A Randomized Prospective Trial of Sequential Neutron - Photon vs. Photon-Neutron Irradiation in Organ Confined Prostate Cancer

Reviewer: Heather Jones, MD
Last Modified: October 7, 2002

Presenter: J. Forman
Presenter's Affiliation: Department of Radiation Oncology, Wayne State University, Detroit, MI, USA
Type of Session: Scientific


    Fast neutrons have been examined as a potential modality to improve the results of therapy for organ confined prostate cancer. The biologic properties of neutrons differ from conventional photon energies, possessing advantages of high-linear-energy transfer. In vitro and in vivo experiments testing the effects of combining photon and neutron irradiation demonstrated that the mixed-beam treatments were more effective if the neutrons were given first. This study was performed to determine if the sequence of neutron and photon irradiation would affect the outcome of patients with organ confined prostate cancer.

Materials and Methods

  • A phase III prospective randomized trial at Wayne State University was carried out between June 1994 and October 1998; 300 patients were entered
  • This study compared sequential neutron/photon irradiation (10Gy neutrons +38-40Gy photons) with photon/neutron irradiation (38-40Gy + 10 Gy neutrons) in patients with Stage T1-2, Nx, No, Mo, Gleason Score <7 adenocarcinoma of the prostate.
  • One hundred and fifty patients were randomized to each arm.
  • There was no significant difference in age, race, stage, Gleason score, pre-radiation PSA levels, dose or the use of neo-adjuvant hormones between the two groups.


  • The patients had a median follow-up of 4 years (range 0.5 to 7.1 years).
  • The 5-year actuarial freedom from relapse rate for patients treated with neutrons first (Arm I) was 88%, vs 76% for patients treated with neutrons last (Arm II), (p=0.03).
  • Acute Grade 2 gastrointestinal toxicity (GI) (<3 months) in Arms I and II was in 24 and 25% of patients, respectively (p=0.84).
  • The rates of acute Grade 2 genitourinary (GU) toxicity were 30 and 36%, respectively (p=0.28).
  • The 5-year actuarial rate of Grade 2 or higher and Grade 3 chronic GU morbidity were 19 and 5% in Arm I and 28 and 8% in Arm II, (p=0.5).

Author's Conclusions

    For patients with localized prostate cancer, sequencing of photon/ neutron radiation did affect outcome. Neutron radiation delivered first resulted in a significant improvement in disease-free survival with no increase in acute or chronic morbidity compared to neutrons delivered last. These results have important implications for other sequenced treatments that combining treatments with different RBE's.

Clinical/Scientific Implications

    This is a very interesting study that sheds light on the sequencing of high RBE therapy with photons. We know that high-linear-energy transfer can lead to a number of biologic effects, including greater relative biologic effectiveness, reduced oxygen enhancement ratio, less sublethal and potentially lethal damage repair, and less cell cycle specificity than photons. This study moves biology into the clinic and demonstrates the clinical advantage of up front use of high LET therapy before the use of photon therapy.

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