A Prospective Phase I/II Study using Proton Beam Radiation to Deliver 82GyE to Men with Localized Prostate Cancer: Preliminary Results of ACR 0312

Reviewer: Nathan Jones DO
Abramson Cancer Center of the University of Pennsylvania
Last Modified: September 24, 2008

Presenter: Anthony Zietman
Presenter's Affiliation: Massachusetts General Hospital, Boston, MA
Type of Session: Scientific


  • Prospective randomized studies have shown dose escalation to be effective in prostate cancer
  • A previous study of dose escalation to 79.2 Gy utilized conformal photon therapy to 50.4 with a proton boost to the prostate
  • With prostate, as well as in other sites, dose escalation is typically associated with increased toxicity, increased conformality, or both
  • The purpose of this study is to assess the toxicity and efficacy of proton therapy alone to 82 GyE to the prostate

Materials and Methods

  • 85 men were enrolled in this single-arm trial from 2004-2006 at Massachusetts General Hospital and Loma Linda University Medical Center
  • Median age was 63 years
  • All patients had T1-T2 tumors with PSA < 15 ng/dL
  • Patients were excluded when they had prior pelvic radiation therapy, history of urethral strictures, or were taking coumadin
  • There was no exclusion based on Gleason grade
  • All patients were treated with opposed lateral proton fields using 2 GyE daily fractions
  • A passive scattering proton beam was utilized
  • Daily guidance was achieved with either ultrasound BAT or fiducials
  • Margins to PTV were 1 cm with 0.5 cm posteriorly for the first 50 Gy and then the GTV alone was treated for the final 32 Gy with no additional margin
  • Primary endpoint was late grade 3-4 GU/GI toxicity on the RTOG scale
  • Secondary endpoints were both PSA and local failure
  • A supplemental endpoint was added for those patients treated at MGH as patients were given a validated questionnaire to report symptoms prior to radiation and 12 months following completion of treatment


  • Median follow-up is 23 months
  • Acute grade 2+ toxicity rates were 1% and 14% for GI and GU respectively
  • Acute grade 3+ toxicity rates were 0% and 1% for GI and GU respectively
  • Late grade 2+ toxicity rates were 12% and 30% for GI and GU respectively
  • Late grade 3+ toxicity rates were 1% and 8% for GI and GU respectively
  • There were 2 grade 4 late toxicities, both in one single patient who experienced both hematuria and rectal ulceration
    • This patient was noted to have a very large prostate
  • Among the 35 men who completed the quality of life questionnaire, a significant increase in obstruction/irritation and sexual dysfunction were noted at 12 months
    • There were no significant changes in incontinence or bowel complaints

Author's Conclusions

  • 82 GyE can be delivered using protons with acceptable morbidity at 2 years
  • Morbidity from protons is similar to that from conformal photon therapy
  • The author provided equipoise in stating that protons may be better, the same, or worse than photon therapy
  • Randomized comparison between proton and photon radiation therapy is warranted in prostate cancer to establish a direct comparison

Clinical/Scientific Implications


  • The optimal dose for prostate radiation therapy is not currently known
  • The tolerability of treatment appears to be related to both the technique of administration and the target dose
  • These data suggest acceptable toxicity with 82 GyE using opposed lateral fields and passively scattered proton beams
  • Care must be used in extrapolating these results into the general practice
    • Margins used in this study were smaller for the final 32 Gy than in prior studies
    • Small variations in pelvic positioning has the potential to significantly alter the dose distribution of a proton beam due to the differential of attenuation through bone
  • Long-term efficacy should be established, ideally through randomized data, prior to routine use of proton therapy for dose escalation in excess of 79.2 Gy