Uncertainties in Proton Therapy
Treatment plans in proton therapy are more sensitive to uncertainties than in conventional photon-based radiotherapy. In addition to setup uncertainties, proton therapy is affected by uncertainties in proton range and relative biological effectiveness (RBE). While to date a constant RBE of 1.1 is commonly assumed, the actual RBE is known to increase towards the distal end of the spread-out Bragg-peak. Several models for variable RBE predictions exist. We work on a model independent framework to evaluate the combined impact and interplay of setup, range and RBE uncertainties in a comprehensive, variance-based sensitivity analysis (SA).
The variance-based SA requires a large number (104-105) of RBE-weighted dose (RWD) calculations. Based on a particle therapy extension of the research treatment planning system CERR, we implemented a fast graphics processing unit (GPU) accelerated pencil beam modeling of patient and range shifts. All uncertain input parameters (patient position, proton range, RBE model parameters) are sampled simultaneously within their assumed probability distributions. Statistical formalisms rank the input parameters according to their influence on the overall uncertainty of RBE-weighted dose-volume histogram (RW-DVH) quantiles and the RWD in every voxel, resulting in relative, normalized sensitivity indices (S=0: non influential input, S=1: only influential input). Results can be visualized as RW-DVHs with error bars and sensitivity maps. The goal of this project is to model all possible uncertainties comprehensively and to eventually improve treatment planning with the newly obtained sensitivity information. This research was the topic of the DFG-funded project “Comprehensive Sensitivity Analysis for Particle Therapy Assessing Uncertainties in Range, Motion and Biological Modeling” (project #286492551).
Fluence modulated proton computed tomography
Range uncertainties in proton therapy may be reduced by performing volumetric imaging with protons instead of x-rays. Proton computed tomography allows direct reconstruction of relative proton stopping powers, thus bypassing the error-prone empirical conversions from photon linear attenuation coefficients typically used clinically. Since the proton beam used for treatment may also be used for imaging, proton CT allows for in-room imaging and daily proton range assessment. To enable such high-frequency imaging, we have developed, in collaboration with the Department of Medical Physics of the Faculty of Physics of the LMU Munich, a low dose imaging technique relying on using modulated proton pencil beams to perform proton CT scans. By modulating the fluence on a pencil-beam per pencil-beam basis, high image quality can be ensured in the treatment area, while reducing imaging dose where not needed. Fluence modulated proton computed tomography (FMpCT) has been shown feasible in computational studies as well as experimentally, and we are currently refining fluence optimization strategies and noise reconstruction theory. This project has received funding from the DFG as “Fluence modulated proton computed tomography: a new approach for low-dose image guidance in particle therapy”, project #388731804.
- Dickmann J, Rit S, Pankuch M, Johnson RP, Schulte RW, Parodi K, Dedes G, Landry G. An optimization algorithm for dose reduction with fluence–modulated proton CT. Medical Physics. 2020 Feb 10.
- Dickmann J, Wesp P, Rädler M, Rit S, Pankuch M, Johnson RP, Bashkirov V, Schulte RW, Parodi K, Landry G, Dedes G. Prediction of image noise contributions in proton computed tomography and comparison to measurements. Physics in Medicine & Biology. 2019 Jul 16;64(14):145016.
- Rädler M, Landry G, Rit S, Schulte RW, Parodi K, Dedes G. Two-dimensional noise reconstruction in proton computed tomography using distance-driven filtered back-projection of simulated projections. Physics in Medicine & Biology. 2018 Oct 24;63(21):215009.
- Dedes G, Johnson RP, Pankuch M, Detrich N, Pols WM, Rit S, Schulte RW, Parodi K, Landry G. Experimental fluence‐modulated proton computed tomography by pencil beam scanning. Medical physics. 2018 Jul;45(7):3287-96.
- Dedes G, De Angelis L, Rit S, Hansen D, Belka C, Bashkirov V, Johnson RP, Coutrakon G, Schubert KE, Schulte RW, Parodi K., Landry G. Application of fluence field modulation to proton computed tomography for proton therapy imaging. Physics in Medicine & Biology. 2017 Jul 12;62(15):6026.