Development and experimental validation of adaptive conformal particle therapy

In radiotherapy, conforming the high dose to the tumor is of special importance to avoid toxicity in critical organs. Scanned ion beam therapy has shown its potential to reduce the dose in the healthy tissue. However, its application is limited for thoracic and abdominal tumors like lung, liver or pancreatic cancer. In those organs, respiratory motion induces considerable changes in tumor position and beam range to the tumor. In current clinical practice, this causes severe dose degradations and necessitates large safety margins that invalidate the conformity gain of ion beam therapy. In order to minimize target margins, the motion has to be compensated by real-time adaptive beam delivery. A major challenge are the irregularities of realistic tumor motion that are unknown during treatment planning. To study the impact of irregular motion, an extension of an RBE-weighted dose calculation algorithm enabling the computation on arbitrarily long series of CT images was experimentally validated. A workflow for simulation studies with irregular motion data for the assessment of plan robustness and treatment quality was presented. A new motion mitigation technique denoted as multi-phase 4D dose delivery with residual tracking (MP4DRT) was implemented into the research version of a clinical dose delivery system. It combines the earlier proposed multi-phase 4D dose delivery (MP4D) technique with lateral beam tracking. MP4D synchronizes the delivery of phase specific treatment plans with the observed motion. It therefore enables conformal, time-resolved 4D treatment planning for periodic motion. It considers range changes and deformations during the optimization process and therefore removes the need for real-time range adjustments. In the new technique, additional lateral beam tracking adapts beam positions in real-time to the unexpected residual component of the observed irregular motion. The potential of MP4DRT was evaluated in a comparative experimental study that included also the other free breathing motion mitigation techniques MP4D, lateral beam tracking and ITV rescanning. Treatment plans were optimized for a digital anthropomorphic lung phantom with a nominal tumor motion amplitude of 20 mm. The plans were delivered at a clinical carbon ion therapy facility to a quality assurance like setup performing regular and irregular motion scenarios including 25 % amplitude variations with and without baseline drift. Treatment quality was assessed using detector measurements and log-file based dose reconstructions. The robustness of the delivery was tested by adding artificial errors to the motion signal during the delivery and rotational tumor motion up to 30° during dose reconstruction. It was demonstrated that MP4DRT is able to deliver highly conformal dose distributions. A target coverage of D95>95 % was achieved irrespective of the motion scenario and rotation amplitude, and for clinically relevant mean absolute tracking errors of the motion monitoring up to 1.9 mm. MP4DRT synergized the complementary strengths of its predecessors and outperformed all other compared motion mitigation techniques in target coverage, dose conformity and homogeneity, organ at risk sparing, and robustness against rotational motion. MP4DRT can deliver conformal and homogeneous dose distributions to moving tumors in a single fraction. After clinical implementation, it therefore might improve treatment quality and enable the treatment of tumors so far unavailable for particle therapy