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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
Ultima Vez Modificado: 24 de septiembre del 2008

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

Background

• 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

Results

• 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