title: Two non-parametric methods for derivation of constraints from radiotherapy dose-histogram data.
abstract: Dose constraints based on histograms provide a convenient and widely-used method for informing and guiding radiotherapy treatment planning. Methods of derivation of such constraints are often poorly described. Two non-parametric methods for derivation of constraints are described and investigated in the context of determination of dose-specific cut-points-values of the free parameter (e.g., percentage volume of the irradiated organ) which best reflect resulting changes in complication incidence. A method based on receiver operating characteristic (ROC) analysis and one based on a maximally-selected standardized rank sum are described and compared using rectal toxicity data from a prostate radiotherapy trial. Multiple test corrections are applied using a free step-down resampling algorithm, which accounts for the large number of tests undertaken to search for optimal cut-points and the inherent correlation between dose-histogram points. Both methods provide consistent significant cut-point values, with the rank sum method displaying some sensitivity to the underlying data. The ROC method is simple to implement and can utilize a complication atlas, though an advantage of the rank sum method is the ability to incorporate all complication grades without the need for grade dichotomization.
authors.affiliation: Department of Radiation Oncology, Sir Charles Gairdner Hospital, Western Australia, Australia. School of Physics, University of Western Australia, Western Australia, Australia.
authors.forename: M A
authors.initials: MA
authors.lastname: Ebert
authors.forename: S L
authors.initials: SL
authors.lastname: Gulliford
authors.forename: F
authors.initials: F
authors.lastname: Buettner
authors.forename: K
authors.initials: K
authors.lastname: Foo
authors.forename: A
authors.initials: A
authors.lastname: Haworth
authors.forename: A
authors.initials: A
authors.lastname: Kennedy
authors.forename: D J
authors.initials: DJ
authors.lastname: Joseph
authors.forename: J W
authors.initials: JW
authors.lastname: Denham
mesh_terms: D005500:Follow-Up Studies; D006801:Humans; D012372:ROC Curve; D011829:Radiation Dosage; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D018709:Statistics, Nonparametric; D016896:Treatment Outcome