Publications by authors named "Guillaume Janssens"

44 Publications

Toward MR-integrated proton therapy: modeling the potential benefits for liver tumors.

Phys Med Biol 2021 Aug 18. Epub 2021 Aug 18.

Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts, UNITED STATES.

Magnetic Resonance Imaging (MRI)-integrated proton therapy (MRiPT) is envisioned to improve treatment quality for many cancer patients. However, given the availability of alternative image-guided strategies, its clinical need is yet to be justified. This study aims to compare the expected clinical outcomes of MRiPT with standard of practice Cone-Beam CT (CBCT)-guided PT, and other MR-guided methods, i.e. offline MR-guided PT and MR-linac, for treatment of liver tumors. Clinical outcomes were assessed by quantifying the dosimetric and biological impact of target margin reduction enabled by each image-guided approach. Planning Target Volume (PTV) margins were calculated using random and systematic setup, delineation and motion uncertainties, which were quantified by analyzing longitudinal MRI data for 10 patients with liver tumors. Proton treatment plans were created using appropriate PTV margins for each image-guided PT method. Photon plans with margins equivalent to MRiPT were generated to represent MR-linac. Normal tissue complication probabilities (NTCP) of the uninvolved liver were compared. We found that PTV margin can be reduced by 20% and 40% for offline MR-guided PT and MRiPT, respectively, compared with CBCT-guided PT. Furthermore, CTV expansion could be largely alleviated when delineating on MRI rather than CT. Dosimetric implications included decreased equivalent mean dose of the uninvolved liver, i.e. up to 24.4 Gy and 27.3 Gy for offline MR-guided PT and MRiPT compared to CBCT-guided PT, respectively. Considering Child-Pugh score increase as endpoint, NTCP of the uninvolved liver was significantly decreased for MRiPT compared to CBCT-guided PT (up to 48.4%, p<0.01), offline MR-guided PT (up to 12.9%, p<0.01) and MR-linac (up to 30.8%, p<0.05). Target underdose was possible in the absence of MRI-guidance (D90 reduction up to 4.2Gy in 20% of cases). In conclusion, MRiPT has the potential to significantly reduce healthy liver toxicities in patients with liver tumors. It is superior to other image-guided techniques currently available.
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http://dx.doi.org/10.1088/1361-6560/ac1ef2DOI Listing
August 2021

Linear Energy Transfer Incorporated Spot-Scanning Proton Arc Therapy Optimization: A Feasibility Study.

Front Oncol 2021 12;11:698537. Epub 2021 Jul 12.

Department of Radiation Oncology, Beaumont Health System, Royal Oak, MI, United States.

Purpose: To integrate dose-averaged linear energy transfer (LET) into spot-scanning proton arc therapy (SPArc) optimization and to explore its feasibility and potential clinical benefits.

Methods: An open-source proton planning platform (OpenREGGUI) has been modified to incorporate LET into optimization for both SPArc and multi-beam intensity-modulated proton therapy (IMPT) treatment planning. SPArc and multi-beam IMPT plans with different beam configurations for a prostate patient were generated to investigate the feasibility of LET-based optimization using SPArc in terms of spatial LET distribution and plan delivery efficiency. One liver and one brain case were studied to further evaluate the advantages of SPArc over multi-beam IMPT.

Results: With similar dose distributions, the efficacy of spatially optimizing LET distributions improves with increasing number of beams. Compared with multi-beam IMPT plans, SPArc plans show substantial improvement in LET distributions while maintaining similar delivery efficiency. Specifically, for the liver case, the average LET in the GTV was increased by 124% for the SPArc plan, and only 9.6% for the 2-beam IMPT plan compared with the 2-beam non-LET optimized IMPT plan. In case of LET optimization for the brain case, the SPArc plan could effectively increase the average LET in the CTV and decrease the values in the critical structures while smaller improvement was observed in 3-beam IMPT plans.

Conclusion: This work demonstrates the feasibility and significant advantages of using SPArc for LET-based optimization, which could maximize the LET distribution wherever is desired inside the target and averts the high LET away from the adjacent critical organs-at-risk.
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http://dx.doi.org/10.3389/fonc.2021.698537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313436PMC
July 2021

Validation of proton dose calculation on scatter corrected 4D cone beam computed tomography using a porcine lung phantom.

Phys Med Biol 2021 Aug 30;66(17). Epub 2021 Aug 30.

Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.

Proton therapy treatment for lungs remains challenging as images enabling the detection of inter- and intra-fractional motion, which could be used for proton dose adaptation, are not readily available. 4D computed tomography (4DCT) provides high image quality but is rarely available in-room, while in-room 4D cone beam computed tomography (4DCBCT) suffers from image quality limitations stemming mostly from scatter detection. This study investigated the feasibility of using virtual 4D computed tomography (4DvCT) as a prior for a phase-per-phase scatter correction algorithm yielding a 4D scatter corrected cone beam computed tomography image (4DCBCT), which can be used for proton dose calculation. 4DCT and 4DCBCT scans of a porcine lung phantom, which generated reproducible ventilation, were acquired with matching breathing patterns. Diffeomorphic Morphons, a deformable image registration algorithm, was used to register the mid-position 4DCT to the mid-position 4DCBCT and yield a 4DvCT. The 4DCBCT was reconstructed using motion-aware reconstruction based on spatial and temporal regularization (MA-ROOSTER). Successively for each phase, digitally reconstructed radiographs of the 4DvCT, simulated without scatter, were exploited to correct scatter in the corresponding CBCT projections. The 4DCBCTwas then reconstructed with MA-ROOSTER using the corrected CBCT projections and the same settings and deformation vector fields as those already used for reconstructing the 4DCBCT. The 4DCBCTand the 4DvCT were evaluated phase-by-phase, performing proton dose calculations and comparison to those of a ground truth 4DCT by means of dose-volume-histograms (DVH) and gamma pass-rates (PR). For accumulated doses, DVH parameters deviated by at most 1.7% in the 4DvCT and 2.0% in the 4DCBCTcase. The gamma PR for a (2%, 2 mm) criterion with 10% threshold were at least 93.2% (4DvCT) and 94.2% (4DCBCT), respectively. The 4DCBCTtechnique enabled accurate proton dose calculation, which indicates the potential for applicability to clinical 4DCBCT scans.
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http://dx.doi.org/10.1088/1361-6560/ac16e9DOI Listing
August 2021

First-In-Human Validation of CT-Based Proton Range Prediction Using Prompt Gamma Imaging in Prostate Cancer Treatments.

Int J Radiat Oncol Biol Phys 2021 Jul 3. Epub 2021 Jul 3.

OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology - OncoRay, Dresden, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; German Cancer Consortium (DKTK), partner site Dresden, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany.

Purpose: Uncertainty in computed tomography (CT)-based range prediction substantially impairs the accuracy of proton therapy. Direct determination of the stopping-power ratio (SPR) from dual-energy CT (DECT) has been proposed (DirectSPR), and initial validation studies in phantoms and biological tissues have proven a high accuracy. However, a thorough validation of range prediction in patients has not yet been achieved by any means. Here, we present the first systematic validation of CT-based proton range prediction in patients using prompt gamma imaging (PGI).

Methods And Materials: A PGI slit camera system with improved positioning accuracy, using a floor-based docking station, was used. Its overall uncertainty for range prediction validation was determined experimentally with both x-ray and beam measurements. The accuracy of range prediction in patients was determined from clinical PGI measurements during hypofractionated treatment of 5 patients with prostate cancer - in total 30 fractions with in-room control-CTs. For each pencil-beam-scanning spot, the range shift was obtained by comparing the PGI measurement to a control-CT-based PGI simulation. Three different SPR prediction approaches were applied in simulations: a standard CT-number-to-SPR conversion (Hounsfield look-up table [HLUT]), an adapted HLUT (DECT optimized), and DirectSPR. The spot-wise weighted mean range shift from all spots served as a measure for the accuracy of the respective range prediction approach.

Results: A mean range prediction accuracy of 0.0% ± 0.5%, 0.3% ± 0.4%, and 1.8% ± 0.4% was obtained for DirectSPR, adapted HLUT, and standard HLUT, respectively. The overall validation uncertainty of the second-generation PGI slit camera is about 1 mm (2σ) for all approaches, which is smaller than the range prediction uncertainty for deep-seated tumors.

Conclusions: For the first time, range prediction accuracy was assessed in clinical routine using PGI range verification in prostate cancer treatments. Both DECT-derived range prediction approaches agree well with the measured proton range from PGI verification, whereas the standard HLUT approach differs relevantly. These results endorse the recent reduction of clinical safety margins in DirectSPR-based treatment planning in our institution.
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http://dx.doi.org/10.1016/j.ijrobp.2021.06.036DOI Listing
July 2021

Thermoacoustic range verification during pencil beam delivery of a clinical plan to an abdominal imaging phantom.

Radiother Oncol 2021 06 30;159:224-230. Epub 2021 Mar 30.

Computerized Imaging Reference Systems, United States.

Purpose: The purpose of this phantom study is to demonstrate that thermoacoustic range verification could be performed clinically. Thermoacoustic emissions generated in an anatomical multimodality imaging phantom during delivery of a clinical plan are compared to simulated emissions to estimate range shifts compared to the treatment plan.

Methods: A single-field 12-layerproton pencil beam scanning (PBS)treatment plancreated in Pinnacle prescribing6 Gy/fractionwas delivered by a superconducting synchrocyclotron to a triple modality (CT, MRI, and US) abdominal imaging phantom.Data was acquired by four acoustic receivers rigidly affixed to a linear ultrasound array. Receivers 1-2 were located distal to the treatment volume, whereas 3-4 were lateral. Receivers' room coordinates were computed relative to the ultrasound image plane after co-registration to the planning CT volume. For each prescribed beamlet, a set of thermoacoustic emissions corresponding to varied beam energies were computed. Simulated emissions were compared to measured emissions to estimate shifts of the Bragg peak.

Results: Shifts were small for high-dose beamlets that stopped in soft tissue. Signals acquired by channels 1-2 yielded shifts of -0.2±0.7mm relative to Monte Carlo simulations for high dose spots (~40 cGy) in the second layer. Additionally, for beam energy ≥125 MeV, thermoacoustic emissions qualitatively tracked lateral motion of pristine beams in a layered gelatin phantom, and time shifts induced by changing phantom layers were self-consistent within nanoseconds.

Conclusions: Acoustic receivers tuned to spectra of thermoacoustic emissions may enable range verification during proton therapy.
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http://dx.doi.org/10.1016/j.radonc.2021.03.027DOI Listing
June 2021

Anthropomorphic lung phantom based validation of in-room proton therapy 4D-CBCT image correction for dose calculation.

Z Med Phys 2020 Nov 25. Epub 2020 Nov 25.

Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany; Department of Medical Physics, Faculty of Physics, Ludwig-Maximilians-Universität München (LMU Munich), Garching, Germany. Electronic address:

Purpose: Ventilation-induced tumour motion remains a challenge for the accuracy of proton therapy treatments in lung patients. We investigated the feasibility of using a 4D virtual CT (4D-vCT) approach based on deformable image registration (DIR) and motion-aware 4D CBCT reconstruction (MA-ROOSTER) to enable accurate daily proton dose calculation using a gantry-mounted CBCT scanner tailored to proton therapy.

Methods: Ventilation correlated data of 10 breathing phases were acquired from a porcine ex-vivo functional lung phantom using CT and CBCT. 4D-vCTs were generated by (1) DIR of the mid-position 4D-CT to the mid-position 4D-CBCT (reconstructed with the MA-ROOSTER) using a diffeomorphic Morphons algorithm and (2) subsequent propagation of the obtained mid-position vCT to the individual 4D-CBCT phases. Proton therapy treatment planning was performed to evaluate dose calculation accuracy of the 4D-vCTs. A robust treatment plan delivering a nominal dose of 60Gy was generated on the average intensity image of the 4D-CT for an approximated internal target volume (ITV). Dose distributions were then recalculated on individual phases of the 4D-CT and the 4D-vCT based on the optimized plan. Dose accumulation was performed for 4D-vCT and 4D-CT using DIR of each phase to the mid position, which was chosen as reference. Dose based on the 4D-vCT was then evaluated against the dose calculated on 4D-CT both, phase-by-phase as well as accumulated, by comparing dose volume histogram (DVH) values (D, D, D, D) for the ITV, and by a 3D-gamma index analysis (global, 3%/3mm, 5Gy, 20Gy and 30Gy dose thresholds).

Results: Good agreement was found between the 4D-CT and 4D-vCT-based ITV-DVH curves. The relative differences ((CT-vCT)/CT) between accumulated values of ITV D, D, D and D for the 4D-CT and 4D-vCT-based dose distributions were -0.2%, 0.0%, -0.1% and -0.1%, respectively. Phase specific values varied between -0.5% and 0.2%, -0.2% and 0.5%, -3.5% and 1.5%, and -5.7% and 2.3%. The relative difference of accumulated D over the lungs was 2.3% and D for the phases varied between -5.4% and 5.8%. The gamma pass-rates with 5Gy, 20Gy and 30Gy thresholds for the accumulated doses were 96.7%, 99.6% and 99.9%, respectively. Phase-by-phase comparison yielded pass-rates between 86% and 97%, 88% and 98%, and 94% and 100%.

Conclusions: Feasibility of the suggested 4D-vCT workflow using proton therapy specific imaging equipment was shown. Results indicate the potential of the method to be applied for daily 4D proton dose estimation.
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http://dx.doi.org/10.1016/j.zemedi.2020.09.004DOI Listing
November 2020

Accounting for prompt gamma emission and detection for range verification in proton therapy treatment planning.

Phys Med Biol 2021 02 16;66(5):055005. Epub 2021 Feb 16.

Ludwig-Maximilians-Universität München, Department of Medical Physics, Munich, Germany. These authors have contributed to this work equally.

Prompt gamma (PG) imaging is widely investigated as one of the most promising methods for proton range verification in proton therapy. The performance of this technique is affected by several factors like tissue heterogeneity, number of protons in the considered pencil beam and the detection device. Our previous work proposed a new treatment planning concept which boosts the number of protons of a few PG monitoring-friendly pencil beams (PBs), selected on the basis of two proposed indicators quantifying the conformity between the dose and PG at the emission level, above the desired detectability threshold. To further explore this method at the detection level, in this work we investigated the response of a knife-edge slit PG camera which was deployed in the first clinical application of PG to proton therapy monitoring. The REGistration Graphical User Interface (REGGUI) is employed to simulate the PG emission, PG detection as well as the corresponding dose distribution. As the PG signal detected by this kind of PG camera is sensitive to the relative position of the camera and PG signal falloff, we optimized our PB selection method for this camera by introducing a new camera position indicator identifying whether the expected falloff of the PG signal is centered in the field of view of the camera or not. Our camera-adapted PB selection method is investigated using computed tomography (CT) scans at two different treatment time points of a head and neck, and a prostate cancer patient under scenarios considering different statistics level. The results show that a precision of 0.8 mm for PG falloff identification can be achieved when a PB has more than 2 × 10 primary protons. Except for one case due to unpredictable and comparably large anatomical changes, the PG signals of most of the PBs recommended by all our indicators are observed to be reliable for proton range verification with deviations between the inter-fractional shift of proton range (as deduced from the PB dose distribution) and the detected PG signal within 2.0 mm. In contrast, a shift difference up to 9.6 mm has been observed for the rejected PBs. The magnitude of the proton range shift due to the inter-fractional anatomical changes is observed to be up to 23 mm. The proposed indicators are shown to be valuable for identifying and recommending reliable PBs to create new PG monitoring-friendly TPs. Comparison between our PB boosting method and the alternative PB aggregation, which combines the signal of nearby PBs to reach the desired counting statistics, is also discussed.
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http://dx.doi.org/10.1088/1361-6560/abc939DOI Listing
February 2021

Evaluation of continuous beam rescanning versus pulsed beam in pencil beam scanned proton therapy for lung tumours.

Phys Med Biol 2020 12 18;65(23):23NT01. Epub 2020 Dec 18.

Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

The treatment of moving targets with pencil beam scanned proton therapy (PBS-PT) may rely on rescanning strategies to smooth out motion induced dosimetric disturbances. PBS-PT machines, such as Proteus®Plus (PPlus) and Proteus®One (POne), deliver a continuous or a pulsed beam, respectively. In PPlus, scaled (or no) rescanning can be applied, while POne implies intrinsic 'rescanning' due to its pulsed delivery. We investigated the efficacy of these PBS-PT delivery types for the treatment of lung tumours. In general, clinically acceptable plans were achieved, and PPlus and POne showed similar effectiveness.
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http://dx.doi.org/10.1088/1361-6560/abc5c8DOI Listing
December 2020

Technical Note: 4D cone-beam CT reconstruction from sparse-view CBCT data for daily motion assessment in pencil beam scanned proton therapy (PBS-PT).

Med Phys 2020 Dec 24;47(12):6381-6387. Epub 2020 Oct 24.

Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, 9713 GZ, The Netherlands.

Purpose: The number of pencil beam scanned proton therapy (PBS-PT) facilities equipped with cone-beam computed tomography (CBCT) imaging treating thoracic indications is constantly rising. To enable daily internal motion monitoring during PBS-PT treatments of thoracic tumors, we assess the performance of Motion-Aware RecOnstructiOn method using Spatial and Temporal Regularization (MA-ROOSTER) four-dimensional CBCT (4DCBCT) reconstruction for sparse-view CBCT data and a realistic data set of patients treated with proton therapy.

Methods: Daily CBCT projection data for nine non-small cell lung cancer (NSCLC) patients and one SCLC patient were acquired at a proton gantry system (IBA Proteus® One). Four-dimensional CBCT images were reconstructed applying the MA-ROOSTER and the conventional phase-correlated Feldkamp-Davis-Kress (PC-FDK) method. Image quality was assessed by visual inspection, contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and the structural similarity index measure (SSIM). Furthermore, gross tumor volume (GTV) centroid motion amplitudes were evaluated.

Results: Image quality for the 4DCBCT reconstructions using MA-ROOSTER was superior to the PC-FDK reconstructions and close to FDK images (median CNR: 1.23 [PC-FDK], 1.98 [MA-ROOSTER], and 1.98 [FDK]; median SNR: 2.56 [PC-FDK], 4.76 [MA-ROOSTER], and 5.02 [FDK]; median SSIM: 0.18 [PC-FDK vs FDK], 0.31 [MA-ROOSTER vs FDK]). The improved image quality of MA-ROOSTER facilitated GTV contour warping and realistic motion monitoring for most of the reconstructions.

Conclusion: MA-ROOSTER based 4DCBCTs performed well in terms of image quality and appear to be promising for daily internal motion monitoring in PBS-PT treatments of (N)SCLC patients.
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http://dx.doi.org/10.1002/mp.14521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821169PMC
December 2020

Prompt gamma imaging for the identification of regional proton range deviations due to anatomic change in a heterogeneous region.

Br J Radiol 2020 Dec 6;93(1116):20190619. Epub 2020 Oct 6.

Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA.

Objectives: Prompt gamma (PG) imaging has previously been demonstrated for use in proton range verification of a brain treatment with a homogeneous target region. In this study, the feasibility of PG imaging to detect anatomic change within a heterogeneous region is presented.

Methods: A prompt gamma camera recorded several fractions of a patient treatment to the base of skull. An evaluation CT revealed a decrease in sinus cavity filling during the treatment course. Comparison of PG profiles between measurement and simulation was performed to investigate range variations between planned and measured pencil beam spot positions.

Results: For one field, an average over range of 3 mm due to the anatomic change could be detected for a subset of spots traversing the sinus cavity region. The two other fields appeared less impacted by the change but predicted range variations could not be detected. These results were partially consistent with the simulations of the evaluation CT.

Conclusion: We report the first clinical application of PG imaging that detected some of the expected small regional proton range deviations due to anatomic change in a heterogeneous region. However, several limitations exist with the technology that may limit its sensitivity to detect range deviations in heterogeneous regions.

Advances In Knowledge: We report on the first detection of range variations due to anatomic change in a heterogeneous region using PGI. The results confirm the feasibility of using PG-based range verification in highly heterogeneous target regions to identify deviations from the treatment plan.
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http://dx.doi.org/10.1259/bjr.20190619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715997PMC
December 2020

Classification of the source of treatment deviation in proton therapy using prompt-gamma imaging information.

Med Phys 2020 Oct 3;47(10):5102-5111. Epub 2020 Aug 3.

OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Dresden, Germany.

Purpose: Prompt-gamma imaging (PGI)-based range verification has been successfully implemented in clinical proton therapy recently and its sensitivity to detect treatment deviations is currently investigated. The cause of treatment deviations can be multiple - for example, computed tomography (CT)-based range prediction, patient setup, and anatomical changes. Hence, it would be beneficial, if PGI-based verification would not only detect a treatment deviation but would also be able to directly identify its most probable source. Here, we propose a heuristically derived decision tree approach to automatically classify the sources of range deviation in proton pencil-beam scanning (PBS) treatments of head and neck tumors based on range information obtained with a PGI slit camera.

Materials And Methods: The decision tree model was iteratively generated on a training dataset of different anatomical complexities, for an anthropomorphic head phantom and patient CT data (planning and control CTs) from five patients. Different range prediction errors, setup changes and relevant and nonrelevant anatomical changes were introduced or derived from control CTs, summing up to a total of 98 training scenarios. Independent validation was performed for another 98 scenarios, derived solely from patient CT data of another seven patients. PBS head and neck treatment plans were generated for the nominal scenario. For all PBS spots in the investigated field, PGI profiles were simulated using a dedicated analytical model of the slit camera for the nominal as well as the different error scenarios. From comparison of PGI profiles for nominal and error scenarios, a spot-wise range shift after spot aggregation with a kernel of 7 mm sigma was determined for each error scenario. The heuristic approach includes a prefiltering of the most suitable PBS spots for PGI treatment verification. From the validation, the accuracy, sensitivity, and specificity of the model were determined.

Results: A five-step consecutive filter was developed to preselect PBS spots. On average, 25% of spots (1044 spots) remained as input for the classification model. The derived heuristic decision tree model is based on five parameters: The coefficient of determination (R ), the slope and intercept of the linear regression between PGI-derived range shifts and the respectively predicted proton ranges for the investigated PBS spots, as well as the average and standard deviation of the PGI-derived shifts. With this approach, 94 of 98 error scenarios could be classified correctly in validation (accuracy of 96%). A sensitivity and specificity of 100% and 86% were reached.

Conclusions: In this simulation study it was demonstrated that the source of a treatment deviation can be identified from simulated noiseless PGI information in head and neck tumor treatments with high sensitivity and specificity. The application, refinement, and evaluation of the approach on measured PGI data will be the next step to show the clinical feasibility of PGI-based error source classification.
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http://dx.doi.org/10.1002/mp.14393DOI Listing
October 2020

Estimation of respiratory phases during proton radiotherapy from a 4D-CT and Prompt gamma detection profiles.

Phys Med 2019 Aug 21;64:33-39. Epub 2019 Jun 21.

Université Catholique de Louvain, Molecular Imaging Radiotherapy and Oncology, Brussels, Belgium; KU Leuven, Department of Oncology, Laboratory of Experimental Radiotherapy, Leuven, Belgium.

Proton radiotherapy has a potential to provide an effective cancer treatment while sparing greater volume of healthy tissue than the conventional X-ray based radiotherapy. However, in lungs this potential is hindered by motion due to breathing. An important quantity in treatment verification is the correlation between the respiratory phases (RP) and the timing of pencil beam scanning (PBS). In this note, we demonstrate how the RP can be estimated using Prompt gamma (PG) detection profiles collected during a treatment. We utilized a 4D-CT of a patient with lung cancer, a treatment plan and a PG simulator. The treatment plan consisted of ten layers corresponding to ten proton energies. The RPs of the 4D-CT were interpolated using a deformable registration algorithm, so as to have fifty RPs in total. Deviations from regular breathing were introduced via time dependent frequency modulation. Fifty unique breathing patterns were generated, for which PG profiles were simulated for each pencil beam. Poisson noise was added to each PG profile to account for photon statistics. The RPs were estimated by comparing the PG profiles with and without Poisson noise via three different methods: the RP associated with each layer was estimated 1) independently of the other layers, 2) using a linear correlation between the layers, and 3) using a quadratic correlation between the layers. The best model, the quadratic model, yielded an average error in RP estimation relative to the breathing period of 5% of the breathing period or less with a 90% confidence interval.
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http://dx.doi.org/10.1016/j.ejmp.2019.06.006DOI Listing
August 2019

Technical Note: Monte Carlo methods to comprehensively evaluate the robustness of 4D treatments in proton therapy.

Med Phys 2019 Oct 31;46(10):4676-4684. Epub 2019 Aug 31.

Center for Molecular Imaging and Experimental Radiotherapy, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, 1200, Brussels, Belgium.

Introduction: Proton therapy is very sensitive to treatment uncertainties. These uncertainties can induce proton range variations and may lead to severe dose distortions. However, most commercial tools only offer a limited integration of these uncertainties during treatment planning. In order to verify the robustness of a treatment plan, this study aims at developing a comprehensive Monte Carlo simulation of the treatment delivery, including the simulation of setup and range errors, variation of the breathing motion, and interplay effect.

Method: Most clinically relevant uncertainties have been modeled and implemented in the fast Monte Carlo dose engine MCsquare. Especially, variation of the breathing motion is taken into account by deforming the initial Four-dimensional computed tomography (4DCT) series and generating multiple new 4DCT series with scaled motion. Systematic and random errors are randomly sampled, following a Monte Carlo approach, to generate individual erroneous treatment scenarios. The robustness of treatment plans is analyzed and reported with dose-volume histogram (DVH) bands. The statistical uncertainty coming from the Monte Carlo scenario sampling is studied.

Results: A validation demonstrated the ability of the motion model to generate new 4DCT series with scaled motion amplitude and improved image quality in comparison to the initial 4DCT. The robustness analysis is applied to a lung tumor treatment. Considering the proposed uncertainty model, the simulation of 300 treatment scenarios was necessary to reach an acceptable level of statistical uncertainty on the DVH band.

Conclusion: A comprehensive and statistically sound method of treatment plan robustness verification is proposed. The uncertainty model presented in this paper is not specific to protons and can also be applied to photon treatments. Moreover, the generated 4DCT series, with scaled motion, can be imported in commercial TPSs.
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http://dx.doi.org/10.1002/mp.13749DOI Listing
October 2019

The first prototype of spot-scanning proton arc treatment delivery.

Radiother Oncol 2019 08 14;137:130-136. Epub 2019 May 14.

Department of Radiation Oncology, Beaumont Health System, Royal Oak, USA. Electronic address:

Purpose: We report the first prototype of spot-scanning arc treatment (SPArc) delivery on a clinical proton beam therapy machine and evaluate its delivery accuracy and efficiency.

Methods And Materials: A new module called Proton Dynamic Arc Delivery (PDAD) was developed to allow simultaneously delivering spot-scanning proton beam treatments while rotating the gantry on an IBA Proteus®One proton machine. A series of measurements was performed to validate the basic beam characteristics. Subsequently, patient specific quality assurance (QA) of a brain SPArc plan was performed. Total SPArc treatment delivery time was also recorded and compared to the clinically delivered intensity modulated proton therapy (IMPT) treatment time. Finally, the log file of the SPArc plan was analyzed and processed to reconstruct the actual delivered dose.

Results: All the basic beam characteristics were confirmed in the PDAD mode, similar as those measured using fixed gantry deliveries in clinical mode. The brain SPArc plan with similar or superior plan quality was delivered in 4 mins compared to total 11 mins for the clinical treatment of the three-field IMPT plan. The patient QA result showed a good agreement between the measured and calculated dose distributions with the gamma index of 98.6% (3%/3 mm). The analysis of the log file confirmed the accuracy of the SPArc plan delivery, with the gamma index of 98.3% (1%/1 mm) between reconstructed and the planned doses.

Conclusion: The first prototype of dynamic proton arc delivery on a clinical proton therapy system was successfully performed. The measurements and simulations demonstrated the feasibility of SPArc treatment within the clinical requirements.
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http://dx.doi.org/10.1016/j.radonc.2019.04.032DOI Listing
August 2019

Validation and application of a fast Monte Carlo algorithm for assessing the clinical impact of approximations in analytical dose calculations for pencil beam scanning proton therapy.

Med Phys 2018 Dec 26;45(12):5631-5642. Epub 2018 Oct 26.

Department of Radiation Oncology, University of Pennsylvania, 3400 Civic Central Blvd, Philadelphia, PA, 19104, USA.

Purpose: Monte Carlo (MC) dose calculation is generally superior to analytical dose calculation (ADC) used in commercial TPS to model the dose distribution especially for heterogeneous sites, such as lung and head/neck patients. The purpose of this study was to provide a validated, fast, and open-source MC code, MCsquare, to assess the impact of approximations in ADC on clinical pencil beam scanning (PBS) plans covering various sites.

Methods: First, MCsquare was validated using tissue-mimicking IROC lung phantom measurements as well as benchmarked with the general purpose Monte Carlo TOPAS for patient dose calculation. Then a comparative analysis between MCsquare and ADC was performed for a total of 50 patients with 10 patients per site (including liver, pelvis, brain, head-and-neck, and lung). Differences among TOPAS, MCsquare, and ADC were evaluated using four dosimetric indices based on the dose-volume histogram (target Dmean, D95, homogeneity index, V95), a 3D gamma index analysis (using 3%/3 mm criteria), and estimations of tumor control probability (TCP).

Results: Comparison between MCsquare and TOPAS showed less than 1.8% difference for all of the dosimetric indices/TCP values and resulted in a 3D gamma index passing rate for voxels within the target in excess of 99%. When comparing ADC and MCsquare, the variances of all the indices were found to increase as the degree of tissue heterogeneity increased. In the case of lung, the D95s for ADC were found to differ by as much as 6.5% from the corresponding MCsquare statistic. The median gamma index passing rate for voxels within the target volume decreased from 99.3% for liver to 75.8% for lung. Resulting TCP differences can be large for lung (≤10.5%) and head-and-neck (≤6.2%), while smaller for brain, pelvis and liver (≤1.5%).

Conclusions: Given the differences found in the analysis, accurate dose calculation algorithms such as Monte Carlo simulations are needed for proton therapy, especially for disease sites with high heterogeneity, such as head-and-neck and lung. The establishment of MCsquare can facilitate patient plan reviews at any institution and can potentially provide unbiased comparison in clinical trials given its accuracy, speed and open-source availability.
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http://dx.doi.org/10.1002/mp.13231DOI Listing
December 2018

Feasibility of online IMPT adaptation using fast, automatic and robust dose restoration.

Phys Med Biol 2018 04 20;63(8):085018. Epub 2018 Apr 20.

Université catholique de Louvain, Center of Molecular Imaging, Radiotherapy and Oncology, Brussels, Belgium.

Intensity-modulated proton therapy (IMPT) offers excellent dose conformity and healthy tissue sparing, but it can be substantially compromised in the presence of anatomical changes. A major dosimetric effect is caused by density changes, which alter the planned proton range in the patient. Three different methods, which automatically restore an IMPT plan dose on a daily CT image were implemented and compared: (1) simple dose restoration (DR) using optimization objectives of the initial plan, (2) voxel-wise dose restoration (vDR), and (3) isodose volume dose restoration (iDR). Dose restorations were calculated for three different clinical cases, selected to test different capabilities of the restoration methods: large range adaptation, complex dose distributions and robust re-optimization. All dose restorations were obtained in less than 5 min, without manual adjustments of the optimization settings. The evaluation of initial plans on repeated CTs showed large dose distortions, which were substantially reduced after restoration. In general, all dose restoration methods improved DVH-based scores in propagated target volumes and OARs. Analysis of local dose differences showed that, although all dose restorations performed similarly in high dose regions, iDR restored the initial dose with higher precision and accuracy in the whole patient anatomy. Median dose errors decreased from 13.55 Gy in distorted plan to 9.75 Gy (vDR), 6.2 Gy (DR) and 4.3 Gy (iDR). High quality dose restoration is essential to minimize or eventually by-pass the physician approval of the restored plan, as long as dose stability can be assumed. Motion (as well as setup and range uncertainties) can be taken into account by including robust optimization in the dose restoration. Restoring clinically-approved dose distribution on repeated CTs does not require new ROI segmentation and is compatible with an online adaptive workflow.
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http://dx.doi.org/10.1088/1361-6560/aaba8cDOI Listing
April 2018

Effect of continuous positive airway pressure administration during lung stereotactic ablative radiotherapy: a comparative planning study.

Strahlenther Onkol 2018 06 15;194(6):591-599. Epub 2018 Feb 15.

Center of Molecular Imaging, Radiotherapy and Oncology (MIRO), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, Avenue Hippocrate 54, box B1.54.07, 1200, Brussels, Belgium.

Purpose: By increasing lung volume and decreasing respiration-induced tumour motion amplitude, administration of continuous positive airway pressure (CPAP) during stereotactic ablative radiotherapy (SABR) could allow for better sparing of the lungs and heart. In this study, we evaluated the effect of CPAP on lung volume, tumour motion amplitude and baseline shift, as well as the dosimetric impact of the strategy.

Methods: Twenty patients with lung tumours referred for SABR underwent 4D-computed tomography (CT) scans with and without CPAP (CPAP/noCPAP) at two timepoints (T0/T1). First, CPAP and noCPAP scans were compared for lung volume, tumour motion amplitude, and baseline shift. Next, CPAP and noCPAP treatment plans were computed and compared for lung dose parameters (mean lung dose (MLD), lung volume receiving 20 Gy (V), 13 Gy (V), and 5 Gy (V)) and mean heart dose (MHD).

Results: On average, CPAP increased lung volume by 8.0% (p < 0.001) and 6.3% (p < 0.001) at T0 and T1, respectively, but did not change tumour motion amplitude or baseline shift. As a result, CPAP administration led to an absolute decrease in MLD, lung V, V and V of 0.1 Gy (p = 0.1), 0.4% (p = 0.03), 0.5% (p = 0.04) and 0.5% (p = 0.2), respectively, while having no significant influence on MHD.

Conclusions: In patients referred for SABR for lung tumours, CPAP increased lung volume without modifying tumour motion or baseline shift. As a result, CPAP allowed for a slight decrease in radiation dose to the lungs, which is unlikely to be clinically significant.
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http://dx.doi.org/10.1007/s00066-018-1278-2DOI Listing
June 2018

Sensitivity of a prompt-gamma slit-camera to detect range shifts for proton treatment verification.

Radiother Oncol 2017 12 4;125(3):534-540. Epub 2017 Nov 4.

OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology - OncoRay, Dresden, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; German Cancer Consortium (DKTK), partner site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address:

Background And Purpose: A prompt-gamma imaging (PGI) slit-camera was recently applied successfully in clinical proton treatments using pencil beam scanning (PBS) and double scattering (DS). However, its full capability under clinical conditions has still to be systematically evaluated. Here, the performance of the slit-camera is systematically assessed in well-defined error scenarios using realistic treatment deliveries to an anthropomorphic head phantom.

Materials And Methods: The sensitivity and accuracy to detect introduced global and local range shifts with the slit-camera was investigated in PBS and DS irradiations. For PBS, measured PGI information of shifted geometries were compared spot-wise with un-shifted PGI information derived from either a reference measurement or a treatment-plan-based simulation. Furthermore, for DS and PBS the integral PGI signal of the whole field was evaluated.

Results: Deviations from the treatment plan were detected with an accuracy better than 2 mm in PBS. The PGI simulation accuracy was well below 1 mm. Interfractional comparisons are more affected by measurement noise. The field-integral PGI sum signal allows the detection of global shifts in DS.

Conclusions: Detection of global and local range shifts under close-to-clinical conditions is possible with the PGI slit-camera. Especially for PBS, high sensitivity and high accuracy in shift detection were found.
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http://dx.doi.org/10.1016/j.radonc.2017.10.013DOI Listing
December 2017

Prompt Gamma Imaging for In Vivo Range Verification of Pencil Beam Scanning Proton Therapy.

Int J Radiat Oncol Biol Phys 2017 09 3;99(1):210-218. Epub 2017 May 3.

Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Purpose: To report the first clinical results and value assessment of prompt gamma imaging for in vivo proton range verification in pencil beam scanning mode.

Methods And Materials: A stand-alone, trolley-mounted, prototype prompt gamma camera utilizing a knife-edge slit collimator design was used to record the prompt gamma signal emitted along the proton tracks during delivery of proton therapy for a brain cancer patient. The recorded prompt gamma depth detection profiles of individual pencil beam spots were compared with the expected profiles simulated from the treatment plan.

Results: In 6 treatment fractions recorded over 3 weeks, the mean (± standard deviation) range shifts aggregated over all spots in 9 energy layers were -0.8 ± 1.3 mm for the lateral field, 1.7 ± 0.7 mm for the right-superior-oblique field, and -0.4 ± 0.9 mm for the vertex field.

Conclusions: This study demonstrates the feasibility and illustrates the distinctive benefits of prompt gamma imaging in pencil beam scanning treatment mode. Accuracy in range verification was found in this first clinical case to be better than the range uncertainty margin applied in the treatment plan. These first results lay the foundation for additional work toward tighter integration of the system for in vivo proton range verification and quantification of range uncertainties.
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http://dx.doi.org/10.1016/j.ijrobp.2017.04.027DOI Listing
September 2017

An individualized radiation dose escalation trial in non-small cell lung cancer based on FDG-PET imaging.

Strahlenther Onkol 2017 Oct 21;193(10):812-822. Epub 2017 Jul 21.

Center of Molecular Imaging, Radiotherapy and Oncology (MIRO), Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Avenue Hippocrate, 54 Bte B1.54.07, 1200, Brussels, Belgium.

Aim: The aim of the study was to assess the feasibility of an individualized 18F fluorodeoxyglucose positron emission tomography (FDG-PET)-guided dose escalation boost in non-small cell lung cancer (NSCLC) patients and to assess its impact on local tumor control and toxicity.

Patients And Methods: A total of 13 patients with stage II-III NSCLC were enrolled to receive a dose of 62.5 Gy in 25 fractions to the CT-based planning target volume (PTV; primary turmor and affected lymph nodes). The fraction dose was increased within the individual PET-based PTV (PTV) using intensity modulated radiotherapy (IMRT) with a simultaneous integrated boost (SIB) until the predefined organ-at-risk (OAR) threshold was reached. Tumor response was assessed during follow-up by means of repeat FDG-PET/computed tomography. Acute and late toxicity were recorded and classified according to the CTCAE criteria (Version 4.0). Local progression-free survival was determined using the Kaplan-Meier method.

Results: The average dose to PTV reached 89.17 Gy for peripheral and 75 Gy for central tumors. After a median follow-up period of 29 months, seven patients were still alive, while six had died (four due to distant progression, two due to grade 5 toxicity). Local progression was seen in two patients in association with further recurrences. One and 2-year local progression free survival rates were 76.9% and 52.8%, respectively. Three cases of acute grade 3 esophagitis were seen. Two patients with central tumors developed late toxicity and died due to severe hemoptysis.

Conclusion: These results suggest that a non-uniform and individualized dose escalation based on FDG-PET in IMRT delivery is feasible. The doses reached were higher in patients with peripheral compared to central tumors. This strategy enables good local control to be achieved at acceptable toxicity rates. However, dose escalation in centrally located tumors with direct invasion of mediastinal organs must be performed with great caution in order to avoid severe late toxicity.
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http://dx.doi.org/10.1007/s00066-017-1168-zDOI Listing
October 2017

Correlation analysis of [F]fluorodeoxyglucose and [F]fluoroazomycin arabinoside uptake distributions in lung tumours during radiation therapy.

Acta Oncol 2017 Sep 24;56(9):1181-1188. Epub 2017 May 24.

a Center of Molecular Imaging, Radiotherapy and Oncology (MIRO), Institut de Recherche Expérimentale et Clinique (IREC) , Université catholique de Louvain , Brussels , Belgium.

Background: PET-guided dose painting (DP) aims to target radioresistant tumour regions in order to improve radiotherapy (RT) outcome. Besides the well-known [F]fluorodeoxyglucose (FDG), the hypoxia positron emission tomography (PET) tracer [F]fluoroazomycin arabinoside (FAZA) could provide further useful information to guide the radiation dose prescription. In this study, we compare the spatial distributions of FDG and FAZA PET uptakes in lung tumours.

Material And Methods: Fourteen patients with unresectable lung cancer underwent FDG and FAZA 4D-PET/CT on consecutive days at three time-points: prior to RT (pre), and during the second (w2), and the third (w3) weeks of RT. All PET/CT were reconstructed in their time-averaged midposition (MidP). The metabolic tumour volume (MTV: FDG standardised uptake value (SUV) > 50% SUV), and the hypoxic volume (HV: FAZA SUV > 1.4) were delineated within the gross tumour volume (GTV). FDG and FAZA intratumoral PET uptake distributions were subsequently pairwise compared, using both volume-, and voxel-based analyses.

Results: Volume-based analysis showed large overlap between MTV and HV: median overlapping fraction was 0.90, 0.94 and 0.94, at the pre, w2 and w3 time-points, respectively. Voxel-wise analysis between FDG and FAZA intratumoral PET uptake distributions showed high correlation: median Spearman's rank correlation coefficient was 0.76, 0.77 and 0.76, at the pre, w2 and w3 time-points, respectively. Interestingly, tumours with high FAZA uptake tended to show more similarity between FDG and FAZA intratumoral uptake distributions than those with low FAZA uptake.

Conclusions: In unresectable lung carcinomas, FDG and FAZA PET uptake distributions displayed unexpectedly strong similarity, despite the distinct pathways targeted by these tracers. Hypoxia PET with FAZA brought very little added value over FDG from the perspective of DP in this population.
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http://dx.doi.org/10.1080/0284186X.2017.1329594DOI Listing
September 2017

Evolution of [F]fluorodeoxyglucose and [F]fluoroazomycin arabinoside PET uptake distributions in lung tumours during radiation therapy.

Acta Oncol 2017 Apr 22;56(4):516-524. Epub 2017 Feb 22.

a Center of Molecular Imaging, Radiotherapy and Oncology (MIRO), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain , Brussels , Belgium.

Background: Dose painting (DP) aims to improve radiation therapy (RT) outcome by targeting radioresistant tumour regions identified through functional imaging, e.g., positron emission tomography (PET). Importantly, the expected benefit of DP relies on the ability of PET imaging to identify tumour areas which could be consistently targeted throughout the treatment. In this study, we analysed the spatial stability of two potential DP targets in lung cancer patients undergoing RT: the tumour burden surrogate [F]fluorodeoxyglucose (FDG) and the hypoxia surrogate [F]fluoroazomycin arabinoside (FAZA).

Materials And Methods: Thirteen patients with unresectable lung tumours underwent FDG and FAZA 4D-PET/CT before (pre), and during the second (w2) and third (w3) weeks of RT. All PET/CT were reconstructed in their time-averaged midposition (MidP) for further analysis. The metabolic tumour volume (MTV: FDG standardised uptake value (SUV) > 50% SUV) and the hypoxic volume (HV: FAZA SUV >1.4) were delineated within the gross tumour volume (GTV). The stability of FDG and FAZA PET uptake distributions during RT was subsequently assessed through volume-overlap analysis and voxel-based correlation analysis.

Results: The volume-overlap analysis yielded median overlapping fraction (OF) of 0.86 between MTV and MTV and 0.82 between MTV and MTV. In patients with a detectable HV, median OF was 0.82 between HV and HV and 0.90 between HV and HV. The voxel-based correlation analysis yielded median Spearman's correlation coefficient (r) of 0.87 between FDG and FDG and 0.83 between FDG and FDG. Median r was 0.78 between FAZA and FAZA and 0.79 between FAZA and FAZA.

Conclusions: FDG and FAZA PET uptake distributions were spatially stable during the 3 first weeks of RT in patients with unresectable lung cancer, both based on volume- and voxel-based indicators. This might allow for a consistent targeting of high FDG or FAZA PET uptake regions as part of a DP strategy.
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http://dx.doi.org/10.1080/0284186X.2017.1287943DOI Listing
April 2017

Evaluation of motion mitigation using abdominal compression in the clinical implementation of pencil beam scanning proton therapy of liver tumors.

Med Phys 2017 Feb 30;44(2):703-712. Epub 2017 Jan 30.

Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA.

Purpose: To determine whether individual liver tumor patients can be safely treated with pencil beam scanning proton therapy. This study reports a planning preparation workflow that can be used for beam angle selection and the evaluation of the efficacy of abdominal compression (AC) to mitigate motion.

Methods: Four-dimensional computed tomography scans (4DCT) with and without AC were available from 10 liver tumor patients with fluoroscopy-proven motion reduction by AC, previously treated using photons. For each scan, the motion amplitudes and the motion-induced variation of water-equivalent thickness (ΔWET) in each voxel of the target volume were evaluated during treatment plan preparation. Optimal proton beam angles were selected after volume analysis of the respective beam-specific planning target volume (BSPTV). M and ΔWET derived from the 80th percentiles of perpendicular motion amplitude (M ) and ΔWET were compared with and without AC. Proton plans were created on the average CT to achieve target coverage similar to that of the conventional photon treatments. 4D dynamic dose calculation was performed postplan by synchronizing proton beam delivery timing patterns to the 4DCT phases to assess interplay and fractionation effects, and to determine motion criteria for subsequent patient treatment.

Results: Selected coplanar beam angles ranged between 180° and 39°, primarily from right lateral (oblique) and posterior (oblique) directions. While AC produced a significant reduction in mean Liver-GTV dose, any reduction in mean heart dose was patient dependent and not significant. Similarly, AC resulted in reductions in M , ΔWET, and BSPTV volumes and improved dose degradation (ΔD and ΔD ) within the CTV. For small motion (M < 7 mm and ΔWET < 5 mm), motion mitigation was not needed. For moderate motion (M 7-10 mm or ΔWET 5-7 mm), AC produced a modest improvement. For large motion (M > 10 mm or ΔWET > 7 mm), AC and/or some other form of mitigation strategies were required.

Conclusion: A workflow for screening patients' motion characteristics and optimizing beam angle selection was established for the pencil beam scanning proton therapy treatment of liver tumors. Abdominal compression was found to be useful at mitigation of moderate and large motion.
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http://dx.doi.org/10.1002/mp.12040DOI Listing
February 2017

Motion-aware temporal regularization for improved 4D cone-beam computed tomography.

Phys Med Biol 2016 09 2;61(18):6856-6877. Epub 2016 Sep 2.

iMagX Project, ICTEAM Institute, Université Catholique de Louvain, Louvain-la-Neuve, Belgium. Université de Lyon, CREATIS; CNRS UMR5220; Inserm U1044; INSA-Lyon; Université Lyon 1; Centre Léon Bérard, France.

Four-dimensional cone-beam computed tomography (4D-CBCT) of the free-breathing thorax is a valuable tool in image-guided radiation therapy of the thorax and the upper abdomen. It allows the determination of the position of a tumor throughout the breathing cycle, while only its mean position can be extracted from three-dimensional CBCT. The classical approaches are not fully satisfactory: respiration-correlated methods allow one to accurately locate high-contrast structures in any frame, but contain strong streak artifacts unless the acquisition is significantly slowed down. Motion-compensated methods can yield streak-free, but static, reconstructions. This work proposes a 4D-CBCT method that can be seen as a trade-off between respiration-correlated and motion-compensated reconstruction. It builds upon the existing reconstruction using spatial and temporal regularization (ROOSTER) and is called motion-aware ROOSTER (MA-ROOSTER). It performs temporal regularization along curved trajectories, following the motion estimated on a prior 4D CT scan. MA-ROOSTER does not involve motion-compensated forward and back projections: the input motion is used only during temporal regularization. MA-ROOSTER is compared to ROOSTER, motion-compensated Feldkamp-Davis-Kress (MC-FDK), and two respiration-correlated methods, on CBCT acquisitions of one physical phantom and two patients. It yields streak-free reconstructions, visually similar to MC-FDK, and robust information on tumor location throughout the breathing cycle. MA-ROOSTER also allows a variation of the lung tissue density during the breathing cycle, similar to that of planning CT, which is required for quantitative post-processing.
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http://dx.doi.org/10.1088/0031-9155/61/18/6856DOI Listing
September 2016

Estimating patient specific uncertainty parameters for adaptive treatment re-planning in proton therapy using in vivo range measurements and Bayesian inference: application to setup and stopping power errors.

Phys Med Biol 2016 09 5;61(17):6281-96. Epub 2016 Aug 5.

IBA Particle Therapy, Chemin du Cyclotron 3, B-1348 Louvain-la-Neuve, Belgium.

In proton therapy, quantification of the proton range uncertainty is important to achieve dose distribution compliance. The promising accuracy of prompt gamma imaging (PGI) suggests the development of a mathematical framework using the range measurements to convert population based estimates of uncertainties into patient specific estimates with the purpose of plan adaptation. We present here such framework using Bayesian inference. The sources of uncertainty were modeled by three parameters: setup bias m, random setup precision r and water equivalent path length bias u. The evolution of the expectation values E(m), E(r) and E(u) during the treatment was simulated. The expectation values converged towards the true simulation parameters after 5 and 10 fractions, for E(m) and E(u), respectively. E(r) settle on a constant value slightly lower than the true value after 10 fractions. In conclusion, the simulation showed that there is enough information in the frequency distribution of the range errors measured by PGI to estimate the expectation values and the confidence interval of the model parameters by Bayesian inference. The updated model parameters were used to compute patient specific lateral and local distal margins for adaptive re-planning.
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http://dx.doi.org/10.1088/0031-9155/61/17/6281DOI Listing
September 2016

Experimental Comparison of Knife-Edge and Multi-Parallel Slit Collimators for Prompt Gamma Imaging of Proton Pencil Beams.

Front Oncol 2016 27;6:156. Epub 2016 Jun 27.

Ion Beam Applications SA , Louvain-la-Neuve , Belgium.

More and more camera concepts are being investigated to try and seize the opportunity of instantaneous range verification of proton therapy treatments offered by prompt gammas emitted along the proton tracks. Focusing on one-dimensional imaging with a passive collimator, the present study experimentally compared in combination with the first, clinically compatible, dedicated camera device the performances of instances of the two main options: a knife-edge slit (KES) and a multi-parallel slit (MPS) design. These two options were experimentally assessed in this specific context as they were previously demonstrated through analytical and numerical studies to allow similar performances in terms of Bragg peak retrieval precision and spatial resolution in a general context. Both collimators were prototyped according to the conclusions of Monte Carlo optimization studies under constraints of equal weight (40 mm tungsten alloy equivalent thickness) and of the specificities of the camera device under consideration (in particular 4 mm segmentation along beam axis and no time-of-flight discrimination, both of which less favorable to the MPS performance than to the KES one). Acquisitions of proton pencil beams of 100, 160, and 230 MeV in a PMMA target revealed that, in order to reach a given level of statistical precision on Bragg peak depth retrieval, the KES collimator requires only half the dose the present MPS collimator needs, making the KES collimator a preferred option for a compact camera device aimed at imaging only the Bragg peak position. On the other hand, the present MPS collimator proves more effective at retrieving the entrance of the beam in the target in the context of an extended camera device aimed at imaging the whole proton track within the patient.
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http://dx.doi.org/10.3389/fonc.2016.00156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4921459PMC
July 2016

First Clinical Investigation of Cone Beam Computed Tomography and Deformable Registration for Adaptive Proton Therapy for Lung Cancer.

Int J Radiat Oncol Biol Phys 2016 May 4;95(1):549-559. Epub 2016 Feb 4.

Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Purpose: An adaptive proton therapy workflow using cone beam computed tomography (CBCT) is proposed. It consists of an online evaluation of a fast range-corrected dose distribution based on a virtual CT (vCT) scan. This can be followed by more accurate offline dose recalculation on the vCT scan, which can trigger a rescan CT (rCT) for replanning.

Methods And Materials: The workflow was tested retrospectively for 20 consecutive lung cancer patients. A diffeomorphic Morphon algorithm was used to generate the lung vCT by deforming the average planning CT onto the CBCT scan. An additional correction step was applied to account for anatomic modifications that cannot be modeled by deformation alone. A set of clinical indicators for replanning were generated according to the water equivalent thickness (WET) and dose statistics and compared with those obtained on the rCT scan. The fast dose approximation consisted of warping the initial planned dose onto the vCT scan according to the changes in WET. The potential under- and over-ranges were assessed as a variation in WET at the target's distal surface.

Results: The range-corrected dose from the vCT scan reproduced clinical indicators similar to those of the rCT scan. The workflow performed well under different clinical scenarios, including atelectasis, lung reinflation, and different types of tumor response. Between the vCT and rCT scans, we found a difference in the measured 95% percentile of the over-range distribution of 3.4 ± 2.7 mm. The limitations of the technique consisted of inherent uncertainties in deformable registration and the drawbacks of CBCT imaging. The correction step was adequate when gross errors occurred but could not recover subtle anatomic or density changes in tumors with complex topology.

Conclusions: A proton therapy workflow based on CBCT provided clinical indicators similar to those using rCT for patients with lung cancer with considerable anatomic changes.
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http://dx.doi.org/10.1016/j.ijrobp.2016.01.055DOI Listing
May 2016

Experimental observation of acoustic emissions generated by a pulsed proton beam from a hospital-based clinical cyclotron.

Med Phys 2015 Dec;42(12):7090-7

Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104.

Purpose: To measure the acoustic signal generated by a pulsed proton spill from a hospital-based clinical cyclotron.

Methods: An electronic function generator modulated the IBA C230 isochronous cyclotron to create a pulsed proton beam. The acoustic emissions generated by the proton beam were measured in water using a hydrophone. The acoustic measurements were repeated with increasing proton current and increasing distance between detector and beam.

Results: The cyclotron generated proton spills with rise times of 18 μs and a maximum measured instantaneous proton current of 790 nA. Acoustic emissions generated by the proton energy deposition were measured to be on the order of mPa. The origin of the acoustic wave was identified as the proton beam based on the correlation between acoustic emission arrival time and distance between the hydrophone and proton beam. The acoustic frequency spectrum peaked at 10 kHz, and the acoustic pressure amplitude increased monotonically with increasing proton current.

Conclusions: The authors report the first observation of acoustic emissions generated by a proton beam from a hospital-based clinical cyclotron. When modulated by an electronic function generator, the cyclotron is capable of creating proton spills with fast rise times (18 μs) and high instantaneous currents (790 nA). Measurements of the proton-generated acoustic emissions in a clinical setting may provide a method for in vivo proton range verification and patient monitoring.
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http://dx.doi.org/10.1118/1.4935865DOI Listing
December 2015

Sensitivity study of prompt gamma imaging of scanned beam proton therapy in heterogeneous anatomies.

Radiother Oncol 2016 Mar 27;118(3):562-7. Epub 2015 Nov 27.

Université catholique de Louvain, Center of Molecular Imaging, Radiotherapy and Oncology, Institut de Recherche Expérimentale et Clinique, Brussels, Belgium. Electronic address:

Background And Purpose: To investigate the use of a fast analytical prediction algorithm in the evaluation of the accuracy in Bragg peak position estimation using prompt gamma imaging in realistic anatomies.

Material And Methods: Brain, nasal cavity and lung spot scanning treatments were planned on an anthropomorphic phantom. Plan delivery in a clinical proton therapy facility was monitored using a prompt gamma camera. A pencil-beam algorithm was developed to simulate prompt gamma acquisition. For each spot, the sensitivity to setup and CT conversion errors was evaluated based on error scenarios.

Results: Good agreement was found between simulations and measurements (average shift of 0.4mm on whole-layer profiles). The spots with greatest sensitivity to setup or CT conversion errors could be identified. The comparison between expected and estimated shifts showed that the errors in shift estimation due to heterogeneities were in average lower than 1mm in all cases except the lung. In the lung case, only 40% of the spots showed accuracy better than 2mm.

Conclusions: The analytical prediction algorithm was successfully used to simulate prompt gamma acquisitions of scanned treatment plans. The accuracy in Bragg peak position estimation was generally sub-millimeter in heterogeneous anatomies, except in lung tissues.
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http://dx.doi.org/10.1016/j.radonc.2015.11.002DOI Listing
March 2016

Impact of motion induced artifacts on automatic registration of lung tumors in Tomotherapy.

Phys Med 2015 Dec 16;31(8):963-968. Epub 2015 Sep 16.

MIRO Lab., Université catholique de Louvain, Saint-Luc University Hospital, Brussels, Belgium. Electronic address:

Purpose: Tomotherapy MV-CT acquisitions of lung tumors lead to artifacts due to breathing-related motion. This could preclude the reliability of tumor based positioning. We investigate the effect of these artifacts on automatic registration and determine conditions under which correct positioning can be achieved.

Materials And Methods: MV-CT and 4D-CT scans of a dynamic thorax phantom were acquired with various motion amplitudes, directions, and periods. For each acquisition, the average kV-CT image was reconstructed from the 4D-CT data and rigidly registered with the corresponding MV-CT scan in a region of interest. Different kV-MV registration strategies have been assessed.

Results: All tested registration methods led to acceptable registration errors (within 1.3 ± 1.2 mm) for motion periods of 3 and 6 s, regardless of the motion amplitude, direction, and phase difference. However, a motion period of 5 s, equal to half the Tomotherapy gantry period, induced asymmetric artifacts within MV-CT and significantly degraded the registration accuracy.

Conclusions: As long as the breathing period differs from 5 s, positioning based on averaged images of the tumor provides information about its daily baseline shift, and might therefore contribute to reducing margins, regardless of the registration method.
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http://dx.doi.org/10.1016/j.ejmp.2015.07.140DOI Listing
December 2015
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