Treatment planning and dosimetry for the Harvard-MIT Phase I clinical trial of cranial neutron capture therapy

Purpose : A Phase I trial of cranial neutron capture therapy (NCT) was conducted at Harvard-MIT. The trial was designed to determine maximum tolerated NCT radiation dose to normal brain. Methods and Materials : Twenty-two patients with brain tumors were treated by infusion of boronophenylalanine-fructose (BPA-f) followed by exposure to epithermal neutrons. The study began with a prescribed biologically weighted dose of 8.8 RBE (relative biologic effectiveness) Gy, escalated in compounding 10% increments, and ended at 14.2 RBE Gy. BPA-f was infused at a dose 250–350 mg/kg body weight. Treatments were planned using MacNCTPlan and MCNP 4B. Irradiations were delivered as one, two, or three fields in one or two fractions. Results : Peak biologically weighted normal tissue dose ranged from 8.7 to 16.4 RBE Gy. The average dose to brain ranged from 2.7 to 7.4 RBE Gy. Average tumor dose was estimated to range from 14.5 to 43.9 RBE Gy, with a mean of 25.7 RBE Gy. Conclusions : We have demonstrated that BPA-f-mediated NCT can be precisely planned and delivered in a carefully controlled manner. Subsequent clinical trials of boron neutron capture therapy at Harvard and MIT will be initiated with a new high-intensity, high-quality epithermal neutron beam.