Annual Report 2020
Department of Neurosurgery and Neuro-Oncology
Yoshitaka Narita, Yasuji Miyakita, Makoto Ohno, Masamichi Takahashi, Takaki Omura, Yukie Tamura, Tadashi Osawa, Shoko Yoshimoto, Hitomi Sato
Introduction
We treat patients with primary and metastatic brain tumors. Approximately 300 patients were admitted and 167 craniotomies for tumor removal were performed in 2020 including 63 gliomas, 59 brain metastases, 2 primary CNS lymphomas, and 16 meningiomas (Table 1). The site of the craniotomy and the extent of tumor removal were visualized on an 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 underwent postoperative radiotherapy and chemotherapy. In order to perform 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 from the Department of Radiation Oncology and Pathology, and from 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 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 one year. R-MPV therapy is administered to the patients with primary CNS lymphoma before radiotherapy.
Table 1. Surgical cases for brain tumors
The decision on the indication for surgery of metastatic brain tumors is not a simple one. Multiplicity of brain metastasis, the stage of the primary malignancy and the patient's performance status should be taken into careful consideration.
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 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 ongoing. A “Randomized Phase III study for unresectable WHO Grade II astrocytoma with radiotherapy alone or chemoradiotherapy with temozolomide (JCOG1303)”, a Phase III randomized study for grade III gliomas (JCOG1016), and Phase III study for glioblastoma (JCOG1308, JCOG1703 and JCOG1910) are underway. These studies, under the surveillance of the 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 and a phase II study of temozolomide and metformin for newly-diagnosed glioblastoma are also ongoing under AMED grants.
Education
Our department plays the pivotal role 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 for malignant brain tumors.
Future Prospects
Malignant brain tumors, especially glioblastoma still have the worse prognosis among all cancers. We continually strive to defeat these brain cancers through a variety of clinical work and research.
List of papers published in 2020
Journal
1. Narita Y, Nagane M, Mishima K, Terui Y, Arakawa Y, Yonezawa H, Asai K, Fukuhara N, Sugiyama K, Shinojima N, Kitagawa J, Aoi A, Nishikawa R. Phase I/II study of tirabrutinib, a second-generation Bruton's tyrosine kinase inhibitor, in relapsed/refractory primary central nervous system lymphoma. Neuro Oncol, 23:122-133, 2021
2. Takahashi S, Takahashi M, Kinoshita M, Miyake M, Kawaguchi R, Shinojima N, Mukasa A, Saito K, Nagane M, Otani R, Higuchi F, Tanaka S, Hata N, Tamura K, Tateishi K, Nishikawa R, Arita H, Nonaka M, Uda T, Fukai J, Okita Y, Tsuyuguchi N, Kanemura Y, Kobayashi K, Sese J, Ichimura K, Narita Y, Hamamoto R. Fine-Tuning Approach for Segmentation of Gliomas in Brain Magnetic Resonance Images with a Machine Learning Method to Normalize Image Differences among Facilities. Cancers (Basel), 13:2021
3. Satomi K, Ohno M, Matsushita Y, Takahashi M, Miyakita Y, Narita Y, Ichimura K, Yoshida A. Utility of methylthioadenosine phosphorylase immunohistochemical deficiency as a surrogate for CDKN2A homozygous deletion in the assessment of adult-type infiltrating astrocytoma. Mod Pathol, 34:688-700, 2021
4. Ozawa T, Kaneko S, Szulzewsky F, Qiao Z, Takadera M, Narita Y, Kondo T, Holland EC, Hamamoto R, Ichimura K. C11orf95-RELA fusion drives aberrant gene expression through the unique epigenetic regulation for ependymoma formation. Acta Neuropathol Commun, 9:36, 2021
5. Matsumoto F, Miyakita Y, Sakai A, Akamatsu M, Matsumoto Y, Matsumura S, Omura G, Kobayashi K, Narita Y, Yoshimoto S. Resection of carcinoma of the external auditory canal in a patient with a high jugular bulb using temporal craniotomy. Auris Nasus Larynx, 48:535-538, 2021
6. Kawauchi D, Takahashi M, Satomi K, Yamamuro S, Kobayashi T, Uchida E, Honda-Kitahara M, Narita Y, Iwadate Y, Ichimura K, Tomiyama A. The ALK inhibitors, alectinib and ceritinib, induce ALK-independent and STAT3-dependent glioblastoma cell death. Cancer Sci, 112:2442-2453, 2021
7. 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
8. Ohno M, Miyakita Y, Takahashi M, Ohmura T, Satomi N, Tamura Y, Matsushita Y, Ichimura K, Narita Y. Clinical Characteristics and Outcome of Patients with Radiation-Induced Glioma. Neuro-Oncology, 22:350-351, 2020
9. 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
10. 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
11. 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
12. 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
13. 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
14. Miki S, Satomi K, Ohno M, Matsushita Y, Kitahara M, Miyakita Y, Takahashi M, Matsuda M, Ishikawa E, Matsumura A, Yoshida A, Narita Y, Ichimura K. Highly sensitive detection of TERT promoter mutations in recurrent glioblastomas using digital PCR. Brain Tumor Pathol, 37:154-158, 2020
15. Kobayashi K, Matsumoto F, Miyakita Y, Arikawa M, Omura G, Matsumura S, Ikeda A, Sakai A, Eguchi K, Narita Y, Akazawa S, Miyamoto S, Yoshimoto S. Risk Factors for Delayed Surgical Recovery and Massive Bleeding in Skull Base Surgery. Biomed Hub, 5:87-100, 2020