Department of Neurosurgery and Neuro-Oncology
Yoshitaka Narita, Yasuji Miyakita, Makoto Ohno, Masamichi Takahashi, Takahiro Ogawa, Shunicihro Miki, Sakura Kuzuoka
Patients with primary and metastatic brain tumors are treated by four neurosurgeons and three senior residents in the Department of Neurosurgery and Neuro-Oncology. A total of 327 patients were admitted and 121 craniotomies for tumor removal were carried out in 2015 including 38 gliomas, 49 brain metastases, six primary central nervous system (CNS) lymphomas, and 12 meningiomas (Table 1). The site of the craniotomy and the extent of tumor removal were visualized on the intraoperative magnetic resonance imaging (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 magnetic resonance (MR) tractography were also used to preserve patient neurological functions. Nine 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, growth factors, cell kinetic studies on individual tumors and several clinical trials are ongoing.
A weekly conference of treatment of patients with brain tumors is held with doctors of the Department of Radiation Oncology and of the Division of Brain Tumor Translational Research. Usually 15-20 patients are hospitalized and two or three 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 two years. The five-year survival rates of the patients with anaplastic astrocytomas and glioblastomas were 66.1% and 10.1%, respectively, which were better than those recorded in the Brain Tumor Registry of Japan (BTRJ). High dose methotrexate 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.
Patients with brain tumors have been registered in the BTRJ since 1969. More than 100,000 patients have been registered and followed up. The Department of Neurosurgery and Neuro-Oncology, the National Cancer Center Hospital, contributes as a managing office of the BTRJ and established on-line registration using the University Hospital Medical Information Network (UMIN) system in 2009. Clinical data during 2005 and 2008 were collected and the report will be published in 2016 as a supplement of the official journal of the Japan Neurosurgical Society.
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 carried out to predict the prognosis of patients with malignant gliomas.
The Japan Clinical Oncology Group (JCOG) – Brain Tumor Study Group was organized in 2002 and a multi-institutional randomized controlled trial is performed. “A randomized controlled phase II/III study of chemoradiotherapy using nimustine hydrochloride (ACNU) versus procarbazine and ACNU for astrocytoma grade 3 and 4 (JCOG0305)” was published. “A multicenter randomized phase II trial of Interferon-beta and Temozolomide combination chemoradiotherapy for newly diagnosed glioblastomas (JCOG 0911)” and “A Randomized phase III trial of postoperative whole brain radiation therapy compared with salvage stereotactic radiosurgery in patients with one to four brain metastasis (JCOG 0504)” was finished.
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. “Phase III randomized Study in patients with anaplastic glioma of radiotherapy with temozolomide versus 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.
Our Department plays the roles of the office of the general secretary of the JCOG – Brain tumor study group and the brain tumor registry of Japan; we have conducted many clinical trials and brain tumor registries. 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.
Malignant brain tumors, especially glioblastoma, still have worse prognosis among cancers. We always make an effort to defeat these brain cancers through various clinical works and research.
List of papers published in 2015
- Arita H, Narita Y, Matsushita Y, Fukushima S, Yoshida A, Takami H, Miyakita Y, Ohno M, Shibui S, Ichimura K. Development of a robust and sensitive pyrosequencing assay for the detection of IDH1/2 mutations in gliomas. Brain Tumor Pathol, 32:22-30, 2015
- Takami H, Yoshida A, Fukushima S, Arita H, Matsushita Y, Nakamura T, Ohno M, Miyakita Y, Shibui S, Narita Y, Ichimura K. Revisiting TP53 Mutations and Immunohistochemistry-A Comparative Study in 157 Diffuse Gliomas. Brain Pathol, 25:256-265, 2015
- Fukushima S, Yoshida A, Narita Y, Arita H, Ohno M, Miyakita Y, Ichimura K, Shibui S. Multinodular and vacuolating neuronal tumor of the cerebrum. Brain Tumor Pathol, 32:131-136, 2015
- Narita Y, Shibui S, Committee of Brain Tumor Registry of Japan Supported by the Japan Neurosurgical Society. Trends and outcomes in the treatment of gliomas based on data during 2001-2004 from the Brain Tumor Registry of Japan. Neurol Med Chir (Tokyo), 55:286-295, 2015
- Narita Y. Bevacizumab for glioblastoma. Ther Clin Risk Manag, 11:1759-1765, 2015
- Okita Y, Narita Y, Miyahara R, Miyakita Y, Ohno M, Shibui S. Health-related quality of life in long-term survivors with Grade II gliomas: the contribution of disease recurrence and Karnofsky Performance Status. Jpn J Clin Oncol, 45:906-913, 2015
- Arita H, Narita Y, Yoshida A, Hashimoto N, Yoshimine T, Ichimura K. IDH1/2 mutation detection in gliomas. Brain Tumor Pathol, 32:79-89, 2015
- Takami H, Fukushima S, Fukuoka K, Suzuki T, Yanagisawa T, Matsushita Y, Nakamura T, Arita H, Mukasa A, Saito N, Kanamori M, Kumabe T, Tominaga T, Kobayashi K, Nagane M, Iuchi T, Tamura K, Maehara T, Sugiyama K, Nakada M, Kanemura Y, Nonaka M, Yokogami K, Takeshima H, Narita Y, Shibui S, Nakazato Y, Nishikawa R, Ichimura K, Matsutani M. Human chorionic gonadotropin is expressed virtually in all intracranial germ cell tumors. J Neurooncol, 124:23-32, 2015
- Ichimura K, Narita Y, Hawkins CE. Diffusely infiltrating astrocytomas: pathology, molecular mechanisms and markers. Acta Neuropathol, 129:789-808, 2015
- Iwakawa R, Kohno T, Totoki Y, Shibata T, Tsuchihara K, Mimaki S, Tsuta K, Narita Y, Nishikawa R, Noguchi M, Harris CC, Robles AI, Yamaguchi R, Imoto S, Miyano S, Totsuka H, Yoshida T, Yokota J. Expression and clinical significance of genes frequently mutated in small cell lung cancers defined by whole exome/RNA sequencing. Carcinogenesis, 36:616-621, 2015