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.

Background: Scanned ion beam therapy of intra-fractionally moving tumors requires motion mitigation. GSI proposed beam tracking and performed several experimental studies to analyse the dosimetric precision of the system for scanned carbon beams. Methods:A beam tracking system has been developed and integrated in the scanned carbon ion beam therapy unit at GSI. The system adapts pencil beam positions and beam energy according to target motion.Motion compensation performance of the beam tracking system was assessed by measurements with radiographic films, a range telescope, a 3D array of 24 ionization chambers, and cell samples for biological dosimetry. Measurements were performed for stationary detectors and moving detectors using the beam tracking system. Results:All detector systems showed comparable data for a moving setup when using beam tracking and the corresponding stationary setup. Within the target volume the mean relative differences of ionization chamber measurements were 0.3% (1.5% standard deviation, 3.7% maximum). Film responses demonstrated preserved lateral dose gradients. Measurements with the range telescope showed agreement of Bragg peak depth under motion induced range variations. Cell survival experiments showed a mean relative difference of -5% (-3%) between measurements and calculations within the target volume for beam tracking (stationary) measurements. Conclusions:The beam tracking system has been successfully integrated. Full functionality has been validated dosimetrically in experiments with several detector types including biological cell systems.

BackgroundTime-resolved volumetric magnetic resonance imaging (4DMRI) offers the potential to analyze 3D motion with high soft-tissue contrast without additional imaging dose. We use 4DMRI to investigate the interplay effect for pencil beam scanning (PBS) proton therapy of pancreatic cancer and to quantify the dependency of residual interplay effects on the number of treatment fractions.MethodsBased on repeated 4DMRI datasets for nine pancreatic cancer patients, synthetic 4DCTs were generated by warping static 3DCTs with 4DMRI deformation vector fields. 4D dose calculations for scanned proton therapy were performed to quantify the interplay effect by CTV coverage (v95) and dose homogeneity (d5/d95) for incrementally up to 28 fractions. The interplay effect was further correlated to CTV motion characteristics. For quality assurance, volume and mass conservation were evaluated by Jacobian determinants and volume-density comparisons.ResultsFor the underlying patient cohort with CTV motion amplitudes < 15 mm, we observed significant correlations between CTV motion amplitudes and both the length of breathing cycles and the interplay effect. For individual fractions, tumor underdosage down to v95 = 70% was observed with pronounced dose heterogeneity (d5/d95 = 1.3). For full × 28 fractionated treatments, we observed a mitigation of the interplay effect with increasing fraction numbers. On average, after seven fractions, a CTV coverage with 95–107% of the prescribed dose was reached with sufficient dose homogeneity. For organs at risk, no significant differences were found between the static and accumulated dose plans for 28 fractions.ConclusionIntrafractional organ motion exhibits a large interplay effect for PBS proton therapy of pancreatic cancer. The interplay effect correlates with CTV motion, but can be mitigated efficiently by fractionation, mainly due to different breathing starting phases in fractionated treatments. For hypofractionated treatments, a further restriction of motion may be required. Repeated 4DMRI measurements are a viable tool for pre- and post-treatment evaluations of the interplay effect.

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