title: Clinical trials of neutron radiotherapy in the United States.
abstract: The development of clinical neutron facilities in the 1980s, capable of delivering high energy neutrons spurred full scale phase III testing of neutron beam radiotherapy in a number of tumors including salivary gland, head and neck, prostate, and non small-cell lung cancer. The Radiation Therapy Oncology Group (RTOG) and the Medical Research Council (MRC) jointly sponsored a randomized trial for the treatment of advanced stage salivary gland tumors comparing neutron to conventional photon and/or electron radiotherapy. Although no improvement in survival was seen, the study demonstrated a striking and statistically significant difference in the local-regional control of unresectable salivary gland tumors (56 vs 17%), favoring neutron beam irradiation. Subsequent clinical trials of neutron beam irradiation were initiated by the Neutron Therapy Collaborative Working Group (NTCWG) sponsored by the National Cancer Institute (NCI). A phase III trial comparing neutron to photon radiotherapy for inoperable regional non-small cell lung cancer showed no overall improvement in survival. However, a statistically significant improvement in survival was observed in the subset of patients with squamous cell histology. The NTCWG trial comparing fast-neutron therapy versus conventional photon irradiation in the treatment of advanced squamous cell carcinomas of the head and neck showed a statistically significant improvement in initial complete response (70 vs 52%) favoring neutrons. However, subsequent failures erased any difference in ultimate local-regional control rates and survival curves were essentially the same in both arms. The randomized study of the NTCWG for locally advanced prostate cancer demonstrated a significant decrease in local-regional failure (11 vs 32%) at 5 years, favoring the neutron arm. Furthermore, biochemical measures of disease control also favored the neutron arm with prostate specific antigen (PSA) levels elevated in 17% of the neutron-treated patients compared to 45% of the photon-treated patients at 5 years. At the 5-year analysis, no significant difference in survival was observed between the two arms; however, longer follow-up is necessary to assess the ultimate impact of improved local-regional control on survival. An analysis of complications in this series revealed the importance of beam shaping and treatment planning capabilities in maintaining long-term sequelae following neutron irradiation at an acceptably low level.
authors.affiliation: Department of Radiation Oncology, University of Washington Medical Center, Seattle 98195, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Lindsley
authors.forename: P
authors.initials: P
authors.lastname: Cho
authors.forename: K J
authors.initials: KJ
authors.lastname: Stelzer
authors.forename: W J
authors.initials: WJ
authors.lastname: Koh
authors.forename: M
authors.initials: M
authors.lastname: Austin-Seymour
authors.forename: K J
authors.initials: KJ
authors.lastname: Russell
authors.forename: G E
authors.initials: GE
authors.lastname: Laramore
authors.forename: T W
authors.initials: TW
authors.lastname: Griffin
mesh_terms: D000206:Actuarial Analysis; D005214:Fast Neutrons; D005260:Female; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D009367:Neoplasm Staging; D009369:Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D017785:Photons; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D011879:Radiotherapy Dosage; D011882:Radiotherapy, High-Energy / Q000379:methods*