Purpose:Respiratory motion and patient setup error both contribute to the dosimetric uncertainty in radiotherapy of lung tumors. Managing these uncertainties for free-breathing treatments is usually done by margin-based approaches or robust optimization. However, breathing motion can be irregular and concerns have been raised for the robustness of the treatment plans. We have previously reported the dosimetric effects of the respiratory motion, without setup uncertainties, in lung tumor photon radiotherapy using free-breathing images. In this study, we include setup uncertainty. Methods:Tumor positions from cine-CT images acquired in free-breathing were combined with per-fraction patient shifts to simulate treatment scenarios. A total of 14 patients with 300 tumor positions were used to evaluate treatment plans based on 4DCT. Four planning methods aiming at delivering 54 Gy as median tumor dose in three fractions were compared. The planning methods were denoted robust 4D (RB4), isodose to the PTV with a central higher dose (ISD), the ISD method normalized to the intended median tumor dose (IRN) and homogeneous fluence to the PTV (FLU). Results:For all planning methods 95% of the intended dose was achieved with at least 90% probability with RB4 and FLU having equal CTV D50% values at this probability. FLU gave the most consistent results in terms of CTV D50% spread and dose homogeneity. Conclusions:Despite the simulated patient shifts and tumor motions being larger than observed in the 4DCTs the dosimetric impact was suggested to be small. RB4 or FLU are recommended for the planning of free-breathing treatments.