Background: The development of a dose-volume-histogram (DVH) estimation model for knowledge-based planning is very time-consuming and it could be inefficient if it was only used for similar upcoming cases as supposed.It is clinically desirable to explore and validate other potential applications for a configured model.This study tests the hypothesis that a supine volumetric modulated arc therapy (VMAT) model can optimize intensity modulated radiotherapy (IMRT) plans of other patient setup orientations.Methods: Based on RapidPlan, a DVH estimation model was trained using 81 supine VMAT rectal plans and validated on 10 similar cases to ensure the robustness of its designed purpose.Attempts were then made to apply the model to re-optimize the dynamic MLC-sequences of the duplicated IMRT plans from 30 historical patients (20 prone and 10 supine) that were treated with the same prescription as for the model (50.6 and 41.8 Gy to 95 % of PGTV and PTVsimultaneously/22 fractions).The performance of knowledge-based re-optimization and the impact of setup orientations were evaluated dosimetrically.Results: The VMAT model validation on similar cases showed comparable target dose distribution and significantly improved organ sparing (by 10.77 ~ 18.65 %) than the original plans.IMRT plans of either setup can be re-optimized using the supine VMAT model, which significantly reduced the dose to the bladder (by 25.88 % from 33.85 ± 2.96 to 25.09 ± 1.32 Gy for D50 % by 22.77 % from 33.99 ± 2.77 to 26.25 ± 1.22 Gy for mean dose) and femoral head (by 12.27 % from 15.65 ± 3.33 to 13.73 ± 1.43 Gy for D50 %;by 10.09 % from 16.26 ± 2.74 to 14.62 ± 1.10 Gy for mean dose), all P < 0.01.Although the dose homogeneity and PGTV conformity index (CI_PGTV) changed slightly (≤0.01),Cl_PTV of IMRT plans was significantly increased (△ =0.17, P < 0.01) by the manually defined target-objectives in the VMAT optimizer.The semi-automated IMRT planning increased the global maximum dose and V107 % due to the missing of hot spot suppression by specific manual optimizing or fluence map editing.Conclusions: The Varian RapidPlan model trained on a technique and orientation can be used for another.Knowledge-based planning improves organ sparing and quality consistency, yet the target-objectives defined for VMAT-optimizer should be readapted to IMRT planning, followed by manual hot spot processing.