Stereotactic image-based histological analysis reveals a correlation between 11C-methionine uptake and MGMT promoter methylation in non-enhancing gliomas

• Project/Area Number: 16K20033
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Osaka International Cancer Institute (2018); National Hospital Organization Osaka National Hospital Institute for Clinical Reserch (2016-2017)
• Principal Investigator: Okita Yoshiko 地方独立行政法人大阪府立病院機構大阪国際がんセンター(研究所), その他部局等, 脳神経外科副部長 (10533797)
• Research Collaborator: Kanemura Yonehiro ; Kinoshita Manabu ; Narita Yoshitaka
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: glioma / MET-PET / MGMT / 11C-methionine PET / 神経膠腫 / MRI

Outline of Final Research Achievements

This study examined the correlation between 11C-methionine uptake and MGMT promoter methylation in non-enhancing gliomas using stereotactic image-based histological analysis. Data were collected from 9 patients with newly diagnosed non-enhancing glioma and from 3 patients during repeat surgery. The correlation between 11C-methionine uptake and MGMT methylation or cell density was analyzed using histological specimens obtained by multiple stereotactic sampling.A total of 31 stereotactic sampling sites were obtained. In newly diagnosed cases, the T/N ratio showed a positive correlation with MGMT methylation (R = 0.54, p = 0.009), and a marginal correlation with cell density (R = 0.42, p = 0.05). In recurrent cases, the T/N ratio showed no correlation with MGMT methylation (R = 0.01, p = 0.97) or cell density (R = 0.15, p = 0.70).A higher uptake of 11C-methionine in PET may reflect increased MGMT promoter methylation, according to stereotactic image-based histological analysis.

Academic Significance and Societal Importance of the Research Achievements

遺伝子変異を画像技術で可視化する試みは手術検体を必要とせず、非侵襲的であり、過去にも試みられているが神経膠腫関連の遺伝子変異を画像評価した報告は限られている。
過去の報告の多くは非定位的評価であり、神経膠腫が病理組織学的に不均一であるだけでなく分子レベルでも不均一という特性があることから画像と実際の組織の一対一対応を正確に評価できていないのではないかという問題が挙げられる。本研究から手術検体が採取できない場合などに画像からMGMTメチル化の評価を定位的に行えることが期待される。

Research Products

• [Journal Article] 総説 成人膠芽腫に対するphase Ⅲ study (2018)
  • Author(s): 沖田 典子、成田 善孝
  • Journal Title: Neurological Surgery 脳神経外科 Volume: 46 Issue: 7 Pages: 561-571
  • DOI: 10.11477/mf.1436203772
  • ISSN: 0301-2603, 1882-1251
  • Year and Date: 2018-07-10
  • Peer Reviewed
• [Journal Article] Lesion location implemented magnetic resonance imaging radiomics for predicting IDH and TERT promoter mutations in grade II/III gliomas (2018)
  • Author(s): Arita Hideyuki、Kinoshita Manabu、Kawaguchi Atsushi、Takahashi Masamichi、Narita Yoshitaka、Terakawa Yuzo、Tsuyuguchi Naohiro、Okita Yoshiko、Nonaka Masahiro、Moriuchi Shusuke、Takagaki Masatoshi、Fujimoto Yasunori、et al.
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 11773-11773
  • DOI: 10.1038/s41598-018-30273-4
  • Peer Reviewed / Open Access
• [Journal Article] Characteristics and outcomes of elderly patients with diffuse gliomas: a multi-institutional cohort study by Kansai Molecular Diagnosis Network for CNS Tumors (2018)
  • Author(s): Sasaki Takahiro、Fukai Junya、Kodama Yoshinori、et al
  • Journal Title: Journal of Neuro-Oncology Volume: 140 Issue: 2 Pages: 329-339
  • DOI: 10.1007/s11060-018-2957-7
  • Peer Reviewed / Open Access
• [Journal Article] Stereotactic image?based histological analysis reveals a correlation between 11C?methionine uptake and MGMT promoter methylation in non?enhancing gliomas (2018)
  • Author(s): Okita Yoshiko、Shofuda Tomoko、Kanematsu Daisuke、Yoshioka Ema、Kodama Yoshinori、Mano Masayuki、Kinoshita Manabu、Nonaka Masahiro、Nakajima Shin、Fujinaka Toshiyuki、Kanemura Yonehiro
  • Journal Title: Oncology Letters Volume: NA Pages: 1924-1930
  • DOI: 10.3892/ol.2018.8866
  • Peer Reviewed / Open Access
• [Journal Article] Clinical outcomes of brain metastases from hepatocellular carcinoma: a multicenter retrospective study and a literature review (2018)
  • Author(s): Okuda Takeshi、Hayashi Nakamasa、Takahashi Masamichi、Uzuka Takeo、Okita Yoshiko、Otani Ryohei、Fujinaka Toshiyuki、Fujita Mitsugu、Kato Amami、Narita Yoshitaka、Nakasu Yoko
  • Journal Title: International Journal of Clinical Oncology Volume: 23 Issue: 6 Pages: 1095-1100
  • DOI: 10.1007/s10147-018-1312-5
  • Peer Reviewed
• [Journal Article] Influence of region-of-interest designs on quantitative measurement of multimodal imaging of MR non-enhancing gliomas (2018)
  • Author(s): Takano Koji、Kinoshita Manabu、Arita Hideyuki、Okita Yoshiko、Chiba Yasuyoshi、Kagawa Naoki、Watanabe Yoshiyuki、Shimosegawa Eku、Hatazawa Jun、Hashimoto Naoya、Fujimoto Yasunori、Kishima Haruhiko
  • Journal Title: Oncology Letters Volume: 15 Pages: 7934-7940
  • DOI: 10.3892/ol.2018.8319
  • Peer Reviewed / Open Access
• [Journal Article] 星細胞腫 (2018)
  • Author(s): 沖田 典子、成田 善孝
  • Journal Title: Clinical Neuroscience Volume: 136
  • Peer Reviewed
• [Journal Article] エビデンスに基づく膠芽腫の治療と課題 (2018)
  • Author(s): 沖田典子
  • Journal Title: 脳神経外科ジャーナル Volume: 27 Pages: 91-98
  • NAID: 130006401301
  • Peer Reviewed
• [Journal Article] A nationwide multi-institutional retrospective study to identify prognostic factors and develop a graded prognostic assessment system for patients with brain metastases from uterine corpus and cervical cancer. (2017)
  • Author(s): Hayashi N, Takahashi H, Hasegawa Y, Higuchi F, Takahashi M, Makino K, Takagaki M, Akimoto J, Okuda T, Okita Y, Mitsuya K, Hirashima Y, Narita Y,Nakasu Y
  • Journal Title: BMC Cancer Volume: 17 Issue: 1 Pages: 397-397
  • DOI: 10.1186/s12885-017-3358-6
  • Peer Reviewed / Open Access
• [Journal Article] Widespread subdural metastasis from breast cancer progressing rapidly with cerebral herniation: A case report. (2017)
  • Author(s): Okita Y
  • Journal Title: Mol Clin Oncol. Volume: 6 Issue: 6 Pages: 960-962
  • DOI: 10.3892/mco.2017.1233
  • Peer Reviewed / Open Access
• [Journal Article] Systemic Intravenous Adoptive Transfer of Autologous Lymphokine-activated αβ T-Cells Improves Temozolomide-induced Lymphopenia in Patients with Glioma. (2017)
  • Author(s): Kanemura Y
  • Journal Title: Anticancer Res. Volume: 37 Pages: 3921-3932
  • Peer Reviewed
• [Journal Article] Comparison of diffusion tensor imaging and 11C-methionine positron emission tomography for reliable prediction of tumor cell density in gliomas. (2016)
  • Author(s): Kinoshita M, Arita H, Okita Y, Kagawa N, Kishima H, Hashimoto N, Tanaka H, Watanabe Y, Shimosegawa E, Hatazawa J, Fujimoto Y, Yoshimine T
  • Journal Title: J Neurosurg Volume: 印刷中 Issue: 5 Pages: 1136-1142
  • DOI: 10.3171/2015.11.jns151848
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Health-related quality of life in outpatients with primary central nervous system lymphoma after radiotherapy and high-dose methotrexate chemotherapy. (2016)
  • Author(s): Okita Y, Narita Y,
  • Journal Title: Molecular and Clinical Oncology Volume: 5 Issue: 3 Pages: 179-185
  • DOI: 10.3892/mco.2016.962
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A combination of TERT promoter mutation and MGMT methylation status predicts clinically relevant subgroups of newly diagnosed glioblastomas. (2016)
  • Author(s): Arita H, Yamasaki K, Matsushita Y, Nakamura T, Shimokawa A, Takami H, Tanaka S, Mukasa A, Shirahata M, Shimizu S, Suzuki K, Saito K, Kobayashi K, Higuchi F, Uzuka T, Otani R, Tamura K, Sumita K, Ohno M, Miyakita Y, Kagawa N, Hashimoto N, Hatae R, Yoshimoto K, Shinojima N, Nakamura H, Kanemura Y, Okita Y, et al.
  • Journal Title: Acta Neuropathol Commun. Volume: 4 Issue: 1 Pages: 79-79
  • DOI: 10.1186/s40478-016-0351-2
  • Peer Reviewed / Open Access
• [Journal Article] A case of pilocytic astrocytoma requiring tumor resection during pregnancy (2016)
  • Author(s): Umehara T, Okita Y, Nonaka M, Kanemura Y, Kodama Y, Mano M, Nakajima S, Fujinaka T.
  • Journal Title: Mol Clin Oncol Volume: 4 Issue: 4 Pages: 567-570
  • DOI: 10.3892/mco.2016.773
  • Peer Reviewed / Open Access
• [Presentation] 神経膠腫の非造影病変での定位的評価によるMET-PETとMGMTメチル化率の相関牲 (2018)
  • Author(s): 沖田典子、正札智子、兼松大介、吉岡絵麻、児玉良典、眞能正幸
  • Organizer: 第23回日本脳腫瘍の外科学会
• [Presentation] 悪性神経膠腫での化学放射線治療後の脳体積変化について (2018)
  • Author(s): 沖田典子、成田善孝 、埜中正博、木下 学、田中英一、中島 伸、藤中俊之
  • Organizer: 日本脳神経外科学会第77回学術総会
• [Presentation] 悪性神経膠腫での化学放射線治療後の脳体積変化について (2018)
  • Author(s): 沖田典子、成田善孝 、埜中正博、木下 学、田中英一、中島 伸、藤中俊之
  • Organizer: 第36回日本脳腫瘍学会学術集会
• [Presentation] エビデンスに基づく膠芽腫の治療と課題 (2017)
  • Author(s): 沖田典子
  • Organizer: 第37回日本脳神経外科コングレス総会
  • Invited
• [Presentation] 神経膠腫の非造影病変での定位的評価によるmethionine PETとMGMTプロモーターメチル化率の相関牲について (2017)
  • Author(s): 沖田典子
  • Organizer: 日本脳神経外科学会第76回学術総会
• [Presentation] 神経膠腫の非造影病変での定位的評価によるMET-PETとMGMTメチル化率の相関牲 (2017)
  • Author(s): 沖田典子
  • Organizer: 第35回日本脳腫瘍学会学術集会
• [Presentation] ヒストン変異症例の臨床的背景について (2016)
  • Author(s): 沖田典子
  • Organizer: 第34回日本脳腫瘍学会学術集会
  • Place of Presentation: 甲府富士屋ホテル
  • Year and Date: 2016-12-04
• [Presentation] 膠芽腫患者でのQOL調査について (2016)
  • Author(s): 沖田典子
  • Organizer: 日本脳神経外科学会 第75会学術総会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2016-09-29
• [Presentation] Health-related quality of life in long-term survivors with grade II gliomas: The contribution of disease recurrence and Karnofsky Performance Status (2016)
  • Author(s): Yoshiko Okita
  • Organizer: 21st International Conference on Brain Tumor Research and Therapy
  • Place of Presentation: Bankoku Shinryokan
  • Year and Date: 2016-04-10
  • Int'l Joint Research
• [Book] 脳腫瘍学 (2016)
  • Author(s): 沖田典子
  • Total Pages: 4
  • Publisher: 日本臨牀社
• [Book] EBMに基づく脳神経疾患の基本治療指針 (2016)
  • Author(s): 沖田典子
  • Total Pages: 3
  • Publisher: MEDICAL VIEW