title: Carbon-ion radiotherapy monitoring in depth using secondary-ion tracking
creator: Ghesquiere-Dierickx, Laura Marie Helene
subject: ddc-500
subject: 500 Natural sciences and mathematics
subject: ddc-530
subject: 530 Physics
subject: ddc-600
subject: 600 Technology (Applied sciences)
subject: ddc-610
subject: 610 Medical sciences Medicine
description: The advantages of carbon-ion pencil beam radiotherapy imply an increased sensitivity of the dose distribution in the patient to any changes in the patient geometry, such as internal anatomical changes or patient misalignment. This can lead to a deterioration of the dose distribution within the patient. Monitoring methods of the internal patient’s dose distribution for carbon-ion beam radiotherapy are therefore of great importance to early detect possible under- or over-dosage in the patient, eventually, reduce the tumor safety margins applied around targeted tumor volumes and thus decrease the delivered dose in healthy tissues. Up to now, several non-invasive in-vivo ion-beam monitoring methods have been developed. These are mostly based on the detection of different kinds of secondary radiation, such as annihilation-photons from β+ emitters, prompt photons, or prompt charged nuclear fragments, emitted from a patient during the treatment delivery. These secondary radiations are the results of nuclear interactions of the primary treatment beam with the irradiated tissue. They potentially carry valuable information about the primary treatment beam range, position, or intensity in the patient. However, so far none of the monitoring methods has reached sufficient maturity for a wide application in clinical routine.  This thesis aimed to develop methods for detection and localization of therapy-relevant geometry variations of 2 mm in head models, mimicking possible inter-fractional changes on the surface or inside patients’ heads. In contrast to previous research which concentrated on single stationary pencil beams, this thesis was focused on entire therapy-like treatment plans composed of thousands of single pencil beams with low numbers of primary-ions and irradiated under clinic-like conditions in terms of dose, dose rate, and tumor volume.  In this thesis, methods were based on the detection and tracking of charged secondary nuclear fragments (secondary ions) emitted from the patient during carbon ion radiotherapy delivery. Subsequently, methods for analysis and interpretation of the measured secondary-ion paths (tracks) were developed. The developed radiation detection methods exploited the capabilities of a novel mini-tracker, based on the Timepix3 technology developed at CERN and positioned behind the patient. The deadtime-free data acquisition enabled a gapless recording of all impacting secondary ion tracks. Moreover, it enabled synchronization of the data with the beam application monitoring system, and thus assign each measured secondary ion with its respective pencil beam, opening entirely new research possibilities.  The experiments were performed at the Heidelberg Ion-Beam Therapy Center (HIT), closely mimicking clinic-like conditions. Single fields of carbon-ion treatment plans with a prescribed fraction dose of 3 Gy (RBE) were used to simulate treatments of spherical tumor volumes in the used head models. Two types of head models were used: a homogeneous plastic cylinder and an anthropomorphic head phantom composed of real bones and tissue-equivalent materials. Secondary ions exiting the head models during irradiation were detected with a mini-tracker composed of two small (2cm²) parallel Timepix3 detectors placed downstream of the head with a certain angle with respect to the beam axis. Inter-fractional changes were modeled by adding or removing 2-mm-thick slabs positioned in front or inside the targeted head models.  Within the thesis, it was demonstrated that the developed method for the analysis of the measured track distributions, taking into account the actual time-dependent position of the pencil beam, approximated the measured position of the secondary ion creation in the head model significantly better than the methods developed up to now. By using this method, surface changes down to 1 mm were found to be detectable even for the anatomical head phantom. Internal changes of 2-mm-thickness extending over the whole lateral tumor dimension (wide changes) were found to be detectable for all investigated positions between the dose plateau and the distal end of the tumor. The significance was at least 3 standard deviations for a single mini-tracker and of at least 9 standard deviations when using 8 mini-trackers at 30°, as it is planned for the future. Correct localization of all the studied changes was achieved within 6.3 mm of their actual position. This is sufficient to provide information to the clinicians about the part of the dose distribution which is affected. The detection of 2-mm-thick changes affecting only a part of the tumor (narrow changes), required the development of a new method based on the additional information on the lateral pencil beam positions. With this technique, internal 2-mm-thick changes as small as 10 mm in diameter placed in front of the tumor, were demonstrated to be detectable with a significance of almost 2 standard deviations. This technique makes the developed monitoring method sensitive to the lateral position of the cavity and thus reaches the third dimension. Positions of the mini-tracker closer to the beam axis were found to provide higher detection efficiencies due to the larger amount of data, but also lead to larger geometrical uncertainties and lower localization accuracies. At larger angles, the accuracy of the change localization was found to be better. For future measurements, multi-angle detection systems are recommended to maximize both detectability and localization accuracy. Finally, the applicability of the monitoring of carbon-ion pencil beam delivery in a real patient treatment was demonstrated by designing a patient-friendly measurement system that was shown to be safely used in a clinical environment. After investigating the influence of the developed system on the beam delivery, and with the fulfillment of all clinical and safety requirements, the integration of this system into the clinical workflow of the HIT facility was achieved. With this detection system, the first measurement of a real patient irradiation fraction was performed. The amount of measured data was sufficient to determine a secondary-ion emission profile along the depth of the patient’s head. And a differentiation between pencil beams with a 1 cm range difference was demonstrated.  In conclusion, this thesis presents novel methods for carbon ion treatment monitoring of external and internal patient geometry changes in the head based on secondary ion tracking, allowing detection changes down to the clinically desired 2 mm. The designed monitoring system was proven to be well incorporable into a clinical workflow. Thus, the presented work paves the way towards monitoring inter-fractional changes along the beam direction during carbon-ion beam therapy and builds the basis for the upcoming clinical trial at the HIT facility.
date: 2022
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/31506/1/Ghesquiere-Dierickx_Laura_10_10_1993_Dissertation.pdf
identifier: DOI:10.11588/heidok.00031506
identifier: urn:nbn:de:bsz:16-heidok-315068
identifier:   Ghesquiere-Dierickx, Laura Marie Helene  (2022) Carbon-ion radiotherapy monitoring in depth using secondary-ion tracking.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/31506/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng