HIGH-ENERGY (42-66 MEV REACTIONS) FAST-NEUTRON DOSE OPTIMIZATION STUDIES IN THE HEAD AND NECK, THORAX, UPPER ABDOMEN, PELVIS AND EXTREMITIES

Five hundred and fifty patients were entered into a set of dose-searching studies designed to determine normal tissue tolerances to high energy (42-66 MeV reactions) fast neutrons delivered in 12 equal fractions over 4 weeks. Participating institutions included: The Fermilab (66 MeV (p) + --> Be), The University of Washington (50 MeV (p) + --> Be), U.C.L.A. (45 MeV (H) - --> Be), M.D. Anderson Hospital (42 MeV (H) - --> Be), and The Cleveland Clinic (42 MeV (p) + --> Be). Patients were stratified by treatment facility and then randomized to receive 16, 18 or 20 Gy for tumors located in the upper abdomen or pelvis, and 18, 20 or 22 Gy for tumors located in the head and neck, thorax or extremities. Following completion of the randomized protocols, additional patients were studied at the 20.4 Gy level in the head and neck, thorax and pelvis. Normal tissue effect scoring was accomplished using the RTOG-EORTC acute and late normal tissue effect scales. Acute Grade 3 + toxicity rates in the head and neck were 19% for 20/20.4 Gy and 20% for 22 Gy. Time adjusted late toxicity rates in the head and neck at 12 months were 15% for 20/20.4 Gy and 0% for 22 Gy. The 18 Gy treatment arm of the head and neck protocol was dropped early in the study after only two patients were accrued. For cases treated in the thorax, acute Grade 3 + toxicity rates were 6% for 18 Gy, 15% for 20/20.4 Gy and 7% for 22 Gy. Late toxicity rates at 12 months were 0% for 18 Gy, 11% for 20/20.4 Gy and 18% for 22 Gy. Acute Grade 3 + toxicity rates in the upper abdomen were 0% for 16 Gy, 8% for 18 Gy and 12% for 20 Gy. There were no Grade 3 + late toxicities in the upper abdomen. In the pelvis, acute Grade 3 + toxicity rates were 0% for 16 Gy, 3% for 18 Gy and 3% for 20/20.4 Gy. Late Grade 3 + toxicities at 24 months were 20% for 16 Gy, 5% for 18 Gy and 24% for 20/20.4 Gy. In extremities, acute Grade 3 + toxicity rates were 7% for 20 Gy and 21% for 22 Gy while at 12 months, late Grade 3 + toxicity rates were 14 and 35%, respectively. The 18 Gy treatment arm of the extremities protocol was dropped early in the study after only two patients were accrued. Factors associated with normal tissue effects in addition to treatment dose are discussed.