Annual Report 2019
Department of Neurosurgery and Neuro-Oncology
Yoshitaka Narita, Yasuji Miyakita, Makoto Ohno, Masamichi Takahashi, Takaki Omura, Natsuko Satomi, Tomoko Omura, Kenji Fujimoto, Yukie Tamura, Masaru Yonezawa
Introduction
We treat patients with primary and metastatic brain tumors. Approximately 300 patients were admitted and 181 craniotomies for tumor removal were carried out in 2019 including 76 gliomas, 74 brain metastases, 8 primary CNS lymphomas, and 12 meningiomas (Table 1). The site of the craniotomy and the extent of tumor removal were visualized on the intraoperative MRI in real time, contributing to safer and more precise surgery. Intraoperative monitoring with motor- and sensory evoked potential (MEP and SEP) recording as well as preoperative functional MRI and MR tractography were also used to preserve patient neurological function. Awake surgeries were also performed, particularly for removal of gliomas near the speech center. Patients with malignant brain tumors were treated with postoperative radiotherapy and chemotherapy. In order to design a more effective chemotherapy regimen, molecular biological studies for drug resistance and growth factors, cell kinetic studies on individual tumors and several clinical trials are ongoing.
The Team and What We Do
A weekly conference on treatment of patients with brain tumors is held with doctors of the Department of Radiation Oncology and Pathology, and of the Division of Brain Tumor Translational Research. Usually 10-15 patients are hospitalized and 3 or 4 of them undergo surgical treatment every week. The patients with malignant brain tumors receive postoperative radiotherapy and chemotherapy. Statistical analysis revealed that surgical removal of as much of the tumor as possible yielded better survival rates even for the most malignant glioblastomas, which usually recur soon after the surgery without radiotherapy. Concomitant use of chemotherapy is considered to enhance the anti-tumor effect of radiotherapy.Temozolomide has been given to all malignant glioma patients during radiotherapy and repeated every month for 1 year. R-MPV therapy is administered to the patients with primary CNS lymphoma before radiotherapy.
The decision on the indication for surgery of metastatic brain tumors is not simple. Multiplicity of brain metastasis, the stage of the primary malignancy and the patient performance status should be taken into careful consideration.
Table 1. Surgical cases for brain tumors
Research activities
An analysis of gene expression profiles in malignant gliomas is being carried out in order to determine specific genes that have an influence on the effects of chemotherapy and radiation therapy in cooperation with the Division of Brain Tumor Translational Research, the National Cancer Center Research Institute. The determination of the methylation status of O6-methylguanine-DNA methyltransferase (MGMT) and the mutation of IDH1/2 and TERT are also being carried out to predict the prognosis of the patients with malignant gliomas.
Clinical trials
The Japan Clinical Oncology Group (JCOG)-Brain Tumor Study Group was organized in 2002 and multi-institutional randomized controlled trials are performed. “Phase III randomized study in patients with anaplastic glioma of radiotherapy with nimustine hydrochloride (ACNU) followed by temozolomide (JCOG1016),” “Phase III Study of High-dose Methotrexate and Whole Brain Radiotherapy With or Without Concomitant and Adjuvant Temozolomide in Patients with Primary CNS Lymphoma (JCGO1114),” “Randomized phase III study for unresectable WHO Grade II astrocytoma with radiotherapy alone or chemoradiotherapy with temozolomide (JCOG1303),” and “A multicenter randomized phase III study for recurrent glioblastoma comparing bevacizumab alone with dose-dense temozolomide followed by bevacizumab (JCOG1308)” are now ongoing. These studies, under the surveillance of JCOG, aim to set a standard protocol for treating malignant brain tumor patients. Moreover, a proper methodology for performing randomized studies will be established in the field of neuro-oncology.
An investigator-initiated phase II clinical trial of eribulin targeting TERT in patients with recurrent glioblastomas is also ongoing.
Education
Our department plays the role of an office of the general secretary of the JCOG-Brain Tumor Study Group and the brain tumor registry of Japan, and we conducted many clinical trials and ran the brain tumor registry. We educate many neurosurgeons and oncologists about surgical techniques of awake craniotomy and intraoperative MRI and the effective usage and adverse effects of many chemotherapeutic agents regarding malignant brain tumors.
Dr. Narita is a co-chairman of the Neuro-Oncology Education Committee of the World Federation of Neurosurgery and he has presented many lectures about surgical treatment of gliomas in developing countries.
Future prospects
Malignant brain tumors, especially glioblastoma still have the worse prognosis among cancers. We continually strive to defeat these brain cancers through a variety of clinical work and research.
List of papers published in 2019
Journal
1. Yamazawa E, Ohno M, Satomi K, Yoshida A, Miyakita Y, Takahashi M, Satomi N, Asanome T, Maeshima A, Shiotsuka M, Iwata S, Yamasaki H, Morishima Y, Sugiyama H, Narita Y. First case of human neurocoenurosis caused by Taenia serialis: A case report. Int J Infect Dis, 92:171-174, 2020
2. Tanaka S, Sato I, Takahashi M, Armstrong TS, Cleeland CS, Mendoza TR, Mukasa A, Takayanagi S, Narita Y, Kamibeppu K, Saito N. Validation study of the Japanese version of MD Anderson Symptom Inventory for Brain Tumor module. Jpn J Clin Oncol, 50:787-793, 2020
3. Takami H, Perry A, Graffeo CS, Giannini C, Narita Y, Nakazato Y, Saito N, Nishikawa R, Matsutani M, Ichimura K, Daniels DJ. Comparison on epidemiology, tumor location, histology, and prognosis of intracranial germ cell tumors between Mayo Clinic and Japanese consortium cohorts. J Neurosurg, 1-11, 2020
4. Takami H, Fukushima S, Aoki K, Satomi K, Narumi K, Hama N, Matsushita Y, Fukuoka K, Yamasaki K, Nakamura T, Mukasa A, Saito N, Suzuki T, Yanagisawa T, Nakamura H, Sugiyama K, Tamura K, Maehara T, Nakada M, Nonaka M, Asai A, Yokogami K, Takeshima H, Iuchi T, Kanemura Y, Kobayashi K, Nagane M, Kurozumi K, Yoshimoto K, Matsuda M, Matsumura A, Hirose Y, Tokuyama T, Kumabe T, Ueki K, Narita Y, Shibui S, Totoki Y, Shibata T, Nakazato Y, Nishikawa R, Matsutani M, Ichimura K. Intratumoural immune cell landscape in germinoma reveals multipotent lineages and exhibits prognostic significance. Neuropathol Appl Neurobiol, 46:111-124, 2020
5. Natsume A, Aoki K, Ohka F, Maeda S, Hirano M, Adilijiang A, Motomura K, Sumi M, Nishikawa R, Narita Y, Muragaki Y, Maruyama T, Ito T, Beppu T, Nakamura H, Kayama T, Sato S, Nagane M, Mishima K, Nakasu Y, Kurisu K, Yamasaki F, Sugiyama K, Onishi T, Iwadate Y, Terasaki M, Kobayashi H, Matsumura A, Ishikawa E, Sasaki H, Mukasa A, Matsuo T, Hirano H, Kumabe T, Shinoura N, Hashimoto N, Aoki T, Asai A, Abe T, Yoshino A, Arakawa Y, Asano K, Yoshimoto K, Shibui S, Okuno Y, Wakabayashi T. Genetic analysis in patients with newly diagnosed glioblastomas treated with interferon-beta plus temozolomide in comparison with temozolomide alone. J Neurooncol, 148:17-27, 2020
6. Miyakita Y, Ohno M, Takahashi M, Kurihara H, Katai H, Narita Y. Usefulness of carbon-11-labeled methionine positron-emission tomography for assessing the treatment response of primary central nervous system lymphoma. Jpn J Clin Oncol, 50:512-518, 2020
7. Iihara K, Tominaga T, Saito N, Suzuki M, Date I, Fujii Y, Hongo K, Houkin K, Kato A, Kato Y, Kawamata T, Kim P, Kinouchi H, Kohmura E, Kurisu K, Maruyama K, Mikuni N, Miyamoto S, Morita A, Nakase H, Narita Y, Nishikawa R, Nozaki K, Ogasawara K, Ohata K, Sakai N, Sakamoto H, Shiokawa Y, Sonoda Y, Takahashi JC, Ueki K, Wakabayashi T, Yamamoto T, Yoshida K, Kayama T, Arai H. The Japan Neurosurgical Database: Overview and Results of the First-year Survey. Neurol Med Chir (Tokyo), 60:165-190, 2020
8. Arakawa A, Mitsutake A, Hideyama T, Sato T, Katsumata J, Seki T, Maekawa R, Ohno M, Narita Y, Shiio Y. A central nervous system metastasis of melanoma with stroke-like onset of left-lower quadrantanopsia. J Gen Fam Med, 21:77-79, 2020
9. Imaizumi J, Shida D, Narita Y, Miyakita Y, Tanabe T, Takashima A, Boku N, Igaki H, Itami J, Kanemitsu Y. Prognostic factors of brain metastases from colorectal cancer. BMC Cancer, 19:755, 2019
10. Sato J, Shimomura A, Kawauchi J, Matsuzaki J, Yamamoto Y, Takizawa S, Sakamoto H, Ohno M, Narita Y, Ochiya T, Tamura K. Brain metastasis-related microRNAs in patients with advanced breast cancer. PLoS One, 14:e0221538, 2019
11. Ohno M, Matsuzaki J, Kawauchi J, Aoki Y, Miura J, Takizawa S, Kato K, Sakamoto H, Matsushita Y, Takahashi M, Miyakita Y, Ichimura K, Narita Y, Ochiya T. Assessment of the Diagnostic Utility of Serum MicroRNA Classification in Patients With Diffuse Glioma. JAMA Netw Open, 2:e1916953, 2019
12. Yamazawa E, Honma Y, Satomi K, Taniguchi H, Takahashi M, Yoshida A, Tominaga K, Miyakita Y, Ohno M, Asanome T, Satomi N, Narita Y. A rare case of brain metastasis from poorly differentiated small bowel adenocarcinoma. Surg Neurol Int, 10:256, 2019
13. Yoshida A, Satomi K, Ohno M, Matsushita Y, Takahashi M, Miyakita Y, Hiraoka N, Narita Y, Ichimura K. Frequent false-negative immunohistochemical staining with IDH1 (R132H)-specific H09 antibody on frozen section control slides: a potential pitfall in glioma diagnosis. Histopathology, 74:350-354, 2019
14. Takami H, Fukuoka K, Fukushima S, Nakamura T, Mukasa A, Saito N, Yanagisawa T, Nakamura H, Sugiyama K, Kanamori M, Tominaga T, Maehara T, Nakada M, Kanemura Y, Asai A, Takeshima H, Hirose Y, Iuchi T, Nagane M, Yoshimoto K, Matsumura A, Kurozumi K, Nakase H, Sakai K, Tokuyama T, Shibui S, Nakazato Y, Narita Y, Nishikawa R, Matsutani M, Ichimura K. Integrated clinical, histopathological, and molecular data analysis of 190 central nervous system germ cell tumors from the iGCT Consortium. Neuro Oncol, 21:1565-1577, 2019
15. Takahashi M, Miki S, Fujimoto K, Fukuoka K, Matsushita Y, Maida Y, Yasukawa M, Hayashi M, Shinkyo R, Kikuchi K, Mukasa A, Nishikawa R, Tamura K, Narita Y, Hamada A, Masutomi K, Ichimura K. Eribulin penetrates brain tumor tissue and prolongs survival of mice harboring intracerebral glioblastoma xenografts. Cancer Sci, 110:2247-2257, 2019
16. Ohno M, Miyakita Y, Takahashi M, Igaki H, Matsushita Y, Ichimura K, Narita Y. Survival benefits of hypofractionated radiotherapy combined with temozolomide or temozolomide plus bevacizumab in elderly patients with glioblastoma aged ≧ 75 years. Radiat Oncol, 14:200, 2019
17. Nomura M, Saito K, Aihara K, Nagae G, Yamamoto S, Tatsuno K, Ueda H, Fukuda S, Umeda T, Tanaka S, Takayanagi S, Otani R, Nejo T, Hana T, Takahashi S, Kitagawa Y, Omata M, Higuchi F, Nakamura T, Muragaki Y, Narita Y, Nagane M, Nishikawa R, Ueki K, Saito N, Aburatani H, Mukasa A. Publisher Correction: DNA demethylation is associated with malignant progression of lower-grade gliomas. Sci Rep, 9:7935, 2019
18. Nomura M, Saito K, Aihara K, Nagae G, Yamamoto S, Tatsuno K, Ueda H, Fukuda S, Umeda T, Tanaka S, Takayanagi S, Otani R, Nejo T, Hana T, Takahashi S, Kitagawa Y, Omata M, Higuchi F, Nakamura T, Muragaki Y, Narita Y, Nagane M, Nishikawa R, Ueki K, Saito N, Aburatani H, Mukasa A. DNA demethylation is associated with malignant progression of lower-grade gliomas. Sci Rep, 9:1903, 2019
19. Nejo T, Matsushita H, Karasaki T, Nomura M, Saito K, Tanaka S, Takayanagi S, Hana T, Takahashi S, Kitagawa Y, Koike T, Kobayashi Y, Nagae G, Yamamoto S, Ueda H, Tatsuno K, Narita Y, Nagane M, Ueki K, Nishikawa R, Aburatani H, Mukasa A, Saito N, Kakimi K. Reduced Neoantigen Expression Revealed by Longitudinal Multiomics as a Possible Immune Evasion Mechanism in Glioma. Cancer Immunol Res, 7:1148-1161, 2019
20. Narita Y, Arakawa Y, Yamasaki F, Nishikawa R, Aoki T, Kanamori M, Nagane M, Kumabe T, Hirose Y, Ichikawa T, Kobayashi H, Fujimaki T, Goto H, Takeshima H, Ueba T, Abe H, Tamiya T, Sonoda Y, Natsume A, Kakuma T, Sugita Y, Komatsu N, Yamada A, Sasada T, Matsueda S, Shichijo S, Itoh K, Terasaki M. A randomized, double-blind, phase III trial of personalized peptide vaccination for recurrent glioblastoma. Neuro Oncol, 21:348-359, 2019
21. Lassman AB, Aldape KD, Ansell PJ, Bain E, Curran WJ, Eoli M, French PJ, Kinoshita M, Looman J, Mehta M, Muragaki Y, Narita Y, Ocampo C, Roberts-Rapp L, Song M, Vogelbaum MA, Walenkamp AME, Wang TJC, Zhang P, van den Bent MJ. Epidermal growth factor receptor (EGFR) amplification rates observed in screening patients for randomized trials in glioblastoma. J Neurooncol, 144:205-210, 2019
22. Kadota T, Saito R, Kumabe T, Mizusawa J, Katayama H, Sumi M, Igaki H, Kinoshita M, Komori T, Ichimura K, Narita Y, Nishikawa R. 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). Jpn J Clin Oncol, 49:1172-1175, 2019
23. Fukuma R, Yanagisawa T, Kinoshita M, Shinozaki T, Arita H, Kawaguchi A, Takahashi M, Narita Y, Terakawa Y, Tsuyuguchi N, Okita Y, Nonaka M, Moriuchi S, Takagaki M, Fujimoto Y, Fukai J, Izumoto S, Ishibashi K, Nakajima Y, Shofuda T, Kanematsu D, Yoshioka E, Kodama Y, Mano M, Mori K, Ichimura K, Kanemura Y, Kishima H. Prediction of IDH and TERT promoter mutations in low-grade glioma from magnetic resonance images using a convolutional neural network. Sci Rep, 9:20311, 2019