A biologically adapted dose-escalation approach, demonstrated for 18F-FET-PET in brain tumors

Purpose: To demonstrate the feasibility of a biologically adapted dose-escatation approach to brain tumors. Material and Methods: Due to the specific accumulation of fluoroethyltyrosine (FET) in brain tumors, F-18-FET-PET imaging is used to derive a voxel-by-voxel dose distribution. Although the kinetics of F-18-FET are not completely understood, the authors regard regions with high tracer uptake as vital and aggressive tumor and use a Linear dose-escalation function between SUV (standard uptake value) 3 and SUV 5. The resulting dose distribution is then planned using the inverse Monte Carlo treatment-planning system IKO. In a theoretical study, the dose range is clinically adapted from 1.8 Gy to 2.68 Gy per fraction (with a total of 30 fractions). In a second study, the maximum dose of the model is increased step by step from 2.5 Gy to 3.4 Gy to investigate whether a significant dose escalation to tracer-accumulating subvolumes is possible without affecting the shell-shaped organ at risk (OAR). For all dose-escalation levels the dose difference Delta D of each voxel inside the target volume is calculated and the mean dose difference Delta(D) over bar and their standard deviation sigma(Delta D) are determined. The dose to the OAR is evaluated by the dose values D-50%(OAR) and D-5%(OAR), which are the dose values not exceeded by 50% and 5% of the volume, respectively. Results: The inhomogeneous dose prescription is achieved with high accuracy (Delta D< 0.03 +/- 0.3 Gy/fraction). The maximum dose can be increased remarkably, without increasing the dose to the OAR (standard deviation of D-50%(OAR) < 0.02 Gy/fraction and of D-5%(OAR) < 0.05 Gy/fraction). Conclusion: Assuming that regions with high tracer uptake can be interpreted as target for radiotherapy, F-18-FET-PET-based dose painting by numbers applied to brain tumors is a feasible approach. The dose, and therefore potentially the chance of tumor control, can be enhanced. The proposed model can easily be transferred to other tracers and tumor entities.