title: Comparison and limitations of DVH-based NTCP models derived from 3D-CRT and IMRT data for prediction of gastrointestinal toxicities in prostate cancer patients by using propensity score matched pair analysis.
abstract: OBJECTIVE
  This study compared normal tissue complication probability (NTCP) modeling of chronic gastrointestinal toxicities following prostate cancer treatment for 2 treatment modalities. Possible factors causing discrepancies in optimal NTCP model parameters between 3-dimensional conformal radiation therapy (3D-CRT) and intensity modulated RT (IMRT) were analyzed and discussed, including the impact of patient characteristics, image guidance, toxicity scoring bias, and NTCP model limitations.
  
  
  METHODS
  Rectal wall dose-volume histograms of 1115 patients treated for prostate cancer under an adaptive radiation therapy protocol were used to model gastrointestinal toxicity grade ≥2 (according to Common Terminology Criteria for Adverse Events). A total of 457 patients were treated with 3D-CRT and 658 with IMRT. 3D-CRT patients were matched to IMRT patients based on various patient characteristics, using a propensity score-based algorithm. Parameters of the Lyman equivalent uniform dose and cut-off dose logistic regression NTCP models were estimated for the 2 matched treatment modalities and the combined group.
  
  
  RESULTS
  After they were matched, the 3D-CRT and IMRT groups contained 275 and 550 patients with a large discrepancy of 28.7% versus 7.8% toxicities, respectively (P<.001). For both NTCP models, optimal parameters found for the 3D-CRT groups did not fit the IMRT patients well and vice versa. Models developed for the combined data overestimated NTCP for the IMRT patients and underestimated NTCP for the 3D-CRT group.
  
  
  CONCLUSIONS
  Our analysis did not reveal a single definitive cause for discrepancies of model parameters between 3D-CRT and IMRT. Patient characteristics and bias in toxicity scoring, as well as image guidance alone, are unlikely causes of the large discrepancy of toxicities. Whether the cause was inherent to the specific NTCP models used in this study needs to be verified by future investigations. Because IMRT is increasingly used clinically, it is important that appropriate NTCP model parameters are determined for this treatment modality.
authors: Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan; Department of Radiotherapy and Radiation Oncology, Ludwig-Maximilians-Universität, Munich, Germany.
authors: Almut
authors: A
authors: Troeller
authors: Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan. Electronic address: dyan@beaumont.edu.
authors: Di
authors: D
authors: Yan
authors: Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan.
authors: Ovidiu
authors: O
authors: Marina
authors: Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan.
authors: Derek
authors: D
authors: Schulze
authors: Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors: Markus
authors: M
authors: Alber
authors: Department of Medical Physics, Ludwig-Maximilians-Universität, Munich, Germany.
authors: Katia
authors: K
authors: Parodi
authors: Department of Radiotherapy and Radiation Oncology, Ludwig-Maximilians-Universität, Munich, Germany.
authors: Claus
authors: C
authors: Belka
authors: Department of Radiotherapy and Radiation Oncology, Ludwig-Maximilians-Universität, Munich, Germany.
authors: Matthias
authors: M
authors: Söhn
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015984:Causality; D015897:Comorbidity; D003198:Computer Simulation; D005767:Gastrointestinal Diseases / Q000453:epidemiology* / Q000209:etiology; D005858:Germany / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D008954:Models, Biological; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000453:epidemiology* / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000453:epidemiology* / Q000209:etiology; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000706:statistics & numerical data*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016896:Treatment Outcome