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Nobuhiro Hata Last modified date:2020.06.10

Lecturer / Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University
Neurosurgery
Kyushu University Hospital


Graduate School


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Homepage
https://kyushu-u.pure.elsevier.com/en/persons/nobuhiro-hata
 Reseacher Profiling Tool Kyushu University Pure
http://www.ns.med.kyushu-u.ac.jp//
Phone
092-642-5524
Fax
092-642-5526
Academic Degree
Ph.D.
Country of degree conferring institution (Overseas)
No
Field of Specialization
Neurosurgery, genomics
Total Priod of education and research career in the foreign country
00years00months
Outline Activities
Clinical Neurosurgery,
Genetic analysis of malignant brain tumor,
Chemotherapy of malignant brain tumor,
Clinical oncology of malignant brain tumor
Research
Research Interests
  • Clinical efficacy of Anti-VEGF therapy for glioma
    keyword : glioma, clinical oncology, bevacizumab, VEGF
    2017.04~2019.04.
  • Development of the novel genetic analysis method, which can lead widespread utilization of taylor-made medicine for gliomas
    keyword : glioma, genetic analysis, taylor-made medicine
    2010.09~2019.03.
Academic Activities
Papers
1. Hata N, Mizoguchi M, Kuga D, Hatae R, Akagi Y, Sangatsuda Y, Amemiya T, Michiwaki Y, Fujioka Y, Takigawa K, Suzuki SO, Yoshitake T, Togao O, Hiwatashi A, Yoshimoto K, Iihara K., First-line bevacizumab contributes to survival improvement in glioblastoma patients complementary to temozolomide, J Neurooncol.2020;146(3):451-458, 10.1007/s11060-019-03339-0, 146, 3, 451-458, 2020.02, Introduction: First-line bevacizumab (BEV) is now available as a treatment option for glioblastoma patients with severe clinical conditions in Japan. However, the survival benefits remain controversial. To elucidate these potential survival benefits, we retrospectively analyzed survival in glioblastoma patients receiving BEV. Methods: We analyzed survival in 120 patients with IDH-wild type glioblastoma treated from 2002 to 2018. Overall survival (OS) was assessed in three treatment era subgroups [pre-temozolomide (TMZ), TMZ, and TMZ–BEV], and the correlations of prognostic factors with survival were evaluated. Results: An improvement in survival was observed after BEV approval (median OS in the pre-TMZ, TMZ, and TMZ–BEV eras: 14.6, 14.9, and 22.1 months, respectively). A Cox proportional hazards model identified extent of resection and MGMT methylation status as significant prognostic factors in the TMZ era; however, these factors were not significant in the TMZ–BEV era. In subgroup analyses, patients with MGMT methylation had improved OS after TMZ introduction (pre-TMZ vs. TMZ, 18.5 vs. 28.1 months; P = 0.13), and those without MGMT methylation had significantly increased OS after BEV approval (TMZ vs. TMZ–BEV, 12.2 vs. 16.7 months; P = 0.04). Conclusions: Our findings imply that optional first-line administration of BEV can overcome the impact of conventional risk factors and prolong survival complementary to TMZ. The patient subgroups benefitting from TMZ and BEV did not seem to overlap, and stratification based on risk factors, including MGMT methylation status, might be effective for selecting patients in whom BEV should be preferentially used as a first-line therapy..
2. Michiwaki Y, Hata N, Mizoguchi M, Hiwatashi A, Kuga D, Hatae R, Akagi Y, Amemiya T, Fujioka Y, Togao O, Suzuki SO, Yoshimoto K, Iwaki T, Iihara K., Relevance of calcification and contrast enhancement pattern for molecular diagnosis and survival prediction of gliomas based on the 2016 World Health Organization Classification, Clinical Neurology and Neurosurgery, 10.1016/j.clineuro.2019.105556, 187, 2019.12, Objectives: The significance of conventional neuroimaging features for predicting molecular diagnosis and patient survival based on the updated World Health Organization (WHO) classification remains uncertain. We assessed the relevance of neuroimaging features (ring enhancement [RE], non-ring enhancement [non-RE], overall gadolinium enhancement [GdE], and intratumoral calcification [IC]) for molecular diagnosis and survival in glioma patients. Patients and methods: We evaluated 234 glioma patients according to the updated WHO classification. Isocitrate dehydrogenase (IDH), H3F3A, BRAF hotspot mutations, TERT promotor mutation, and chromosome 1p/19q co-deletion were examined. RE, non-RE, GdE, and IC were evaluated as significant neuroimaging findings. Kaplan-Meier analyses were performed to evaluate overall survival (OS) and the correlations of prognostic factors were evaluated by log-rank tests. Univariate and multivariate analyses were performed to detect prognostic factors for OS. Results: A total of 207 patients were eligible. In 110 patients presenting RE, 102 (93%) were glioblastoma (GBM), IDH-wild type. In 97 patients without RE, presence of GdE or IC were not significantly different between IDH-mutant and -wild type tumors, whereas presence of GdE was a significant indicator of higher WHO grades. IC was the only significant finding for 1p/19q co-deleted tumors. TERT promoter mutation was observed in 7/17 patients with diffuse astrocytic glioma, IDH-wild type; recently-defined as “molecular GBM.” IC, RE, and GdE were observed with lower prevalence in molecular GBMs. While presence of RE, GdE, and absence of IC were significant factors of OS in overall cohort, presence of GdE was not significant in OS in cases without RE, and IDH-mutant tumors. IC was a significant predictor of favorable OS in cases without RE and IDH-wild type tumors. Multivariate analysis also validated these findings. Conclusion: GdE alone is not a significant predictor of IDH mutation status, but the pattern of enhancement is a significant predictor with RE demonstrating high sensitivity and specificity for GBM, IDH-wild type. Predicting “molecular GBM” by conventional neuroimaging is difficult. Moreover, GdE is not a significant factor of survival analyzed with pattern of enhancement or molecular stratifications. IC is an important radiographic finding for predicting molecular diagnosis and survival in glioma patients..
3. Michiwaki Y, Hata N, Amano T, Suzuki SO, Akagi Y, Kuga D, Onozuka D, Momosaki S, Nakamizo A, Yoshimoto K, Yoshimoto K, Iwaki T, Iihara K, Predictors of recurrence and postoperative outcomes in patients with non-skull base meningiomas based on modern neurosurgical standards, Interdisciplinary Neurosurgery 15:30-37. 2019, 15, 30-37, 2019.03.
4. Kuga D, Hata N, Akagi Y, Amemiya T, Sangatsuda Y, Hatae R, Yoshimoto K, Mizoguchi M, Iihara K., The Effectiveness of Salvage Treatments for Recurrent Lesions of Oligodendrogliomas Previously Treated with Upfront Chemotherapy., World Neurosurg. S1878-8750(18)30547-3, 10.1016/j.wneu.2018.03.069., 2018.06.
5. Akagi Y, Yoshimoto K, Hata N, Kuga D, Hatae R, Amemiya T, Sangatsuda Y, Suzuki SO, Iwaki T, Mizoguchi M, Iihara K., Reclassification of 400 consecutive glioma cases based on the revised 2016WHO classification, Brain Tumor Pathology. 2018, 10.1007/s10014-018-0313-4, 2018.04.
6. Nobuhiro Hata, Ryusuke Hatae, Koji Yoshimoto, Hideki Murata, DAISUKE KUGA, Yojiro Akagi, Yuhei Sangatsuda, Satoshi O Suzuki, Toru Iwaki, Masahiro Mizoguchi, Koji Iihara, Insular primary glioblastomas with IDH mutations: Clinical and biological specificities., Neuropathology, 10.1111/neup.12362., in press, 2017.01, Isocitrate dehydrogenase (IDH) mutation is a good prognostic marker for glioblastoma (GBM). Although it is infrequent in primary tumors, it is found in most lower grade gliomas. Thus, it is unclear whether IDH mutation is
a marker for a specific phenotype of apparently primary de novo GBMs (pGBMs), or a marker for secondary tumors
(sGBMs). We addressed this issue by analyzing clinical, radiographic and molecular findings in our institutional case
series. Our cases included 92 pGBMs, with five cases of IDH1 mutations at R132 and no IDH2 mutations. The
median overall survival of these five patients was 29 months (range: 4 to >40 months), which is considered good prognoses. Clinical and radiographic characteristics were distinct from IDH-wildtype (IDH-wt) pGBMs. IDH-mutant
(IDH-mut) tumors consistently involved insular lesions and were subdivided into: (i) the two cases of elderly patients with long clinical histories and features implying multistep tumor development; and (ii) the three cases of younger patients with diffusely swelling insular tumors, slight contrast enhancement and no necrosis. Genetic and expression analyses of IDH-mut pGBMs were similar to those of sGBMs, suggesting that they are indeed distinct from their IDH-wt counterparts. TERT promoter mutation, a genetic marker of oligodendroglial derivation, was detected in one long-surviving case, but genetic alterations in the astrocyte sGBM pathway were generally prevalent in IDH-mut pGBMs. Our results present a unique phenotype of IDH-mutpGBMs arising frominsular cortex region, the molecular backgrounds of which are similar to sGBMs..
7. Nobuhiro Hata, Koji Yoshimoto, Ryusuke Hatae, DAISUKE KUGA, Yojiro Akagi, Yuhei Sangatsuda, Satoshi O Suzuki, Tadahisa Shono, Masahiro Mizoguchi, Koji Iihara, Add-on bevacizumab can prevent early clinical deterioration and prolong survival in newly diagnosed partially resected glioblastoma patients with a poor performance status., Oncotargets and Therapy, 10.2147/OTT.S125587, 10, 429-437, 2017.01, Purpose: The AVAglio trial established the beneficial effect of add-on bevacizumab (BEV) for the treatment of newly diagnosed glioblastomas (nd-GBMs) that led to the approval of BEV for the treatment of these patients in Japan. However, the rationality of using BEV as a first-line treatment for nd-GBMs remains controversial. The purpose of this study was to analyze the outcomes of a case series of nd-GBM patients.
Patients and methods: The outcomes of 69 nd-GBM patients treated after 2006 were retrospectively analyzed. Clinical and genetic analyses were performed, and estimates of progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan–Meier method. Since add-on BEV therapy was only used for partially resected GBMs (pr-GBMs) after its approval in 2013, the patients were subdivided into 3 treatment groups: Type I, partial removal with temozolomide (TMZ)/BEV and concurrent radiotherapy (CCRT); Type II, partial removal with TMZ and CCRT; and Type III, gross total removal with TMZ and CCRT.
Results: The PFS rate of Type I patients was significantly higher than that of Type II patients (P=0.014), but comparable to that of Type III patients. Differences in OS rates between Type I and Type II patients were less apparent (P=0.075), although the median OS of Type I patients was ∼8 months higher than that of Type II patients (17.4 vs 9.8 months, respectively). The clinical deterioration rate during initial treatment was significantly (P=0.024) lower in Type I than in Type II patients (7.7% vs 47.4%, respectively). Differences in OS rates between Type I and Type II patients with a poor performance status (PS) were significant (P=0.017).
Conclusion: Our findings suggest that add-on BEV can prevent early clinical deterioration of pr-GBM patients and contribute to a prolonged survival, especially for those with a poor PS..
8. Nobuhiro Hata, Koji Yoshimoto, Ryusuke Hatae, DAISUKE KUGA, Yojiro Akagi, Satoshi O Suzuki, Toru Iwaki, Tadahisa Shono, Masahiro Mizoguchi, Koji Iihara, Deferred radiotherapy and upfront procarbazine-ACNU-vincristine administration for 1p19q codeleted oligodendroglial tumors are associated with favorable outcome without compromising patient performance, regardless of WHO grade., OncoTargets and Therapy, 10.2147/OTT.S115911, 9, 7123-7131, 2016.12, [URL].
9. Ryusyke Hatae, Nobuhiro Hata, Koji Yoshimoto, DAISUKE KUGA, Yojiro Akagi, Hideki Murata, Satoshi O Suzuki, Masahiro Mizoguchi, Koji Iihara, Precise Detection of IDH1/2 and BRAF Hotspot Mutations in Clinical Glioma Tissues by a Differential Calculus Analysis of High-Resolution Melting Data., PLOS ONE, 11, 8, e0160489, 2016.08.
10. Ryusuke Hatae, Nobuhiro Hata, Satoshi O Suzuki, Koji Yoshimoto, DAISUKE KUGA, Hideki Murata, Yojiro Akagi, Yuhei Sangatsuda, Toru Iwaki, Masahiro Mizoguchi, Koji Iihara, A comprehensive analysis identifies BRAF hotspot mutations associated with gliomas with peculiar epithelial morphology., Neuropathology, 10.1111/neup.12347., in press, 2016.08.
11. Hata N, Hisada K, Torisu R, Suzuki SO, Kameda K, Sasaki T., Foreign body granuloma associated with dura-cranioplasty after resection of convexity meningioma with extracranial extension: case report., Neurol Med Chir (Tokyo), 51, 3, 236-238, 2011.03.
12. Guan Y, Hata N, Kuga D, Yoshimoto K, Mizoguchi M, Shono T, Suzuki SO, Tahira T, Kukita Y, Higasa K, Yokoyama N, Nagata S, Iwaki T, Sasaki T, Hayashi K, Narrowing of the regions of allelic losses of chromosome 1p36 in meningioma tissues by an improved SSCP analysis., Int J Cancer 122: 1820-1826. 2008, 122, 8, 1820-1826, 2008.04.
13. Hata N, Shinojima N, Gumin J, Yong R, Marini F, Andreeff M, Lang FF., Platelet-derived growth factor BB mediates the tropism of human mesenchymal stem cells for malignant gliomas., Neurosurgery. 66: 144-156. 2010, 66, 1, 144-156, 2010.01.
14. Hata N, Yoshimoto K, Yokoyama N, Mizoguchi M, Shono T, Guan Y, Tahira T, Kukita Y, Higasa K, Nagata S, Iwaki T, Sasaki T, Hayashi K, Allelic losses of chromosome 10 in glioma tissues detected by quantitative single-strand conformation polymorphism analysis. , Clin Chem. 52: 370-378. 2006, 52, 3, 370-378, 2006.03.
Presentations
1. Nobuhiro Hata, Masahiro Mizoguchi, Daisuke Kuga, Ryusuke Hatae, Yuhei Sangatsuda, Yojiro Akagi, Koji Yoshimoto, Koji Iihara , First-line bevacizumab contributes to survival improvement in glioblastoma patients complementary to temozolomide, 16th ASNO meeting, , 2019.09, Introduction: First-line bevacizumab (BEV) is now available as a treatment option for glioblastoma patients with severe clinical conditions in Japan. However, the survival benefits remain controversial. To elucidate these potential survival benefits, we retrospectively analyzed survival in glioblastoma patients receiving BEV.
Methods: We analyzed survival in 120 patients with IDH-wild type glioblastoma treated from 2002 to 2018. Overall survival (OS) was assessed in three subgroups (pre-temozolomide [TMZ], TMZ, and TMZ-BEV), and the correlations of prognostic factors with survival were evaluated.
Results: An improvement in survival was observed after BEV approval (median OS in the pre-TMZ, TMZ, and TMZ-BEV eras: (14.6, 14.9, and 22.1 months, respectively). A Cox proportional hazards model identified extent of resection and MGMT methylation status as significant prognostic factors in the TMZ era; however, these factors were not significant in the TMZ-BEV era. In subgroup analyses, patients with MGMT methylation had improved OS after TMZ introduction (pre-TMZ vs TMZ, 18.5 vs 28.1 months; P = 0.13), and those without MGMT methylation had increased OS after BEV approval (TMZ vs TMZ-BEV, 12.2 vs 16.7 months; P = 0.04). Conclusions: Our findings imply that optional first-line administration of BEV can overcome the impact of conventional risk factors and prolong survival complementary to TMZ. The patient subgroups benefitting from TMZ and BEV did not seem not overlap, and stratification based on risk factors, including MGMT methylation status, might be effective for selecting patients in whom BEV should be preferentially used as a first-line therapy.
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2. Hata N, Mizoguchi M, Akagi Y, Suzuki SO, Kuga D, Amemiya T, Hatae R, Yoshimoto K, Iwaki T, Iihara K., The correlation between 1p19q and TERT promoter mutation status in IDH-mutant gliomas, 36th Annual Meeting of the Japan Society of Brain Tumor Pathology, 2018.09, (Background) The revised WHO 2016 classification established the consensus that the diagnosis of oligodendrogliomas should be confirmed by IDH mutation and 1p19q codeletion. As these tumors are known to harbor TERT promoter mutation also, TERT status seems to be useful as a surrogate marker for 1p19q. Herein, we aim to verify this theory by analyzing the correlation between 1p19q and TERT status. (Methods) IDH and TERT status were determined by Sanger sequencing. 1p19q codeletion was confirmed by LOH on total arms using multiple microsatellite markers. We reviewed our case series of 70 gliomas with IDH mutation whose 1p19q and TERT status were examined. (Results) Whereas 65 out of 70 showed the consistency of 1p19q and TERT status, the remaining 5 were 1p19q non-codel/TERT mutant. In these 5 cases, 3 showed consistent clinical, radiographic and pathological features of oligodendroglioma. In contrast, the pathological diagnoses of the remaining 2 were anaplastic astrocytoma and glioblastoma, both of which also showed astrocytic molecular findings. (Conclusion) This study seems to support the theory that, in general, TERT mutation can be used as an effective surrogate marker of 1p19q for IDH mutant gliomas. Although, there were a few exceptional cases, thereby, we need further efforts to elucidate the correlation between 1p19q and TERT status..
3. Nobuhiro Hata, Koji Yoshimoto, Ryusuke Hatae, Daisuke Kuga, Yojiro Akagi, Yuhei Sangatsuda, Takeo Amemiya, Tadahisa Shono, Masahiro Mizoguchi, Koji Iihara , Add-on bevacizumab can prevent early clinical deterioration and prolong survival in newly diagnosed partially resected glioblastoma patients with a poor performance status , ASNO, 2017.10, Purpose: The rationality of using Bevacizumab (BEV) for newly-diagnosed glioblastomas (nd-GBMs) remains controversial. The purpose of this study was to analyze the outcomes of this treatment.
Methods: The outcomes of 69 nd-GBM patients treated after 2006 were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Since add-on BEV therapy was only used for partially resected GBMs (pr-GBMs) after its approval in 2013, the patients were subdivided into three treatment groups: Type I, partial removal with TMZ/BEV and concurrent radiotherapy (CCRT); Type II, partial removal with TMZ and CCRT; and Type III, gross total removal with TMZ and CCRT.
Results: The PFS rate of Type I patients was significantly higher than that of Type II patients (P = 0.014), but comparable to that of Type III patients. Differences in OS rates between Type I and Type II patients were less apparent (P = 0.075), although the median OS of Type I patients was approximately 8 months higher than that of Type II patients (17.4 vs 9.8 months, respectively). The clinical deterioration rate during initial treatment was significantly (P = 0.024) lower in Type I than in Type II patients (7.7 vs 47.4%, respectively). Differences in OS rates between Type I and Type II patients with a poor performance status (PS) were significant (P = 0.017).
Conclusions: Our findings suggest that add-on BEV can prevent early clinical deterioration of pr-GBM patients and contribute to a prolonged survival, especially for those with a poor PS.
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4. Usefulness of FISH and bioluminescent imaging for evaluation the fate of
human mesenchymal stem cell of gliomas.