title: Comparison of different contouring definitions of the rectum as organ at risk (OAR) and dose-volume parameters predicting rectal inflammation in radiotherapy of prostate cancer: which definition to use?
abstract: OBJECTIVE
  The objective of this retrospective planning study was to find a contouring definition for the rectum as an organ at risk (OAR) in curative three-dimensional external beam radiotherapy (EBRT) for prostate cancer (PCa) with a predictive correlation between the dose-volume histogram (DVH) and rectal toxicity.
  
  
  METHODS
  In a pre-study, the planning CT scans of 23 patients with PCa receiving definitive EBRT were analyzed. The rectum was contoured according to 13 different definitions, and the dose distribution was correlated with the respective rectal volumes by generating DVH curves. Three definitions were identified to represent the most distinct differences in the shapes of the DVH curves: one anatomical definition recommended by the Radiation Therapy Oncology Group (RTOG) and two functional definitions based on the target volume. In the main study, the correlation between different relative DVH parameters derived from these three contouring definitions and the occurrence of rectal toxicity during and after EBRT was studied in two consecutive collectives. The first cohort consisted of 97 patients receiving primary curative EBRT and the second cohort consisted of 66 patients treated for biochemical recurrence after prostatectomy. Rectal toxicity was investigated by clinical investigation and scored according to the Common Terminology Criteria for Adverse Events. Candidate parameters were the volume of the rectum, mean dose, maximal dose, volume receiving at least 60 Gy (V60), area under the DVH curve up to 25 Gy and area under the DVH curve up to 75 Gy in dependence of each chosen rectum definition. Multivariable logistic regression considered other clinical factors such as pelvine lymphatics vs local target volume, diabetes, prior rectal surgery, anticoagulation or haemorrhoids too.
  
  
  RESULTS
  In Cohort 1 (primary EBRT), the mean rectal volumes for definitions "RTOG", planning target volume "(PTV)-based" and "PTV-linked" were 100 cm3[standard deviation (SD) 43 cm3], 60 cm3(SD 26 cm3) and 74 cm3(SD 31 cm3), respectively (p < 0.01; analysis of variance). The mean rectal doses according to these definitions were 35 Gy (SD 8 Gy), 48 Gy (SD 4 Gy) and 44 Gy (SD 5 Gy) (p < 0.01). In Cohort 2 (salvage EBRT), the mean rectal volumes were 114 cm3(SD 47 cm3), 64 cm3(SD 26 cm3) and 81 cm3(SD 30 cm3) (p < 0.01) and the mean doses received by the rectum were 36 Gy (SD 8 Gy), 49 Gy (SD 5 Gy) and 44 Gy (SD 5 Gy) (p < 0.01). Acute or subacute rectal inflammation occurred in 69 (71.9%) patients in Cohort 1 and in 43 (70.5%) in Cohort 2. We did not find a correlation between all investigated DVH parameters and rectal toxicity, irrespective of the investigated definition. By adding additional variables in multivariate analysis, the predictive ability was substantially improved. Still, there was essentially no difference in the probability of predicting rectal inflammation occurrence between the tested contouring definitions.
  
  
  CONCLUSIONS
  The RTOG anatomy-based recommendations are questionable in comparison with functional definitions, as they result in higher variances in several relative DVH parameters. Moreover, the anatomy-based definition is no better and no worse in the predictive value concerning clinical end points. Advances in knowledge: Functional definitions for the rectum as OAR are easier to apply, faster to contour, have smaller variances and do not offer less information than the anatomy-based RTOG definition.
authors.affiliation: 1 Zentrum für Strahlentherapie und Radioonkologie, Bremen, Germany.|2 Klinik für Strahlentherapie, Karl-Lennert Krebscentrum, Universität Kiel, Kiel, Germany.
authors.forename: Mirko
authors.initials: M
authors.lastname: Nitsche
authors.affiliation: 3 Abteilung Biometrie, Kompetenzzentrum für Klinische Studien, Universität Bremen, Bremen, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Brannath
authors.affiliation: 3 Abteilung Biometrie, Kompetenzzentrum für Klinische Studien, Universität Bremen, Bremen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Brückner
authors.affiliation: 1 Zentrum für Strahlentherapie und Radioonkologie, Bremen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Wagner
authors.affiliation: 4 Abteilung für Unfallchirurgie und Orthopädie, Bundeswehrkrankenhaus Westerstede, Westerstede, Germany.|5 Core Facility Quality Management and Health Technology Assessment in Transplantation, Integrated Research and Treatment Center Transplantation (IFB-Tx), Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kaltenborn
authors.affiliation: 1 Zentrum für Strahlentherapie und Radioonkologie, Bremen, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Temme
authors.affiliation: 1 Zentrum für Strahlentherapie und Radioonkologie, Bremen, Germany.|6 Strahlentherapie und Spezielle Onkologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hermann
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging / Q000209:etiology*; D008297:Male; D058958:Organs at Risk / Q000000981:diagnostic imaging*; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000000981:diagnostic imaging / Q000517:prevention & control*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects*; D012007:Rectum / Q000000981:diagnostic imaging / Q000528:radiation effects*; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed