Annual Report 2022
Department of Neurosurgery and Neuro-Oncology
Yoshitaka Narita, Yasuji Miyakita, Masamichi Takahashi, Makoto Ohno, Shunsuke Yanagisawa, Takayasu Mukai, Yuki Kawaguchi
Introduction
We treat patients with primary and metastatic brain tumors. Approximately 300 patients were admitted and 182 craniotomies for tumor removal were performed in 2022 including 63 gliomas, 59 brain metastases, 6 primary CNS lymphomas, and 16 meningiomas (Table 1). The extent of tumor removal was 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) recordings and preoperative functional MRI and MR tractography were also used to preserve patient neurological function. Awake surgeries were also performed, particularly for the removal of gliomas near the speech center. Patients with malignant brain tumors underwent postoperative radiotherapy and chemotherapy. New intraoperative MRI was updated.
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.
Table 1. Surgical cases of brain tumors
The Team and What We Do
A weekly conference on the treatment of patients with brain tumors is held with doctors from the Department of Radiation Oncology and Pathology and the Division of Brain Tumor Translational Research. Usually, 10-15 patients are hospitalized, and 3 or 4 of them undergo surgical treatment every week. 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 most malignant glioblastomas, which usually recur immediately after surgery without radiotherapy. Concomitant use of chemotherapy is considered to enhance the anti-tumor effect of radiotherapy.
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 performance status should be carefully considered.
Research Activities
Gene expression profiles in malignant gliomas are analyzed to determine specific genes that influence 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 performed to predict the prognosis of patients with malignant gliomas.
Clinical Trials
The Japan Clinical Oncology Group (JCOG)-Brain Tumor Study Group was organized in 2003 and multi-institutional randomized controlled trials are performed. “Randomized phase III study for unresectable WHO Grade II astrocytoma with radiotherapy alone or chemoradiotherapy with temozolomide (JCOG1303)”, Phase III randomized study for grade III gliomas (JCOG1016), and phase III study for glioblastoma (JCOG1308, JCOG1703 and JCOG1910) are ongoing. These studies, under the surveillance of the JCOG, aim to establish 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 I/II clinical trial of metformin and temozolomide for newly-diagnosed glioblastomas is performed under AMED grants.
Education
We held an annual meeting of the Japan Society for Neuro-Oncology and Japan Awake surgery conference (photo). Our department plays a pivotal role in the JCOG-Brain Tumor Study Group and the brain tumor registry of Japan, and we have conducted many clinical trials and run 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 worse prognosis among cancers. We continually strive to eradicate these brain cancers through a variety of clinical work and research.
List of papers published in 2022
Journal
1. Narita Y, Okita Y, Arakawa Y. Evaluation of the efficacy and safety of TAS0313 in adults with recurrent glioblastoma. Cancer immunology, immunotherapy, 71:2703-2715, 2022
2. Ohno M, Kitanaka C, Miyakita Y, Tanaka S, Sonoda Y, Mishima K, Ishikawa E, Takahashi M, Yanagisawa S, Ohashi K, Nagane M, Narita Y. Metformin with Temozolomide for Newly Diagnosed Glioblastoma: Results of Phase I Study and a Brief Review of Relevant Studies. Cancers, 14:4222, 2022
3. Ohno M, Miyakita Y, Takahashi M, Yanagisawa S, Tamura Y, Kawauchi D, Kikuchi M, Igaki H, Yoshida A, Satomi K, Matsushita Y, Ichimura K, Narita Y. Assessment of therapeutic outcome and role of reirradiation in patients with radiation-induced glioma. Radiation oncology (London, England), 17:85, 2022
4. Ohno M, Kitano S, Satomi K, Yoshida A, Miyakita Y, Takahashi M, Yanagisawa S, Tamura Y, Ichimura K, Narita Y. Assessment of radiographic and prognostic characteristics of programmed death-ligand 1 expression in high-grade gliomas. Journal of neuro-oncology, 160:463-472, 2022
5. Ohno M, Miyakita Y, Takahashi M, Yanagisawa S, Tamura Y, Narita Y. Continuing maintenance temozolomide therapy beyond 12 cycles confers no clinical benefit over discontinuation at 12 cycles in patients with IDH1/2-wildtype glioblastoma. Japanese journal of clinical oncology, 52:1134-1142, 2022
6. Kawauchi D, Ohno M, Miyakita Y, Takahashi M, Yanagisawa S, Omura T, Yoshida A, Kubo Y, Igaki H, Ichimura K, Narita Y. Early Diagnosis and Surgical Intervention Within 3 Weeks From Symptom Onset Are Associated With Prolonged Survival of Patients With Glioblastoma. Neurosurgery, 91:741-748, 2022
7. Kawauchi D, Ohno M, Honda-Kitahara M, Miyakita Y, Takahashi M, Yanagisawa S, Tamura Y, Kikuchi M, Ichimura K, Narita Y. The clinical characteristics and outcomes of incidentally discovered glioblastoma. Journal of neuro-oncology, 156:551-557, 2022
8. Hosoya T, Takahashi M, Honda-Kitahara M, Miyakita Y, Ohno M, Yanagisawa S, Omura T, Kawauchi D, Tamura Y, Kikuchi M, Nakano T, Yoshida A, Igaki H, Matsushita Y, Ichimura K, Narita Y. MGMT gene promoter methylation by pyrosequencing method correlates volumetric response and neurological status in IDH wild-type glioblastomas. Journal of neuro-oncology, 157:561-571, 2022
9. Hosoya T, Yonezawa H, Matsuoka A, Ohno M, Miyakita Y, Takahashi M, Yanagisawa S, Tamura Y, Kikuchi M, Nakano T, Oishi Y, Manabe S, Sato T, Narita Y. Combination of asleep and awake craniotomy as a novel strategy for resection in patients with butterfly glioblastoma: Two case reports. Surgical neurology international, 13:492, 2022
10. Hosoya T, Takahashi M, Davey C, Sese J, Honda-Kitahara M, Miyakita Y, Ohno M, Yanagisawa S, Omura T, Kawauchi D, Ozeki Y, Kikuchi M, Nakano T, Yoshida A, Igaki H, Matsushita Y, Ichimura K, Narita Y. Volumetric Analysis of Glioblastoma for Determining Which CpG Sites Should Be Tested by Pyrosequencing to Predict Temozolomide Efficacy. Biomolecules, 12:1379, 2022
11. Omura T, Takahashi M, Ohno M, Miyakita Y, Yanagisawa S, Tamura Y, Kikuchi M, Kawauchi D, Nakano T, Hosoya T, Igaki H, Satomi K, Yoshida A, Sunami K, Hirata M, Shimoi T, Sudo K, Okuma HS, Yonemori K, Suzuki H, Ichimura K, Narita Y. Clinical Application of Comprehensive Genomic Profiling Tests for Diffuse Gliomas. Cancers, 14:2454, 2022
12. Natsume A, Arakawa Y, Narita Y, Sugiyama K, Hata N, Muragaki Y, Shinojima N, Kumabe T, Saito R, Motomura K, Mineharu Y, Miyakita Y, Yamasaki F, Matsushita Y, Ichimura K, Ito K, Tachibana M, Kakurai Y, Okamoto N, Asahi T, Nishijima S, Yamaguchi T, Tsubouchi H, Nakamura H, Nishikawa R. The first-in-human phase I study of a brain-penetrant mutant IDH1 inhibitor DS-1001 in patients with recurrent or progressive IDH1-mutant gliomas. Neuro-oncology, 25:326-336, 2023
13. Chiba Y, Sudo K, Kojima Y, Okuma H, Kohsaka S, Machida R, Ichimura M, Anjo K, Kurishita K, Okita N, Nakamura K, Kinoshita I, Takahashi M, Matsubara J, Kusaba H, Yonemori K, Takahashi M. A multicenter investigator-initiated Phase 2 trial of E7090 in patients with advanced or recurrent solid tumor with fibroblast growth factor receptor (FGFR) gene alteration: FORTUNE trial. BMC cancer, 22:869, 2022
14. Nakano T, Fujimoto K, Tomiyama A, Takahashi M, Achiha T, Arita H, Kawauchi D, Yasukawa M, Masutomi K, Kondo A, Narita Y, Maehara T, Ichimura K. Eribulin prolongs survival in an orthotopic xenograft mouse model of malignant meningioma. Cancer science, 113:697-708, 2022
15. Yoshida A, Satomi K, Kobayashi E, Ryo E, Matsushita Y, Narita Y, Ichimura K, Kawai A, Mori T. Soft-tissue sarcoma with MN1-BEND2 fusion: A case report and comparison with astroblastoma. Genes, chromosomes & cancer, 61:427-431, 2022
16. Takami H, Elzawahry A, Mamatjan Y, Fukushima S, Fukuoka K, Suzuki T, Yanagisawa T, Matsushita Y, Nakamura T, Satomi K, Tanaka S, Mukasa A, Saito N, Kanamori M, Kumabe T, Tominaga T, Kobayashi K, Nagane M, Iuchi T, Tamura K, Maehara T, Sugiyama K, Yoshimoto K, Sakai K, Nonaka M, Asai A, Yokogami K, Takeshima H, Narita Y, Shibui S, Nakazato Y, Hama N, Totoki Y, Kato M, Shibata T, Nishikawa R, Matsutani M, Ichimura K. Transcriptome and methylome analysis of CNS germ cell tumor finds its cell-of-origin in embryogenesis and reveals shared similarities with testicular counterparts. Neuro-oncology, 24:1246-1258, 2022
17. Satomi K, Ohno M, Kubo T, Honda-Kitahara M, Matsushita Y, Ichimura K, Narita Y, Ichikawa H, Yoshida A. Central nervous system sarcoma with ATXN1::DUX4 fusion expands the concept of CIC-rearranged sarcoma. Genes, chromosomes & cancer, 61:683-688, 2022
18. Satomi K, Yoshida A, Matsushita Y, Sugino H, Fujimoto K, Honda-Kitahara M, Takahashi M, Ohno M, Miyakita Y, Narita Y, Yatabe Y, Shibahara J, Ichimura K. Clinical application of a highly sensitive digital PCR assay to detect a small fraction of IDH1 R132H-mutant alleles in diffuse gliomas. Brain tumor pathology, 39:210-217, 2022
19. Kobayashi K, Miyakita Y, Matsumoto F, Omura G, Matsumura S, Ikeda A, Eguchi K, Ito A, Narita Y, Akazawa S, Yoshimoto S. Olfactory Preservation in Craniofacial Resection of Tumor Invading Hemianterior Skull Base: Operative Video. Journal of neurological surgery. Part B, Skull base, 83:e639-e640, 2022
20. Nagane M, Ichimura K, Onuki R, Narushima D, Honda-Kitahara M, Satomi K, Tomiyama A, Arai Y, Shibata T, Narita Y, Uzuka T, Nakamura H, Nakada M, Arakawa Y, Ohnishi T, Mukasa A, Tanaka S, Wakabayashi T, Aoki T, Aoki S, Shibui S, Matsutani M, Ishizawa K, Yokoo H, Suzuki H, Morita S, Kato M, Nishikawa R. Bevacizumab beyond Progression for Newly Diagnosed Glioblastoma (BIOMARK): Phase II Safety, Efficacy and Biomarker Study. Cancers, 14:5522, 2022