Neurosurgery Division

Introduction
Patients with primary and metastatic brain tumors are treated by four neurosurgeons in the Neurosurgery Division. In 2001, 208 patients were admitted and 65 craniotomies were carried out including 22 gliomas, 16 metastatic brain tumors, and 11 meningiomas (Table). Thirteen minor surgeries such as placement of Ommaya s reservoir (11 patients) and ventriculo-peritoneal shunt (2 patients) were performed and most of them were emergency operations. The surgical navigation system (Stealth station) was introduced in 2001. The site of craniotomy and the extent of tumor removal are pointed out on the CRT of this system in real time. It contributes to safer and more precise surgery. Postoperative radiotherapy and chemo-therapy are carried out for malignant tumors, but it is still difficult to obtain complete response. In order to design a more effective chemotherapy regimen, molecular biological studies for drug resistance, growth factors and cell kinetic studies on individual tumors are ongoing.

Routine Activities
Four neurosurgeons have a weekly conference with doctors of Radiation Oncology Division on diagnosis and treatment of the patients with brain tumors. Usually 14 patients are hospitalized and one or two of them undergo surgical treatment every week. Stealth navigation system is used for surgical planning during every craniotomy. 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 even for the most malignant glioblastomas. However, they usually recur soon after the surgery without radiotherapy. Concomitant use of chemotherapy is considered to enhance the anti-tumor effect of radiotherapy. ACNU (nimustin hydrochloride) and the other chemotherapeutic agents are administered intravenously during radiotherapy. One-year and 2-year survival rates of the patients with anaplastic astrocytomas were 79.4% and 58.0%, which were better than those of Brain Tumor Registry of Japan (Table). Decision on the indication for surgery of metastatic brain tumors is not simple. Multiplicity of brain metastasis, stage of primary malignancy and performance status of patients should be taken into careful consideration. After induction therapy for malignant brain tumors, maintenance chemotherapy is carried out for a few years. However, most of these tumors recur and are usually resistant to the previous treatment. Alternative chemotherapy such as carboplatin and etoposide is provided with some patients showing response. But the five-year survival rate of patients with glioblastomas, as well as that of patients with metastatic brain tumors, is still less than 10%.

Research Activities
Patients with brain tumors have been registered in Brain Tumor Registry of Japan (BTRJ) since 1969. More than 80,000 patients were registered and followed up. Neurosurgery Division of National Cancer Center Hospital contributes as a managing office of BTRJ. Statistical analyses were performed and brain tumors in Japan were overviewed. A higher incidence of pineal region tumors in Asian countries was reported based on the data of BTRJ (Nomura). Recent progress in surgical technique and effective chemotherapy improved the prognosis of the patients.
Immunohistochemical studies using monoclonal antibodies such as anti-bromodeoxyuridine (BrdU), MIB-1 (Ki-67) and anti-epidermal growth factor receptor (EGFR) are performed to examine proliferation activities of the tumor cells. Flow cytometric analysis is also carried out to detect DNA aneuploidy and each fraction size of G1, S and G2/M phase. These findings provide information on the grade of malignancy and the possibility of recurrence of the tumor.

Clinical Trials
Multiinstitutional clinical study is being conducted to investigate the efficacy of maintenance chemotherapy with ACNU for malignant gliomas. Patients are randomly allocated into two groups after postoperative radiotherapy. Treatment group receives ACNU every two months and control group does not. The survival rates and the time to tumor progression are compared between the two groups.
Another multiinstitutional phase II study is ongoing in order to establish a postsurgical combined chemotherapy and radiation therapy for patients with primary germ cell tumors of the brain. After surgical debulking of the tumor, patients receive chemotherapy such as carboplatin-etoposide or ifosfamide-cisplatin-etoposide prior to radiotherapy. This treatment protocol is considered to be effective to germ cell tumors and better quality of life of the patients is expected by reduction of total dose of irradiation. On the other hand, long-term follow up study is carried out to investigate the intellectual activities of patients with brain tumor who received radiotherapy in childhood.

S. SHIBUI

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