title: Predictors of rectal tolerance observed in a dose-escalated phase 1-2 trial of stereotactic body radiation therapy for prostate cancer.
abstract: OBJECTIVE
  To convey the occurrence of isolated cases of severe rectal toxicity at the highest dose level tested in 5-fraction stereotactic body radiation therapy (SBRT) for localized prostate cancer; and to rationally test potential causal mechanisms to guide future studies and experiments to aid in mitigating or altogether avoiding such severe bowel injury.
  
  
  METHODS
  Clinical and treatment planning data were analyzed from 91 patients enrolled from 2006 to 2011 on a dose-escalation (45, 47.5, and 50 Gy in 5 fractions) phase 1/2 clinical study of SBRT for localized prostate cancer.
  
  
  RESULTS
  At the highest dose level, 6.6% of patients treated (6 of 91) developed high-grade rectal toxicity, 5 of whom required colostomy. Grade 3+ delayed rectal toxicity was strongly correlated with volume of rectal wall receiving 50 Gy >3 cm(3) (P<.0001), and treatment of >35% circumference of rectal wall to 39 Gy (P=.003). Grade 2+ acute rectal toxicity was significantly correlated with treatment of >50% circumference of rectal wall to 24 Gy (P=.010).
  
  
  CONCLUSIONS
  Caution is advised when considering high-dose SBRT for treatment of tumors near bowel structures, including prostate cancer. Threshold dose constraints developed from physiologic principles are defined, and if respected can minimize risk of severe rectal toxicity.
authors.affiliation: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: D W Nathan
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, University of Minnesota, Minneapolis, Minnesota.
authors.forename: L Chinsoo
authors.initials: LC
authors.lastname: Cho
authors.affiliation: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Christopher
authors.initials: C
authors.lastname: Straka
authors.affiliation: Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Alana
authors.initials: A
authors.lastname: Christie
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.affiliation: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: David
authors.initials: D
authors.lastname: Pistenmaa
authors.affiliation: Department of Radiation Oncology, University of Colorado, Denver, Colorado.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Kavanagh
authors.affiliation: Department of Radiation Oncology, University of Florida Health Cancer Center at Orlando Health, Orlando, Florida.
authors.forename: Akash
authors.initials: A
authors.lastname: Nanda
authors.affiliation: Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, California.
authors.forename: Patrick
authors.initials: P
authors.lastname: Kueplian
authors.affiliation: Prairie Lakes Hospital, Watertown, South Dakota.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Brindle
authors.affiliation: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Susan
authors.initials: S
authors.lastname: Cooley
authors.affiliation: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Alida
authors.initials: A
authors.lastname: Perkins
authors.affiliation: Department of Radiation Oncology, University of Colorado, Denver, Colorado.
authors.forename: David
authors.initials: D
authors.lastname: Raben
authors.affiliation: Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Xian-Jin
authors.initials: XJ
authors.lastname: Xie
authors.affiliation: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address: robert.timmerman@utsouthwestern.edu.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Timmerman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D058958:Organs at Risk / Q000528:radiation effects*; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000209:etiology* / Q000517:prevention & control; D011836:Radiation Tolerance; D016634:Radiosurgery / Q000009:adverse effects* / Q000379:methods; D011879:Radiotherapy Dosage; D012007:Rectum / Q000528:radiation effects*; D047368:Tumor Burden