Christopher Kurz

Distributions of secondary particles in proton and carbon-ion therapy: a comparison between GATE/Geant4 and FLUKA Monte Carlo codes

Monte Carlo simulations play a crucial role for in-vivo treatment monitoring based on PET and prompt gamma imaging in proton and carbon-ion therapies. The accuracy of the nuclear fragmentation models implemented in these codes might affect the quality of the treatment verification. In this paper, we investigate the nuclear models implemented in GATE/Geant4 and FLUKA by comparing the angular and energy distributions of secondary particles exiting a homogeneous target of PMMA. Comparison results were restricted to fragmentation of (16)O and (12)C. Despite the very simple target and set-up, substantial discrepancies were observed between the two codes. For instance, the number of high energy (>1 MeV) prompt gammas exiting the target was about twice as large with GATE/Geant4 than with FLUKA both for proton and carbon ion beams. Such differences were not observed for the predicted annihilation photon production yields, for which ratios of 1.09 and 1.20 were obtained between GATE and FLUKA for the proton beam and the carbon ion beam, respectively. For neutrons and protons, discrepancies from 14% (exiting protons-carbon ion beam) to 57% (exiting neutrons-proton beam) have been identified in production yields as well as in the energy spectra for neutrons.

Implementation and initial clinical experience of offline PET/CT-based verification of scanned carbon ion treatment

BACKGROUND AND PURPOSE We report on the implementation of offline PET/CT-based treatment verification at the Heidelberg Ion Beam Therapy Centre (HIT) and present first clinical cases for post-activation measurements after scanned carbon ion irradiation. Key ingredient of this in-vivo treatment verification is the comparison of irradiation-induced patient activation measured by a PET scanner with a prediction simulated by means of Monte Carlo techniques. MATERIAL AND METHODS At HIT, a commercial full-ring PET/CT scanner has been installed in close vicinity to the treatment rooms. After selected irradiation fractions, the patient either walks to the scanner for acquisition of the activation data or is transported using a shuttle system. The expected activity distribution is obtained from the production of β(+)-active isotopes simulated by the FLUKA code on the basis of the patient-specific treatment plan, post-processed considering the time course of the respective treatment fraction, the estimated biological washout of the induced activity and a simplified model of the imaging process. RESULTS We present four patients with different indications of head, head/neck, liver and pelvic tumours. A clear correlation between the measured PET signal and the simulated activity pattern is observed for all patients, thus supporting a proper treatment delivery. In the case of a pelvic tumour patient it was possible to detect minor treatment delivery inaccuracies. CONCLUSIONS The initial clinical experience proves the feasibility of the implemented strategy for offline confirmation of scanned carbon ion irradiation and therefore constitutes a first step towards a comprehensive PET/CT-based treatment verification in the clinical routine at HIT.

Monte Carlo calculations of positron emitter yields in proton radiotherapy

Positron emission tomography (PET) is a promising tool for monitoring the three-dimensional dose distribution in charged particle radiotherapy. PET imaging during or shortly after proton treatment is based on the detection of annihilation photons following the ß(+)-decay of radionuclides resulting from nuclear reactions in the irradiated tissue. Therapy monitoring is achieved by comparing the measured spatial distribution of irradiation-induced ß(+)-activity with the predicted distribution based on the treatment plan. The accuracy of the calculated distribution depends on the correctness of the computational models, implemented in the employed Monte Carlo (MC) codes that describe the interactions of the charged particle beam with matter and the production of radionuclides and secondary particles. However, no well-established theoretical models exist for predicting the nuclear interactions and so phenomenological models are typically used based on parameters derived from experimental data. Unfortunately, the experimental data presently available are insufficient to validate such phenomenological hadronic interaction models. Hence, a comparison among the models used by the different MC packages is desirable. In this work, starting from a common geometry, we compare the performances of MCNPX, GATE and PHITS MC codes in predicting the amount and spatial distribution of proton-induced activity, at therapeutic energies, to the already experimentally validated PET modelling based on the FLUKA MC code. In particular, we show how the amount of ß(+)-emitters produced in tissue-like media depends on the physics model and cross-sectional data used to describe the proton nuclear interactions, thus calling for future experimental campaigns aiming at supporting improvements of MC modelling for clinical application of PET monitoring.

Ultrasound tracking for intra-fractional motion compensation in radiation therapy.

Modern techniques as ion beam therapy or 4D imaging require precise target position information. However, target motion particularly in the abdomen due to respiration or patient movement is still a challenge and demands methods that detect and compensate this motion. Ultrasound represents a non-invasive, dose-free and model-independent alternative to fluoroscopy, respiration belt or optical tracking of the patient surface. Thus, ultrasound based motion tracking was integrated into irradiation with actively scanned heavy ions. In a first in vitro experiment, the ultrasound tracking system was used to compensate diverse sinusoidal target motions in two dimensions. A time delay of ∼200 ms between target motion and reported position data was compensated by a prediction algorithm (artificial neural network). The irradiated films proved feasibility of the proposed method. Furthermore, a practicable and reliable calibration workflow was developed to enable the transformation of ultrasound tracking data to the coordinates of the treatment delivery or imaging system - even if the ultrasound probe moves due to respiration. A first proof of principle experiment was performed during time-resolved positron emission tomography (4DPET) to test the calibration workflow and to show the accuracy of an ultrasound based motion tracking in vitro. The results showed that optical ultrasound tracking can reach acceptable accuracies and encourage further research.

Comparing cone-beam CT intensity correction methods for dose recalculation in adaptive intensity-modulated photon and proton therapy for head and neck cancer

ABSTRACT Background. Adaptive intensity-modulated photon and proton radiotherapy (IMRT and IMPT) of head and neck (H&N) cancer requires frequent three-dimensional (3D) dose calculation. We compared two approaches for dose recalculation on the basis of intensity-corrected cone-beam (CB) x-ray computed tomography (CT) images. Material and methods. For nine H&N tumor patients, virtual CTs (vCT) were generated by deformable image registration of the planning CT (pCT) to the CBCT. The second intensity correction approach used population-based lookup tables for scaling CBCT intensities to the pCT HU range (CBCTLUT). IMRT and IMPT plans were generated with a commercial treatment planning system. Dose recalculations on vCT and CBCTLUT were analyzed using a (3%, 3 mm) gamma-index analysis and comparison of normal tissue and tumor dose/volume parameters. A replanning CT (rpCT) acquired within three days of the CBCT served as reference. Single field uniform dose (SFUD) proton plans were created and recalculated on vCT and CBCTLUT for proton range comparison. Results. Dose/volume parameters showed minor differences between rpCT, vCT and CBCTLUT in IMRT, but clinically relevant deviations between CBCTLUT and rpCT in the spinal cord for IMPT. Gamma-index pass-rates were found increased for vCT with respect to CBCTLUT in IMPT (by up to 21 percentage points) and IMRT (by up to 9 percentage points) for most cases. The SFUD-based proton range assessment showed improved agreement of vCT and rpCT, with 88–99% of the depth dose profiles in beams eye view agreeing within 3 mm. For CBCTLUT, only 80–94% of the profiles fulfilled this criterion. Conclusion. vCT and CBCTLUT are suitable options for dose recalculation in adaptive IMRT. In the scope of IMPT, the vCT approach is preferable.

First experimental-based characterization of oxygen ion beam depth dose distributions at the Heidelberg Ion-Beam Therapy Center

Over the last decades, the application of proton and heavy-ion beams to external beam radiotherapy has rapidly increased. Due to the favourable lateral and depth dose profile, the superposition of narrow ion pencil beams may enable a highly conformal dose delivery to the tumour, with better sparing of the surrounding healthy tissue in comparison to conventional radiation therapy with photons. To fully exploit the promised clinical advantages of ion beams, an accurate planning of the patient treatments is required. The clinical treatment planning system (TPS) at the Heidelberg Ion-Beam Therapy Center (HIT) is based on a fast performing analytical algorithm for dose calculation, relying, among others, on laterally integrated depth dose distributions (DDDs) simulated with the FLUKA Monte Carlo (MC) code. Important input parameters of these simulations need to be derived from a comparison of the simulated DDDs with measurements. In this work, the first measurements of (16)O ion DDDs at HIT are presented with a focus on the determined Bragg peak positions and the understanding of factors influencing the shape of the distributions. The measurements are compared to different simulation approaches aiming to reproduce the acquired data at best. A simplified geometrical model is first used to optimize important input parameters, not known a priori, in the simulations. This method is then compared to a more realistic, but also more time-consuming simulation approach better accounting for the experimental set-up and the measuring process. The results of this work contributed to a pre-clinical oxygen ion beam database, which is currently used by a research TPS for corresponding radio-biological cell experiments. A future extension to a clinical database used by the clinical TPS at HIT is foreseen. As a side effect, the performed investigations showed that the typical water equivalent calibration approach of experimental data acquired with water column systems leads to slight deviations between the experimentally determined and the real Bragg peak positions. For improved accuracy, the energy dependence of the stopping power, and herewith the water equivalent thickness, of the material downstream of the water tank should be considered in the analysis of measured data.

TPS(PET)-A TPS-based approach for in vivo dose verification with PET in proton therapy.

Since the interest in ion-irradiation for tumour therapy has significantly increased over the last few decades, intensive investigations are performed to improve the accuracy of this form of patient treatment. One major goal is the development of methods for in vivo dose verification. In proton therapy, a PET (positron emission tomography)-based approach measuring the irradiation-induced tissue activation inside the patient has been already clinically implemented. The acquired PET images can be compared to an expectation, derived under the assumption of a correct treatment application, to validate the particle range and the lateral field position in vivo. In the context of this work, TPSPET is introduced as a new approach to predict proton-irradiation induced three-dimensional positron emitter distributions by means of the same algorithms of the clinical treatment planning system (TPS). In order to perform additional activity calculations, reaction-channel-dependent input positron emitter depth distributions are necessary, which are determined from the application of a modified filtering approach to the TPS reference depth dose profiles in water. This paper presents the implementation of TPSPET on the basis of the research treatment planning software treatment planning for particles. The results are validated in phantom and patient studies against Monte Carlo simulations, and compared to β(+)-emitter distributions obtained from a slightly modified version of the originally proposed one-dimensional filtering approach applied to three-dimensional dose distributions. In contrast to previously introduced methods, TPSPET provides a faster implementation, the results show no sensitivity to lateral field extension and the predicted β(+)-emitter densities are fully consistent to the planned treatment dose as they are calculated by the same pencil beam algorithms. These findings suggest a large potential of the application of TPSPET for in vivo dose verification in the daily clinical routine.

Monitoring of patients treated with particle therapy using positron-emission-tomography (PET): the MIRANDA study.

BackgroundThe purpose of this clinical study is to investigate the clinical feasibility and effectiveness of offline Positron-Emission-Tomography (PET) quality assurance for promoting the accuracy of proton and carbon ion beam therapy.Methods/DesignA total of 240 patients will be recruited, evenly sampled among different analysis groups including tumors of the brain, skull base, head and neck region, upper gastrointestinal tract including the liver, lower gastrointestinal tract, prostate and pelvic region. From the comparison of the measured activity with the planned dose and its corresponding simulated activity distribution, conclusions on the delivered treatment will be inferred and, in case of significant deviations, correction strategies will be elaborated.DiscussionThe investigated patients are expected to benefit from this study, since in case of detected deviations between planned and actual treatment delivery a proper intervention (e.g., correction) could be performed in a subsequent irradiation fraction. In this way, an overall better treatment could be achieved than without any in-vivo verification. Moreover, site-specific patient-population information on the precision of the ion range at HIT might enable improvement of the CT-range calibration curve as well as safe reduction of the treatment margins to promote enhanced treatment plan conformality and dose escalation for full clinical exploitation of the promises of ion beam therapy.Trial RegistrationNCT01528670

Challenges of radiotherapy: Report on the 4D treatment planning workshop 2013

This report, compiled by experts on the treatment of mobile targets with advanced radiotherapy, summarizes the main conclusions and innovations achieved during the 4D treatment planning workshop 2013. This annual workshop focuses on research aiming to advance 4D radiotherapy treatments, including all critical aspects of time resolved delivery, such as in-room imaging, motion detection, motion managing, beam application, and quality assurance techniques. The report aims to revise achievements in the field and to discuss remaining challenges and potential solutions. As main achievements advances in the development of a standardized 4D phantom and in the area of 4D-treatment plan optimization were identified. Furthermore, it was noticed that MR imaging gains importance and high interest for sequential 4DCT/MR data sets was expressed, which represents a general trend of the field towards data covering a longer time period of motion. A new point of attention was work related to dose reconstructions, which may play a major role in verification of 4D treatment deliveries. The experimental validation of results achieved by 4D treatment planning and the systematic evaluation of different deformable image registration methods especially for inter-modality fusions were identified as major remaining challenges. A challenge that was also suggested as focus for future 4D workshops was the adaptation of image guidance approaches from conventional radiotherapy into particle therapy. Besides summarizing the last workshop, the authors also want to point out new evolving demands and give an outlook on the focus of the next workshop.

Investigating deformable image registration and scatter correction for CBCT-based dose calculation in adaptive IMPT

PURPOSE This work aims at investigating intensity corrected cone-beam x-ray computed tomography (CBCT) images for accurate dose calculation in adaptive intensity modulated proton therapy (IMPT) for prostate and head and neck (H&N) cancer. A deformable image registration (DIR)-based method and a scatter correction approach using the image data obtained from DIR as prior are characterized and compared on the basis of the same clinical patient cohort for the first time. METHODS Planning CT (pCT) and daily CBCT data (reconstructed images and measured projections) of four H&N and four prostate cancer patients have been considered in this study. A previously validated Morphons algorithm was used for DIR of the planning CT to the current CBCT image, yielding a so-called virtual CT (vCT). For the first time, this approach was translated from H&N to prostate cancer cases in the scope of proton therapy. The warped pCT images were also used as prior for scatter correction of the CBCT projections for both tumor sites. Single field uniform dose and IMPT (only for H&N cases) treatment plans have been generated with a research version of a commercial planning system. Dose calculations on vCT and scatter corrected CBCT (CBCTcor) were compared by means of the proton range and a gamma-index analysis. For the H&N cases, an additional diagnostic replanning CT (rpCT) acquired within three days of the CBCT served as additional reference. For the prostate patients, a comprehensive contour comparison of CBCT and vCT, using a trained physicians delineation, was performed. RESULTS A high agreement of vCT and CBCTcor was found in terms of the proton range and gamma-index analysis. For all patients and indications between 95% and 100% of the proton dose profiles in beams eye view showed a range agreement of better than 3 mm. The pass rate in a (2%,2 mm) gamma-comparison was between 96% and 100%. For H&N patients, an equivalent agreement of vCT and CBCTcor to the reference rpCT was observed. However, for the prostate cases, an insufficient accuracy of the vCT contours retrieved from DIR was found, while the CBCTcor contours showed very high agreement to the contours delineated on the raw CBCT. CONCLUSIONS For H&N patients, no considerable differences of vCT and CBCTcor were found. For prostate cases, despite the high dosimetric agreement, the DIR yields incorrect contours, probably due to the more pronounced anatomical changes in the abdomen and the reduced soft-tissue contrast in the CBCT. Using the vCT as prior, these inaccuracies can be overcome and images suitable for accurate delineation and dose calculation in CBCT-based adaptive IMPT can be retrieved from scatter correction of the CBCT projections.