Normal tissue reactions and complications following high-energy neutron beam therapy: I. Crude response rates.

The incidence of significant complications (fibrosis, ulceration, necrosis of bone or soft tissue or serious functional impairment) was determined in relation to neutron dosage and follow-up time for 5 anatomical sites totalling 617 patients who had survived 2 or more years following treatment. The regions studied were head and neck (268 patients), thorax (lung and esophagus, 76 patients), upper abdomen (132 patients), pelvis (prostate and bladder, 114 patients) and extremities (27 patients). Neutron doses ranged from 16 to 28 Gy. All patients were followed until death or up to 10 years after treatment. A total of 109 complications were observed yielding a crude complication rate of 18% for the whole series. Observed complication rates were 7% in the 16-20 Gy dose range, 19% between 20 and 24 Gy, and 33% in patients receiving more than 24 Gy. Probit analysis of the data indicated a median effective dose (50% complications) of 29 (+/- 0.5) Gy with an estimated standard deviation of 8 Gy. A reasonable estimate of "tolerance" may then be taken as 29 - 8 = 21 Gy. Comparing the 5 anatomical sites revealed no significant differences in estimated tolerance doses. With the available data, no effect of field-size or target volume could be demonstrated. The incidence of complications apparently increases with time in long-term survivors. Although the overall incidence is only 18%, actuarial analysis of the data suggests that the complication rate might have exceeded 50% if all treated patients had survived 10 years. It is concluded that, with the exception of the nervous system and possibly other viscera, a neutron dose of 20 Gy (in 12 fractions over 4 weeks) represents a practical tolerance limit for all sites.