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We demonstrate the first ever recorded PET imaging and dosimetry of a FLASH proton beam at the Proton Center of the MD~Anderson Cancer Center. Two scintillating LYSO crystal arrays, read out by silicon photomultipliers, were configured with a partial field of view of a~cylindrical PMMA phantom irradiated by a FLASH proton beam. The proton beam had a kinetic energy of 75.8\,MeV and an intensity of about $3.5\times10^{10}$ protons that were extracted over 101.5\,ms-long spills. The radiation environment was characterized by CZT and plastic scintillator counters. Preliminary results indicate that the PET technology used in our tests can efficiently record FLASH beam events. The instrument yielded informative and quantitative imaging and dosimetry of beam-activated isotopes in a PMMA phantoms, as supported by Monte Carlo simulations. These studies open a new PET modality that can lead to improved imaging and monitoring of FLASH proton therapy.

Radiation therapy (RT) is an integral component of potentially curative management of esophageal cancer (EC). However, RT can cause significant acute and late morbidity due to excess radiation exposure to nearby critical organs, especially the heart and lungs. Sparing these organs from both low and high radiation dose has been demonstrated to achieve clinically meaningful reductions in toxicity and may improve long-term survival. Accruing dosimetry and clinical evidence support the consideration of proton beam therapy (PBT) for the management of EC. There are critical treatment planning and delivery uncertainties that should be considered when treating EC with PBT, especially as there may be substantial motion-related interplay effects. The Particle Therapy Co-operative Group Thoracic and Gastrointestinal Subcommittees jointly developed guidelines regarding patient selection, treatment planning, clinical trials, and future directions of PBT for EC.

One technical challenge in developing a large-size scintillator detector with multiple Silicon Photomultiplier (SiPM) arrays is to read out a large number of detector output channels. To achieve this, different signal multiplexing circuits have been studied and applied with different performances and cost-effective tradeoffs. Resistor-based multiplexing circuits exhibit simplicity and signal integrity, but also present the disadvantage of timing shift among different channels. In this study, a resistor-based multiplexing circuit for a large-sized SiPM array readout was developed and evaluated by simulation and experimental studies. Similarly to a multiplexing circuit used for multi-anode PMT, grounding and branching resistors were connected to each SiPM output channel. The grounding resistor was used to simultaneously reduce the signal crosstalk among different channels and to improve timing performance. Both grounding and branching resistor values were optimized to maintain a balanced performance of the event energy, timing, and positioning. A multiplexing circuit was implemented on a compact PCB and applied for a flat-panel detector which consisted of a 32×32 LYSO scintillator crystals optically coupled to 5×5 SiPM arrays for a total 20×20 output channels. Test results showed excellent crystal identification for all 1024 LYSO crystals (each with 2×2×30 mm(3) size) with (22)Na flood-source irradiation. The measured peak-to-valley ratio from typical crystal map profile is around 3:1 to 6.6:1, an average single crystal energy resolution of about 17.3%, and an average single crystal timing resolution of about 2 ns. Timing shift among different crystals, as reported in some other resistor-based multiplexing circuit designs, was not observed. In summary, we have designed and implemented a practical resistor-based multiplexing circuit that can be readily applied for reading out a large SiPM array with good detector performance.

Background and purpose We hypothesized that a plan’s robustness to anatomical changes can be improved by optimizing with multiple CT scans of a patient. The purpose of this study was to determine whether an intensity modulated proton therapy (IMPT) plan could be developed to meet dose criteria on both planning and adaptive CT plans. Material and methods Eight lung cancer patients who underwent adaptive IMPT were retrospectively selected. Each patient had two CTs: a primary planning CT (PCT) and an adaptive planning CT (ACT), and IMPT plans associated with the scans. PCT and ACT were then used in combination to optimize one plan (MCT plan). The doses to the target and organs at risk from the PCT plan, ACT plan, P-ACT plan (PCT plan calculated on ACT data), and MCT plans calculated on both CTs were compared. Results The MCT plan maintained the D 95% on both CTs (mean, 65.99 Gy on PCT and 66.02 Gy on ACT). Target dose coverage on ACT was significantly better with the MCT plan than with the P-ACT plan ( p = 0.01). MCT plans had slightly higher lung V 20 (0.6%, p = 0.02) than did PCT plans. The various plans showed no statistically significant difference in heart and spinal cord dose. Conclusions The results of this study indicate that an IMPT plan can meet the dose criteria on both PCT and ACT, and that MCT optimization can improve the plan’s robustness to anatomical change.

The capabilities of the Eclipse treatment planning system (TPS) (Varian Medical Systems, Palo Alto, CA) for proton therapy treatment planning are described. Various steps involved in the planning process to produce a 3-dimensional (3D) dose distribution both for the passive scattering and pencil beam scanning proton beam therapy are outlined. Mitigation of range and setup uncertainties through robust optimization is discussed. Use of verification plans for patient treatment field dosimetry quality assurance (QA) is presented. Limitations of the Eclipse TPS and future developments are discussed.

Purpose: To provide a series of suggestions for other Medical Physics practices to follow in order to provide effective radiation therapy treatments during the COVID-19 pandemic. Methods and Materials: We reviewed our entire Radiation Oncology infrastructure to identify a series of workflows and policy changes that we implemented during the pandemic that yielded more effective practices during this time. Results: We identified a structured list of several suggestions that can help other Medical Physics practices overcome the challenges involved in delivering high quality radiotherapy services during this pandemic. Conclusions: Our facility encompasses 4 smaller Houston Area Locations (HALs), a main campus with 8 distinct services based on treatment site (ie. Thoracic, Head and Neck, Breast, Gastrointestinal, Gynecology, Genitourinary, Hematologic Malignancies, Melanoma and Sarcoma and Central Nervous System/Pediatrics), a Proton Center facility, an MR-Linac, a Gamma Knife clinic and an array of brachytherapy services. Due to the scope of our services, we have gained experience in dealing with the rapidly changing pandemic effects on our clinical practice. Our paper provides a resource to other Medical Physics practices in search of workflows that have been resilient during these challenging times.

Purpose To systematically analyze and present the properties of a small-field, double-scattering proton beam line intended to be used for the treatment of ocular cancer, and to provide configuration data for commission of the Eclipse Ocular Proton Planning System. Methods Measurements were made using ionization chambers, diodes, and films to determine dose profiles and output factors of the proton beams of the beam line at the Proton Therapy Center Houston. In parallel, Monte Carlo simulations were performed to validate the measured data and to provide additional insight into detailed beam parameters that are hard to measure, such as field size factors and a comparison of output factors as a function of circular and rectangular fields. Results The presented data comprises depth dose profiles, including distal and proximal profiles used to configure the Eclipse Ocular Proton Planning system EOPP, distal fall-off widths, lateral profiles and penumbrae sizes, as well as output factors as a function of field size, SOBP width, range shifter thickness, snout position and source to surface distance. Conclusions We have completed a comprehensive characterization of the beam line. The data will be useful to characterize proton beams in clinical and experimental small field applications. This article is protected by copyright. All rights reserved.

Pencil-beam scanning (PBS) proton therapy (PT), particularly intensity modulated PT, represents the latest advanced PT technology for treating cancers, including thoracic malignancies. On the basis of virtual clinical studies, PBS-PT appears to have great potential in its ability to tightly tailor the dose to the target while sparing critical structures, thereby reducing treatment-related toxicities, particularly for tumors in areas with complicated anatomy. However, implementing PBS-PT for moving targets has several additional technical challenges compared with intensity modulated photon radiation therapy or passive scattering PT. Four-dimensional computed tomographye based motion management and robust optimization and evaluation are crucial for minimizing uncertainties associated with beam range and organ motion. Rigorous quality assurance is required to validate dose delivery both before and during the course of treatment. Active motion management (eg, breath hold), beam gating, rescanning, tracking, or adaptive planning may be needed for cases involving significant motion or changes in motion or anatomy over the course of treatment. (C) 2017 The Authors. Published by Elsevier Inc.

PURPOSE: The authors aimed to illustrate the potential dose differences to clinical target volumes (CTVs) and organs-at-risk (OARs) volumes after proton adaptive treatment planning was used. PATIENTS AND METHODS: The records of 10 patients with oropharyngeal cancer were retrospectively reviewed. Each patient's treatment plan was generated by using the Eclipse treatment planning system. Verification computed tomography (CT) scan was performed during the fourth week of treatment. Deformable image registrations were performed between the 2 CT image sets, and the CTVs and major OARs were transferred to the verification CT images to generate the adaptive plan. We compared the accumulated doses to CTVs and OARs between the original and adaptive plans, as well as between the adaptive and verification plans to simulate doses that would have been delivered if the adaptive plans were not used. RESULTS: Body contours were different on planning and week-4 verification CTs. Mean volumes of all CTVs were reduced by 4% to 8% (P ≤ .04), and the volumes of left and right parotid glands also decreased (by 11% to 12%, P ≤ .004). Brainstem and oral cavity volumes did not significantly differ (all P ≥ .14). All mean doses to the CTV were decreased for up to 7% (P ≤ .04), whereas mean doses to the right parotid and oral cavity increased from a range of 5% to 8% (P ≤ .03), respectively. CONCLUSION: Verification and adaptive planning should be recommended during the course of proton therapy for patients with head and neck cancer to ensure adequate dose deliveries to the planned CTVs, while safe doses to OARs can be respected.

BACKGROUND Human papillomavirus (HPV)-positive oropharyngeal carcinomas response better to X-ray therapy (XRT) than HPV-negative disease. Whether HPV status influences the sensitivity of head and neck cancer cells to proton therapy or the relative biological effectiveness (RBE) of protons versus XRT is unknown. METHODS Clonogenic survival was used to calculate the RBE; immunocytochemical analysis and neutral comet assay were used to evaluate unrepaired DNA double-strand breaks. RESULTS HPV-positive cells were more sensitive to protons and the unrepaired double-strand breaks were more numerous in HPV-positive cells than in HPV-negative cells (p 1.06). Cell line type and radiation fraction size influenced the RBE. CONCLUSION HPV-positive cells were more sensitive to protons than HPV-negative cells maybe through the effects of HPV on DNA damage and repair. The RBE for protons depends more on cell type and fraction size than on HPV status. © 2016 Wiley Periodicals, Inc. Head Neck 39: 708-715, 2017.

Purpose Kilo‐voltage cone‐beam computed tomography (CBCT) is widely used for patient alignment, contour propagation, and adaptive treatment planning in radiation therapy. In this study, we evaluated the accuracy of deformable image registration (DIR) for CBCT under various imaging protocols with different noise and patient dose levels. Methods A physical phantom previously developed to facilitate end‐to‐end testing of the DIR accuracy was used with Varian Velocity v4.0 software to evaluate the performance of image registration from CT to CT, CBCT to CT, and CBCT to CBCT. The phantom is acrylic and includes several inserts that simulate different tissue shapes and properties. Deformations and anatomic changes were simulated by changing the rotations of both the phantom and the inserts. CT images (from a head and neck protocol) and CBCT images (from pelvis, head and “Image Gently” protocols) were obtained with different image noise and dose levels. Large inserts were filled with Mobil DTE oil to simulate soft tissue, and small inserts were filled with bone materials. All inserts were contoured before the DIR process to provide a ground truth contour size and shape for comparison. After the DIR process, all deformed contours were compared with the originals using Dice similarity coefficient (DSC) and mean distance to agreement (MDA). Both large and small volume of interests (VOIs) for DIR volume selection were tested by simulating a DIR process that included whole patient image volume and clinical target volumes (CTV) only (for CTVs propagation). Results For cross‐modality DIR registration (CT to CBCT), the DSC were >0.8 and the MDA were 0.8 and MDA

Background Proton radiotherapy (PRT) may be a less toxic alternative to photon radiotherapy (XRT) for patients with head and neck squamous cell carcinoma (HNSCC). However, the molecular responses of HNSCC cells to PRT vs XRT are unclear. Methods Proteomics analyses of protein expression profiles by reverse-phase protein arrays were done for two human papillomavirus [HPV]-negative and two HPV+ cell lines. Expression patterns of 175 proteins involved in several signaling pathways were tested. Results Compared with PRT, XRT tended to induce lower expression of DNA damage repair-and cell cycle arrest-related proteins and higher expression of cell survival- and proliferation-related proteins. Conclusions Under these experimental conditions, PRT and XRT induced different protein expression and activation profiles. Further preclinical verification is needed, as are studies of tumor pathway mutations as biomarkers for choice of treatment or as radiosensitization targets to improve the response of HNSCC to PRT or XRT.

Objective: This study is part of ongoing efforts aiming to transit from measurement-based to combined patient-specific quality assurance (PSQA) in intensity-modulated proton therapy (IMPT). A Monte Carlo (MC) dose-calculation algorithm is used to improve the independent dose calculation and to reveal the beam modeling deficiency of the analytical pencil beam (PB) algorithm. Methods: A set of representative clinical IMPT plans with suboptimal PSQA results were reviewed. Verification plans were recalculated using an MC algorithm developed in-house. Agreements of PB and MC calculations with measurements that quantified by the γ passing rate were compared. Results: The percentage of dose planes that met the clinical criteria for PSQA (>90% γ passing rate using 3%/3 mm criteria) increased from 71.40% in the original PB calculation to 95.14% in the MC recalculation. For fields without beam modifiers, nearly 100% of the dose planes exceeded the 95% γ passing rate threshold using the MC algorithm. The model deficiencies of the PB algorithm were found in the proximal and distal regions of the SOBP, where MC recalculation improved the γ passing rate by 11.27% (p < 0.001) and 16.80% (p < 0.001), respectively. Conclusions: The MC algorithm substantially improved the γ passing rate for IMPT PSQA. Improved modeling of beam modifiers would enable the use of the MC algorithm for independent dose calculation, completely replacing additional depth measurements in IMPT PSQA program. For current users of the PB algorithm, further improving the long-tail modeling or using MC simulation to generate the dose correction factor is necessary. Advances in knowledge: We justified a change in clinical practice to achieve efficient combined PSQA in IMPT by using the MC algorithm that was experimentally validated in almost all the clinical scenarios in our center. Deficiencies in beam modeling of the current PB algorithm were identified and solutions to improve its dose-calculation accuracy were provided.

A mini-ridge filter is often used to widen the Bragg peak in the longitudinal direction at low energies but not high energies. To facilitate the clinical use of a mini-ridge filter, we performed a planning study for the feasibility of a mini-ridge filter as an integral part of the synchrotron nozzle (IMRF). Dose models with and without IMRF were commissioned in a commercial Treatment planning system (TPS). Dosimetric characteristics in a homogenous water phantom were compared between plans with and without IMRF for a fixed spread-out Bragg peak width of 4 cm with distal ranges varying from 8 to 30 g/cm2. Six clinical cases were then used to compare the plan quality between plans. The delivery efficiency was also compared between plans in both the phantom and the clinical cases. The Bragg peak width was increased by 0.18 cm at the lowest energy and by only about 0.04 cm at the highest energy. The IMRF increased the spot size (σ) by up to 0.1 cm at the lowest energy and by only 0.02 cm at the highest energy. For the phantom, the IMRF negligibly affected dose at high energies but increased the lateral penumbra by up to 0.12 cm and the distal penumbra by up to 0.06 cm at low energies. For the clinical cases, the IMRF slightly increased dose to the organs at risk. However, the beam delivery time was reduced from 18.5% to 47.1% for the lung, brain, scalp, and head and neck cases, and dose uniformities of target were improved up to 2.9% for these cases owing to the reduced minimum monitor unit effect. In conclusion, integrating a mini-ridge filter into a synchrotron nozzle is feasible for improving treatment efficiency without significantly sacrificing the plan quality.

In proton therapy, passive scattered proton plans use compensators to conform the dose to the distal surface of the planning volume. These devices are custom made from acrylic or wax for each treatment field using either a plunge-drilled or smooth-milled compensator design. The purpose of this study was to investigate if there is a clinical benefit of generating passive scattered proton radiation treatment plans with the smooth compensator design. We generated 4 plans with different techniques using the smooth compensators. We chose 5 sites and 5 patients for each site for the range of dosimetric effects to show adequate sample. The plans were compared and evaluated using multicriteria (MCA) plan quality metrics for plan assessment and comparison using the Quality Reports [EMR] technology by Canis Lupus LLC. The average absolute difference for dosimetric metrics from the plunged-depth plan ranged from -4.7 to +3.0 and the average absolute performance results ranged from -6.6% to +3%. The manually edited smooth compensator plan yielded the best dosimetric metric, +3.0, and performance, + 3.0% compared to the plunged-depth plan. It was also superior to the other smooth compensator plans. Our results indicate that there are multiple approaches to achieve plans with smooth compensators similar to the plunged-depth plans. The smooth compensators with manual compensator edits yielded equal or better target coverage and normal tissue (NT) doses compared with the other smooth compensator techniques. Further studies are under investigation to evaluate the robustness of the smooth compensator design.

Background Photon (X-ray) radiotherapy (XRT) kills cells via DNA damage, however, how proton radiotherapy (PRT) causes cell death in head and neck squamous cell carcinoma (HNSCC) is unclear. We investigated mechanisms of HNSCC cell death after XRT versus PRT. Methods We assessed type of death in 2 human papillomavirus (HPV)-positive and two HPV-negative cell lines: necrosis and apoptosis (Annexin-V fluorescein isothiocyanate [FITC]); senescence (β-galactosidase); and mitotic catastrophe (γ-tubulin and diamidino-phenylindole [DAPI]). Results The XRT-induced or PRT-induced cellular senescence and mitotic catastrophe in all cell lines studied suggested that PRT caused cell death to a greater extent than XRT. After PRT, mitotic catastrophe peaked in HPV-negative and HPV-positive cells at 48 and 72 hours, respectively. No obvious differences were noted in the extent of cell necrosis or apoptosis after XRT versus PRT. Conclusion Under the conditions and in the cell lines reported here, mitotic catastrophe and senescence were the major types of cell death induced by XRT and PRT, and PRT may be more effective.

Purpose: To evaluate the effectiveness of three different immobilization devices for lungradiation therapy with daily and/or weekly cone‐beam CTs (CBCT).Methods: Three different immobilization devices, short (IM1) and long (Im2) Vac‐lok cushion with wing boards (Civco), BodyFix (Im3, Elekta), were investigated. Repeated CBCTimages for 3 SBRT patients immobilized with Im3, and 6 IMRT patients immobilized with IM1 and Im2 (3 each) were acquired. Each SBRT patient received 70 Gy in 10 fractions and setup daily with CBCT, while IM1 and Im2 patients were setup daily with orthogonal kV, and weekly CBCT (week 0–6). The day 1, 6 and 10 CBCT for Im3 were considered week 0–2 CBCT. Patient setup was first based on skins markers then shifts were made based on bony landmarks in kV and GTV with CBCT. Skin contours, which are further away from the isocenter and thus more sensitive to rotation and skin folding, were extracted in each CBCT data set and the difference on skin contours were investigated for both before and after shifts. Results: Over 2 weeks of treatment, Im3 has the smallest standard deviation for setup shifts (0.09, 0.16, 0.20 cm on LR, UD and IO directions) compared to IM1 (0.29, 0.35, 0.34 cm) and Im2 (0.11, 0.19, 0.40 cm), which indicates setup based on skin markers were the most reproducible for Im3. Over 6 weeks of treatment, Im2 (0.16, 0.18, 0.42 cm) is more reproducible than IM1 (0.44, 0.45, 0.35 cm). All 3 patients with IM1 and 2 patients with Im2 were found to have >1 cm difference in skin contour even after shifts were made. 1 patient with IM1 was found to have non‐reproducing skin folding of >3 cm difference. Conclusions: Information derived from repeated CTimages could be used to evaluate the effectiveness of the immobilization devices.

Purpose: To evaluate treatment deviations and the impact of treatment modality in the presence of breathing motion and anatomical changes during the course of lungcancerradiotherapy.Methods: Two non‐small cell lungcancer patients were enrolled in a randomized clinical trial to compare IMRT and proton therapy. To rigorously evaluate the impact of motion and anatomical changes, we used a ‘5D’ dose accumulation approach to sum dose distributions from phase‐to‐phase and week‐to‐week to the reference (end‐expiration) phase of the original planning 4DCT data set. Six to eight weekly 4DCT data sets that consisted of 10 breathing phases were acquired during the treatment course. The original plan was re‐calculated for each phase and deformably mapped to the reference phase to compare the ‘delivered’ dose distribution with the planned dose distribution of both the IMRT plan and the proton plan for each patient. DVHs derived from delivereddose distribution were compared to that from the planned dose distribution. Results: The delivereddose showed 3% and 2% increase in the dose to the CTV for IMRT and proton plan respectively. Target coverage remained acceptable despite tumor shrinkage from 29% to 49%. The doses to normal structures, such as lung and heart, increased more in the proton plan than in the IMRT plan. The V20 of the total lung volume increased by 4% and 6% from the delivereddose compared to the planned dose for IMRT and proton plan, respectively. Conclusions: The results showed sufficient target coverage was maintained for both modalities. Increases in lungdose were observed in both modalities, but more in the proton arm, perhaps due to weight loss and tumor shrinkage. Adaptive proton therapy strategy is recommended to minimize normal tissue doses. Supported in part by NCI P01 CA021239‐29A1

Background and purpose Due to the long life expectancy after treatment, the risk of late effects after radiotherapy (RT) is of particular importance for patients with Hodgkin lymphoma (HL). Both deep inspiration breath hold (DIBH) and proton therapy have been shown to reduce the dose to normal tissues for mediastinal HL, but the impact of these techniques in combination is unknown. The purpose of this study was to compare the life years lost (LYL) attributable to late effects after RT for mediastinal HL using intensity modulated radiation therapy (IMRT) in free breathing (FB) and DIBH, and proton therapy in FB and DIBH. Materials and methods Plans for each technique were created for 22 patients with HL. Doses were extracted and the risk of late effects and LYL were estimated. Results We found that the use of DIBH, proton therapy, and the combination significantly reduced the LYL compared to IMRT in FB. The lowest LYL was found for proton therapy in DIBH. However, when IMRT in DIBH was compared to proton therapy in FB, no significant difference was found. Conclusions Patient-specific plan comparisons should be used to select the optimal technique when comparing IMRT in DIBH and proton therapy in FB.

We developed and investigated a positron emission tomography (PET) system for use with on-line (both in-beam and intra-fraction) image-guided adaptive proton therapy applications. The PET has dual rotating depth-of-interaction measurable detector panels by using solid-state photomultiplier (SSPM) arrays and LYSO scintillators. It has a 44 mm diameter trans-axial and 30 mm axial field-of-view (FOV). A 38 mm diameter polymethyl methacrylate phantom was placed inside the FOV. Both PET and phantom axes were aligned with a collimated 179.2 MeV beam. Each beam delivered ∼50 spills (0.5 s spill and 1.5 s inter-spill time, 3.8 Gy at Bragg peak). Data from each beam were acquired with detectors at a given angle. Nine datasets for nine beams with detectors at nine different angles over 180° were acquired for full-tomographic imaging. Each dataset included data both during and 5 min after irradiations. The positron activity-range was measured from the PET image reconstructed from all nine datasets and compared to the results from simulated images. A (22)Na disc-source was also imaged after each beam to monitor the PET system's performance. PET performed well except for slight shifts of energy photo-peak positions (1%) after each beam, due mainly to the neutron exposure of SSPM that increased the dark-count noise. This minor effect was corrected offline with a shifting 350-650 keV energy window for each dataset. The results show a fast converging of activity-ranges measured by the prototype PET with high sensitivity and uniform resolution. Sub-mm activity-ranges were achieved with minimal 6 s acquisition time and three spill irradiations. These results indicate the feasibility of PET for intra-fraction beam-range verification. Further studies are needed to develop and apply a novel clinical PET system for on-line image-guided adaptive proton therapy.

Human papillomavirus (HPV)-positive oropharyngeal carcinomas response better to X-ray therapy (XRT) than HPV-negative disease. Whether HPV status influences the sensitivity of head and neck cancer cells to proton therapy or the relative biological effectiveness (RBE) of protons versus XRT is unknown.Clonogenic survival was used to calculate the RBE; immunocytochemical analysis and neutral comet assay were used to evaluate unrepaired DNA double-strand breaks.HPV-positive cells were more sensitive to protons and the unrepaired double-strand breaks were more numerous in HPV-positive cells than in HPV-negative cells (p .001). Protons killed more cells than did XRT at all fraction sizes (all RBEs 1.06). Cell line type and radiation fraction size influenced the RBE.HPV-positive cells were more sensitive to protons than HPV-negative cells maybe through the effects of HPV on DNA damage and repair. The RBE for protons depends more on cell type and fraction size than on HPV status. © 2016 Wiley Periodicals, Inc. Head Neck 39: 708-715, 2017.

This chapter aims to review the currently practiced radiation dosimetry principles and procedures for passively scattered and magnetically scanned proton pencil beam spots (PPBS). Usefulness and limitations of various dose measuring devices, like ion chambers, films, solid-state detectors, gel, and plastic and liquid scintillators that are used in proton dosimetry are reviewed. Absolute or reference dosimetry procedures using calorimeter, ion chambers and Faraday cup are described. Relative dosimetry techniques for beam data collection are presented. Monitor unit calculation procedure for patient treatment fields for passively scattered fields using simple dosimetry factors is discussed. The detector size effects in the measurement of PPBS profiles and integral depth-dose are described. The importance of the contribution of low-dose envelopes present in PPBS profiles to 3-D dose distribution is discussed, and possible ways to measure and account for them in the modeling of PPBS in the treatment planning system are outlined. The feasibility of 3-D dosimetry using gel and liquid scintillators is discussed. Our experience at the Proton Therapy Center in Houston with the dosimetry of passively scattered and discrete spot-scanned proton beams including dose verification of patient treatment fields with intensity-modulated proton therapy is presented.

Although Bortfeld's analytical formula is useful for describing Bragg curves, measured data can deviate from the values predicted by the model. Thus, we sought to determine the parameters of a closed analytical expression of multiple Bragg curves for scanning proton pencil beams using a simultaneous optimization algorithm and to determine the minimum number of energies that need to be measured in treatment planning so that complete Bragg curves required by the treatment planning system (TPS) can be accurately predicted. We modified Bortfeld's original analytical expression of Bragg curves to accurately describe the dose deposition resulting from secondary particles. The parameters of the modified analytical expression were expressed as the parabolic cylinder function of the ranges of the proton pencil beams in water. Thirty-nine discrete Bragg curves were measured in our center using a PTW Bragg Peak chamber during acceptance and commission of the scanning beam proton delivery system. The coefficients of parabolic function were fitted by applying a simultaneous optimization algorithm to seven measured curves. The required Bragg curves for 45 energies in the TPS were calculated using our parameterized analytical expression. Finally, the 10 cm width of spread-out Bragg peaks (SOBPs) of beams with maximum energies of 221.8 and 121.2 MeV were then calculated in the TPS and compared with measured data. Compared with Bortfeld's original formula, our modified formula improved fitting of the measured depth dose curves at depths around three-quarters of the maximum range and in the beam entrance region. The parabolic function described the relationship between the parameters of the analytic expression of different energies. The predicted Bragg curves based on the parameters fitted using the seven measured curves accurately described the Bragg curves of proton pencil beams of 45 energies configured in our TPS. When we used the calculated Bragg curves as the input to TPS, the standard deviations of the measured and calculated data points along the 10 cm SOBPs created with proton pencil beams with maximum energies of 221.8 and 121.2 MeV were 1.19% and 1.18%, respectively, using curves predicted by the algorithm generated from the seven measured curves. Our method would be a valuable tool to analyze measured Bragg curves without the need for time-consuming measurements and correctly describe multiple Bragg curves using a closed analytical expression.

A Monte Carlo model of the MD Anderson Cancer Center clinical scanning proton beam is created using the TOol for PArticle Simulations (TOPAS). This model is based on the commissioning data of integrated depth dose curves (IDDs) and lateral profiles of single proton spots. The mean range errors on the Bragg Peak (BP) for all energies are

Purpose: To investigate the effect of monitor unit (MU) constraints on the dose distribution created by intensity modulated proton therapy (IMPT) treatment planning using single-field optimization (SFO). Methods: Ninety-four energies between 72.5 and 221.8 MeV are available for scanning beam IMPT delivery at our institution. The minimum and maximum MUs for delivering each pencil beam (spot) are 0.005 and 0.04, respectively. These MU constraints are not considered during optimization by the treatment planning system; spots are converted to deliverable MUs during postprocessing. Treatment plans for delivering uniform doses to rectangular volumes with and without MU constraints were generated for different target doses, spot spacings, spread-out Bragg peak (SOBP) widths, and ranges in a homogeneous phantom. Four prostate cancer patients were planned with and without MU constraints using different spot spacings. Rounding errors were analyzed using an in-house software tool. Results: From the phantom study, the authors have found that both the number of spots that have rounding errors and the magnitude of the distortion of the dose distribution from the ideally optimized distribution increases as the field dose, spot spacing, and range decrease and as the SOBP width increases. From our study of patient plans, it is clear that asmore » the spot spacing decreases the rounding error increases, and the dose coverage of the target volume becomes unacceptable for very small spot spacings. Conclusions: Constraints on deliverable MU for each spot could create a significant distortion from the ideally optimized dose distributions for IMPT fields using SFO. To eliminate this problem, the treatment planning system should incorporate the MU constraints in the optimization process and the delivery system should reliably delivery smaller minimum MUs.« less

Proton radiotherapy (PRT) has shown to be less toxic in the treatment of head and neck cancers (HNSCC) than photon radiotherapy (XRT). XRT causes multiple types of cancer cell death by inducing DNA double-strand breaks. The DNA damage induced by PRT is more complex and has more severe biological consequences versus XRT. The present study was undertaken to uncover the cell death caused by PRT versus XRT in human papillomavirus positive (HPV+, frequently p53 wild-type, p16 positive; p53, p16 are key factors for cell death) and HPV-negative (HPV-, frequently p53 mutant, p16 negative) HNSCC cells. HNSCC cell lines HN5, SqCC/Y1 (HPV-) and UMSCC-47, UPCI-SCC-154 (HPV+) were used. Single doses of 4 Gy irradiation induced cell apoptosis, necrosis, mitotic catastrophe, and senescence were determined. Clinical 200-MeV proton beams (18 cm × 18 cm field) or 6-MV X-ray beams (25 cm × 25 cm field) were used. Cells were positioned in the centers of the irradiation fields (in the middle of the spread-out Bragg peak for PRT). At 4 hours (h), 24h and 48h after PRT or XRT, cell necrosis and apoptosis were determined by Annexin VFITC-conjugated staining. XRT and PRT caused increased cell necrosis in the HPV– SqCC/Y1 (moderate at 24h, significant at 48h [p all < 0.05]) and HN5 (moderate at 24h, 48h) cells, at slightly higher rates in PRT versus XRT treated cells; and in the HPV+ UPCI-SCC-154 (moderate at 4h) and UMSCC-47 (moderate at 48h) cells, with no difference between PRT versus XRT treatment groups. XRT and PRT induced a small percentage of cell apoptosis (range: 1.1 ± 0.5 to 7.6 ± 2.9). Cell apoptosis was only moderately increased in the HPV+ UMSCC-47 (at 4h, 24h, 48h) and HPV– SqCC/Y1 (at 24h, 48h) cells, with slightly more apoptosis seen in the XRT versus the PRT group. Cell senescence was assessed using a well-established senescence-associated biomarker (SA-β-gal). XRT and PRT induced significantly increased cellular senescence at both 4 and 6 days in all four cell lines (p all < 0.01), with PRT treatment leading to a significantly higher percentage of senescence in cells than XRT (p all < 0.01). Mitotic catastrophe, an important cell death mechanism by which solid tumors respond to clinical radiotherapy, was determined using co-staining for cytoplasm with γ- tubulin (with Texas red) and for nucleus with Dapi (blue). XRT and PRT both led to a significantly increased number of cells undergoing mitotic catastrophe at 4h, 24h, 48h and 72h (p all < 0.05) in all four cell lines, with significantly higher rates seen in PRT treated versus XRT treated (p all < 0.05). Moreover, the peak of cell mitotic catastrophe induced by PRT occurred at 48h in the HPV– cells, versus at 72h in the HPV+ cells; while no obvious peak was observed in the XRT treated group. In conclusion, mitotic catastrophe and senescence are the major types of cell death induced by both XRT and PRT, in which PRT inducing higher levels of both types of cell death as compared to XRT. Citation Format: Li Wang, Shichao Han, Jinming Zhu, Xiaochun Wang, Yuting Li, Zeming Wang, Eric Lin, Xiaofang Wang, David P. Molkentine, Pierre Blanchard, Yining Yang, Ruiping Zhang, Narayan Sahoo, Michael Gillin, Xiaorong Ronald Zhu, Xiaodong Zhang, Jeffrey N. Myers, Steven J. Frank. Proton versus photon irradiation induced cell death in head and neck cancer cells with different human papillomavirus status [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 69.

Radiation dose escalation has been shown to improve local control and survival in patients with non-small cell lung cancer in some studies, but randomized data have not supported this premise, possibly owing to adverse effects. Because of the physical characteristics of the Bragg peak, proton therapy (PT) delivers minimal exit dose distal to the target volume, resulting in better sparing of normal tissues in comparison to photon-based radiation therapy. This is particularly important for lung cancer given the proximity of the lung, heart, esophagus, major airways, large blood vessels, and spinal cord. However, PT is associated with more uncertainty because of the finite range of the proton beam and motion for thoracic cancers. PT is more costly than traditional photon therapy but may reduce side effects and toxicity-related hospitalization, which has its own associated cost. The cost of PT is decreasing over time because of reduced prices for the building, machine, maintenance, and overhead, as well as newer, shorter treatment programs. PT is improving rapidly as more research is performed particularly with the implementation of 4-dimensional computed tomography-based motion management and intensity modulated PT. Given these controversies, there is much debate in the oncology community about which patients with lung cancer benefit significantly from PT. The Particle Therapy Co-operative Group (PTCOG) Thoracic Subcommittee task group intends to address the issues of PT indications, advantages and limitations, cost-effectiveness, technology improvement, clinical trials, and future research directions. This consensus report can be used to guide clinical practice and indications for PT, insurance approval, and clinical or translational research directions.

Head scatter factors for high energy photon beams from linear accelerators can be modeled using a two-source model consisting of focal and extrafocal radiation. The focal radiation can be approximated as a point source, and the distribution of the extrafocal radiation is a two-dimensional (2D) radial symmetric function. Various methods, including analytical, Monte Carlo, and empirical trial functions, have been used to determine the radial symmetric function of extrafocal radiation distribution. This article describes a method for directly determining the extrafocal radiation distribution without assuming any empirical trial function. The extrafocal radiation distribution is determined with measured head scatter factors for rectangular fields defined by the lower jaw ( X ) fixed at 40 cm and the upper jaw ( Y ) varying from 3 to 40 cm . The derivatives of the measured head scatter factors, with respect to the Y jaw position projected in the plane of extrafocal radiation, are proportional to the one-dimensional (1D) projection (also called the line spread function) of the extrafocal radiation distribution. Two methods are used to solve the radial function of extrafocal radiation from the 1D projection. The first method uses a 2D filtered backprojection algorithm, originally developed for parallel beam computed tomography reconstruction, to directly derive the radial dependence of the extrafocal radiation distribution. The method has been applied to 6 and 18 MV photon beams from a Siemens linear accelerator and has been tested by comparing measured and calculated head scatter factors for square and rectangular fields. The second method uses a Fourier transform followed by a Fourier–Bessel transform to solve the problem. The distributions of extrafocal radiation derived from these two methods are virtually identical.

Purpose Intensity modulated proton therapy (IMPT) plans are normally generated utilizing multiple field optimization (MFO) techniques. Similar to photon based IMRT, MFO allows for the utilization of a simultaneous integrated boost in which multiple target volumes are treated to discrete doses simultaneously, potentially improving plan quality and streamlining quality assurance and treatment delivery. However, MFO may render plans more sensitive to the physical uncertainties inherent to particle therapy. Here we present clinical examples of a single-field integrated boost (SFIB) technique for spot scanning proton therapy based on single field optimization (SFO) treatment-planning techniques. Methods and materials We designed plans of each type for illustrative patients with central nervous system (brain and spine), prostate and head and neck malignancies. SFIB and IMPT plans were constructed to deliver multiple prescription dose levels to multiple targets using SFO or MFO, respectively. Dose and fractionation schemes were based on the current clinical practice using X-ray IMRT in our clinic. For inverse planning, dose constraints were employed to achieve the desired target coverage and normal tissue sparing. Conformality and inhomogeneity indices were calculated to quantify plan quality. We also compared the worst-case robustness of the SFIB, sequential boost SFUD, and IMPT plans. Results The SFIB technique produced more conformal dose distributions than plans generated by sequential boost using a SFUD technique (conformality index for prescription isodose levels; 0.585 ± 0.30 vs. 0.435 ± 0.24, SFIB vs. SFUD respectively, Wilcoxon matched-pair signed rank test, p < 0.01). There was no difference in the conformality index between SFIB and IMPT plans (0.638 ± 0.27 vs. 0.633 ± 0.26, SFIB vs. IMPT, respectively). Heterogeneity between techniques was not significantly different. With respect to clinical metrics, SFIB plans proved more robust than the corresponding IMPT plans. Conclusions SFIB technique for scanning beam proton therapy (SSPT) is now routinely employed in our clinic. The SFIB technique is a natural application of SFO and offers several advantages over SFUD, including more conformal plans, seamless treatment delivery and more efficient planning and QA. SFIB may be more robust than IMPT and has been the treatment planning technique of choice for some patients.

Background and purpose: There is concern over the stepped edges of multileaf collimator (MLC) fields for target coverage compared with those of cerrobend. Despite recent reports dispelling this concern, users are still cautious when using MLCs for small fields. Leaf orientation can be a problem if one is required to orient the leaves along an axis not ideal for conformity (such as dynamic or universal wedge cases). In this study we examined the dependence of MLC field conformity on field size and elongation. Materials and methods: We examined circles of varying diameter and ellipses of varying eccentricity with leaves oriented along the major and minor axes of ellipses. The tests were both geometric, comparing areas of overblocking or underblocking (leaves inside and outside the field), and dosimetric, using radiographic films at depth in the beam's eye view plane. Results: For the geometric comparison there is a rapid increase in non-conformity, defined as the percentage of overblocking or underblocking area, as the circle diameter decreases. For ellipses, when the leaves move along one axis direction, the conformity does not depend on the diameter of the same axis, but instead improves as the dimension of the axis in the non-leaf motion direction increases. The best conformity is achieved when the maximum number of leaves is used to shape the field. When the dosimetry is analyzed, the predictability of these trends decreases due to the impact of undulations (scatter), leaf inaccuracies and dosimetric uncertainties. Conclusions: We recommend that for small round fields MLC should be used with caution and that for ellipses the direction of leaf movement should be aligned with the minor axis whenever possible. Though these experiments are for idealized geometries, the observations can be applied to clinical fields. An MLC with a thinner leaf width could be beneficial for small round fields.

We conducted Monte Carlo simulations to investigate the feasibility of the proton beam-range verification with few beam spills before the start of treatment to provide rapid feedback for treatment plan verification and re-planning (if necessary) for improving the accuracy of treatment targeting: a potentially novel intra-treatment image-guided adaptive proton therapy. MCNPX package was used to generate the distributions of positron emitters in a uniform cylinder PMMA phantom irradiated by a collimated 180MeV pristine proton beam. Two PET systems, a small dual-panel rotational PET and a stationary brain PET, with depth-of-interaction (DOI) measurement, were simulated with GATE for imaging. The images were reconstructed with list-mode MLEM algorithm using simulated coincidence data accumulated during- and post-irradiations. Positron activity-ranges were measured as a function of number of beam spills, total acquisition time, crystal cross-section size, crystal length, and the number of coincidence events. Results show that the accuracy of activity-range measurement is a function of data statistics but converging rapidly within few beam spills under simulated conditions; few spills can be sufficient to measure the activity-range within 1.0 mm from the final converged value; the number of spills can be further reduced if acquiring 30–60sec post-irradiation data, which is still considered a rapid intra-treatment imaging. The accuracy and precision of activity-range measurement was also calculated as a function of count statistics under the simulated conditions, providing a general and very useful guideline to calculate the required statistics for an accurate intra-treatment “in-beam” activity-range measurement.

Radiation therapy for head and neck malignancies can have side effects that impede quality of life. Theoretically, proton therapy can reduce treatment-related morbidity by minimizing the dose to critical normal tissues. We evaluated the feasibility of spot-scanning proton therapy for head and neck malignancies and compared dosimetry between those plans and intensity-modulated radiation therapy (IMRT) plans. Plans from 5 patients who had undergone IMRT for primary tumors of the head and neck were used for planning proton therapy. Both sets of plans were prepared using computed tomography (CT) scans with the goals of achieving 100% of the prescribed dose to the clinical target volume (CTV) and 95% to the planning TV (PTV) while maximizing conformity to the PTV. Dose-volume histograms were generated and compared, as were conformity indexes (CIs) to the PTVs and mean doses to the organs at risk (OARs). Both modalities in all cases achieved 100% of the dose to the CTV and 95% to the PTV. Mean PTV CIs were comparable (0.371 IMRT, 0.374 protons, p = 0.953). Mean doses were significantly lower in the proton plans to the contralateral submandibular (638.7 cGy IMRT, 4.3 cGy protons, p = 0.002) and parotid (533.3 cGy IMRT, 48.5 cGy protons, p = 0.003) glands; oral cavity (1760.4 cGy IMRT, 458.9 cGy protons, p = 0.003); spinal cord (2112.4 cGy IMRT, 249.2 cGy protons, p = 0.002); and brainstem (1553.52 cGy IMRT, 166.2 cGy protons, p = 0.005). Proton plans also produced lower maximum doses to the spinal cord (3692.1 cGy IMRT, 2014.8 cGy protons, p = 0.034) and brainstem (3412.1 cGy IMRT, 1387.6 cGy protons, p = 0.005). Normal tissue V10, V30, and V50 values were also significantly lower in the proton plans. We conclude that spot-scanning proton therapy can significantly reduce the integral dose to head and neck critical structures. Prospective studies are underway to determine if this reduced dose translates to improved quality of life.

The conventional kilovoltage (kV) x-ray-based dual-energy CT (DECT) imaging using two different x-ray energy spectra is sensitive to image noise and beam hardening effects. The purpose of this study was to evaluate the theoretical advantage of the DECT method for determining proton stopping power ratios (SPRs) using a combination of kV and megavoltage (MV) x-ray energies. We investigated three representative x-ray energy pairs: 100-kVp and 140-kVp comprised the kV-kV pair, 100-kVp and 1-MV comprised the kV-MV pair, and two 1-MV x-ray beams – one with and one without external filtration comprised the MV-MV pair. The SPRs of 34 human tissues were determined using the DECT method with these three x-ray energy pairs. Small perturbations were introduced into the CT numbers and x-ray spectra used for the DECT calculation to simulate the effects of random noise and beam hardening. An error propagation analysis was performed on the DECT calculation algorithm to investigate the propagation of CT number uncertainty to final SPR estimation and to suggest the best x-ray energy combination. We found that the DECT method using each of the three beam pairs achieved similar accuracy in determining the SPRs of human tissues in ideal conditions. However, when CT number uncertainties and artifacts such as imaging noise and beam hardening effects were considered, the kV-MV DECT improved the accuracy of SPR estimation substantially over the kV-kV or MV-MV DECT methods. Furthermore, our error propagation analysis showed that the combination of 100-kVp and 1-MV beams was close to the optimal selection when using the DECT method to determine SPRs. Overall, the kV-MV combination makes the DECT method more robust in resolving the effective atomic numbers for biological tissues than the traditional kV-kV DECT method.

We discovered an empirical relationship between the logarithm of mean excitation energy (ln Im) and the effective atomic number (EAN) of human tissues, which allows for computing patient-specific proton stopping power ratios (SPRs) using dual-energy CT (DECT) imaging. The accuracy of the DECT method was evaluated for 'standard' human tissues as well as their variance. The DECT method was compared to the existing standard clinical practice-a procedure introduced by Schneider et al at the Paul Scherrer Institute (the stoichiometric calibration method). In this simulation study, SPRs were derived from calculated CT numbers of known material compositions, rather than from measurement. For standard human tissues, both methods achieved good accuracy with the root-mean-square (RMS) error well below 1%. For human tissues with small perturbations from standard human tissue compositions, the DECT method was shown to be less sensitive than the stoichiometric calibration method. The RMS error remained below 1% for most cases using the DECT method, which implies that the DECT method might be more suitable for measuring patient-specific tissue compositions to improve the accuracy of treatment planning for charged particle therapy. In this study, the effects of CT imaging artifacts due to the beam hardening effect, scatter, noise, patient movement, etc were not analyzed. The true potential of the DECT method achieved in theoretical conditions may not be fully achievable in clinical settings. Further research and development may be needed to take advantage of the DECT method to characterize individual human tissues.

Photothermal grating spectroscopy is applied to study the nongeminate atom recombination of photodissociated iodine in liquids. A theoretical model is developed to describe the time dependence of diffraction signals. The excitation intensity dependence of diffraction from the anharmonic thermal grating, created by saturated optical absorption, is used to estimate the quantum yield ofthephotodissociation, which is critical to determine the number of iodine atoms produced and hence to the recombination rate. The rateconstant of nongeminate atom recombination is extracted from the dependence of the time-resolved photothermal diffraction signals on the atom concentration. From the relative amplitudes of the diffraction transients, we can also derive the enthalpy of the recombination reaction.

In recent years, the Monte Carlo method has been used in a large number of research studies in radiation therapy. For applications such as treatment planning, it is essential to validate the dosimetric accuracy of the Monte Carlo simulations in heterogeneous media. The AAPM Report no 105 addresses issues concerning clinical implementation of Monte Carlo based treatment planning for photon and electron beams, however for proton-therapy planning, such guidance is not yet available. Here we present the results of our validation of the Monte Carlo model of the double scattering system used at our Proton Therapy Center in Houston. In this study, we compared Monte Carlo simulated depth doses and lateral profiles to measured data for a magnitude of beam parameters. We varied simulated proton energies and widths of the spread-out Bragg peaks, and compared them to measurements obtained during the commissioning phase of the Proton Therapy Center in Houston. Of 191 simulated data sets, 189 agreed with measured data sets to within 3% of the maximum dose difference and within 3 mm of the maximum range or penumbra size difference. The two simulated data sets that did not agree with the measured data sets were in the distal falloff of the measured dose distribution, where large dose gradients potentially produce large differences on the basis of minute changes in the beam steering. Hence, the Monte Carlo models of medium- and large-size double scattering proton-therapy nozzles were valid for proton beams in the 100 MeV-250 MeV interval.

The laser-induced anharmonic thermal grating technique has been used to study the excited-state absorption and photoisomerization of two cyanine dyes, 3,3′-diethyloxatricarbocyanine iodide (DOTCI) and 1,3,3,1′,3′,3′-hexamethylindotricarbocyanine iodide (HITCI). An anomalous excitation intensity dependence of the diffraction efficiency is observed for both dye molecules; the anomaly is caused by diffraction from multiple thermal gratings which are 180° out of phase. The previously developed theory for anharmonic thermal gratings based on a quasi-plane-wave approximation (QPWA) cannot quantitatively fit the measured results. A more recently developed, general numerical method for calculating diffraction from anharmonic thermal gratings accounts for the observed anomalous behavior in terms of an excited-state and trap-state formation model. For DOTCI, the nonlinear absorption in ethanol is caused by the saturation of the ground-state absorption and strong excited-state absorption, while for HITCI, in addition to these two absorption processes, photoisomer absorption may also be an important process contributing to the nonlinear absorption at the excitation wavelength (532 nm).

Purpose: To demonstrate the importance of optimizing compensator parameters in passive scattering proton therapy (PSPT). Method:We examined the plans of four patients treated for lung tumors at MD Anderson Cancer Center. Comparable IMRT and PSPT plans had been created for each of these patients. The clinical PSPT plans were calculated using 5 mm drill bit compensators with smearing values of 0.5 to 0.9 cm. Two new plans were created for each patient: one with a smearing value of 0 cm and a second with 0 cm smearing and smooth compensators. The prescribed isodose line of each plan was changed so that PTV D95 was equal in a given patient's plans and robustness analysis was performed to evaluate the impact of the compensator changes. A plan was considered robust if ITV D95 remained greater than 95% of the prescribed dose in the worst case scenario for target coverage. The robust plan with altered compensator parameters and most improved normal tissue sparing was considered to be the compensator optimized plan. Results: Mean lung dose for the 4 patients is 19.8, 12.7, 11.9 and 12.4 Gy in the compensator optimized plans compared to 21.8, 14.2, 12.9 and 13.6 Gy in the clinical plans; esophagus V60 is 39.2%, 13.4%, 7.7% and 17.7% compared to 48.6%, 18.1%, 11.6% and 20.7%; mean heart dose is 23.3, 1.2, 8.2 and 4.6 Gy compared to 24.7, 2.4, 9.5 and 8.3 Gy. Conclusion: Robustness analysis allows reduction of the smearing parameter while keeping confidence that the plan is robust against range and setup uncertainties. Compensator parameters should be individually optimized if PSPT plans are to display maximum advantage over IMRT plans in terms of dose volume data.

Purpose: To apply two semi‐empirical formulas to calculate the spread out Bragg peak ( SOBP ) factors ( SOBPFs ) and range shifter ( RS ) factors (RSFs) used for monitor unit calculation1 of passively scattered proton beams (PSPB). Methods: Following two recently developed2 and refined formulas were used to calculate the SOBPFs and RSFs from measured depth dose curves for various options in our PSPB. For a specific option,SOBPF(W)=PDDWr(0)/PDDW(0).((SSD+dcW)/(SSD+dcWr))2 .NSF ( W).For the same SOBP width and option, but for different RS thickness, t,RSF (W, t) = (( SSD+dcWt) /)( SSD+dcW)) 2.( PDDW( 0) /PDDW(t)). NSF(W,t) ,W is the width of the SOBP under consideration, Wr is the reference SOBP width relative to which other SOBPF are determined, SSD is the source to surface distance for the percentage depth dose (PDD) measurement, PDDWr(0) and PDDW(0) are PDDs at the surface, and dcW and dcWr are the depths of the centers of SOBP under consideration and reference SOBP respectively, t is the RS thickness, dcWt and dcW are the depths of the centers of SOBP under consideration with RS of thickness t and without any RS respectively, and PDDw(t) and PDDw(0) are the PDD at depth t and surface respectively for the SOBP width W for which the RSFs are being determined. NSF(W) and NSF (W,t) accounts for the contribution of the nozzle elements including the aperture to the back scatter dose at the dose monitor. Results: The SOBPFs and RSFs calculated using above formulas agreed within 2 percent with their respective measured values using an ionization chamber in a water tank for all of our clinically used options for PSPB. Conclusion: The proposed formulas were found to be valid to calculate the required SOBPFs and RSFs for monitor unit calculation of PSPB fields from measured PDD curves. 1N. Sahoo et. al, Med. Phys. 35, 5088, (2008).2N. Sahoo et. al, IJROBP, 84(3S) S849, (2012).

Purpose: To measure the low‐dose envelope of spot scanning proton pencil beams. Method and Materials: Measurements were performed in the spot scanning proton pencil beam nozzle at M. D. Anderson Cancer Center. We directly measured the low‐dose envelope by measuring single pencil beams' lateral profiles at central axis to relative dose levels that were a factor of 10−4 lower than the central axis dose. We also indirectly measure the low‐dose envelope by measuring the effect of the filed size on central axis point doses using a plane parallel ionization chamber.Results: For lowest (72.5 MeV) and highest (221.8 MeV) energy beams in‐air at isocenter plane, the full width (FW) at half maximum ranged from 1.26 ± 0.02 cm to 3.43 ± 0.02 cm; the FW at 1% maximum ranged from 3.99 ± 0.25 cm to 11.41± 0.25 cm; and the FW at 0.1% maximum ranged from 6.6 ± 0.5 cm to 17.9 ± 0.5 cm, respectively. The effect of the field size on central axis point doses showed strong dependence with energy and depth. Conclusion: We showed that it is possible to accurately measure the low‐dose envelope down to a dose level of 10−4 of the central axis dose using standard dosimetric equipment. Because of the large lateral extent of the beams, care should be taken when measuring integral depth doses, which are input parameters for analytical dose calculation algorithms. Additionally, we observed that the in‐air fluence of the pencil beams has various components due to scattering in the beam line and cannot be accurately described by a single Gaussian function. Finally, we showed that because of the low‐dose envelope, the dose output's dependence on field size can vary for fields as large as 20 cm × 20 cm.

Background For treatment of the entire cranium using passive scattering proton therapy (PSPT) compensators are often employed in order to reduce lens and cochlear exposure. We sought to assess the advantages and consequences of utilizing compensators for the treatment of the whole brain as a component of craniospinal radiation (CSI) with PSPT. Moreover, we evaluated the potential benefits of spot scanning beam delivery in comparison to PSPT. Methods Planning computed tomography scans for 50 consecutive CSI patients were utilized to generate passive scattering proton therapy treatment plans with and without Lucite compensators (PSW and PSWO respectively). A subset of 10 patients was randomly chosen to generate scanning beam treatment plans for comparison. All plans were generated using an Eclipse treatment planning system and were prescribed to a dose of 36 Gy(RBE), delivered in 20 fractions, to the whole brain PTV. Plans were normalized to ensure equal whole brain target coverage. Dosimetric data was compiled and statistical analyses performed using a two-tailed Student’s t-test with Bonferroni corrections to account for multiple comparisons. Results Whole brain target coverage was comparable between all methods. However, cribriform plate coverage was superior in PSWO plans in comparison to PSW (V95%; 92.9 ± 14 vs. 97.4 ± 5, p

Purpose: To build and experimentally validate an accurate Monte Carlo (MC) model of a discrete spot scanning beam nozzle and to use this model to assess the dosimetric consequences of the “halo” dose (i.e., that due to scattering from beam line components and nuclear interactions).Method and Materials: An accurate model of the scanning nozzle at our institution was implemented using the MC system MCNPX version 2.5.0 according to the blueprints provided by the manufacturer of the proton therapy system (Hitachi Ltd., Tokyo, Japan). The MC model was validated against measurements of percentage depth doses (PDDs), lateral profiles in‐air (LPA) and in‐water (LPW), field size factors (FSFs), and spread out Bragg peaks. The validated MC model presented in this study was used to generate data for clinical configuration of our treatment planning system (TPS). Results: Distance to agreement between measured and simulated ranges, LPAs and LPWs were within 0.16 cm, 0.05 cm and 0.1 cm, respectively. Comparisons between measured FSFs and TPS predictions, which may not model the halo dose properly, reveled differences of up to 9.5%, whereas comparison with MC simulations showed maximum differences of 3.6%. We found that ion chambers with radius as large as 4.2 cm are insufficient to measure the integral energy deposition. Conclusion: Because of the halo dose, which broadens lateral sizes of the proton beamlets, care should be taken when measuring integral energy deposition for configuration of the TPSs. Furthermore, the halo dose must be properly modeled in the dose algorithm used by TPS for accurate prediction of scanned proton beam doses.

Purpose: To study the characteristics of scatter in kilo‐voltage CBCTimaging, and to develop a method of reducing or removing scatter related artifacts and improve CBCTimage quality. Methods and Materials: The scattered radiations were modeled as depth‐dependents pencil‐beam kernels, which were derived using an edge‐spread‐function (ESF) method, for a CBCTimaging system. The ESF geometry was achieved with a half‐beam block created by a 3‐mm‐thick lead sheet placed on top of a stack of slab solid‐water phantoms. Measurements for 8 water‐equivalent thicknesses (range from 0 to 41 cm) were taken with (half‐blocked) and without (unblocked) the lead sheet, and corresponding pencil‐beam scatter kernels or point‐spread‐functions (PSF), were then derived without assuming any empirical trial function. Scatter correction was incorporated into the reconstruction process to improve CBCTimage quality. The process is summarized as the following: 1) The ESF was extracted from the half‐blocked images; 2) The line‐spread‐function (LSF) of the system was calculated by taking the derivative of the ESF; 3) By assuming a symmetrical scatter kernel, the PSF was derived using a filtered‐back‐projection technique; 4) For thicknesses not measured, the corresponding PSF was interpolated from the measured data; 5) An iterative method was used to remove scatter from the projection image; 6) A reconstruction algorithm was applied to the scatter removed projection to derive CBCTimages with improved image quality. Results: The scatter kernels were successfully derived and verified with phantoms. The scatter artifacts were reduced and the image quality was improved for CBCTimages incorporating the scatter removal technique. For a 32 cm‐diameter uniform phantom, the flatness of reconstruction image was improved from 21.6% to 3.8%. Conclusion: We developed a method to determine the scatter kernel in CBCT system and reduce the scatter related artifacts utilizing the derived kernel. Conflict of Interest: Supported by Varian.