The sharp dose gradients which are possible in intensity modulated proton therapy (IMPT) not only offer the possibility of generating excellent target coverage while sparing neighbouring organs at risk, but can also lead to treatment plans which are very sensitive to uncertainties in treatment variables such as the range of individual Bragg peaks. We developed a method to account for uncertainties of treatment variables in the optimization based on a worst case dose distribution. The worst case dose distribution is calculated using several possible realizations of the uncertainties. This information is used by the objective function of the inverse treatment planning system to generate treatment plans which are acceptable under all considered realizations of the uncertainties. The worst case optimization method was implemented in our in-house treatment planning software KonRad in order to demonstrate the usefulness of this approach for clinical cases. In this paper, we investigated range uncertainties, setup uncertainties and a combination of both uncertainties. Using our method the sensitivity of the resulting treatment plans to these uncertainties is considerably reduced.

To study the effects of a variable relative biological effectiveness (RBE) in inverse treatment planning for proton therapy, fast methods for three-dimensional RBE calculations are required. We therefore propose a simple phenomenological model for the RBE in therapeutic proton beams. It describes the RBE as a function of the dose, the linear energy transfer (LET) and tissue specific parameters. Published experimental results for the dependence of the parameters alpha and beta from the linear-quadratic model on the dose averaged LET were evaluated. Using a linear function for alpha(LET) in the relevant LET region below 30 keV per micrometre and a constant beta, a simple formula for the RBE could be derived. The new model was able to reproduce the basic dependences of RBE on dose and LET, and the RBE values agreed well with experimental results. The model was also applied to spread-out Bragg peaks (SOBP), where the main effects of a variable RBE are an increase of the RBE along the SOBP plateau, and a shift in depth of the distal falloff. The new method allows fast RBE estimations and has therefore potential applications in iterative treatment planning for proton therapy.

The symmetric configuration of EBT3 presents a major improvement for film handling. EBT3 has similar dosimetric performance as its precursor EBT2 and can, thus, be applied to dose verification in IMRT in the same way. For dose verification in proton therapy the underresponse in the Bragg peak region has to be taken into account.