Setup and range uncertainties compromise radiotherapy plan robustness. We introduce a method to evaluate the clinical effect of these uncertainties on the population using tumor control probability (TCP) and normal tissue complication probability (NTCP) models. Eighteen oropharyngeal cancer patients treated with curative intent were retrospectively included. Both photon (VMAT) and proton (IMPT) plans were created using a planning target volume as planning objective. Plans were recalculated for uncertainty scenarios: two for range over/undershoot (IMPT) or CT-density scaling (VMAT), six for shifts. An average shift scenario () was calculated to assess random errors. Dose differences between nominal and scenarios were translated to TCP (2 models) and NTCP (15 models). A weighted average (W-Avg) of the TCP\NTCP based on Gaussian distribution over the variance scenarios was calculated to assess the clinical effect of systematic errors on the population. TCP/NTCP uncertainties were larger in IMPT compared to VMAT. Although individual perturbations showed risks of plan deterioration, the scenario did not show a substantial decrease in any of the TCP endpoints suggesting evaluated plans in this cohort were robust for random errors. Evaluation of the W-Avg scenario to assess systematic errors showed in VMAT no substantial decrease in TCP endpoints and in IMPT a limited decrease. In IMPT, the W-Avg scenario had a mean TCP loss of 0%-2% depending on plan type and primary or nodal control. The W-Avg for NTCP endpoints was around 0%, except for mandible necrosis in IMPT (W-Avg: 3%). The estimated population impact of setup and range uncertainties on TCP/NTCP following VMAT or IMPT of oropharyngeal cancer patients was small for both treatment modalities. The use of TCP/NTCP models allows for clinical interpretation of the population effect and could be considered for incorporation in robust evaluation methods. Highlights: - TCP/NTCP models allow for a clinical evaluation of uncertainty scenarios. - For this cohort, in silico-PTV based IMPT plans and VMAT plans were robust for random setup errors. - Effect of systematic errors on the population was limited: mean TCP loss was 0%-2%.
Hamming-Vrieze, O., Depauw, N., Craft, D. L., Chan, A. W., Rasch, C. R. N., Verheij, M., ... Kooy, H. M. (2019). Impact of setup and range uncertainties on TCP and NTCP following VMAT or IMPT of oropharyngeal cancer patients. Physics in Medicine and Biology, 64(9), . https://doi.org/10.1088/1361-6560/ab1459