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Ebert, M.A.* ; Gulliford, S.L.* ; Buettner, F. ; Foo, K.* ; Haworth, A.* ; Kennedy, A.* ; Joseph, D.J.* ; Denham, J.W.*

Two non-parametric methods for derivation of constraints from radiotherapy dose-histogram data.

Phys. Med. Biol. 59, N101-N111 (2014)

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Open Access Green as soon as Postprint is submitted to ZB.

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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.

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