. Herein, we investigated intracranial glioblastoma and demonstrated the importance of spinal screening using gadolinium enhanced spinal magnetic resonance imaging (Gd-MRI). METHODS: Consecutive adult patients with intracranial glioblastoma were treated between 2010 and 2014 and received spinal screening using Gd-MRI. Spinal screening was performed regardless of spine-related symptoms, and patients presenting with and without initial spinal metastasis (spinal and non-spinal groups, respectively) were compared based on patient demographics, tumor characteristics, radiological and molecular features, and overall survival (OS). RESULTS: During the study period, 116 glioblastoma cases were treated and 87 of these (76%) underwent spinal screening. Among these patients, 11 (13%) were included in the spinal group, and 76 (87%) were included in the non-spinal group. All patients of the spinal group were free of symptoms related to spinal lesions. Compared with the non-spinal group, intracranial lesions of the spinal group presented higher incidences of intracranial dissemination and were located at subventricular zones (P = 0.0012 and 0.020, respectively). MIB-1 labeling index, molecular alterations such as IDH1 mutation, TERT promoter mutation, and immunoreactivity of ATRX and MGMT did not differ between two groups. OS was significantly shorter in the spinal group than in the non-spinal group (P = 0.0054). CONCLUSIONS: This study revealed a relatively high incidence of spinal metastasis. A subset of glioblastoma patients benefited from spinal screening, through which early detection of asymptomatic spinal metastasis was achieved.

DOI： 10.1007/s11060-018-03036-4

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Papers - SAITO Ryuta