Improving the therapeutic ratio of radiation in locally advanced prostate cancer: Mixed neutron/photon vs. hyperfractionated photon irradiation

In an attempt to improve the probability of complication-free local control, a series of dose finding studies have been conducted at Wayne State University using either conformal neutron or hyperfractionated photon irradiation. In total, 96 patients with locally advanced prostate cancer (Stage T3/T4, N0/N1, M0, and/or Gleason score ≥8) were treated on two prospective dose-finding studies. Forty-seven patients received conformal neutron/photon irradiation (15NeutronGray + 18Gy). Forty-nine patients were treated on a dose escalation study using hyperfractionated conformal photon irradiation. Twenty-five patients received 78Gy and 24 patients received 83Gy. The median follow-up for both studies was 27 months (range 14–46). There was no significant difference in the rate of chronic gastrointestinal or genitourinary morbidity between the two groups. However, the neutron treated patients had a significantly higher rate of moderate (30%) and severe (12%) pelvic muscle fibrosis. The biochemical complete response rate and 12 month negative biopsy were comparable between the two groups. An estimated RBE for rectal and bladder injury of 3.3 was calculated. The RBE for tumor control was 3.9. Therefore, the therapeutic gain of neutron irradiation was estimated to be 1.2. In conclusion, a 2GY/fraction equivalent dose of 78Gy in conjunction with neoadjuvant hormones appears comparable to the mixed neutron-photon dose of 15NGy + 18Gy. Further efforts at comparing these regimens and assessing the potential benefits of neoadjuvant hormonal therapy should be undertaken. Radiat Oncol Invest 1996;4:129–134. © 1996 Wiley-Liss, Inc.