@article{Newhauser2015, abstract = {The physics of proton therapy has advanced considerably since it was proposed in 1946. Today analytical equations and numerical simulation methods are available to predict and characterize many aspects of proton therapy. This article reviews the basic aspects of the physics of proton therapy, including proton interaction mechanisms, proton transport calculations, the determination of dose from therapeutic and stray radiations, and shielding design. The article discusses underlying processes as well as selected practical experimental and theoretical methods. We conclude by briefly speculating on possible future areas of research of relevance to the physics of proton therapy.}, author = {Wayne D. Newhauser and Rui Zhang}, doi = {10.1088/0031-9155/60/8/R155}, issn = {13616560}, issue = {8}, journal = {Physics in Medicine and Biology}, title = {The physics of proton therapy}, volume = {60}, year = {2015} } @article{Karger2010, abstract = {Recently, ion beam radiotherapy (including protons as well as heavier ions) gained considerable interest. Although ion beam radiotherapy requires dose prescription in terms of iso-effective dose (referring to an iso-effective photon dose), absorbed dose is still required as an operative quantity to control beam delivery, to characterize the beam dosimetrically and to verify dose delivery. This paper reviews current methods and standards to determine absorbed dose to water in ion beam radiotherapy, including (i) the detectors used to measure absorbed dose, (ii) dosimetry under reference conditions and (iii) dosimetry under non-reference conditions. Due to the LET dependence of the response of films and solid-state detectors, dosimetric measurements are mostly based on ion chambers. While a primary standard for ion beam radiotherapy still remains to be established, ion chamber dosimetry under reference conditions is based on similar protocols as for photons and electrons although the involved uncertainty is larger than for photon beams. For non-reference conditions, dose measurements in tissue-equivalent materials may also be necessary. Regarding the atomic numbers of the composites of tissue-equivalent phantoms, special requirements have to be fulfilled for ion beams. Methods for calibrating the beam monitor depend on whether passive or active beam delivery techniques are used. QA measurements are comparable to conventional radiotherapy; however, dose verification is usually single field rather than treatment plan based. Dose verification for active beam delivery techniques requires the use of multi-channel dosimetry systems to check the compliance of measured and calculated dose for a representative sample of measurement points. Although methods for ion beam dosimetry have been established, there is still room for developments. This includes improvement of the dosimetric accuracy as well as development of more efficient measurement techniques. © 2010 Institute of Physics and Engineering in Medicine Printed in the UK.}, author = {Christian P. Karger and Oliver Jäkel and Hugo Palmans and Tatsuaki Kanai}, doi = {10.1088/0031-9155/55/21/R01}, issn = {00319155}, issue = {21}, journal = {Physics in Medicine and Biology}, title = {Dosimetry for ion beam radiotherapy}, volume = {55}, year = {2010} } @article{Perl2012, abstract = {Purpose: While Monte Carlo particle transport has proven useful in many areas (treatment head design, dose calculation, shielding design, and imaging studies) and has been particularly important for proton therapy (due to the conformal dose distributions and a finite beam range in the patient), the available general purpose Monte Carlo codes in proton therapy have been overly complex for most clinical medical physicists. The learning process has large costs not only in time but also in reliability. To address this issue, we developed an innovative proton Monte Carlo platform and tested the tool in a variety of proton therapy applications. Methods: Our approach was to take one of the already-established general purpose Monte Carlo codes and wrap and extend it to create a specialized user-friendly tool for proton therapy. The resulting tool, TOol for PArticle Simulation (TOPAS), should make Monte Carlo simulation more readily available for research and clinical physicists. TOPAS can model a passive scattering or scanning beam treatment head, model a patient geometry based on computed tomography (CT) images, score dose, fluence, etc., save and restart a phase space, provides advanced graphics, and is fully four-dimensional (4D) to handle variations in beam delivery and patient geometry during treatment. A custom-designed TOPAS parameter control system was placed at the heart of the code to meet requirements for ease of use, reliability, and repeatability without sacrificing flexibility. Results: We built and tested the TOPAS code. We have shown that the TOPAS parameter system provides easy yet flexible control over all key simulation areas such as geometry setup, particle source setup, scoring setup, etc. Through design consistency, we have insured that user experience gained in configuring one component, scorer or filter applies equally well to configuring any other component, scorer or filter. We have incorporated key lessons from safety management, proactively removing possible sources of user error such as line-ordering mistakes. We have modeled proton therapy treatment examples including the UCSF eye treatment head, the MGH stereotactic alignment in radiosurgery treatment head and the MGH gantry treatment heads in passive scattering and scanning modes, and we have demonstrated dose calculation based on patient-specific CT data. Initial validation results show agreement with measured data and demonstrate the capabilities of TOPAS in simulating beam delivery in 3D and 4D. Conclusions: We have demonstrated TOPAS accuracy and usability in a variety of proton therapy setups. As we are preparing to make this tool freely available for researchers in medical physics, we anticipate widespread use of this tool in the growing proton therapy community. © 2012 American Association of Physicists in Medicine.}, author = {J. Perl and J. Shin and J. Schümann and B. Faddegon and H. Paganetti}, doi = {10.1118/1.4758060}, issn = {00942405}, issue = {11}, journal = {Medical Physics}, title = {TOPAS: An innovative proton Monte Carlo platform for research and clinical applications}, volume = {39}, year = {2012} } @article{Paganetti2012, abstract = {The main advantages of proton therapy are the reduced total energy deposited in the patient as compared to photon techniques and the finite range of the proton beam. The latter adds an additional degree of freedom to treatment planning. The range in tissue is associated with considerable uncertainties caused by imaging, patient setup, beam delivery and dose calculation. Reducing the uncertainties would allow a reduction of the treatment volume and thus allow a better utilization of the advantages of protons. This paper summarizes the role of Monte Carlo simulations when aiming at a reduction of range uncertainties in proton therapy. Differences in dose calculation when comparing Monte Carlo with analytical algorithms are analyzed as well as range uncertainties due to material constants and CT conversion. Range uncertainties due to biological effects and the role of Monte Carlo for in vivo range verification are discussed. Furthermore, the current range uncertainty recipes used at several proton therapy facilities are revisited. We conclude that a significant impact of Monte Carlo dose calculation can be expected in complex geometries where local range uncertainties due to multiple Coulomb scattering will reduce the accuracy of analytical algorithms. In these cases Monte Carlo techniques might reduce the range uncertainty by several mm. © 2012 Institute of Physics and Engineering in Medicine.}, author = {Harald Paganetti}, doi = {10.1088/0031-9155/57/11/R99}, issn = {00319155}, issue = {11}, journal = {Physics in Medicine and Biology}, title = {Range uncertainties in proton therapy and the role of Monte Carlo simulations}, volume = {57}, year = {2012} } @book{Paganetti2016, author = {Harald Paganetti}, doi = {10.1201/9781032616858}, title = {Proton Therapy Physics}, publisher = {CRC Press}, year = {2016} } @article{Lomax2008a, abstract = {The effects of calculational uncertainties on 3D and distal edge tracking (DET) intensity modulated proton therapy (IMPT) treatment plans have been investigated. Dose calculation uncertainties have been assessed by comparing analytical and Monte Carlo dose calculations, and potential range uncertainties by recalculating plans with all CT values modified by ±3%. Analysis of the volume of PTV agreeing to within ±3% between the two calculations shows that the 3D approach provides significantly improved agreement (87.1 versus 80.3% of points for the 3D and DET approaches, respectively). For the DET approach, doses in the CTV have also been found to globally change by 5% as a result of 3% changes in CT value. When varying the intra-field gradients of the plans a similar trend is seen, but with the more complex plans also being found to be more sensitive to both uncertainties. In conclusion, the DET approach has been found to be relatively sensitive to the calculational errors investigated here. In contrast, the 3D approach appears to be quite robust, unless strong internal gradients are present. Nevertheless, the routine use of uncertainty analysis is advised when assessing all forms of IMPT plans. © 2008 Institute of Physics and Engineering in Medicine.}, author = {A. J. Lomax}, doi = {10.1088/0031-9155/53/4/014}, issn = {00319155}, issue = {4}, journal = {Physics in Medicine and Biology}, title = {Intensity modulated proton therapy and its sensitivity to treatment uncertainties 1: The potential effects of calculational uncertainties}, volume = {53}, year = {2008} } @article{Lomax2008b, abstract = {Simple tools for studying the effects of inter-fraction and inter-field motions on intensity modulated proton therapy (IMPT) plans have been developed, and have been applied to both 3D and distal edge tracking (DET) IMPT plans. For the inter-fraction motion, we have investigated the effects of misaligned density heterogeneities, whereas for the inter-field motion analysis, the effects of field misalignment on the plans have been assessed. Inter-fraction motion problems have been analysed using density differentiated error (DDE) distributions, which specifically show the additional problems resulting from misaligned density heterogeneities for proton plans. Likewise, for inter-field motion, we present methods for calculating motion differentiated error (MDE) distributions. DDE and MDE analysis of all plans demonstrate that the 3D approach is generally more robust to both inter-fraction and inter-field motions than the DET approach, but that strong in-field dose gradients can also adversely affect a plan's robustness. An important additional conclusion is that, for certain IMPT plans, even inter-fraction errors cannot necessarily be compensated for by the use of a simple PTV margins, implying that more sophisticated tools need to be developed for uncertainty management and assessment for IMPT treatments at the treatment planning level. © 2008 Institute of Physics and Engineering in Medicine.}, author = {A. J. Lomax}, doi = {10.1088/0031-9155/53/4/015}, issn = {00319155}, issue = {4}, journal = {Physics in Medicine and Biology}, title = {Intensity modulated proton therapy and its sensitivity to treatment uncertainties 2: The potential effects of inter-fraction and inter-field motions}, volume = {53}, year = {2008} } @article{Bai2019, abstract = {Robust optimization (RO) methods are applied to intensity-modulated proton therapy (IMPT) treatment plans to ensure their robustness in the face of treatment delivery uncertainties, such as proton range and patient setup errors. However, the impact of those uncertainties on the biological effect of protons has not been specifically considered. In this study, we added biological effect-based objectives into a conventional RO cost function for IMPT optimization to minimize the variation in biological effect. One brain tumor case, one prostate tumor case and one head & neck tumor case were selected for this study. Three plans were generated for each case using three different optimization approaches: planning target volume (PTV)-based optimization, conventional RO, and RO incorporating biological effect (BioRO). In BioRO, the variation in biological effect caused by IMPT delivery uncertainties was minimized for voxels in both target volumes and critical structures, in addition to a conventional voxel-based worst-case RO objective function. The biological effect was approximated by the product of dose-averaged linear energy transfer (LET) and physical dose. All plans were normalized to give the same target dose coverage, assuming a constant relative biological effectiveness (RBE) of 1.1. Dose, biological effect, and their uncertainties were evaluated and compared among the three optimization approaches for each patient case. Compared with PTV-based plans, RO plans achieved more robust target dose coverage and reduced biological effect hot spots in critical structures near the target. Moreover, with their sustained robust dose distributions, BioRO plans not only reduced variations in biological effect in target and normal tissues but also further reduced biological effect hot spots in critical structures compared with RO plans. Our findings indicate that IMPT could benefit from the use of conventional RO, which would reduce the biological effect in normal tissues and produce more robust dose distributions than those of PTV-based optimization. More importantly, this study provides a proof of concept that incorporating biological effect uncertainty gap into conventional RO would not only control the IMPT plan robustness in terms of physical dose and biological effect but also achieve further reduction of biological effect in normal tissues.}, author = {Xuemin Bai and Gino Lim and David Grosshans and Radhe Mohan and Wenhua Cao}, doi = {10.1088/1361-6560/aaf5e9}, issn = {13616560}, issue = {2}, journal = {Physics in Medicine and Biology}, title = {Robust optimization to reduce the impact of biological effect variation from physical uncertainties in intensity-modulated proton therapy}, volume = {64}, year = {2019} } @article{Lomax2020, abstract = {Range uncertainty is a much discussed topic in proton therapy. Although a very real aspect of proton therapy, its magnitude and consequences are sometimes misunderstood or overestimated. In this article, the sources and consequences of range uncertainty are reviewed, a number of myths associated with the effect discussed with the aim of putting range uncertainty into clinical context and attempting to de-bunk some of the more exaggerated claims made as to its consequences.}, author = {Antony John Lomax}, doi = {10.1259/bjr.20190582}, issn = {0007-1285}, issue = {1107}, journal = {The British Journal of Radiology}, title = {Myths and realities of range uncertainty}, volume = {93}, year = {2020} } @article{Fredriksson2014, abstract = {Purpose: To critically evaluate and compare three worst case optimization methods that have been previously employed to generate intensity-modulated proton therapy treatment plans that are robust against systematic errors. The goal of the evaluation is to identify circumstances when the methods behave differently and to describe the mechanism behind the differences when they occur. Methods: The worst case methods optimize plans to perform as well as possible under the worst case scenario that can physically occur (composite worst case), the combination of the worst case scenarios for each objective constituent considered independently (objectivewise worst case), and the combination of the worst case scenarios for each voxel considered independently (voxelwise worst case). These three methods were assessed with respect to treatment planning for prostate under systematic setup uncertainty. An equivalence with probabilistic optimization was used to identify the scenarios that determine the outcome of the optimization. Results: If the conflict between target coverage and normal tissue sparing is small and no dose-volume histogram (DVH) constraints are present, then all three methods yield robust plans. Otherwise, they all have their shortcomings: Composite worst case led to unnecessarily low plan quality in boundary scenarios that were less difficult than the worst case ones. Objectivewise worst case generally led to nonrobust plans. Voxelwise worst case led to overly conservative plans with respect to DVH constraints, which resulted in excessive dose to normal tissue, and less sharp dose fall-off than the other two methods. Conclusions: The three worst case methods have clearly different behaviors. These behaviors can be understood from which scenarios that are active in the optimization. No particular method is superior to the others under all circumstances: composite worst case is suitable if the conflicts are not very severe or there are DVH constraints whereas voxelwise worst case is advantageous if there are severe conflicts but no DVH constraints. The advantages of composite and voxelwise worst case outweigh those of objectivewise worst case. © 2014 American Association of Physicists in Medicine.}, author = {Albin Fredriksson and Rasmus Bokrantz}, doi = {10.1118/1.4883837}, issn = {00942405}, issue = {8}, journal = {Medical Physics}, title = {A critical evaluation of worst case optimization methods for robust intensity-modulated proton therapy planning}, volume = {41}, year = {2014} } @article{Pflugfelder2008, abstract = {The sharp dose gradients which are possible in intensity modulated proton therapy (IMPT) not only offer the possibility of generating excellent target coverage while sparing neighbouring organs at risk, but can also lead to treatment plans which are very sensitive to uncertainties in treatment variables such as the range of individual Bragg peaks. We developed a method to account for uncertainties of treatment variables in the optimization based on a worst case dose distribution. The worst case dose distribution is calculated using several possible realizations of the uncertainties. This information is used by the objective function of the inverse treatment planning system to generate treatment plans which are acceptable under all considered realizations of the uncertainties. The worst case optimization method was implemented in our in-house treatment planning software KonRad in order to demonstrate the usefulness of this approach for clinical cases. In this paper, we investigated range uncertainties, setup uncertainties and a combination of both uncertainties. Using our method the sensitivity of the resulting treatment plans to these uncertainties is considerably reduced. © 2008 Institute of Physics and Engineering in Medicine.}, author = {D. Pflugfelder and J. J. Wilkens and U. Oelfke}, doi = {10.1088/0031-9155/53/6/013}, issn = {00319155}, issue = {6}, journal = {Physics in Medicine and Biology}, title = {Worst case optimization: A method to account for uncertainties in the optimization of intensity modulated proton therapy}, volume = {53}, year = {2008} } @article{Tattenberg2021, abstract = {Purpose: Proton therapy allows for more conformal dose distributions and lower organ at risk and healthy tissue doses than conventional photon-based radiotherapy, but uncertainties in the proton range currently prevent proton therapy from making full use of these advantages. Numerous developments therefore aim to reduce such range uncertainties. In this work, we quantify the benefits of reductions in range uncertainty for treatments of skull base tumors. Methods: The study encompassed 10 skull base patients with clival tumors. For every patient, six treatment plans robust to setup errors of 2 mm and range errors from 0% to 5% were created. The determined metrics included the brainstem and optic chiasm normal tissue complication probability (NTCP) with the endpoints of necrosis and blindness, respectively, as well as the healthy tissue volume receiving at least 70% of the prescription dose. Results: A range uncertainty reduction from the current level of 4% to a potentially achievable level of 1% reduced the probability of brainstem necrosis by up to 1.3 percentage points in the nominal scenario in which neither setup nor range errors occur and by up to 2.9 percentage points in the worst-case scenario. Such a range uncertainty reduction also reduced the optic chiasm NTCP with the endpoint of blindness by up to 0.9 percentage points in the nominal scenario and by up to 2.2 percentage points in the worst-case scenario. The decrease in the healthy tissue volume receiving at least 70% of the prescription dose ranged from −7.8 to 24.1 cc in the nominal scenario and from −3.4 to 38.4 cc in the worst-case scenario. Conclusion: The benefits quantified as part of this study serve as a guideline of the OAR and healthy tissue dose benefits that range monitoring techniques may be able to achieve. Benefits were observed between all levels of range uncertainty. Even smaller range uncertainty reductions may therefore be beneficial.}, author = {Sebastian Tattenberg and Thomas M. Madden and Bram L. Gorissen and Thomas Bortfeld and Katia Parodi and Joost Verburg}, doi = {10.1002/mp.15097}, issn = {24734209}, issue = {9}, journal = {Medical Physics}, title = {Proton range uncertainty reduction benefits for skull base tumors in terms of normal tissue complication probability (NTCP) and healthy tissue doses}, volume = {48}, year = {2021} } @article{Arjomandy2019, abstract = {Purpose: Task Group (TG) 224 was established by the American Association of Physicists in Medicine's Science Council under the Radiation Therapy Committee and Work Group on Particle Beams. The group was charged with developing comprehensive quality assurance (QA) guidelines and recommendations for the three commonly employed proton therapy techniques for beam delivery: scattering, uniform scanning, and pencil beam scanning. This report supplements established QA guidelines for therapy machine performance for other widely used modalities, such as photons and electrons (TG 142, TG 40, TG 24, TG 22, TG 179, and Medical Physics Practice Guideline 2a) and shares their aims of ensuring the safe, accurate, and consistent delivery of radiation therapy dose distributions to patients. Methods: To provide a basis from which machine-specific QA procedures can be developed, the report first describes the different delivery techniques and highlights the salient components of the related machine hardware. Depending on the particular machine hardware, certain procedures may be more or less important, and each institution should investigate its own situation. Results: In lieu of such investigations, this report identifies common beam parameters that are typically checked, along with the typical frequencies of those checks (daily, weekly, monthly, or annually). The rationale for choosing these checks and their frequencies is briefly described. Short descriptions of suggested tools and procedures for completing some of the periodic QA checks are also presented. Conclusion: Recommended tolerance limits for each of the recommended QA checks are tabulated, and are based on the literature and on consensus data from the clinical proton experience of the task group members. We hope that this and other reports will serve as a reference for clinical physicists wishing either to establish a proton therapy QA program or to evaluate an existing one.}, author = {Bijan Arjomandy and Paige Taylor and Christopher Ainsley and Sairos Safai and Narayan Sahoo and Mark Pankuch and Jonathan B. Farr and Sung Yong Park and Eric Klein and Jacob Flanz and Ellen D. Yorke and David Followill and Yuki Kase}, doi = {10.1002/mp.13622}, issn = {24734209}, issue = {8}, journal = {Medical Physics}, title = {AAPM task group 224: Comprehensive proton therapy machine quality assurance}, volume = {46}, year = {2019} } @article{Zhu2015, abstract = {An intensity-modulated proton therapy (IMPT) patient-specific quality assurance (PSQA) program based on measurement alone can be very time consuming due to the highly modulated dose distributions of IMPT fields. Incorporating independent dose calculation and treatment log file analysis could reduce the time required for measurements. In this article, we summarize our effort to develop an efficient and effective PSQA program that consists of three components: measurements, independent dose calculation, and analysis of patient-specific treatment delivery log files. Measurements included two-dimensional (2D) measurements using an ionization chamber array detector for each field delivered at the planned gantry angles with the electronic medical record (EMR) system in the QA mode and the accelerator control system (ACS) in the treatment mode, and additional measurements at depths for each field with the ACS in physics mode and without the EMR system. Dose distributions for each field in a water phantom were calculated independently using a recently developed in-house pencil beam algorithm and compared with those obtained using the treatment planning system (TPS). The treatment log file for each field was analyzed in terms of deviations in delivered spot positions from their planned positions using various statistical methods. Using this improved PSQA program, we were able to verify the integrity of the data transfer from the TPS to the EMR to the ACS, the dose calculation of the TPS, and the treatment delivery, including the dose delivered and spot positions. On the basis of this experience, we estimate that the in-room measurement time required for each complex IMPT case (e.g., a patient receiving bilateral IMPT for head and neck cancer) is less than 1 h using the improved PSQA program. Our experience demonstrates that it is possible to develop an efficient and effective PSQA program for IMPT with the equipment and resources available in the clinic.}, author = {X. Ronald Zhu and Yupeng Li and Dennis Mackin and Heng Li and Falk Poenisch and Andrew K. Lee and Anita Mahajan and Steven J. Frank and Michael T. Gillin and Narayan Sahoo and Xiaodong Zhang}, doi = {10.3390/cancers7020631}, issn = {20726694}, issue = {2}, journal = {Cancers}, title = {Towards effective and efficient patient-specific quality assurance for spot scanning proton therapy}, volume = {7}, year = {2015} } @article{Rana2019, abstract = {Purpose: The main purpose of this study is to demonstrate the clinical implementation of a comprehensive pencil beam scanning (PBS) daily quality assurance (QA) program involving a number of novel QA devices including the Sphinx/Lynx/parallel-plate (PPC05) ion chamber and HexaCheck/multiple imaging modality isocentricity (MIMI) imaging phantoms. Additionally, the study highlights the importance of testing the connectivity among oncology information system (OIS), beam delivery/imaging systems, and patient position system at a proton center with multi-vendor equipment and software. Methods: For dosimetry, a daily QA plan with spot map of four different energies (106, 145, 172, and 221 MeV) is delivered on the delivery system through the OIS. The delivery assesses the dose output, field homogeneity, beam coincidence, beam energy, width, distal-fall-off (DFO), and spot characteristics — for example, position, size, and skewness. As a part of mechanical and imaging QA, a treatment plan with the MIMI phantom serving as the patient is transferred from OIS to imaging system. The HexaCheck/MIMI phantoms are used to assess daily laser accuracy, imaging isocenter accuracy, image registration accuracy, and six-dimensional (6D) positional correction accuracy for the kV imaging system and robotic couch. Results: The daily QA results presented herein are based on 202 daily sets of measurements over a period of 10 months. Total time to perform daily QA tasks at our center is under 30 min. The relative difference (Δ rel ) of daily measurements with respect to baseline was within ± 1% for field homogeneity, ±0.5 mm for range, width and DFO, ±1 mm for spots positions, ±10% for in-air spot sigma, ±0.5 spot skewness, and ±1 mm for beam coincidence (except 1 case: Δ rel  = 1.3 mm). The average Δ rel in dose output was −0.2% (range: −1.1% to 1.5%). For 6D IGRT QA, the average absolute difference (Δ abs ) was ≤0.6 ± 0.4 mm for translational and ≤0.5° for rotational shifts. Conclusion: The use of novel QA devices such as the Sphinx in conjunction with the Lynx, PPC05 ion chamber, HexaCheck/MIMI phantoms, and myQA software was shown to provide a comprehensive and efficient method for performing daily QA of a number of system parameters for a modern proton PBS-dedicated treatment delivery unit.}, author = {Suresh Rana and Jaafar Bennouna and E. James Jebaseelan Samuel and Alonso N. Gutierrez}, doi = {10.1002/acm2.12556}, issn = {15269914}, issue = {4}, journal = {Journal of Applied Clinical Medical Physics}, title = {Development and long-term stability of a comprehensive daily QA program for a modern pencil beam scanning (PBS) proton therapy delivery system}, volume = {20}, year = {2019} } @article{Trnkov2016, abstract = {Purpose: A detailed analysis of 2728 intensity modulated proton therapy (IMPT) fields that were clinically delivered to patients between 2007 and 2013 at Paul Scherrer Institute (PSI) was performed. The aim of this study was to analyze the results of patient specific dosimetric verifications and to assess possible correlation between the quality assurance (QA) results and specific field metrics. Methods: Dosimetric verifications were performed for every IMPT field prior to patient treatment. For every field, a steering file was generated containing all the treatment unit information necessary for treatment delivery: beam energy, beam angle, dose, size of air gap, nuclear interaction (NI) correction factor, number of range shifter plates, number of Bragg peaks (BPs) with their position and weight. This information was extracted and correlated to the results of dosimetric verification of each field which was a measurement of two orthogonal profiles using an orthogonal ionization chamber array in a movable water column. Results: The data analysis has shown more than 94% of all verified plans were within defined clinical tolerances. The differences between measured and calculated dose depend critically on the number of BPs, total thickness of all range shifter plates inserted in the beam path, and maximal range. An increase of the dose difference was observed with smaller number of BPs (i.e., smaller tumor) and smaller ranges (i.e., superficial tumors). The results of the verification do not depend, however, on the prescribed dose, NI correction, or the size of the air gap. There is no dependency of the transversal and longitudinal spot position precision on the beam angle. The value of NI correction depends on the number of spots and number of range shifter plates. Conclusions: The presented study has shown that the verification method used at Centre for Proton Therapy at Paul Scherrer Institute is accurate and reproducible for performing patient specific QA. The results confirmed that the dose discrepancy is dependent on the size and location of the tumor.}, author = {P. Trnková and A. Bolsi and F. Albertini and D. C. Weber and A. J. Lomax}, doi = {10.1118/1.4964449}, issn = {24734209}, issue = {11}, journal = {Medical Physics}, title = {Factors influencing the performance of patient specific quality assurance for pencil beam scanning IMPT fields}, volume = {43}, year = {2016} } @article{Miften2018, abstract = {Purpose: Patient-specific IMRT QA measurements are important components of processes designed to identify discrepancies between calculated and delivered radiation doses. Discrepancy tolerance limits are neither well defined nor consistently applied across centers. The AAPM TG-218 report provides a comprehensive review aimed at improving the understanding and consistency of these processes as well as recommendations for methodologies and tolerance limits in patient-specific IMRT QA. Methods: The performance of the dose difference/distance-to-agreement (DTA) and γ dose distribution comparison metrics are investigated. Measurement methods are reviewed and followed by a discussion of the pros and cons of each. Methodologies for absolute dose verification are discussed and new IMRT QA verification tools are presented. Literature on the expected or achievable agreement between measurements and calculations for different types of planning and delivery systems are reviewed and analyzed. Tests of vendor implementations of the γ verification algorithm employing benchmark cases are presented. Results: Operational shortcomings that can reduce the γ tool accuracy and subsequent effectiveness for IMRT QA are described. Practical considerations including spatial resolution, normalization, dose threshold, and data interpretation are discussed. Published data on IMRT QA and the clinical experience of the group members are used to develop guidelines and recommendations on tolerance and action limits for IMRT QA. Steps to check failed IMRT QA plans are outlined. Conclusion: Recommendations on delivery methods, data interpretation, dose normalization, the use of γ analysis routines and choice of tolerance limits for IMRT QA are made with focus on detecting differences between calculated and measured doses via the use of robust analysis methods and an in-depth understanding of IMRT verification metrics. The recommendations are intended to improve the IMRT QA process and establish consistent, and comparable IMRT QA criteria among institutions.}, author = {Moyed Miften and Arthur Olch and Dimitris Mihailidis and Jean Moran and Todd Pawlicki and Andrea Molineu and Harold Li and Krishni Wijesooriya and Jie Shi and Ping Xia and Nikos Papanikolaou and Daniel A. Low}, doi = {10.1002/mp.12810}, issn = {24734209}, issue = {4}, journal = {Medical Physics}, title = {Tolerance limits and methodologies for IMRT measurement-based verification QA: Recommendations of AAPM Task Group No. 218}, volume = {45}, year = {2018} } @article{Bizzocchi2017, abstract = {In a radiotherapy center, daily quality assurance (QA) measurements are performed to ensure that the equipment can be safely used for patient treatment on that day. In a pencil beam scanning (PBS) proton therapy center, spot positioning, spot size, range, and dose output are usually verified every day before treatments. We designed, built, and tested a new, reliable, sensitive, and inexpensive phantom, coupled with an array of ionization chambers, for daily QA that reduces the execution times while preserving the reliability of the test. The phantom is provided with 2 pairs of wedges to sample the Bragg peak at different depths to have a transposition on the transverse plane of the depth dose. Three “boxes” are used to check spot positioning and delivered dose. The box thickness helps spread the single spot and to fit a Gaussian profile on a low resolution detector. We tested whether our new QA solution could detect errors larger than our action levels: 1 mm in spot positioning, 2 mm in range, and 10% in spot size. Execution time was also investigated. Our method is able to correctly detect 98% of spots that are actually in tolerance for spot positioning and 99% of spots out of 1 mm tolerance. All range variations greater than the threshold (2 mm) were correctly detected. The analysis performed over 1 month showed a very good repeatability of spot characteristics. The time taken to perform the daily quality assurance is 20 minutes, a half of the execution time of the former multidevice procedure. This “in-house build” phantom substitutes 2 very expensive detectors (a multilayer ionization chamber [MLIC] and a strip chamber, reducing by 5 times the cost of the equipment. We designed, built, and validated a phantom that allows for accurate, sensitive, fast, and inexpensive daily QA procedures in proton therapy with PBS.}, author = {Nicola Bizzocchi and Francesco Fracchiolla and Marco Schwarz and Carlo Algranati}, doi = {10.1016/j.meddos.2017.05.001}, issn = {18734022}, issue = {3}, journal = {Medical Dosimetry}, title = {A fast and reliable method for daily quality assurance in spot scanning proton therapy with a compact and inexpensive phantom}, volume = {42}, year = {2017} } @article{Mackin2014, abstract = {Purpose:We report the outcomes of patient-specific quality assurance (PSQA) for spot- scanning proton therapy (SSPT) treatment plans by disease site. Patients and Methods: We analyzed quality assurance outcomes for 309 SSPT plans. The PSQA measurements consisted of 2 parts: (1) an end-to-end test in which the beam was delivered at the prescribed gantry angle and (2) dose plane measurements made from gantry angle 2708. The HPlusQ software was used for gamma analysis of the dose planes using dose-tolerance and distance-to-agreement levels of 2%, 2 mm and 3%, 3 mm, respectively. Passingwas defined as a gamma score,1 in at least 90%of the pixels. Results: The overall quality assurance measurement passing rate was 96.2% for the gamma index criteria of 3%, 3mmbut fell to 85.3%when the criteria were tightened to 2%, 2 mm. The passing rate was dependent on the treatment site.With the 3%, 3 mm criteria, the passing rate was 95%for head-and-neck treatment plans and 100% for prostate plans. No significant difference was found between passing rates for multi-field and single-field optimized plans. The passing rate was 94.8% 6 0.6% for fields with range shifters and 99.0% 6 0.6% for those without (P¼ .002). Most low gamma index scores were due to steep dose gradients transverse to the measured plane. A less frequent cause of failures was an apparent systematic overestimation of the calculated dose at depths proximal to the spread-out Bragg peak. Conclusion: A comprehensive PSQA program serves to ensure the safety of a specific treatment plan and acts as a check on the entire treatment system. We propose that the 3%, 3 mm with 90% pixel passing rate is a reasonable action level for 2-dimensional comparisons of dose planes in SSPT, although more restrictive tolerance levels would be appropriate for prostate treatment plans}, author = {Dennis Mackin and X. Ronald Zhu and Falk Poenisch and Heng Li and Narayan Sahoo and Matthew Kerr and Charles Holmes and Yupeng Li and MingFwu Lii and Richard Wu and Kazumichi Suzuki and Michael T. Gillin and Steven J. Frank and David Grosshans and Xiaodong Zhang}, doi = {10.14338/ijpt-14-00017.1}, issn = {23315180}, issue = {3}, journal = {International Journal of Particle Therapy}, title = {Spot-Scanning Proton Therapy Patient-Specific Quality Assurance: Results from 309 Treatment Plans}, volume = {1}, year = {2014} } @article{Chan2017, abstract = {Background and Aims—Cardiovascular disease (CVD) is among the leading causes of morbidity and mortality worldwide. Traditional risk factors predict 75-80% of an individual's risk of incident CVD. However, the role of early life experiences in future disease risk is gaining attention. The Barker hypothesis proposes fetal origins of adult disease, with consistent evidence demonstrating the deleterious consequences of birth weight outside the normal range. In this study, we investigate the role of birth weight in CVD risk prediction. Methods and Results—The Women's Health Initiative (WHI) represents a large national cohort of post-menopausal women with 63 815 participants included in this analysis. Univariable proportional hazards regression analyses evaluated the association of 4 self-reported birth weight categories against 3 CVD outcome definitions, which included indicators of coronary heart disease, ischemic stroke, coronary revascularization, carotid artery disease and peripheral arterial disease. The role of birth weight was also evaluated for prediction of CVD events in the presence of traditional risk factors using 3 existing CVD risk prediction equations: one body mass index (BMI)-based and two laboratory-based models. Low birth weight (LBW) (< 6 lbs.) was significantly associated with all CVD outcome definitions in univariable analyses (HR=1.086, p=0.009). LBW was a significant covariate in the BMI-based model (HR=1.128, p<0.0001) but not in the lipid-based models. Conclusion—LBW (<6 lbs.) is independently associated with CVD outcomes in the WHI cohort. This finding supports the role of the prenatal and postnatal environment in contributing to the development of adult chronic disease.}, author = {Maria F. Chan and Chin-Cheng Chen and Chengyu Shi and Jingdong Li and Xiaoli Tang and Xiang Li and Dennis Mah}, doi = {10.4236/ijmpcero.2017.62011}, issn = {2168-5436}, issue = {02}, journal = {International Journal of Medical Physics, Clinical Engineering and Radiation Oncology}, title = {Patient-Specific QA of Spot-Scanning Proton Beams Using Radiochromic Film}, volume = {06}, year = {2017} } @article{Wolter2025, author = {Lukas Cornelius Wolter and Fabian Hennings and Jozef Bokor and Christian Richter and Kristin Stuetzer}, doi = {10.1002/mp.17637}, issn = {0094-2405}, issue = {5}, journal = {Medical Physics}, pages = {3173-3182}, title = {Validity of one-time phantomless patient-specific quality assurance in proton therapy with regard to the reproducibility of beam delivery}, volume = {52}, year = {2025} } @article{Li2013, abstract = {Purpose: The purpose of this work was to assess the monitor unit (MU) values and position accuracy of spot scanning proton beams as recorded by the daily treatment logs of the treatment control system, and furthermore establish the feasibility of using the delivered spot positions and MU values to calculate and evaluate delivered doses to patients. Methods: To validate the accuracy of the recorded spot positions, the authors generated and executed a test treatment plan containing nine spot positions, to which the authors delivered ten MU each. The spot positions were measured with radiographic films and Matrixx 2D ion-chambers array placed at the isocenter plane and compared for displacements from the planned and recorded positions. Treatment logs for 14 patients were then used to determine the spot MU values and position accuracy of the scanning proton beam delivery system. Univariate analysis was used to detect any systematic error or large variation between patients, treatment dates, proton energies, gantry angles, and planned spot positions. The recorded patient spot positions and MU values were then used to replace the spot positions and MU values in the plan, and the treatment planning system was used to calculate the delivered doses to patients. The results were compared with the treatment plan. Results: Within a treatment session, spot positions were reproducible within ±0.2 mm. The spot positions measured by film agreed with the planned positions within ±1 mm and with the recorded positions within ±0.5 mm. The maximum day-to-day variation for any given spot position was within ±1 mm. For all 14 patients, with ∼1 500 000 spots recorded, the total MU accuracy was within 0.1% of the planned MU values, the mean (x, y) spot displacement from the planned value was (-0.03 mm, -0.01 mm), the maximum (x, y) displacement was (1.68 mm, 2.27 mm), and the (x, y) standard deviation was (0.26 mm, 0.42 mm). The maximum dose difference between calculated dose to the patient based on the plan and recorded data was within 2%. Conclusions: The authors have shown that the treatment log file in a spot scanning proton beam delivery system is precise enough to serve as a quality assurance tool to monitor variation in spot position and MU value, as well as the delivered dose uncertainty from the treatment delivery system. The analysis tool developed here could be useful for assessing spot position uncertainty and thus dose uncertainty for any patient receiving spot scanning proton beam therapy. © 2013 American Association of Physicists in Medicine.}, author = {Heng Li and Narayan Sahoo and Falk Poenisch and Kazumichi Suzuki and Yupeng Li and Xiaoqiang Li and Xiaodong Zhang and Andrew K. Lee and Michael T. Gillin and X. Ronald Zhu}, doi = {10.1118/1.4773312}, issn = {00942405}, issue = {2}, journal = {Medical Physics}, title = {Use of treatment log files in spot scanning proton therapy as part of patient-specific quality assurance}, volume = {40}, year = {2013} } @article{Belosi2017, abstract = {Dose distributions delivered at Gantry 2 at the Paul Scherrer Institut (PSI) can be reconstructed on the patient anatomy based on machine log files. With the present work, the dependency of the log file calculation on the planning optimization technique and on other planning parameters, such as field direction and tumour size, has been investigated. Interestingly, and despite the typically higher modulation of Intensity Modulated Proton Therapy (IMPT) plans, the results for both Single Field Uniform Distribution and IMPT approaches have been found to be similar. In addition, complex fields with steep in-field dose gradients, such as Simultaneous Integrated Boost, and with couch movements in between the delivery, also resulted in good agreement between planned and reconstructed doses. Nevertheless, highly modulated plans can have regions of larger local dose deviations and attention should therefore be paid during the planning stage to the location of isolated, highly weighted pencil beams. We propose also, that further effort should be invested in order to predict field robustness to delivery fluctuations before the clinical delivery of the plan as part of the plan specific Quality Assurance.}, author = {Maria Francesca Belosi and Robert van der Meer and Paz Garcia de Acilu Laa and Alessandra Bolsi and Damien C. Weber and Antony J. Lomax}, doi = {10.1016/j.radonc.2017.09.037}, issn = {18790887}, issue = {3}, journal = {Radiotherapy and Oncology}, title = {Treatment log files as a tool to identify treatment plan sensitivity to inaccuracies in scanned proton beam delivery}, volume = {125}, year = {2017} } @article{Matter2020, abstract = {In daily adaptive proton therapy (DAPT), the treatment plan is re-optimized on a daily basis. It is a straightforward idea to incorporate information from the previous deliveries during the optimization to refine this daily proton delivery. A feedback signal was used to correct for delivery errors and errors from an inaccurate dose calculation used for plan optimization. This feedback signal consisted of a dose distribution calculated with a Monte Carlo algorithm and was based on the spot delivery information from the previous deliveries in the form of log-files. We therefore called the method Update On Yesterday's Dose (UYD). The UYD method was first tested with a simulated DAPT treatment and second with dose measurements using an anthropomorphic phantom. For both, the simulations and the measurements, a better agreement between the delivered and the intended dose distribution could be observed using UYD. Gamma pass rates (1%/1 mm) increased from around 75% to above 90%, when applying the closed-loop correction for the simulations, as well as the measurements. For a DAPT treatment, positioning errors or anatomical changes are incorporated during the optimization and therefore are less dominant in the overall dose uncertainty. Hence, the relevance of algorithm or delivery machine errors even increases compared to standard therapy. The closed-loop process described here is a method to correct for these errors, and potentially further improve DAPT.}, author = {M. Matter and L. Nenoff and L. Marc and D. C. Weber and A. J. Lomax and F. Albertini}, doi = {10.1088/1361-6560/ab9f5e}, issn = {13616560}, issue = {19}, journal = {Physics in Medicine and Biology}, title = {Update on yesterday's dose-Use of delivery log-files for daily adaptive proton therapy (DAPT)}, volume = {65}, year = {2020} } @article{Winterhalter2019, abstract = {Patient specific quality assurance is crucial to guarantee safety in proton pencil beam scanning. In current clinical practice, this requires extensive, time consuming measurements. Additionally, these measurements do not consider the influence of density heterogeneities in the patient and are insensitive to delivery errors. In this work, we investigate the use of log file based Monte Carlo calculations for dose reconstructions in the patient CT, which takes the combined influence of calculational and delivery errors into account. For one example field, 87%/90% of the voxels agree within ±3% when taking either calculational or delivery uncertainties into account (analytical versus Monte Carlo calculation/Monte Carlo from planned versus Monte Carlo from log file). 78% agree when considering both uncertainties simultaneously (nominal field versus Monte Carlo from log files). We then show the application of the log file based Monte Carlo calculations as a patient specific quality assurance tool for a set of five patients (16 fields) treated for different indications. For all fields, absolute dose scaling factors based on the log file Monte Carlo agree within ±3% to the measurement based absolute dose scaling. Relative comparison shows that more than 90% of the voxels agree within ± 5% between the analytical calculated plan and the Monte Carlo based on log files. The log file based Monte Carlo approach is an end-to-end test incorporating all requirements of patient specific quality assurance. It has the potential to reduce the workload and therefore to increase the patient throughput, while simultaneously enabling more accurate dose verification directly in the patient geometry.}, author = {Carla Winterhalter and Gabriel Meier and David Oxley and Damien C. Weber and Antony J. Lomax and Sairos Safai}, doi = {10.1088/1361-6560/aaf82d}, issn = {13616560}, issue = {3}, journal = {Physics in Medicine and Biology}, title = {Log file based Monte Carlo calculations for proton pencil beam scanning therapy}, volume = {64}, year = {2019} } @article{Meijers2020, abstract = {Purpose: Patient specific quality assurance (PSQA) is required to verify the treatment delivery and the dose calculation by the treatment planning system (TPS). The objective of this work is to demonstrate the feasibility to substitute resource consuming measurement based PSQA (PSQAM) by independent dose recalculations (PSQAIDC), and that PSQAIDC results may be interpreted in a clinically relevant manner using normal tissue complication probability (NTCP) and tumor control probability (TCP) models. Methods and materials: A platform for the automatic execution of the two following PSQAIDC workflows was implemented: (i) using the TPS generated plan and (ii) using treatment delivery log files (log-plan). 30 head and neck cancer (HNC) patients were retrospectively investigated. PSQAM results were compared with those from the two PSQAIDC workflows. TCP/NTCP variations between PSQAIDC and the initial TPS dose distributions were investigated. Additionally, for two example patients that showed low passing PSQAM results, eight error scenarios were simulated and verified via measurements and log-plan based calculations. For all error scenarios ΔTCP/NTCP values between the nominal and the log-plan dose were assessed. Results: Results of PSQAM and PSQAIDC from both implemented workflows agree within 2.7% in terms of gamma pass ratios. The verification of simulated error scenarios shows comparable trends between PSQAM and PSQAIDC. Based on the 30 investigated HNC patients, PSQAIDC observed dose deviations translate into a minor variation in NTCP values. As expected, TCP is critically related to observed dose deviations. Conclusions: We demonstrated a feasibility to substitute PSQAM with PSQAIDC. In addition, we showed that PSQAIDC results can be interpreted in clinically more relevant manner, for instance using TCP/NTCP.}, author = {Arturs Meijers and Gabriel Guterres Marmitt and Kelvin Ng Wei Siang and Arjen van der Schaaf and Antje C. Knopf and Johannes A. Langendijk and Stefan Both}, doi = {10.1016/j.radonc.2020.06.027}, issn = {18790887}, journal = {Radiotherapy and Oncology}, title = {Feasibility of patient specific quality assurance for proton therapy based on independent dose calculation and predicted outcomes}, volume = {150}, year = {2020} } @article{Matter2018, abstract = {Patient specific verification (PSV) measurements for pencil beam scanning (PBS) proton therapy are resource-consuming and necessitate substantial beam time outside of clinical hours. As such, efforts to safely reduce the PSV-bottleneck in the clinical work-flow are of great interest. Here, capabilities of current PSV methods to ensure the treatment integrity were investigated and compared to an alternative approach of reconstructing the dose distribution directly from the machine control- or delivery log files with the help of an independent dose calculation (IDC). Scenarios representing a wide range of delivery or work-flow failures were identified (e.g. error in spot position, air gap or pre-absorber setting) and machine files were altered accordingly. This yielded 21 corrupted treatment files, which were delivered and measured with our clinical PSV protocol. IDC machine- and log file checks were also conducted and their sensitivity at detecting the errors compared to the measurements. Although some of the failure scenarios induced clinically relevant dose deviations in the patient geometry, the PSV measurement protocol only detected one out of 21 error scenarios. However, 11 and all 21 error scenarios were detected using dose reconstructions based on the log and machine files respectively. Our data suggests that, although commonly used in particle therapy centers, PSV measurements do a poor job detecting data transfer failures and imperfect delivery machine performance. Machine- and log-file IDCs have been shown to successfully detect erroneous work-flows and to represent a reliable addition to the QA procedure, with the potential to replace PSV.}, author = {M. Matter and L. Nenoff and G. Meier and D. C. Weber and A. J. Lomax and F. Albertini}, doi = {10.1088/1361-6560/aae2f4}, issn = {13616560}, issue = {20}, journal = {Physics in Medicine and Biology}, title = {Alternatives to patient specific verification measurements in proton therapy: A comparative experimental study with intentional errors}, volume = {63}, year = {2018} } @article{Ding2021, abstract = {Demand for proton therapy (PT) continues to grow due to its dosimetric advantages over conventional radiotherapy. New PT facilities being constructed to meet this demand will need quality assurance (QA) programs to ensure that treatments are delivered safely and accurately. However, in contrast to conventional radiotherapy, proton QA practices are constantly evolving and few commercial solutions are available. As a result, QA programs at most operational proton facilities rely on a variety of in-house developed hardware and software. An important part of these QA programs is proton daily QA, which verifies clinically-acceptable proton delivery system operation each morning before starting patient treatment. In this review article, we summarize current proton daily QA practices by providing a brief introduction to PT, describing proton delivery techniques and their particular QA requirements, and then reviewing implementations of several proton daily QA programs. Although the QA instrumentation is quite heterogeneous, the literature shows that the dosimetric daily QA results among proton facilities are comparable. We also present a typical set of proton daily QA data from our institution that includes output, range, and spot position measurements. Based on the literature review and our institutional experience, we make recommendations for future proton daily QA programs.}, author = {Xiaoning Ding and James E. Younkin and Jiajian Shen and Martin Bues and Wei Liu}, doi = {10.21037/TRO-21-11}, issn = {26162768}, journal = {Therapeutic Radiology and Oncology}, title = {A critical review of the practices of proton daily quality assurance programs}, volume = {5}, year = {2021} } @article{Actis2017, abstract = {There are several general recommendations for quality assurance (QA) measures, which have to be performed at proton therapy centres. However, almost each centre uses a different therapy system. In particular, there is no standard procedure for centres employing pencil beam scanning and each centre applies a specific QA program. Gantry 2 is an operating therapy system which was developed at PSI and relies on the most advanced technological innovations. We developed a comprehensive daily QA program in order to verify the main beam characteristics to assure the functionality of the therapy delivery system and the patient safety system. The daily QA program entails new hardware and software solutions for a highly efficient clinical operation. In this paper, we describe a dosimetric phantom used for verifying the most critical beam parameters and the software architecture developed for a fully automated QA procedure. The connection between our QA software and the database allows us to store the data collected on a daily basis and use it for trend analysis over longer periods of time. All the data presented here have been collected during a time span of over two years, since the beginning of the Gantry 2 clinical operation in 2013. Our procedure operates in a stable way and delivers the expected beam quality. The daily QA program takes only 20 min. At the same time, the comprehensive approach allows us to avoid most of the weekly and monthly QA checks and increases the clinical beam availability.}, author = {O. Actis and D. Meer and S. König and D. C. Weber and A. Mayor}, doi = {10.1088/1361-6560/aa5131}, issn = {13616560}, issue = {5}, journal = {Physics in Medicine and Biology}, title = {A comprehensive and efficient daily quality assurance for PBS proton therapy}, volume = {62}, year = {2017} }