Modelling duodenum radiotherapy toxicity using cohort dose-volume-histogram data

Background and purpose Gastro-intestinal toxicity is dose-limiting in abdominal radiotherapy and correlated with duodenum dose-volume parameters. We aimed to derive updated NTCP model parameters using published data and prospective radiotherapy quality-assured cohort data. Material and methods A systematic search identified publications providing duodenum dose-volume histogram (DVH) statistics for clinical studies of conventionally-fractionated radiotherapy. Values for the Lyman-Kutcher-Burman (LKB) NTCP model were derived through sum-squared-error minimisation and using leave-one-out cross-validation. Data were corrected for fraction size and weighted according to patient numbers, and the model refined using individual patient DVH data for two further cohorts from prospective clinical trials. Results Six studies with published DVH data were utilised, and with individual patient data included outcomes for 531 patients in total (median follow-up 16 months). Observed gastro-intestinal toxicity rates ranged from 0% to 14% (median 8%). LKB parameter values for unconstrained fit to published data were: n = 0.070, m = 0.46, TD₅₀₍₁₎ [Gy] = 183.8, while the values for the model incorporating the individual patient data were n = 0.193, m = 0.51, TD₅₀₍₁₎ [Gy] = 299.1. Conclusions LKB parameters derived using published data are shown to be consistent to those previously obtained using individual patient data, supporting a small volume-effect and dependence on exposure to high threshold dose.