title: Efficacy of high dose per fraction radiation for implanted human prostate cancer in a nude mouse model.
abstract: OBJECTIVE
  SBRT is a new therapeutic paradigm using large dose per fraction treatments (aggressive hypofractionation). While SBRT has shown efficacy for treating patients with lung, liver and spine tumors, to our knowledge there have been no preclinical studies evaluating the efficacy of this treatment for prostate cancer. We investigated the dose-response characteristics of SBRT for treating human prostate cancer in a nude mouse model.
  
  
  METHODS
  Nude mice were injected subcutaneously into the right flank with C4-2 prostate cancer cells grown in culture. A dose escalation trial was performed to assess toxicity and response. Tumor bearing animals were radiated with 3 fractions (1 per week) for a total dose of 15 Gy in 11, 22.5 Gy in 9 and 45 Gy in 10, while 8 untreated animals served as controls. The mice were weighed, and tumor volume and PSA measurements were performed at baseline and weekly until 4 weeks after treatment.
  
  
  RESULTS
  There was no treatment related toxicity. There was a significant difference in the tumor response to higher radiation doses. In the 15 and 22.5 Gy groups mean tumor volume decreased to 58% and 90% of the original volume, respectively, but the rats experienced progressive tumor regrowth within 1 week after the completion of therapy. The 45 Gy group had a mean tumor volume and PSA decrease of greater than 90%, which was sustained 1 month after treatment in all except 2 mice.
  
  
  CONCLUSIONS
  SBRT dose level treatments were able to significantly decrease tumor volume and PSA. However, using 15 and 22.5 Gy durable responses were not achieved except in a few mice. The 45 Gy group demonstrated sustained PSA and tumor volume decreases in most mice. These results clearly show an increasing dose-response relationship for a range of hypofractionated dose levels, as used in SBRT.
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9110, USA.
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.forename: Jennifer
authors.initials: J
authors.lastname: Stanfield
authors.forename: L Chinsoo
authors.initials: LC
authors.lastname: Cho
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Sherwood
authors.forename: Khaled F
authors.initials: KF
authors.lastname: Abdel-Aziz
authors.forename: Cheng-Hui
authors.initials: CH
authors.lastname: Chang
authors.forename: Kenneth
authors.initials: K
authors.lastname: Forster
authors.forename: Wareef
authors.initials: W
authors.lastname: Kabbani
authors.forename: Jer-Tsong
authors.initials: JT
authors.lastname: Hsieh
authors.forename: Hak
authors.initials: H
authors.lastname: Choy
authors.forename: Robert
authors.initials: R
authors.lastname: Timmerman
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019583:Dose Fractionation, Radiation; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000532:radiotherapy*