A PHASE-I TRIAL OF NEUTRON BRACHYTHERAPY FOR THE TREATMENT OF MALIGNANT GLIOMAS

We performed a phase I trial to test the feasibility of neutron brachy therapy using californium-252 (Cf-252) as the sole source of radiation , and to determine the maximum tolerable dose (MTD), for the treatment of malignant gliomas. Previous studies using external beam neutron ra diation have shown that neutrons are capable of totally eradicating ma lignant gliomas. However, in most cases, fatal widespread radiation ne crosis resulted. Radioactive implants are a logical method of increasi ng the dose to the tumour and decreasing the dose to normal brain. Cf- 252 is a relatively stable neutron-emitting isotope suitable for impla nt therapy. The study was an open ended dose-escalation study. All rad iation was delivered by using only Cf-252 implants, without external b eam therapy of any type. The first dose step was 900 neutron cGy(ncGy) ; each subsequent step was increased by 100 ncGy. Three patients with newly diagnosed malignant gliomas were entered at each dose step, and the number was increased to six patients in dose steps at which necros is of brain occurred. The study ended when two patients at any dose st ep developed radiation necrosis of brain outside the prescribed radiat ion field. 33 patients were entered into the study. 10 patients develo ped scalp necrosis associated with scalp doses above 900 ncGy. The stu dy ended when two patients at the 1300 ncGy dose step developed radiat ion necrosis of brain. We conclude: (1) neutron brachytherapy using Cf -252 as the sole source of radiation is a feasible treatment for malig nant gliomas; (2) the scalp tolerates less neutron radiation than the brain (3) the MTD (and the recommended dose for a phase II trial) of i nterstitial neutron brachytherapy is 1200 ncGy.