title: Conformal irradiation of the prostate: estimating long-term rectal bleeding risk using dose-volume histograms.
abstract: OBJECTIVE
  Dose-volume histograms (DVHs) may be very useful tools for estimating probability of normal tissue complications (NTCP), but there is not yet an agreed upon method for their analysis. This study introduces a statistical method of aggregating and analyzing primary data from DVHs and associated outcomes. It explores the dose-volume relationship for NTCP of the rectum, using long-term data on rectal wall bleeding following prostatic irradiation.
  
  
  METHODS
  Previously published data were reviewed and updated on 41 patients with Stages T3 and T4 prostatic carcinoma treated with photons followed by perineal proton boost, including dose-volume histograms (DVHs) of each patient's anterior rectal wall and data on the occurrence of postirradiation rectal bleeding (minimum FU > 4 years). Logistic regression was used to test whether some individual combination of dose and volume irradiated might best separate the DVHs into categories of high or low risk for rectal bleeding. Further analysis explored whether a group of such dose-volume combinations might be superior in predicting complication risk. These results were compared with results of the "critical volume model," a mathematical model based on assumptions of underlying radiobiological interactions.
  
  
  RESULTS
  Ten of the 128 tested dose-volume combinations proved to be "statistically significant combinations" (SSCs) distinguishing between bleeders (14 out of 41) and nonbleeders (27 out of 41), ranging contiguously between 60 CGE (Cobalt Gray Equivalent) to 70% of the anterior rectal wall and 75 CGE to 30%. Calculated odds ratios for each SSC were not significantly different across the individual SSCs; however, analysis combining SSCs allowed segregation of DVHs into three risk groups: low, moderate, and high. Estimates of probabilities of normal tissue complications (NTCPs) based on these risk groups correlated strongly with observed data (p = 0.003) and with biomathematical model-generated NTCPs.
  
  
  CONCLUSIONS
  There is a dose-volume relationship for rectal mucosal bleeding in the region between 60 and 75 CGE; therefore, efforts to spare rectal wall volume using improved treatment planning and delivery techniques are important. Stratifying dose-volume histograms (DVHs) into risk groups, as done in this study, represents a useful means of analyzing empirical data as a function of hetereogeneous dose distributions. Modeling efforts may extend these results to more heterogeneous treatment techniques. Such analysis of DVH data may allow practicing clinicians to better assess the risk of various treatments, fields, or doses, when caring for an individual patient.
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Hartford
authors.forename: A
authors.initials: A
authors.lastname: Niemierko
authors.forename: J A
authors.initials: JA
authors.lastname: Adams
authors.forename: M M
authors.initials: MM
authors.lastname: Urie
authors.forename: W U
authors.initials: WU
authors.lastname: Shipley
mesh_terms: D004307:Dose-Response Relationship, Radiation; D006471:Gastrointestinal Hemorrhage / Q000209:etiology* / Q000517:prevention & control; D006801:Humans; D007413:Intestinal Mucosa / Q000528:radiation effects; D016015:Logistic Models; D008297:Male; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000150:complications* / Q000517:prevention & control; D012002:Rectal Diseases / Q000209:etiology* / Q000517:prevention & control; D012007:Rectum / Q000528:radiation effects*