Review of clinical results of fast neutron therapy in the USA.

Fast neutron radiotherapy in the United States is entering a new era in which dedicated hospital-based generators with isocentric beam capability are replacing treatment facilities based on fixed beams extracted from physics accelerators. All available clinical data, however, come from the older facilities. The majority of randomized trials conducted in the U.S. have used neutrons in a mixed schedule with photons, in which the aim was to deliver two-fifths of the total dose with neutrons; the neutron dose per fraction was set as the estimated equivalent of 2 Gy photons in terms of late normal tissue injury. Overall treatment time was held constant compared with the control photon therapy regimens (usually six to eight weeks). Random studies of this type showed no evidence of a therapeutic gain in the treatment of advanced primary carcinomas of the head and neck, lung, uterine cervix, or pancreas. A statistically significant benefit in favor of the mixed schedule is presently apparent for local control and survival in patients with advanced prostate cancer, and for clearance of neck nodes in patients with advanced squamous carcinoma of the head and neck. Based on encouraging results in a pilot study of mixed scheduled irradiation preoperatively for bladder cancer, a random study was begun in 1981, but too few cases have been accrued for analysis. Other randomized trials comparing protracted neutron only regimens with photon therapy have been conducted. These were negative for lung and pancreatic cancer, but a suggestion of a therapeutic gain (with small patient numbers) has been observed for treatment of inoperable salivary gland tumors and advanced squamous carcinomas of the head and neck. Two large randomized studies of various neutron doses delivered as a boost to high grade astrocytomas after or concurrently with photon irradiation have failed to define any therapeutic window between tumor destruction and brain necrosis. Based on a reassessment of all the available clinical and radiobiological data, and taking advantage of the greater technical flexibility offered by hospital-based facilities, the strategy of fast neutron therapy for future trials has been changed. In these trials neutrons are being used in a twelve fraction, four week regimen to treat gross disease, with elective therapy being given wherever possible using low LET irradiation. Concomitantly, research is proceeding to define predictors of tumor response to high LET radiations in order to better select patients for fast neutron radiotherapy.