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.

The poor treatment prognosis for tumours with oxygen-deficient areas is usually attributed to the increased radioresistance of hypoxic cells. It can be expressed by the oxygen enhancement ratio (OER), which decreases with increasing linear energy transfer (LET) suggesting a potential clinical advantage of high-LET radiotherapy with heavy ion beams compared to low-LET photon or proton irradiation. The aim of this work is to review the experimental cell survival data from the literature and, based on them, to develop a simple OER model to estimate the clinical impact of OER variations. For this purpose, the standard linear-quadratic model and the Alper-Howard-Flanders model are used. According to our calculations for a carbon ion spread-out Bragg peak at clinically relevant intermediate oxygen levels (0.5-20 mmHg), the advantage of carbon ions might be relatively moderate, with OER values about 1%-15% smaller than for protons. Furthermore, the variations of OER with LET are much smaller in vivo than in vitro due to different oxygen partial pressures used in cell experiments or measured inside tumours. The proposed OER model is a simple tool to quantify the oxygen effect in a practical way and provides the possibility to do hypoxia-based biological optimization in treatment planning.

In this work, the authors generated CBCT based stopping power distributions using DIR of the pCT to a CBCT scan. DIR accuracy was below 1.4 mm as evaluated by the SIFT algorithm. Dose distributions calculated on the vCT agreed well to those calculated on the rpCT when using gamma index evaluation as well as DVH statistics based on the same contours. The use of DIR generated contours introduced variability in DVH statistics.

These results show that proton minibeam radiation therapy results in reduced adverse effects compared with conventional homogeneous broad-beam irradiation and, therefore, might have the potential to decrease the incidence of side effects resulting from clinical proton and/or heavy ion therapy.

As the relative biological effectiveness of protons depends on the linear energy transfer (LET), simple methods for LET calculations are desired for the optimization of proton therapy. This work provides an analytical model for the LET on the central axis of broad proton beams in water, which can also be applied to spread-out Bragg peaks. For realistic treatment situations with polyenergetic beams, the LET is here defined as a local mean of the proton stopping power, weighted by the local energy spectrum. The proposed model considers only Coulomb interactions and neglects nonelastic nuclear interactions. By assuming a Gaussian shape for the energy spectrum and by using a suitable parametrization of the stopping power, analytical expressions for the track averaged and the dose averaged LET are derived, which account for range straggling as well as for the initial width of the energy spectrum. The analytical model was evaluated by Monte Carlo simulations with GEANT 3.21. Local energy spectra were simulated to obtain LET distributions for several cases, using clinical energies between 70 and 250 MeV and varying widths of the initial energy spectrum. Good agreement was found between the analytical model and the Monte Carlo simulations (with maximum deviations of 0.5 keV per micrometer), which justifies the assumptions used in the derivation of the analytical model.

The application of a microchannel proton irradiation was compared to homogeneous irradiation in a three-dimensional human skin model. The goal is to minimize the risk of normal tissue damage by microchannel irradiation, while preserving local tumor control through a homogeneous irradiation of the tumor that is achieved because of beam widening with increasing track length. 20 MeV protons were administered to the skin models in 10- or 50-μm-wide irradiation channels on a quadratic raster with distances of 500 μm between each channel (center to center) applying an average dose of 2 Gy. For comparison, other samples were irradiated homogeneously at the same average dose. Normal tissue viability was significantly enhanced after microchannel proton irradiation compared to homogeneous irradiation. Levels of inflammatory parameters, such as Interleukin-6, TGF-Beta, and Pro-MMP1, were significantly lower in the supernatant of the human skin tissue after microchannel irradiation than after homogeneous irradiation. The genetic damage as determined by the measurement of micronuclei in keratinocytes also differed significantly. This difference was quantified via dose modification factors (DMF) describing the effect of each irradiation mode relative to homogeneous X-ray irradiation, so that the DMF of 1.21 ± 0.20 after homogeneous proton irradiation was reduced to 0.23 ± 0.11 and 0.40 ± 0.12 after microchannel irradiation using 10- and 50-μm-wide channels, respectively. Our data indicate that proton microchannel irradiation maintains cell viability while significantly reducing inflammatory responses and genetic damage compared to homogeneous irradiation, and thus might improve protection of normal tissue after irradiation.