PTCOG Ocular Statement: Expert Summary of Current Practices and Future Developments in Ocular Proton Therapy.

Although rare cancers, ocular tumors are a threat to vision, quality of life, and potentially life expectancy of a patient. Ocular proton therapy (OPT) is a powerful tool for successfully treating this disease. The Particle Therapy Co-Operative Ocular Group (PTCOG Ocular) formulated an Evidence and Expert-Based Executive Summary of Current Practices and Future Developments in OPT: Comparative dosimetric and clinical analysis with the different OPT systems is essential to set up planning guidelines, implement best practices, and establish benchmarks for eye preservation, vision, and quality of life measures. Contemporary prospective trials in select subsets of patients (e.g., tumors near the optic disc and/or macula) may allow for dosimetric and clinical analysis between different radiation modalities and beamline systems to evaluate differences in radiation delivery and penumbra, and resultant tumor control, normal tissue complication rates, and overall clinical cost-effectiveness. To date, the combination of multimodal imaging (fundus photography, ultrasound, etc.), ophthalmologist assessment, and clip surgery with radiation planning have been keys to successful treatment. Increased use of 3D imaging (CT/MRI) is anticipated although its spatial resolution might be a limiting factor (e.g., detection of flat diffuse tumor parts). Commercially produced ocular treatment planning systems are under development and their future use is expected to expand across OPT centers. Future continuity of OPT will depend on (i) maintaining and upgrading existing older dedicated low-energy facilities, (ii) maintaining shared, degraded beamlines at large proton therapy centers, and (iii) developing adapted gantry beams of sufficient quality to maintain the clinical benefits of sharp beam conformity. Option (i) potentially offers the sharpest beams, minimizing impact on healthy tissues, whilst (ii) and (iii) potentially offer the advantage of substantial long-term technical support and development as well as the introduction of new approaches. Significant patient throughputs and close cooperation between medical physics, ophthalmology, and radiotherapy, underpinned by mutual understanding, is crucial for a successful OPT service.

Effect of the initial energy layer and spot placement parameters on IMPT delivery efficiency and plan quality.

PURPOSE: Improving efficiency of intensity modulated proton therapy (IMPT) treatment can be achieved by shortening the beam delivery time. The purpose of this study is to reduce the delivery time of IMPT, while maintaining the plan quality, by finding the optimal initial proton spot placement parameters. METHODS: Seven patients previously treated in the thorax and abdomen with gated IMPT and voluntary breath-hold were included. In the clinical plans, the energy layer spacing (ELS) and spot spacing (SS) were set to 0.6-0.8 (as a scale factor of the default values). For each clinical plan, we created four plans with ELS increased to 1.0, 1.2, 1.4, and SS to 1.0 while keeping all other parameters unchanged. All 35 plans (130 fields) were delivered on a clinical proton machine and the beam delivery time was recorded for each field. RESULTS: Increasing ELS and SS did not cause target coverage reduction. Increasing ELS had no effect on critical organ-at-risk (OAR) doses or the integral dose, while increasing SS resulted in slightly higher integral and selected OAR doses. Beam-on times were 48.4 ± 9.2 (range: 34.1-66.7) seconds for the clinical plans. Time reductions were 9.2 ± 3.3 s (18.7 ± 5.8%), 11.6 ± 3.5 s (23.1 ± 5.9%), and 14.7 ± 3.9 s (28.9 ± 6.1%) when ELS was changed to 1.0, 1.2, and 1.4, respectively, corresponding to 0.76-0.80 s/layer. SS change had a minimal effect (1.1 ± 1.6 s, or 1.9 ± 2.9%) on the beam-on time. CONCLUSION: Increasing the energy layers spacing can reduce the beam delivery time effectively without compromising IMPT plan quality; increasing the SS had no meaningful impact on beam delivery time and resulted in plan-quality degradation in some cases.

A component method to delineate surgical spine implants for proton Monte Carlo dose calculation.

PURPOSE: Metallic implants have been correlated to local control failure for spinal sarcoma and chordoma patients due to the uncertainty of implant delineation from computed tomography (CT). Such uncertainty can compromise the proton Monte Carlo dose calculation (MCDC) accuracy. A component method is proposed to determine the dimension and volume of the implants from CT images. METHODS: The proposed component method leverages the knowledge of surgical implants from medical supply vendors to predefine accurate contours for each implant component, including tulips, screw bodies, lockers, and rods. A retrospective patient study was conducted to demonstrate the feasibility of the method. The reference implant materials and samples were collected from patient medical records and vendors, Medtronic and NuVasive. Additional CT images with extensive features, such as extended Hounsfield units and various reconstruction diameters, were used to quantify the uncertainty of implant contours. RESULTS: For in vivo patient implant estimation, the reference and the component method differences were 0.35, 0.17, and 0.04 cm3 for tulips, screw bodies, and rods, respectively. The discrepancies by a conventional threshold method were 5.46, 0.76, and 0.05 cm3 , respectively. The mischaracterization of implant materials and dimensions can underdose the clinical target volume coverage by 20 cm3 for a patient with eight lumbar implants. The tulip dominates the dosimetry uncertainty as it can be made from titanium or cobalt-chromium alloys by different vendors. CONCLUSIONS: A component method was developed and demonstrated using phantom and patient studies with implants. The proposed method provides more accurate implant characterization for proton MCDC and can potentially enhance the treatment quality for proton therapy. The current proof-of-concept study is limited to the implant characterization for lumbar spine. Future investigations could be extended to cervical spine and dental implants for head-and-neck patients where tight margins are required to spare organs at risk.

Treatment of Uveal Melanoma With Radioactive Iodine 125 Implant Compared With Proton Beam Radiotherapy.

OBJECTIVE: To review the current state of radiation therapy for uveal melanoma and compare particle radiation and brachytherapy. PATIENTS AND METHODS: The medical records of 156 patients treated for uveal melanoma between May 30, 2012, and March 16, 2020, were retrospectively reviewed. Treatments consisted of either radioactive iodine 125 implant (RAI) or fractionated proton radiation (proton beam therapy [PBT]). Baseline characteristics were compared using a Wilcoxon rank sum test or χ2 test. Outcomes were compared using Cox proportional hazards regression models or logistic regression models. RESULTS: The median length of follow-up after treatment was 2.7 years (range, 0.5 to 9.0 years). Patients who underwent treatment with RAI were older (median age, 67 vs 59 years; P<.001) and had a lower tumor classification (American Joint Commission on Cancer; P=.001) compared with those who underwent PBT. There was no significant difference between RAI and PBT in the outcomes of liver metastases, death, enucleation, tearing, vision loss, retinal detachment, tumor thickness, conjunctivitis, optic neuropathy, iris neovascularization, or neovascular glaucoma (all P>.05). Patients who underwent RAI treatment had significantly higher risk of diplopia (P<.001), cataract progression (P<.001), and maculopathy (P=.03) compared with those who received PBT. Patients who underwent RAI were at higher risk of eyelash loss (P=.006) compared with the PBT group. CONCLUSION: Treatment with PBT and RAI has similar efficacy; however, there are differences in the adverse outcomes associated with these 2 modalities.

Characterization of the HollandPTC proton therapy beamline dedicated to uveal melanoma treatment and an interinstitutional comparison.

PURPOSE: Eye-dedicated proton therapy (PT) facilities are used to treat malignant intraocular lesions, especially uveal melanoma (UM). The first commercial ocular PT beamline from Varian was installed in the Netherlands. In this work, the conceptual design of the new eyeline is presented. In addition, a comprehensive comparison against five PT centers with dedicated ocular beamlines is performed, and the clinical impact of the identified differences is analyzed. MATERIAL/METHODS: The HollandPTC eyeline was characterized. Four centers in Europe and one in the United States joined the study. All centers use a cyclotron for proton beam generation and an eye-dedicated nozzle. Differences among the chosen ocular beamlines were in the design of the nozzle, nominal energy, and energy spectrum. The following parameters were collected for all centers: technical characteristics and a set of distal, proximal, and lateral region measurements. The measurements were performed with detectors available in-house at each institution. The institutions followed the International Atomic Energy Agency (IAEA) Technical Report Series (TRS)-398 Code of Practice for absolute dose measurement, and the IAEA TRS-398 Code of Practice, its modified version or International Commission on Radiation Units and Measurements Report No. 78 for spread-out Bragg peak normalization. Energy spreads of the pristine Bragg peaks were obtained with Monte Carlo simulations using Geant4. Seven tumor-specific case scenarios were simulated to evaluate the clinical impact among centers: small, medium, and large UM, located either anteriorly, at the equator, or posteriorly within the eye. Differences in the depth dose distributions were calculated. RESULTS: A pristine Bragg peak of HollandPTC eyeline corresponded to the constant energy of 75 MeV (maximal range 3.97 g/cm2 in water) with an energy spread of 1.10 MeV. The pristine Bragg peaks for the five participating centers varied from 62.50 to 104.50 MeV with an energy spread variation between 0.10 and 0.70 MeV. Differences in the average distal fall-offs and lateral penumbrae (LPs) (over the complete set of clinically available beam modulations) among all centers were up to 0.25 g/cm2 , and 0.80 mm, respectively. Average distal fall-offs of the HollandPTC eyeline were 0.20 g/cm2 , and LPs were between 1.50 and 2.15 mm from proximal to distal regions, respectively. Treatment time, around 60 s, was comparable among all centers. The virtual source-to-axis distance of 120 cm at HollandPTC was shorter than for the five participating centers (range: 165-350 cm). Simulated depth dose distributions demonstrated the impact of the different beamline characteristics among institutions. The largest difference was observed for a small UM located at the posterior pole, where a proximal dose between two extreme centers was up to 20%. CONCLUSIONS: HollandPTC eyeline specifications are in accordance with five other ocular PT beamlines. Similar clinical concepts can be applied to expect the same high local tumor control. Dosimetrical properties among the six institutions induce most likely differences in ocular radiation-related toxicities. This interinstitutional comparison could support further research on ocular post-PT complications. Finally, the findings reported in this study could be used to define dosimetrical guidelines for ocular PT to unify the concepts among institutions.

Clinical commissioning of intensity-modulated proton therapy systems: Report of AAPM Task Group 185.

Proton therapy is an expanding radiotherapy modality in the United States and worldwide. With the number of proton therapy centers treating patients increasing, so does the need for consistent, high-quality clinical commissioning practices. Clinical commissioning encompasses the entire proton therapy system's multiple components, including the treatment delivery system, the patient positioning system, and the image-guided radiotherapy components. Also included in the commissioning process are the x-ray computed tomography scanner calibration for proton stopping power, the radiotherapy treatment planning system, and corresponding portions of the treatment management system. This commissioning report focuses exclusively on intensity-modulated scanning systems, presenting details of how to perform the commissioning of the proton therapy and ancillary systems, including the required proton beam measurements, treatment planning system dose modeling, and the equipment needed.

A standardized commissioning framework of Monte Carlo dose calculation algorithms for proton pencil beam scanning treatment planning systems.

PURPOSE: Treatment planning systems (TPSs) from different vendors can involve different implementations of Monte Carlo dose calculation (MCDC) algorithms for pencil beam scanning (PBS) proton therapy. There are currently no guidelines for validating non-water materials in TPSs. Furthermore, PBS-specific parameters can vary by 1-2 orders of magnitude among different treatment delivery systems (TDSs). This paper proposes a standardized framework on the use of commissioning data and steps to validate TDS-specific parameters and TPS-specific heterogeneity modeling to potentially reduce these uncertainties. METHODS: A standardized commissioning framework was developed to commission the MCDC algorithms of RayStation 8A and Eclipse AcurosPT v13.7.20 using water and non-water materials. Measurements included Bragg peak depth-dose and lateral spot profiles and scanning field outputs for Varian ProBeam. The phase-space parameters were obtained from in-air measurements and the number of protons per MU from output measurements of 10 × 10 cm2 square fields at a 2 cm depth. Spot profiles and various PBS field measurements at additional depths were used to validate TPS. Human tissues in TPS, Gammex phantom materials, and artificial materials were used for the TPS benchmark and validation. RESULTS: The maximum differences of phase parameters, spot sigma, and divergence between MCDC algorithms are below 4.5 µm and 0.26 mrad in air, respectively. Comparing TPS to measurements at depths, both MC algorithms predict the spot sigma within 0.5 mm uncertainty intervals, the resolution of the measurement device. Beam Configuration in AcurosPT is found to underestimate number of protons per MU by ~2.5% and requires user adjustment to match measured data, while RayStation is within 1% of measurements using Auto model. A solid water phantom was used to validate the range accuracy of non-water materials within 1% in AcurosPT. CONCLUSIONS: The proposed standardized commissioning framework can detect potential issues during PBS TPS MCDC commissioning processes, and potentially can shorten commissioning time and improve dosimetric accuracies. Secondary MCDC can be used to identify the root sources of disagreement between primary MCDC and measurement.

Impact of intrafraction prostate motion on clinical target coverage in proton therapy: A simulation study of dosimetric differences in two delivery techniques.

PURPOSE: To investigate the dosimetric impact of prostate intrafraction motion on proton double-scattering (DS) and uniform scanning (US) treatments using electromagnetic transponder-based prostate tracking data in simulated treatment deliveries. METHODS: In proton DS delivery, the spread-out Bragg peak (SOBP) is created almost instantaneously by the constant rotation of the range modulator. US, however, delivers each entire energy layer of the SOBP sequentially from distal to proximal direction in time, which can interplay with prostate intrafraction motion. This spatiotemporal interplay during proton treatment was simulated to evaluate its dosimetric impact. Prostate clinical target volume (CTV) dose was obtained by moving CTV through dose matrices of the energy layers according to prostate-motion traces. Fourteen prostate intrafraction motion traces of each of 17 prostate patients were used in the simulated treatment deliveries. Both single fraction dose-volume histograms (DVHs) and fraction-cumulative DVHs were obtained for both 2 Gy per fraction and 7.25 Gy per fraction stereotactic body radiotherapy (SBRT). RESULTS: The simulation results indicated that CTV dose degradation depends on the magnitude and direction of prostate intrafraction motion and is patient specific. For some individual fractions, prescription dose coverage decreased in both US and DS treatments, and hot and cold spots inside the CTV were observed in the US results. However, fraction-cumulative CTV dose coverage showed much reduced dose degradation for both DS and US treatments for both 2 Gy per fraction and SBRT simulations. CONCLUSIONS: This study indicated that CTV dose inhomogeneity may exist for some patients with severe prostate intrafraction motion during US treatments. However, there are no statistically significant dose differences between DS and US treatment simulations. Cumulative dose of multiple-fractions significantly reduced dose uncertainties.

TOPAS Monte Carlo simulation for double scattering proton therapy and dosimetric evaluation.

PURPOSE: To construct and commission a double scattering (DS) proton beam model in TOPAS Monte Carlo (MC) code. Dose comparisons of MC calculations to the measured and treatment planning system (TPS) calculated dose were performed. METHODS: The TOPAS nozzle model was based on the manufacturer blueprints. Nozzle set-up and beam current modulations were calculated using room-specific calibration data. This model was implemented to reproduce pristine peaks, spread-out Bragg peaks (SOBP) and lateral profiles. A stair-shaped target plan in water phantom was calculated and compared to measured data to verify range compensator (RC) modeling. RESULTS: TOPAS calculated pristine peaks agreed well with measurements, with accuracies of 0.03 cm for range R90 and 0.05 cm for distal dose fall-off (DDF). The calculated SOBP range, modulation width and DDF differences between MC calculations and measurements were within 0.05 cm, 0.5 cm and 0.03 cm respectively. MC calculated lateral penumbra agreed well with measured data, with difference less than 0.05 cm. For RC calculation, TPS underestimated the additional depth dose tail due to the nuclear halo effect. Lateral doses by TPS were 10% lower than measurement outside the target, while maximum difference of MC calculation was within 2%. At deeper depths inside the target volume, TPS overestimated doses by up to 25% while TOPAS predicted the dose to within 5% of measurements. CONCLUSION: We have successfully developed and commissioned a MC based DS nozzle model. The performance of dose accuracy by TOPAS was superior to TPS, especially for highly inhomogeneous compensator.

Evaluation of the range shifter model for proton pencil-beam scanning for the Eclipse v.11 treatment planning system.

Existing proton therapy pencil-beam scanning (PBS) systems have limitations on the minimum range to which a patient can be treated. This limitation arises from practical considerations, such as beam current intensity, layer spacing, and delivery time. The range shifter (RS) - a slab of stopping material inserted between the nozzle and the patient - is used to reduce the residual range of the incident beam so that the treatment ranges can be extended to shallow depths. Accurate modeling of the RS allows one to calculate the beam spot size entering the patient, given the proton energy, for arbitrary positions and thicknesses of the RS in the beam path. The Eclipse version 11 (v11) treatment planning system (TPS) models RS-induced beam widening by incorporating the scattering properties of the RS material into the V-parameter. Monte Carlo simulations with Geant4 code and analytical calculations using the Fermi-Eyges (FE) theory with Highland approximation of multiple Coulomb scattering (MCS) were employed to calculate proton beam widening due to scattering in the RS. We demonstrated that both methods achieved consistent results and could be used as a benchmark for evaluating the Eclipse V-parameter model. In most cases, the V-parameter model correctly predicted the beam spot size after traversing the RS. However, Eclipse did not enforce the constraint for a nonnegative covariance matrix when fitting the spot sizes to derive the phase space parameters, which resulted in incorrect calculations under specific conditions. In addition, Eclipse v11 incorrectly imposed limits on the individual values of the phase space parameters, which could lead to incorrect spot size values in the air calculated for beams with spot sigmas <3.8 mm. Notably, the TPS supplier (Varian) and hardware vendor (Ion Beam Applications) inconsistently refer to the RS position, which may result in improper spot size calculations.

A simplified methodology to produce Monte Carlo dose distributions in proton therapy.

The purpose of this study was to develop a simplified methodology that will produce Monte Carlo (MC) dose distribution for proton therapy which can be used as a clinical aid in determining the adequacy of proton plans produced from the treatment planning system (TPS). The Geant4 Monte Carlo toolkit was used for all simulations. The geometry of the double scatter nozzle in the simulation was a simplification of the treatment nozzle. The proton source was modeled as discrete energy layers, each with a unique energy distribution and weighting factor. The simplified MC system was designed to give the same dose distribution as the measured data used to commission the TPS. After the simplified MC system was finalized, a series of verification comparisons were made between it, measurements, and the clinically used TPS. Comparisons included the lateral profile of a stair-shaped compensator that simulated a sharp lateral heterogeneity and depth-dose measurements through heterogeneous materials. The simplified MC system matched measurements to within 2% or 2 mm for all commissioning data under investigation; moreover, the distal edge and lateral penumbra was within 1 mm of the measurements. The simplified MC system was able to better reproduce the measured profiles for a stair-shaped compensator than the TPS. Both MC and TPS matched the measured depth dose through heterogeneous materials to within 2% or 2 mm. The simplified MC system was straightforward to implement, and produced accurate results when compared to measurements. Therefore, it holds promise as a clinically useful methodology to validate the relative dose distribution of patient treatment plans produced by the treatment planning systems.

Dosimetric evaluation of hybrid brass/stainless-steel apertures for proton therapy.

In passive scattering proton therapy, patient specific collimators (apertures) are used to laterally shape the proton beam, and compensators are employed to distally conform proton dose to the target. Brass is a commonly used material for apertures and recently a hybrid brass/stainless-steel (BR/SST) aperture design has been introduced to reduce treatment cost without clinical flow change. We measured stopping power and leakage dose for apertures made of stainless steel and brass in the Proton Therapy system. The linear stopping power ratios for stainless steel (type 304) and brass to water were calculated to be 5.46 and 5.51, respectively. Measured stopping power ratios of SST and BR were 5.51  ±  0.04 and 5.56  ±  0.08, respectively, which agrees with the calculated values within 1%. Leakage dose on the downstream surface of two slabs of Ø18 cm stainless steel apertures (total thickness of 6.5 cm) for the maximum available proton energy (235 MeV) was 1.283% ± 0.004% of the prescription dose, and was smaller compared to the 1.358% ± 0.005% leakage dose measured for existing brass apertures of identical physical dimensions. Therefore, the existing beam range limits for brass aperture slabs used at our institution with safety margin allowances for material composition and delivered beam range uncertainties can be safely applied for the new BR/SST aperture design. Potential range differences in the brass and stainless steel interface regions of the hybrid design were further investigated using EBT3 GafChromic film. Film dosimetry revealed no discernible range variations across the brass and stainless steel interface regions. Neutron dose to the patient from brass and stainless steel apertures was simulated using the Monte Carlo method. The results indicate that stainless steel produces similar patient neutron dose compared to brass. Material activation dose rates of stainless steel were measured over a period of 7 d after irradiation. The measurements showed that the proton induced SST activity is initially lower and also decays at a faster rate than that induced in brass, therefore requires no changes in radiation protection requirements on material disposals. The Monte Carlo simulation confirmed higher initial activity of brass than stainless steel shortly after irradiation. The hybrid BR/SST aperture design is suitable for clinical use to replace the current brass apertures for all clinically used proton ranges. The existing aperture disposal procedures also satisfy radiation protection requirements for the new hybrid type apertures.

An experimental investigation into the effect of periodic motion on proton dosimetry using polymer gel dosimeters and a programmable motion platform.

Organ motion in proton therapy affects treatment dose distribution during both double-scattering (DS) and uniform-scanning (US) deliveries. We investigated the dosimetric impact of target motion using three-dimensional polymer gel dosimeters and a programmable motion platform. A simple one-beam treatment plan with 16 cm range and 6 cm modulation was generated from the treatment planning system (TPS) in both the DS and US modes. One gel dosimeter was irradiated with a stationary DS beam. Two other gel dosimeters were irradiated with the DS and US beams while they moved in the same sinusoidal motion profile using a programmable motion platform. The dose distribution of the stationary DS delivery agreed with the TPS plan. Dosimetric comparisons between DS motion delivery and the MATLAB-based motion model showed insignificant differences. Dose-volume histograms of a cylindrical target volume inside the gel dosimeters showed target coverage degradation caused by motion. A three-dimensional gamma index calculation (3% and 3 mm) confirmed different dosimetric impacts from DS and US with the same target motion. This polymer-gel-dosimeter-based study confirmed the dosimetric impact of intrafraction target motion and its interplay with temporal delivery of different energy layers in US proton treatments.

Comparison of three-dimensional (3D) conformal proton radiotherapy (RT), 3D conformal photon RT, and intensity-modulated RT for retroperitoneal and intra-abdominal sarcomas.

PURPOSE: To compare three-dimensional conformal proton radiotherapy (3DCPT), intensity-modulated photon radiotherapy (IMRT), and 3D conformal photon radiotherapy (3DCRT) to predict the optimal RT technique for retroperitoneal sarcomas. METHODS AND MATERIALS: 3DCRT, IMRT, and 3DCPT plans were created for treating eight patients with retroperitoneal or intra-abdominal sarcomas. The clinical target volume (CTV) included the gross tumor plus a 2-cm margin, limited by bone and intact fascial planes. For photon plans, the planning target volume (PTV) included a uniform expansion of 5 mm. For the proton plans, the PTV was nonuniform and beam-specific. The prescription dose was 50.4 Gy/Cobalt gray equivalent CGE. Plans were normalized so that >95% of the CTV received 100% of the dose. RESULTS: The CTV was covered adequately by all techniques. The median conformity index was 0.69 for 3DCPT, 0.75 for IMRT, and 0.51 for 3DCRT. The median inhomogeneity coefficient was 0.062 for 3DCPT, 0.066 for IMRT, and 0.073 for 3DCRT. The bowel median volume receiving 15 Gy (V15) was 16.4% for 3DCPT, 52.2% for IMRT, and 66.1% for 3DCRT. The bowel median V45 was 6.3% for 3DCPT, 4.7% for IMRT, and 15.6% for 3DCRT. The median ipsilateral mean kidney dose was 22.5 CGE for 3DCPT, 34.1 Gy for IMRT, and 37.8 Gy for 3DCRT. The median contralateral mean kidney dose was 0 CGE for 3DCPT, 6.4 Gy for IMRT, and 11 Gy for 3DCRT. The median contralateral kidney V5 was 0% for 3DCPT, 49.9% for IMRT, and 99.7% for 3DCRT. Regardless of technique, the median mean liver dose was <30 Gy, and the median cord V50 was 0%. The median integral dose was 126 J for 3DCPT, 400 J for IMRT, and 432 J for 3DCRT. CONCLUSIONS: IMRT and 3DCPT result in plans that are more conformal and homogenous than 3DCRT. Based on Quantitative Analysis of Normal Tissue Effects in Clinic benchmarks, the dosimetric advantage of proton therapy may be less gastrointestinal and genitourinary toxicity.

Dosimetric uncertainty in prostate cancer proton radiotherapy.

PURPOSE: The authors we evaluate the uncertainty in proton therapy dose distribution for prostate cancer due to organ displacement, varying penumbra width of proton beams, and the amount of rectal gas inside the rectum. METHODS AND MATERIALS: Proton beam treatment plans were generated for ten prostate patients with a minimum dose of 74.1 cobalt gray equivalent (CGE) to the planning target volume (PTV) while 95% of the PTV received 78 CGE. Two lateral or lateral oblique proton beams were used for each plan. The authors we investigated the uncertainty in dose to the rectal wall (RW) and the bladder wall (BW) due to organ displacement by comparing the dose-volume histograms (DVH) calculated with the original or shifted contours. The variation between DVHs was also evaluated for patients with and without rectal gas in the rectum for five patients who had 16 to 47 cc of visible rectal gas in their planning computed tomography (CT) imaging set. The uncertainty due to the varying penumbra width of the delivered protons for different beam setting options on the proton delivery system was also evaluated. RESULTS: For a 5 mm anterior shift, the relative change in the RW volume receiving 70 CGE dose (V70) was 37.9% (5.0% absolute change in 13.2% of a mean V70). The relative change in the BW volume receiving 70 CGE dose (V70) was 20.9% (4.3% absolute change in 20.6% of a mean V70) with a 5 mm inferior shift. A 2 mm penumbra difference in beam setting options on the proton delivery system resulted in the relative variations of 6.1% (0.8% absolute change) and 4.4% (0.9% absolute change) in V70 of RW and BW, respectively. The data show that the organ displacements produce absolute DVH changes that generally shift the entire isodose line while maintaining the same shape. The overall shape of the DVH curve for each organ is determined by the penumbra and the distance of the target in beam's eye view (BEV) from the block edge. The beam setting option producing a 2 mm sharper penumbra at the isocenter can reduce the magnitude of maximal doses to the RW by 2% compared to the alternate option utilizing the same block margin of 7 mm. The dose to 0.1 cc of the femoral head on the distal side of the lateral-posterior oblique beam is increased by 25 CGE for a patient with 25 cc of rectal gas. CONCLUSION: Variation in the rectal and bladder wall DVHs due to uncertainty in the position of the organs relative to the location of sharp dose falloff gradients should be accounted for when evaluating treatment plans. The proton beam delivery option producing a sharper penumbra reduces maximal doses to the rectal wall. Lateral-posterior oblique beams should be avoided in patients prone to develop a large amount of rectal gas.

Clinical implementation of full Monte Carlo dose calculation in proton beam therapy.

The goal of this work was to facilitate the clinical use of Monte Carlo proton dose calculation to support routine treatment planning and delivery. The Monte Carlo code Geant4 was used to simulate the treatment head setup, including a time-dependent simulation of modulator wheels (for broad beam modulation) and magnetic field settings (for beam scanning). Any patient-field-specific setup can be modeled according to the treatment control system of the facility. The code was benchmarked against phantom measurements. Using a simulation of the ionization chamber reading in the treatment head allows the Monte Carlo dose to be specified in absolute units (Gy per ionization chamber reading). Next, the capability of reading CT data information was implemented into the Monte Carlo code to model patient anatomy. To allow time-efficient dose calculation, the standard Geant4 tracking algorithm was modified. Finally, a software link of the Monte Carlo dose engine to the patient database and the commercial planning system was established to allow data exchange, thus completing the implementation of the proton Monte Carlo dose calculation engine ('DoC++'). Monte Carlo re-calculated plans are a valuable tool to revisit decisions in the planning process. Identification of clinically significant differences between Monte Carlo and pencil-beam-based dose calculations may also drive improvements of current pencil-beam methods. As an example, four patients (29 fields in total) with tumors in the head and neck regions were analyzed. Differences between the pencil-beam algorithm and Monte Carlo were identified in particular near the end of range, both due to dose degradation and overall differences in range prediction due to bony anatomy in the beam path. Further, the Monte Carlo reports dose-to-tissue as compared to dose-to-water by the planning system. Our implementation is tailored to a specific Monte Carlo code and the treatment planning system XiO (Computerized Medical Systems Inc.). However, this work describes the general challenges and considerations when implementing proton Monte Carlo dose calculation in a clinical environment. The presented solutions can be easily adopted for other planning systems or other Monte Carlo codes.

Sensitivities in the production of spread-out Bragg peak dose distributions by passive scattering with beam current modulation.

A spread-out Bragg peak (SOBP) is used in proton beam therapy to create a longitudinal conformality of the required dose to the target. In order to create this effect in a passive beam scattering system, a variety of components must operate in conjunction to produce the desired beam parameters. We will describe how the SOBP is generated and will explore the tolerances of the various components and their subsequent effect on the dose distribution. A specific aspect of this investigation includes a case study involving the use of a beam current modulated system. In such a system, the intensity of the beam current can be varied in synchronization with the revolution of the range-modulator wheel. As a result, the weights of the pulled-back Bragg peaks can be individually controlled to produce uniform dose plateaus for a large range of treatment depths using only a small number of modulator wheels.

Incorporation of the aperture thickness in proton pencil-beam dose calculations.

Field-specific apertures, of sufficient range-absorbing thickness, are used in the majority of proton-therapy treatments today. In current practice, these apertures are modelled as objects of infinitesimal thickness. Such an approximation, however, is not accurate if the aperture edge is close to, or extends over, the beam axis. Practical situations in which this occurs include off-axis patch fields, small apertures, and fields shaped with a multileaf collimator. We develop an extension of the pencil-beam dose model to incorporate the aperture thickness. We derive an exact solution as well as a computationally simpler approximate implementation. The model is validated using measurements of the lateral penumbra. For a set-up with a source size of 2.76 cm, a source-to-axis distance of 227 cm, and a aperture-to-axis distance of 35 cm, the maximum increase in penumbra for a 6 cm thick aperture compared to the thin-aperture model is about 2 mm. The maximum shift in the 95% isodose contour line is larger. The overall effect depends on the aperture thickness, the position of the aperture edge and the intrinsic source size and SAD, but is fairly insensitive to aperture-to-skin distance and depth in patient.

The prediction of output factors for spread-out proton Bragg peak fields in clinical practice.

The reliable prediction of output factors for spread-out proton Bragg peak (SOBP) fields in clinical practice remained unrealized due to a lack of a consistent theoretical framework and the great number of variables introduced by the mechanical devices necessary for the production of such fields. These limitations necessitated an almost exclusive reliance on manual calibration for individual fields and empirical, ad hoc, models. We recently reported on a theoretical framework for the prediction of output factors for such fields. In this work, we describe the implementation of this framework in our clinical practice. In our practice, we use a treatment delivery nozzle that uses a limited, and constant, set of mechanical devices to produce SOBP fields over the full extent of clinical penetration depths, or ranges, and modulation widths. This use of a limited set of mechanical devices allows us to unfold the physical effects that affect the output factor. We describe these effects and their incorporation into the theoretical framework. We describe the calibration and protocol for SOBP fields, the effects of apertures and range-compensators and the use of output factors in the treatment planning process.