title: Age and comorbid illness are associated with late rectal toxicity following dose-escalated radiation therapy for prostate cancer.
abstract: OBJECTIVE
  To assess the impacts of patient age and comorbid illness on rectal toxicity following external beam radiation therapy (EBRT) for prostate cancer and to assess the Qualitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) normal tissue complication probability (NTCP) model in this context.
  
  
  METHODS
  Rectal toxicity was analyzed in 718 men previously treated for prostate cancer with EBRT (≥75 Gy). Comorbid illness was scored using the Charlson Comorbidity Index (CCMI), and the NTCP was evaluated with the QUANTEC model. The influence of clinical and treatment-related parameters on rectal toxicity was assessed by Kaplan-Meier and Cox proportional hazards models.
  
  
  RESULTS
  The cumulative incidence of rectal toxicity grade ≥2 was 9.5% and 11.6% at 3 and 5 years and 3.3% and 3.9% at 3 and 5 years for grade ≥3 toxicity, respectively. Each year of age predicted an increasing relative risk of grade ≥2 (P<.03; hazard ratio [HR], 1.04 [95% confidence interval {CI}, 1.01-1.06]) and ≥3 rectal toxicity (P<.0001; HR, 1.14 [95% CI,1.07-1.22]). Increasing CCMI predicted rectal toxicity where a history of either myocardial infarction (MI) (P<.0001; HR, 5.1 [95% CI, 1.9-13.7]) or congestive heart failure (CHF) (P<.0006; HR, 5.4 [95% CI, 0.6-47.5]) predicted grade ≥3 rectal toxicity, with lesser correlation with grade ≥2 toxicity (P<.02 for MI, and P<.09 for CHF). An age comorbidity model to predict rectal toxicity was developed and confirmed in a validation cohort. The use of anticoagulants increased toxicity independent of age and comorbidity. NTCP was prognostic for grade ≥3 (P=.015) but not grade ≥2 (P=.49) toxicity. On multivariate analysis, age, MI, CHF, and an NTCP >20% all correlated with late rectal toxicity.
  
  
  CONCLUSIONS
  Patient age and a history of MI or CHF significantly impact rectal toxicity following EBRT for the treatment of prostate cancer, even after controlling for NTCP.
authors.affiliation: Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Hamstra
authors.forename: Matt H
authors.initials: MH
authors.lastname: Stenmark
authors.forename: Tim
authors.initials: T
authors.lastname: Ritter
authors.forename: Dale
authors.initials: D
authors.lastname: Litzenberg
authors.forename: William
authors.initials: W
authors.lastname: Jackson
authors.forename: Skyler
authors.initials: S
authors.lastname: Johnson
authors.forename: Liesel
authors.initials: L
authors.lastname: Albrecht-Unger
authors.forename: Alex
authors.initials: A
authors.lastname: Donaghy
authors.forename: Laura
authors.initials: L
authors.lastname: Phelps
authors.forename: Kevin
authors.initials: K
authors.lastname: Blas
authors.forename: Schuyler
authors.initials: S
authors.lastname: Halverson
authors.forename: Robin
authors.initials: R
authors.lastname: Marsh
authors.forename: Karin
authors.initials: K
authors.lastname: Olson
authors.forename: Felix Y
authors.initials: FY
authors.lastname: Feng
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D015897:Comorbidity; D006333:Heart Failure / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000453:epidemiology; D058958:Organs at Risk / Q000528:radiation effects*; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000453:epidemiology* / Q000473:pathology; D011879:Radiotherapy Dosage; D061089:Radiotherapy, Image-Guided; D050397:Radiotherapy, Intensity-Modulated; D012007:Rectum / Q000528:radiation effects*; D013997:Time Factors
chemical_list: D000925:Anticoagulants