title: Patient Specific Characteristics Are an Important Factor That Determines the Risk of Acute Grade ≥ 2 Rectal Toxicity in Patients Treated for Prostate Cancer with IMRT and Daily Image Guidance Based on Implanted Gold Markers.
abstract: OBJECTIVE
  To model acute rectal toxicity in Intensity Modulated Radiation Therapy (IMRT) for prostate cancer using dosimetry and patient specific characteristics.
  
  
  METHODS
  A database of 79 prostate cancer patients treated with image guided IMRT was used to fit parameters of Lyman-Kutcher-Burman (LKB) and logistic regression Normal Tissue Complications Probability (NTCP) models to acute grade ≥ 2 rectal toxicities. We used a univariate regression model to find the dosimetric index which was most correlated with toxicity and a multivariate logistic regression model with machine learning algorithm to integrate dosimetry with patient specific characteristics. We used Receiver Operating Characteristics (ROC) analysis and the area under the ROC curve (AUC) to quantify the predictive power of models.
  
  
  RESULTS
  Sixteen patients (20.3%) developed acute grade≥2 rectal toxicity. Our best estimate (95% confidence interval) of LKB model parameters for acute rectal toxicity are exponent n=0.13 (0.1-0.16), slope m=0.09 (0.08-0.11), and threshold dose TD50=56.8 (53.7-59.9) Gy. The best dosimetric indices in the univariate logistic regression NTCP model were D25% and V50Gy. The best AUC of dosimetry only modeling was 0.67 (0.54, 0.8). In the multivariate logistic regression two patient specific variables were particularly strongly correlated with acute rectal toxicity, the use of statin drugs and PSA level prior to IMRT, while two additional variables, age and diabetes were weakly correlated. The AUC of the logistic regression NTCP model improved to 0.88 (0.8, 0.96) when patient specific characteristics were included. In a group of 79 patients, 40 took Statins and 39 did not. Among patients who took statins, (4/40)=10% developed acute grade ≥2 rectal toxicity, compared to (12/39)=30.8% who did not take statins (p=0.03). The average and standard deviation of PSA distribution for patients with acute rectal toxicity wasPSAtox= 5.77 ± 2.27 and it wasPSAnotox= 9.5 ± 7.8 for the remainder (p=0.01).
  
  
  CONCLUSIONS
  Patient specific characteristics strongly influence the likelihood of acute grade ≥ 2 rectal toxicity in radiation therapy for prostate cancer.
authors.affiliation: School of Computing, Informatics, Decision Systems Engineering, Arizona State University, Tempe Arizona, USA.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Liu
authors.affiliation: School of Computing, Informatics, Decision Systems Engineering, Arizona State University, Tempe Arizona, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Computing, Informatics, Decision Systems Engineering, Arizona State University, Tempe Arizona, USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Radiation Oncology, Mayo Clinic Arizona, Phoenix Arizona, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Schild
authors.affiliation: Department of Radiation Oncology, Mayo Clinic Arizona, Phoenix Arizona, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Schild
authors.affiliation: Department of Radiation Oncology, Mayo Clinic Arizona, Phoenix Arizona, USA.
authors.forename: William
authors.initials: W
authors.lastname: Wong
authors.affiliation: Department of Radiation Oncology, Mayo Clinic Arizona, Phoenix Arizona, USA.
authors.forename: Sujay
authors.initials: S
authors.lastname: Vora
authors.affiliation: Department of Radiation Oncology, Mayo Clinic Arizona, Phoenix Arizona, USA.
authors.forename: Mirek
authors.initials: M
authors.lastname: Fatyga
keywords: Acute rectal toxicity; IMRT; LASSO; Logistic regression; PSA; Prostate cancer; Radiation therapy; Statins; Toxicity modeling