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

Microwave injection for the ALPHATRAP experiment and developments of the multi-reflection time-of-flight technique of the ISOLTRAP experiment

This thesis presents work done at the ALPHATRAP g-factor experiment at the MPIK in Heidelberg and at the mass spectrometry experiment ISOLTRAP at ISOLDE/CERN. At ALPHATRAP a system for microwave transmission from the room temperature environment to the cryogenic trap tower was designed. Microwave horns were used for contact free power transfer in a first step to a 77K temperature shield and in a second step to the trap tower cooled to 4.2 K. Additional devices for the alignment of a laser beam with the microwaves and a mode filter were designed. At ISOLTRAP, studies for multi-reflection time-of-flight mass measurements (MR-ToF MS) were performed. A distortion of the peaks in the time-of-flight spectrum due to the radiofrequency field in the RFQ used for beam preparation was investigated and reduced. In order to improve the ion optics, a new Einzel lens was designed and a new quadrupole bender was commissioned. The stability of mass measurements using the ISOLTRAP MR-ToF MS with ions from an off-line reference ion source were investigated. For measurements with a total recording time of more than one minute, a systematic error on the order of 100 keV was determined. It was reduced for shorter measurement cycles, where the uncertainty due to low statistics dominates

Ion transport from plasma ion source at ISOLTRAP

In this report, my work as CERN Summer Student at the ISOLTRAP experiment at ISOLDE is described. A new plasma ion source used as oine source for calibration and implemented before my arrival was commissioned and transportation settings for the produced ions to the ion traps were found. The cyclotron frequencies of 40Ar and the xenon isotopes 129-132Xe were measured using time-of-flight and phase-imaging ion-cyclotron-resonance mass spectroscopy

Dosimetric Validation of a System to Treat Moving Tumors Using Scanned Ion Beams That Are Synchronized With Anatomical Motion

PURPOSE: The purpose of this study was to validate the dosimetric performance of scanned ion beam deliveries with motion-synchronization to heterogenous targets. METHODS: A 4D library of treatment plans, comprised of up to 10 3D sub-plans, was created with robust and conventional 4D optimization methods. Each sub-plan corresponded to one phase of periodic target motion. The plan libraries were delivered to a test phantom, comprising plastic slabs, dosimeters, and heterogenous phantoms. This phantom emulated range changes that occur when treating moving tumors. Similar treatment plans, but without motion synchronization, were also delivered to a test phantom with a stationary target and to a moving target; these were used to assess how the target motion degrades the quality of dose distributions and the extent to which motion synchronization can improve dosimetric quality. The accuracy of calculated dose distributions was verified by comparison with corresponding measurements. Comparisons utilized the gamma index analysis method. Plan quality was assessed based on conformity, dose coverage, overdose, and homogeneity values, each extracted from calculated dose distributions. RESULTS: High pass rates for the gamma index analysis confirmed that the methods used to calculate and reconstruct dose distributions were sufficiently accurate for the purposes of this study. Calculated and reconstructed dose distributions revealed that the motion-synchronized and static deliveries exhibited similar quality in terms of dose coverage, overdose, and homogeneity for all deliveries considered. Motion-synchronization substantially improved conformity in deliveries with moving targets. Importantly, measurements at multiple locations within the target also confirmed that the motion-synchronized delivery system satisfactorily compensated for changes in beam range caused by the phantom motion. Specifically, the overall planning and delivery approach achieved the desired dose distribution by avoiding range undershoots and overshoots caused by tumor motion. CONCLUSIONS: We validated a dose delivery system that synchronizes the movement of the ion beam to that of a moving target in a test phantom. Measured and calculated dose distributions revealed that this system satisfactorily compensated for target motion in the presence of beam range changes due to target motion. The implication of this finding is that the prototype system is suitable for additional preclinical research studies, such as irregular anatomic motion

Dosimetric Validation of a System to Treat Moving Tumors Using Scanned Ion Beams That Are Synchronized With Anatomical Motion

Purpose: The purpose of this study was to validate the dosimetric performance of scanned ion beam deliveries with motion-synchronization to heterogenous targets. Methods: A 4D library of treatment plans, comprised of up to 10 3D sub-plans, was created with robust and conventional 4D optimization methods. Each sub-plan corresponded to one phase of periodic target motion. The plan libraries were delivered to a test phantom, comprising plastic slabs, dosimeters, and heterogenous phantoms. This phantom emulated range changes that occur when treating moving tumors. Similar treatment plans, but without motion synchronization, were also delivered to a test phantom with a stationary target and to a moving target; these were used to assess how the target motion degrades the quality of dose distributions and the extent to which motion synchronization can improve dosimetric quality. The accuracy of calculated dose distributions was verified by comparison with corresponding measurements. Comparisons utilized the gamma index analysis method. Plan quality was assessed based on conformity, dose coverage, overdose, and homogeneity values, each extracted from calculated dose distributions. Results: High pass rates for the gamma index analysis confirmed that the methods used to calculate and reconstruct dose distributions were sufficiently accurate for the purposes of this study. Calculated and reconstructed dose distributions revealed that the motion-synchronized and static deliveries exhibited similar quality in terms of dose coverage, overdose, and homogeneity for all deliveries considered. Motion-synchronization substantially improved conformity in deliveries with moving targets. Importantly, measurements at multiple locations within the target also confirmed that the motion-synchronized delivery system satisfactorily compensated for changes in beam range caused by the phantom motion. Specifically, the overall planning and delivery approach achieved the desired dose distribution by avoiding range undershoots and overshoots caused by tumor motion. Conclusions: We validated a dose delivery system that synchronizes the movement of the ion beam to that of a moving target in a test phantom. Measured and calculated dose distributions revealed that this system satisfactorily compensated for target motion in the presence of beam range changes due to target motion. The implication of this finding is that the prototype system is suitable for additional preclinical research studies, such as irregular anatomic motion

Preliminary tests of dosimetric quality and projected therapeutic outcomes of multi-phase 4D radiotherapy with proton and carbon ion beams

Objective. The purpose of this study was to perform preliminary pre-clinical tests to compare the dosimetric quality of two approaches to treating moving tumors with ion beams: synchronously delivering the beam with the motion of a moving planning target volume (PTV) using the recently developed multi-phase 4D dose delivery (MP4D) approach, and asynchronously delivering the ion beam to a motion-encompassing internal tumor volume (ITV) combined with rescanning. Approach. We created 4D optimized treatment plans with proton and carbon ion beams for two patients who had previously received treatment for non-small cell lung cancer. For each patient, we created several treatment plans, using approaches with and without motion mitigation: MP4D, ITV with rescanning, static deliveries to a stationary PTV, and deliveries to a moving tumor without motion compensation. Two sets of plans were optimized with margins or robust uncertainty scenarios. Each treatment plan was delivered using a recently-developed motion-synchronized dose delivery system (M-DDS); dose distributions in water were compared to measurements using gamma index analysis to confirm the accuracy of the calculations. Reconstructed dose distributions on the patient CT were analyzed to assess the dosimetric quality of the deliveries (conformity, uniformity, tumor coverage, and extent of hotspots). Main results. Gamma index analysis pass rates confirmed the accuracy of dose calculations. Dose coverage was \u3e95% for all static and MP4D treatments. The best conformity and the lowest lung doses were achieved with MP4D deliveries. Robust optimization led to higher lung doses compared to conventional optimization for ITV deliveries, but not for MP4D deliveries. Significance. We compared dosimetric quality for two approaches to treating moving tumors with ion beams. Our findings suggest that the MP4D approach, using an M-DDS, provides conformal motion mitigation, with full target coverage and lower OAR doses

A Modular System for Treating Moving Anatomical Targets With Scanned Ion Beams at Multiple Facilities: Pre-Clinical Testing for Quality and Safety of Beam Delivery

Background: Quality management and safety are integral to modern radiotherapy. New radiotherapy technologies require new consensus guidelines on quality and safety. Established analysis strategies, such as the failure modes and effects analysis (FMEA) and incident learning systems have been developed as tools to assess the safety of several types of radiation therapies. An extensive literature documents the widespread application of risk analysis methods to photon radiation therapy. Relatively little attention has been paid to performing risk analyses of nascent radiation therapy systems to treat moving tumors with scanned heavy ion beams. The purpose of this study was to apply a comprehensive safety analysis strategy to a motion-synchronized dose delivery system (M-DDS) for ion therapy. Methods: We applied a risk analysis method to new treatment planning and treatment delivery processes with scanned heavy ion beams. The processes utilize a prototype, modular dose delivery system, currently undergoing preclinical testing, that provides new capabilities for treating moving anatomy. Each step in the treatment process was listed in a process map, potential errors for each step were identified and scored using the risk probability number in an FMEA, and the possible causes of each error were described in a fault tree analysis. Solutions were identified to mitigate the risk of these errors, including permanent corrective actions, periodic quality assurance (QA) tests, and patient specific QA (PSQA) tests. Each solution was tested experimentally. Results: The analysis revealed 58 potential errors that could compromise beam delivery quality or safety. Each of the 14 binary (pass-or-fail) tests passed. Each of the nine QA and four PSQA tests were within anticipated clinical specifications. The modular M-DDS was modified accordingly, and was found to function at two centers. Conclusion: We have applied a comprehensive risk analysis strategy to the M-DDS and shown that it is a clinically viable motion mitigation strategy. The described strategy can be utilized at any ion therapy center that operates with the modular M-DDS. The approach can also be adapted for use at other facilities and can be combined with existing safety analysis systems