title: Role of principal component analysis in predicting toxicity in prostate cancer patients treated with hypofractionated intensity-modulated radiation therapy.
abstract: OBJECTIVE
  To determine if principal component analysis (PCA) and standard parameters of rectal and bladder wall dose-volume histograms (DVHs) of prostate cancer patients treated with hypofractionated image-guided intensity-modulated radiotherapy (hypo-IMRT) can predict acute and late gastrointestinal (GI) toxicity.
  
  
  METHODS
  One hundred twenty-one patients underwent hypo-IMRT at 3 Gy/fraction, 5 days/week to either 60 Gy or 66 Gy, with daily online image guidance. Acute and late GI and genitourinary (GU) toxicity were recorded weekly during treatment and at each follow-up. All Radiation Therapy Oncology Group (RTOG) criteria toxicity scores were dichotomized as <2 and ≥2. Standard dosimetric parameters and the first five to six principal components (PCs) of bladder and rectal wall DVHs were tested for association with the dichotomized toxicity outcomes, using logistic regression.
  
  
  RESULTS
  Median follow-up of all patients was 47 months (60 Gy cohort = 52 months; 66 Gy cohort = 31 months). The incidence rates of ≥2 acute GI and GU toxicity were 14% and 29%, respectively, with no Grade ≥3 acute GU toxicity. Late GI and GU toxicity scores ≥2 were 16% and 15%, respectively. There was a significant difference in late GI toxicity ≥2 when comparing the 66 Gy to the 60 Gy cohort (38% vs. 8%, respectively, p = 0.0003). The first PC of the rectal DVH was associated with late GI toxicity (odds ratio [OR], 6.91; p < 0.001), though it was not significantly stronger than standard DVH parameters such as Dmax (OR, 6.9; p < 0.001) or percentage of the organ receiving a 50% dose (V50) (OR, 5.95; p = 0 .001).
  
  
  CONCLUSIONS
  Hypofractionated treatment with 60 Gy in 3 Gy fractions is well tolerated. There is a steep dose response curve between 60 Gy and 66 Gy for RTOG Grade ≥2 GI effects with the dose constraints employed. Although PCA can predict late GI toxicity for patients treated with hypo-IMRT for prostate cancer, it provides no additional information over using more standard DVH parameters.
authors.affiliation: Department of Radiation Oncology, Sunnybrook Odette Cancer Center, Toronto, Ontario, Canada.
authors.forename: Danny
authors.initials: D
authors.lastname: Vesprini
authors.forename: Michael
authors.initials: M
authors.lastname: Sia
authors.forename: Gina
authors.initials: G
authors.lastname: Lockwood
authors.forename: Douglas
authors.initials: D
authors.lastname: Moseley
authors.forename: Tara
authors.initials: T
authors.lastname: Rosewall
authors.forename: Andrew
authors.initials: A
authors.lastname: Bayley
authors.forename: Robert
authors.initials: R
authors.lastname: Bristow
authors.forename: Peter
authors.initials: P
authors.lastname: Chung
authors.forename: Cynthia
authors.initials: C
authors.lastname: Ménard
authors.forename: Michael
authors.initials: M
authors.lastname: Milosevic
authors.forename: Padraig
authors.initials: P
authors.lastname: Warde
authors.forename: Charles
authors.initials: C
authors.lastname: Catton
mesh_terms: D000368:Aged; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D041981:Gastrointestinal Tract / Q000528:radiation effects; D006801:Humans; D015994:Incidence; D008297:Male; D058958:Organs at Risk / Q000528:radiation effects*; D025341:Principal Component Analysis; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000453:epidemiology / Q000209:etiology*; D061089:Radiotherapy, Image-Guided / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects* / Q000379:methods; D012007:Rectum / Q000528:radiation effects*; D001743:Urinary Bladder / Q000528:radiation effects*; D014566:Urogenital System / Q000528:radiation effects