title: Stereotactic hypofractionated accurate radiotherapy of the prostate (SHARP), 33.5 Gy in five fractions for localized disease: first clinical trial results.
abstract: OBJECTIVE
  To evaluate the feasibility and toxicity of stereotactic hypofractionated accurate radiotherapy (SHARP) for localized prostate cancer.
  
  
  METHODS
  A Phase I/II trial of SHARP performed for localized prostate cancer using 33.5 Gy in 5 fractions, calculated to be biologically equivalent to 78 Gy in 2 Gy fractions (alpha/beta ratio of 1.5 Gy). Noncoplanar conformal fields and daily stereotactic localization of implanted fiducials were used for treatment. Genitourinary (GU) and gastrointestinal (GI) toxicity were evaluated by American Urologic Association (AUA) score and Common Toxicity Criteria (CTC). Prostate-specific antigen (PSA) values and self-reported sexual function were recorded at specified follow-up intervals.
  
  
  RESULTS
  The study includes 40 patients. The median follow-up is 41 months (range, 21-60 months). Acute toxicity Grade 1-2 was 48.5% (GU) and 39% (GI); 1 acute Grade 3 GU toxicity. Late Grade 1-2 toxicity was 45% (GU) and 37% (GI). No late Grade 3 or higher toxicity was reported. Twenty-six patients reported potency before therapy; 6 (23%) have developed impotence. Median time to PSA nadir was 18 months with the majority of nadirs less than 1.0 ng/mL. The actuarial 48-month biochemical freedom from relapse is 70% for the American Society for Therapeutic Radiology and Oncology definition and 90% by the alternative nadir + 2 ng/mL failure definition.
  
  
  CONCLUSIONS
  SHARP for localized prostate cancer is feasible with minimal acute or late toxicity. Dose escalation should be possible.
authors.affiliation: Section of Radiation Oncology, Virginia Mason Medical Center, Seattle, WA 98101, USA. ronblm@vmmc.org
authors.forename: Berit L
authors.initials: BL
authors.lastname: Madsen
authors.forename: R Alex
authors.initials: RA
authors.lastname: Hsi
authors.forename: Huong T
authors.initials: HT
authors.lastname: Pham
authors.forename: Jack F
authors.initials: JF
authors.lastname: Fowler
authors.forename: Laura
authors.initials: L
authors.lastname: Esagui
authors.forename: John
authors.initials: J
authors.lastname: Corman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D019583:Dose Fractionation, Radiation; D005240:Feasibility Studies; D006471:Gastrointestinal Hemorrhage / Q000209:etiology; D041981:Gastrointestinal Tract / Q000528:radiation effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011467:Prostate; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D019736:Prostheses and Implants; D020266:Radiotherapy, Conformal; D012007:Rectum; D013238:Stereotaxic Techniques; D014566:Urogenital System / Q000528:radiation effects
chemical_list: D017430:Prostate-Specific Antigen