The technical performance of an integrated three-dimensional carbon ion pencil beam tracking system that was developed at GSI was investigated in phantom studies. Aim of the beam tracking system is to accurately treat tumours that are subject to respiratory motion with scanned ion beams. The current system provides real-time control of ion pencil beams to track a moving target laterally using the scanning magnets and longitudinally with a dedicated range shifter. The system response time was deduced to be approximately 1 ms for lateral beam tracking. The range shifter response time has been measured for various range shift amounts. A value of 16 +/- 2 ms was achieved for a water equivalent shift of 5 mm. An additional communication delay of 11 +/- 2 ms was taken into account in the beam tracking process via motion prediction. Accuracy of the lateral beam tracking was measured with a multi-wire position detector to < or =0.16 mm standard deviation. Longitudinal beam tracking accuracy was parameterized based on measured responses of the range shifter and required time durations to maintain a specific particle range. For example, 5 mm water equivalence (WE) longitudinal beam tracking results in accuracy of 1.08 and 0.48 mm WE in root mean square for time windows of 10 and 50 ms, respectively.

Treatment of moving targets with scanned particle beams results in local over-and under-dosage due to interplay of beam and target motion. To mitigate the impact of respiratory motion, a motion tracking system has been developed and integrated in the therapy control system at Gesellschaft für Schwerionenforschung. The system adapts pencil beam positions as well as the beam energy according to target motion to irradiate the planned position. Motion compensation performance of the tracking system was assessed by measurements with radiographic films and a 3D array of 24 ionization chambers. Measurements were performed for stationary detectors and moving detectors using the tracking system. Film measurements showed comparable homogeneity inside the target area. Relative differences of 3D dose distributions within the target volume were 1 ± 2% with a maximum of 4%. Dose gradients and dose to surrounding areas were in good agreement. The motion tracking system successfully preserved dose distributions delivered to moving targets and maintained target conformity.

The growing number of particle therapy facilities worldwide landmarks a novel era of precision oncology. Implementation of robust biophysical readouts is urgently needed to assess the efficacy of different radiation qualities. This is the first report on biophysical evaluation of Monte Carlo simulated predictive models of prescribed dose for four particle qualities i.e., proton, helium-, carbon- or oxygen ions using raster-scanning technology and clinical therapy settings at HIT. A high level of agreement was found between the in silico simulations, the physical dosimetry and the clonogenic tumor cell survival. The cell fluorescence ion track hybrid detector (Cell-Fit-HD) technology was employed to detect particle traverse per cell nucleus. Across a panel of radiobiological surrogates studied such as late ROS accumulation and apoptosis (caspase 3/7 activation), the relative biological effectiveness (RBE) chiefly correlated with the radiation species-specific spatio-temporal pattern of DNA double strand break (DSB) formation and repair kinetic. The size and the number of residual nuclear γ-H2AX foci increased as a function of linear energy transfer (LET) and RBE, reminiscent of enhanced DNA-damage complexity and accumulation of non-repairable DSB. These data confirm the high relevance of complex DSB formation as a central determinant of cell fate and reliable biological surrogates for cell survival/RBE. The multi-scale simulation, physical and radiobiological characterization of novel clinical quality beams presented here constitutes a first step towards development of high precision biologically individualized radiotherapy.

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Despite high applied doses, C12 re-irradiation shows moderate side-effects, response rates even in these heavily pre-treated patients are encouraging and present a good alternative to palliative chemotherapy. Though most local recurrences occur within the high-dose area, further dose escalation should be viewed with caution.