BackgroundIt is expected that physical dose deposition properties render charged particle dose distributions sensitive to targeting uncertainties. Purpose of this work was to investigate the robustness of scanned-beam particle therapy plans against setup errors for different optimization modalities, beam setups and ion species.Material and methodsFor 15 patients with skull base tumors, localized in regions of severe tissue density heterogeneity, scanned lateral-opposed-beam treatment plans were prepared with the treatment planning system TRiP98, employing different optimization settings (single- and multiple-field modulation) and ion species (carbon ions and protons). For 10 of the patients, additional plans were prepared with individually selected beam setups, aiming at avoiding severe tissue heterogeneities. Subsequently, multiple rigid positioning errors of magnitude 1–2 mm (i.e. within planning target expansion) were simulated by introducing a shift of the irradiation fields with respect to the computed tomography (CT) data and recomputing the plans.ResultsIn presence of shifts, in carbon ion plans using a lateral-opposed beam setup and fulfilling clinical healthy tissue dose constraints, the median reduction in CTV V95% was up to 0.7 percentage points (pp) and 3.5 pp, for shifts of magnitude 1 mm and 2 mm respectively, however, in individual cases, the reduction reached 5.1 pp and 9.7 pp. In the corresponding proton plans similar median CTV V95% reductions of up to 0.9 pp (1 mm error) and 3.4 pp (2 mm error) were observed, with respective individual-case reductions of at most 3.2 pp and 11.7 pp. Unconstrained plans offered slightly higher coverage values, while no relevant differences were observed between different field modulation methods. Individually selected beam setups had a visible dosimetric advantage over lateral-opposed beams, for both particle species. While carbons provided more conformal plans and generally more advantageous absolute dose values, in presence of setup errors, protons showed greater dosimetric stability, in most of the investigated scenarios.ConclusionResidual patient setup errors may lead to substantial dose perturbation in scanned-beam particle therapy of skull base tumors, which cannot be dealt with by planning target expansion alone. Choice of irradiation directions avoiding extreme density heterogeneities can improve plan stability against such delivery-time uncertainties.