title: Rectal toxicity after proton therapy for prostate cancer: an analysis of outcomes of prospective studies conducted at the university of Florida Proton Therapy Institute.
abstract: OBJECTIVE
  Study goals were to characterize gastrointestinal effects of proton therapy (PT) in a large cohort of patients treated for prostate cancer, identify factors associated with rectal bleeding (RB), and compare RB between patients receiving investigational protocols versus those in outcome-tracking protocols.
  
  
  METHODS
  A total of 1285 consecutive patients were treated with PT between August 2006 and May 2010. Potential pre-existing clinical and treatment-related risk factors for rectal toxicity were recorded. Common Terminology Criteria for Adverse Events version 3.0 was used to score toxicity.
  
  
  RESULTS
  Transient RB was the predominant grade 2 or higher (GR2+) toxicity after PT, accounting for 95% of gastrointestinal events. GR1 RB occurred in 217 patients (16.9%), GR2 RB in 187 patients (14.5%), and GR3 in 11 (0.9%) patients. There were no GR4 or GR5 events. Univariate analyses showed correlations between GR2+ RB and anticoagulation therapy (P=.008) and rectal and rectal wall dose-volume histogram (DVH) parameters (P<.001). On multivariate analysis, anticoagulation therapy (P=.0034), relative volume of rectum receiving 75 Gy (V75; P=.0102), and relative rectal wall V75 (P=.0017) were significant predictors for G2+ RB. Patients treated with investigational protocols had toxicity rates similar to those receiving outcome-tracking protocols.
  
  
  CONCLUSIONS
  PT was associated with a low rate of GR2+ gastrointestinal toxicity, predominantly transient RB, which was highly correlated with anticoagulation and rectal DVH parameters. Techniques that limit rectal exposure should be used when possible.
authors.affiliation: The University of Florida Proton Therapy Institute, Jacksonville, Florida.
authors.forename: Rovel J
authors.initials: RJ
authors.lastname: Colaco
authors.affiliation: The University of Florida Proton Therapy Institute, Jacksonville, Florida.
authors.forename: Bradford S
authors.initials: BS
authors.lastname: Hoppe
authors.affiliation: The University of Florida Proton Therapy Institute, Jacksonville, Florida.
authors.forename: Stella
authors.initials: S
authors.lastname: Flampouri
authors.affiliation: Baptist Health Medical Center, Department of Surgery, Jacksonville, Florida.
authors.forename: Brian T
authors.initials: BT
authors.lastname: McKibben
authors.affiliation: The University of Florida Proton Therapy Institute, Jacksonville, Florida.
authors.forename: Randal H
authors.initials: RH
authors.lastname: Henderson
authors.affiliation: The University of Florida Proton Therapy Institute, Jacksonville, Florida.
authors.forename: Curtis
authors.initials: C
authors.lastname: Bryant
authors.affiliation: The University of Florida Proton Therapy Institute, Jacksonville, Florida.
authors.forename: Romaine C
authors.initials: RC
authors.lastname: Nichols
authors.affiliation: The University of Florida Proton Therapy Institute, Jacksonville, Florida.
authors.forename: William M
authors.initials: WM
authors.lastname: Mendenhall
authors.affiliation: The University of Florida Proton Therapy Institute, Jacksonville, Florida.
authors.forename: Zuofeng
authors.initials: Z
authors.lastname: Li
authors.affiliation: The University of Florida Proton Therapy Institute, Jacksonville, Florida.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Su
authors.affiliation: Baptist Health Medical Center, Department of Surgery, Jacksonville, Florida.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Morris
authors.affiliation: The University of Florida Proton Therapy Institute, Jacksonville, Florida. Electronic address: menden@floridaproton.org.
authors.forename: Nancy P
authors.initials: NP
authors.lastname: Mendenhall
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000925:Anticoagulants / Q000009:adverse effects; D057918:Fiducial Markers; D005431:Florida; D006471:Gastrointestinal Hemorrhage / Q000209:etiology*; D041981:Gastrointestinal Tract / Q000528:radiation effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D061766:Proton Therapy / Q000009:adverse effects*; D011832:Radiation Injuries / Q000150:complications* / Q000473:pathology; D012002:Rectal Diseases / Q000209:etiology*; D012007:Rectum / Q000528:radiation effects*; D014495:Universities; D001743:Urinary Bladder
chemical_list: D000925:Anticoagulants