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Objective. Protons have advantageous dose distributions and are increasingly used in cancer therapy. At the depth of the Bragg peak range, protons produce a mixed radiation field consisting of low- and high-linear energy transfer (LET) components, the latter of which is characterized by an increased ionization density on the microscopic scale associated with increased biological effectiveness. Prediction of the yield and LET of primary and secondary charged particles at a certain depth in the patient is performed by Monte Carlo simulations but is difficult to verify experimentally. Approach. Here, the results of measurements performed with Timepix detector in the mixed radiation field produced by a therapeutic proton beam in water are presented and compared to Monte Carlo simulations. The unique capability of the detector to perform high-resolution single particle tracking and identification enhanced by artificial intelligence allowed to resolve the particle type and measure the deposited energy of each particle comprising the mixed radiation field. Based on the collected data, biologically important physics parameters, the LET of single protons and dose-averaged LET, were computed. Main results. An accuracy over 95% was achieved for proton recognition with a developed neural network model. For recognized protons, the measured LET spectra generally agree with the results of Monte Carlo simulations. The mean difference between dose-averaged LET values obtained from measurements and simulations is 17%. We observed a broad spectrum of LET values ranging from a fraction of keV μ m -1 to about 10 keV μ m -1 for most of the measurements performed in the mixed radiation fields. Significance. It has been demonstrated that the introduced measurement method provides experimental data for validation of LET D or LET spectra in any treatment planning system. The simplicity and accessibility of the presented methodology make it easy to be translated into a clinical routine in any proton therapy facility., (Creative Commons Attribution license.)

Proton computed tomography (pCT) is a promising tomographic imaging modality allowing direct reconstruction of proton relative stopping power (RSP) required for proton therapy dose calculation. In this review article, we aim at highlighting the role of Monte Carlo (MC) simulation in pCT studies. After describing the requirements for performing proton computed tomography and the various pCT scanners actively used in recent research projects, we present an overview of available MC simulation platforms. The use of MC simulations in the scope of investigations of image reconstruction, and for the evaluation of optimal RSP accuracy, precision and spatial resolution omitting detector effects is then described. In the final sections of the review article, we present specific applications of realistic MC simulations of an existing pCT scanner prototype, which we describe in detail., (Copyright © 2020. Published by Elsevier GmbH.)

This topical review summarizes underlying concepts of nanodosimetry. It describes the development and current status of nanodosimetric detector technology. It also gives an overview of Monte Carlo track structure simulations that can provide nanodosimetric parameters for treatment planning of proton and ion therapy. Classical and modern radiobiological assays that can be used to demonstrate the relationship between the frequency and complexity of DNA lesion clusters and nanodosimetric parameters are reviewed. At the end of the review, existing approaches of treatment planning based on relative biological effectiveness (RBE) models or dose-averaged linear energy transfer are contrasted with an RBE-independent approach based on nandosimetric parameters. Beyond treatment planning, nanodosimetry is also expected to have applications and give new insights into radiation protection dosimetry., (© 2021 Institute of Physics and Engineering in Medicine.)

Particle therapy treatment planning requires accurate volumetric maps of the relative stopping power, which can directly be acquired using proton computed tomography (pCT). With fluence-modulated pCT (FMpCT) imaging fluence is concentrated in a region-of-interest (ROI), which can be the vicinity of the treatment beam path, and imaging dose is reduced elsewhere. In this work we present a novel optimization algorithm for FMpCT which, for the first time, calculates modulated imaging fluences for joint imaging dose and image variance objectives. Thereby, image quality is maintained in the ROI to ensure accurate calculations of the treatment dose, and imaging dose is minimized outside the ROI with stronger minimization penalties given to imaging organs-at-risk. The optimization requires an initial scan at uniform fluence or a previous x-ray CT scan. We simulated and optimized FMpCT images for three pediatric patients with tumors in the head region. We verified that the target image variance inside the ROI was achieved and demonstrated imaging dose reductions outside of the ROI of 74% on average, reducing the imaging dose from 1.2 to 0.3 mGy. Such dose savings are expected to be relevant compared to the therapeutic dose outside of the treatment field. Treatment doses were re-calculated on the FMpCT images and compared to treatment doses re-recalculated on uniform fluence pCT scans using a 1% criterion. Passing rates were above 98.3% for all patients. Passing rates comparing FMpCT treatment doses to the ground truth treatment dose were above 88.5% for all patients. Evaluation of the proton range with a 1 mm criterion resulted in passing rates above 97.5% (FMpCT/pCT) and 95.3% (FMpCT/ground truth). Jointly optimized fluence-modulated pCT images can be used for proton dose calculation maintaining the full dosimetric accuracy of pCT but reducing the required imaging dose considerably by three quarters. This may allow for daily imaging during particle therapy ensuring a safe and accurate delivery of the therapeutic dose and avoiding excess dose from imaging.

Proton computed tomography (pCT) has high accuracy and dose efficiency in producing spatial maps of the relative stopping power (RSP) required for treatment planning in proton therapy. With fluence-modulated pCT (FMpCT), prescribed noise distributions can be achieved, which allows to decrease imaging dose by employing object-specific dynamically modulated fluence during the acquisition. For FMpCT acquisitions we divide the image into region-of-interest (ROI) and non-ROI volumes. In proton therapy, the ROI volume would encompass all treatment beams. An optimization algorithm then calculates dynamically modulated fluence that achieves low prescribed noise inside the ROI and high prescribed noise elsewhere. It also produces a planned noise distribution, which is the expected noise map for that fluence, as calculated with a Monte Carlo simulation. The optimized fluence can be achieved by acquiring pCT images with grids of intensity modulated pencil beams. In this work, we interfaced the control system of a clinical proton beam line to deliver the optimized fluence. Using three phantoms we acquired images with uniform fluence, with a constant noise prescription, and with an FMpCT task. Image noise distributions as well as fluence maps were compared to the corresponding planned distributions as well as to the prescription. Furthermore, we propose a correction method that removes image artifacts stemming from the acquisition with pencil beams having a spatially varying energy distribution that is not seen in clinical operation. RSP accuracy of FMpCT scans was compared to uniform scans and was found to be comparable to standard pCT scans. While we identified technical improvements for future experimental acquisitions, in particular related to an unexpected pencil beam size reduction and a misalignment of the fluence pattern, agreement with the planned noise was satisfactory and we conclude that FMpCT optimized for specific image noise prescriptions is experimentally feasible.

Visual illusions from astronauts in space have been reported to be associated with the passage of high energy charged particles through visual structures (retina, optic nerve, brain). Similar effects have also been reported by patients under proton and heavy ion therapies. This prompted us to investigate whether protons at the Loma Linda University Proton Therapy and Research Center (PTRC) may also affect other sensory systems beside evoking similar perceptions on the visual system. A retrospective review of proton radiotherapy patient records at PTRC identified 29 sensory reports from 19 patients who spontaneously reported visual, olfactory, auditory and gustatory illusions during treatment. Our results suggest that protons can evoke neuronal responses sufficient to elicit conscious sensory illusion experiences, in four senses (auditory, taste, smell, and visual) analogous to those from normal sensory inputs. The regions of the brain receiving the highest doses corresponded with the anatomical structures associated with each type of illusion. Our findings suggest that more detailed queries about sensory illusions during proton therapy are warranted, possibly integrated with quantitative effect descriptions (such as electroencephalography) and can provide additional physiological basis for understanding the effects of protons on central nervous system tissues, needed for radiation risk assessment in advance of deep space human exploration., Competing Interests: Declaration of Competing Interest The authors do not have any identified or perceived conflicts of interest associated with this study., (Copyright © 2020 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.)

Purpose: Proton CT (pCT) has the ability to reduce inherent uncertainties in proton treatment by directly measuring the relative proton stopping power with respect to water, thereby avoiding the uncertain conversion of X-ray CT Hounsfield unit to relative stopping power and the deleterious effect of X- ray CT artifacts. The purpose of this work was to further evaluate the potential of pCT for pretreatment positioning using experimental pCT data of a head phantom., Methods: The performance of a 3D image registration algorithm was tested with pCT reconstructions of a pediatric head phantom. A planning pCT simulation scan of the phantom was obtained with 200 MeV protons and reconstructed with a 3D filtered back projection (FBP) algorithm followed by iterative reconstruction and a representative pretreatment pCT scan was reconstructed with FBP only to save reconstruction time. The pretreatment pCT scan was rigidly transformed by prescribing random errors with six degrees of freedom or deformed by the deformation field derived from a head and neck cancer patient to the pretreatment pCT reconstruction, respectively. After applying the rigid or deformable image registration algorithm to retrieve the original pCT image before transformation, the accuracy of the registration was assessed. To simulate very low-dose imaging for patient setup, the proton CT images were reconstructed with 100%, 50%, 25%, and 12.5% of the total number of histories of the original planning pCT simulation scan, respectively., Results: The residual errors in image registration were lower than 1 mm and 1° of magnitude regardless of the anatomic directions and imaging dose. The mean residual errors ranges found for rigid image registration were from -0.29 ± 0.09 to 0.51 ± 0.50 mm for translations and from -0.05 ± 0.13 to 0.08 ± 0.08 degrees for rotations. The percentages of sub-millimetric errors found, for deformable image registration, were between 63.5% and 100%., Conclusion: This experimental head phantom study demonstrated the potential of low-dose pCT imaging for 3D image registration. Further work is needed to confirm the value pCT for pretreatment image-guided proton therapy., (© 2019 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Details of the pattern of ionization formed by particle tracks extends knowledge of dose effects on the nanometer scale. Ionization detail (ID), frequently characterized by ionization cluster size distributions (ICSD), is obtained through time-consuming Monte Carlo (MC) track-structure simulations. In this work, TOPAS-nBio was used to generate a highly precise database of biologically significant ID quantities, sampled with randomly oriented 2.3 nm diameter cylinders, 3.4 nm (10 base pairs) long, inside a chromatin-size cylinder, irradiated by 1-1000 MeV/u ions of Z  =  1-8. A macroscopic method developed to utilize the database using condensed-history MC was used to calculate distributions of the ICSD first moment [Formula: see text] and cumulative probability [Formula: see text] in a 20  ×  20  ×  40 cm 3 water phantom irradiated with proton and carbon spread-out Bragg peak (SOBP) of 10.5 cm range, 2 cm width. Results were verified against detailed MC track-structure simulations using phase space scored at several depths. ID distributions were then obtained for intensity modulated proton and carbon radiotherapy plans in a digitized anthropomorphic phantom of a base of skull tumor to demonstrate clinical application of this approach. The database statistical uncertainties were 0.5% (3 standard deviations). Fluence-averaged ID as implemented proved unsuitable for macroscopic calculation. E dep -averaged ID agreed with track-structure results within 0.8% for protons. For carbon, maximum absolute differences of 2.9%  ±  1.6% and 5.6%  ±  1.9% for [Formula: see text], 1.7%  ±  0.8% and 1.9%  ±  0.4% (1 standard deviation) for [Formula: see text], were found in the plateau and SOBP, respectively, up to 11.5%  ±  5.6% in the tail region. Macroscopic ID calculation was demonstrated for a realistic treatment plan. Computation times with or without ID calculation were comparable in all cases. Pre-calculated nanodosimetric data may be used for condensed-history MC for nanodosimetric ID-based treatment planning in ion radiotherapy in the future. The macroscopic approach developed has the calculation speed of condensed-history MC while approaching the accuracy of full track structure simulations.

This simulation study presents the application of fluence field modulated computed tomography, initially developed for x-ray CT, to proton computed tomography (pCT). By using pencil beam (PB) scanning, fluence modulated pCT (FMpCT) may achieve variable image quality in a pCT image and imaging dose reduction. Three virtual phantoms, a uniform cylinder and two patients, were studied using Monte Carlo simulations of an ideal list-mode pCT scanner. Regions of interest (ROI) were selected for high image quality and only PBs intercepting them preserved full fluence (FF). Image quality was investigated in terms of accuracy (mean) and noise (standard deviation) of the reconstructed proton relative stopping power compared to reference values. Dose calculation accuracy on FMpCT images was evaluated in terms of dose volume histograms (DVH), range difference (RD) for beam-eye-view (BEV) dose profiles and gamma evaluation. Pseudo FMpCT scans were created from broad beam experimental data acquired with a list-mode pCT prototype. FMpCT noise in ROIs was equivalent to FF images and accuracy better than  -1.3%(-0.7%) by using 1% of FF for the cylinder (patients). Integral imaging dose reduction of 37% and 56% was achieved for the two patients for that level of modulation. Corresponding DVHs from proton dose calculation on FMpCT images agreed to those from reference images and 96% of BEV profiles had RD below 2 mm, compared to only 1% for uniform 1% of FF. Gamma pass rates (2%, 2 mm) were 98% for FMpCT while for uniform 1% of FF they were as low as 59%. Applying FMpCT to preliminary experimental data showed that low noise levels and accuracy could be preserved in a ROI, down to 30% modulation. We have shown, using both virtual and experimental pCT scans, that FMpCT is potentially feasible and may allow a means of imaging dose reduction for a pCT scanner operating in PB scanning mode. This may be of particular importance to proton therapy given the low integral dose found outside the target.

A split feasibility formulation for the inverse problem of intensity-modulated radiation therapy treatment planning with dose-volume constraints included in the planning algorithm is presented. It involves a new type of sparsity constraint that enables the inclusion of a percentage-violation constraint in the model problem and its handling by continuous (as opposed to integer) methods. We propose an iterative algorithmic framework for solving such a problem by applying the feasibility-seeking CQ-algorithm of Byrne combined with the automatic relaxation method that uses cyclic projections. Detailed implementation instructions are furnished. Functionality of the algorithm was demonstrated through the creation of an intensity-modulated proton therapy plan for a simple 2D C-shaped geometry and also for a realistic base-of-skull chordoma treatment site. Monte Carlo simulations of proton pencil beams of varying energy were conducted to obtain dose distributions for the 2D test case. A research release of the Pinnacle 3 proton treatment planning system was used to extract pencil beam doses for a clinical base-of-skull chordoma case. In both cases the beamlet doses were calculated to satisfy dose-volume constraints according to our new algorithm. Examination of the dose-volume histograms following inverse planning with our algorithm demonstrated that it performed as intended. The application of our proposed algorithm to dose-volume constraint inverse planning was successfully demonstrated. Comparison with optimized dose distributions from the research release of the Pinnacle 3 treatment planning system showed the algorithm could achieve equivalent or superior results.

Purpose: The primary objective of this work is to measure the secondary neutron field produced by an uncollimated proton pencil beam impinging on different tissue-equivalent phantom materials using organic scintillation detectors. Additionally, the Monte Carlo code mcnpx-PoliMi was used to simulate the detector response for comparison to the measured data. Comparison of the measured and simulated data will validate this approach for monitoring secondary neutron dose during proton therapy., Methods: Proton beams of 155- and 200-MeV were used to irradiate a variety of phantom materials and secondary particles were detected using organic liquid scintillators. These detectors are sensitive to fast neutrons and gamma rays: pulse shape discrimination was used to classify each detected pulse as either a neutron or a gamma ray. The mcnpx-PoliMi code was used to simulate the secondary neutron field produced during proton irradiation of the same tissue-equivalent phantom materials., Results: An experiment was performed at the Loma Linda University Medical Center proton therapy research beam line and corresponding models were created using the mcnpx-PoliMi code. The authors' analysis showed agreement between the simulations and the measurements. The simulated detector response can be used to validate the simulations of neutron and gamma doses on a particular beam line with or without a phantom., Conclusions: The authors have demonstrated a method of monitoring the neutron component of the secondary radiation field produced by therapeutic protons. The method relies on direct detection of secondary neutrons and gamma rays using organic scintillation detectors. These detectors are sensitive over the full range of biologically relevant neutron energies above 0.5 MeV and allow effective discrimination between neutron and photon dose. Because the detector system is portable, the described system could be used in the future to evaluate secondary neutron and gamma doses on various clinical beam lines for commissioning and prospective data collection in pediatric patients treated with proton therapy.

Background: Exploiting biologic imaging, studies have been performed to boost dose to gross intraprostatic tumor volumes (GTV) while reducing dose elsewhere in the prostate. Interest in proton beams has increased due to superior normal-tissue sparing they afford. Our goal was to dosimetrically compare 3D conformal proton boost plans with intensity-modulated radiation therapy (IMRT) plans with respect to target coverage and avoiding organs at risk., Methods: Treatment planning computer tomography scans of ten patients were selected. For each patient, two hypothetical but realistic GTVs each with a fixed volume were contoured in different anatomical locations of the prostate. IMRT and proton beam plans were created with a prescribed dose of 50.4 Gy to the initial planning target volume (PTV) including the PTV of the seminal vesicles (PSV), 70.2 Gy to the PTV of the prostate (PPS), and 90 Gy to the PTV of the gross tumor volumes (PGTVs). For proton plans, uncertainties of range and patient setup were accounted for; apertures were adjusted until the dose-volume coverage of PTVs matched that of the IMRT plan. For both plans, prescribed PTV doses were made identical to allow for comparing normal-tissue doses., Results: Protons delivered more homogeneous but less conformal doses to PGTVs than IMRT did and comparable doses to PSV and PPS. Volumes of bladder and rectum receiving doses higher than 65 Gy were similar for both plans. However, volumes receiving less than 65 Gy were significantly reduced, i.e., protons reduced integral dose by 45.6 % and 26.5 % for rectum and bladder, respectively. This volume-sparing was also seen in femoral heads and penile bulb., Conclusions: Protons delivered comparable doses to targets in dose homogeneity and conformity and spared normal tissues from intermediate-to-low doses better than IMRT did. Further improvement of dose sparing and changes in homogeneity and conformity may be achieved by reducing proton range uncertainties and from implementing intensity modulation.

Immobilization devices can impact not only the inter- and intra-fraction motion of the patient, but also the range uncertainty of the treatment beam in proton therapy. In order to limit additional range uncertainty, the water equivalent thickness (WET) of the immobilization device needs to be well known and accurately reflected in the calculations by the treatment planning system (TPS). The method presented here focusses on the use of a nozzle-mounted variable range shifter and precision-machined polystyrene blocks of known WET to evaluate commercial immobilization devices prior to clinical implementation. CT studies were also completed to evaluate the internal uniformity of the immobilization devices under study. Mul- tiple inserts of the kVue platform (Qfix Systems, Avondale, PA) were evaluated as part of this study. The results indicate that the inserts are largely interchangeable across a given design type and that the measured WET values agree with those generated by the TPS with a maxi- mum difference less than 1 mm. The WET of the devices, as determined by the TPS, was not impacted by CT beam hardening normally experienced during clinical use. The reproduc- ibility of the WET method was also determined to be better than ±0.02 mm. In conclusion, the testing of immobilization prior to implementation in proton therapy is essential in order to ascertain their impact on the proton treatment and the methodology described here can also be applied to other immobilization systems.

Purpose: To develop and test a method for optimizing and constructing a dual scattering system in passively scattered proton therapy., Methods: A beam optics optimization algorithm was developed to optimize the thickness of the first scatterer (S1) and the profile (of both the high-Z material and Lexan) of the second scatterer (S2) to deliver a proton beam matching a given set of parameters, including field diameter, fluence, flatness, and symmetry. A new manufacturing process was also tested that allows the contoured second scattering foil to be created much more economically and quickly using Cerrobend casting. Two application-specific scattering systems were developed and tested using both experimental and Monte Carlo techniques to validate the optimization process described., Results: A scattering system was optimized and constructed to deliver large uniform irradiations of radiobiology samples at low dose rates. This system was successfully built and tested using film and ionization chambers. The system delivered a uniform radiation field of 50 cm diameter (to a dose of ± 7% of the central axis) while the depth dose profile could be tuned to match the specifications of the particular investigator using modulator wheels and range shifters. A second scattering system for intermediate field size (4 cm < diameter < 10 cm) stereotactic radiosurgery and radiation therapy (SRS and SRT) treatments was also developed and tested using GEANT4. This system improved beam efficiency by over 70% compared with existing scattering systems while maintaining field flatness and depth dose profile. In both cases the proton range uniformity across the radiation field was maintained, further indicating the accuracy of the energy loss formalism in the optimization algorithm., Conclusions: The methods described allow for rapid prototyping of scattering foils to meet the demands of both research and clinical beam delivery applications in proton therapy.

Purpose: Proton therapy (PT) utilizes high energy particle proton beam to kill cancer cells at the target region for target cancer therapy. Due to the physical properties of the proton beam, PT delivers dose with higher precision and no exit dose compared to conventional radiotherapy. In PT, patient data are distributed among multiple systems, a hindrance to research on efficacy and effectiveness. A data mining method and a treatment plan navigator utilizing the infrastructure and data repository of a PT electronic patient record (ePR) was developed to minimize radiation toxicity and improve outcomes in prostate cancer treatment. MATERIALS/METHOD(S): The workflow of a proton therapy treatment in a radiation oncology department was reviewed, and a clinical data model and data flow were designed. A prototype PT ePR system with DICOM compliance was developed to manage prostate cancer patient images, treatment plans, and related clinical data. The ePR system consists of four main components: (1) Data Gateway; (2) ePR Server; (3) Decision Support Tools; and (4) Visualization and Display Tools. Decision support and visualization tools are currently developed based on DICOM images, DICOM-RT and DICOM-RT-ION objects data from prostate cancer patients treated with hypofractionation protocol proton therapy were used for evaluating ePR system effectiveness. Each patient data set includes a set of computed tomography (CT) DICOM images and four DICOM-RT and RT-ION objects. In addition, clinical outcomes data collected from PT cases were included to establish a knowledge base for outcomes analysis., Results: A data mining search engine and an intelligent treatment plan navigator (ITPN) were developed and integrated with the ePR system. Evaluation was based on a data set of 39 PT patients and a hypothetical patient., Conclusions: The ePR system was able to facilitate the proton therapy workflow. The PT ePR system was feasible for prostate cancer patient treated with hypofractionation protocol in proton therapy. This ePR system improves efficiency in data collection and integration to facilitate outcomes analysis.

Purpose: Previous Monte Carlo and experimental studies involving secondary neutrons in proton therapy have employed a number of phantom materials that are designed to represent human tissue. In this study, the authors determined the suitability of common phantom materials for dosimetry of secondary neutrons, specifically for pediatric and intracranial proton therapy treatments., Methods: This was achieved through comparison of the absorbed dose and dose equivalent from neutrons generated within the phantom materials and various ICRP tissues. The phantom materials chosen for comparison were Lucite, liquid water, solid water, and A150 tissue equivalent plastic, These phantom materials were compared to brain, muscle, and adipose tissues., Results: The magnitude of the doses observed were smaller than those reported in previous experimental and Monte Carlo studies, which incorporated neutrons generated in the treatment head. The results show that for both neutron absorbed dose and dose equivalent, no single phantom material gives agreement with tissue within 5% at all the points considered. Solid water gave the smallest mean variation with the tissues out of field where neutrons are the primary contributor to the total dose., Conclusions: Of the phantom materials considered, solid water shows best agreement with tissues out of field.

Purpose: Microdosimetric measurements were performed at Massachusetts General Hospital, Boston, MA, to assess the dose equivalent external to passively delivered proton fields for various clinical treatment scenarios., Methods and Materials: Treatment fields evaluated included a prostate cancer field, cranial and spinal medulloblastoma fields, ocular melanoma field, and a field for an intracranial stereotactic treatment. Measurements were completed with patient-specific configurations of clinically relevant treatment settings using a silicon-on-insulator microdosimeter placed on the surface of and at various depths within a homogeneous Lucite phantom. The dose equivalent and average quality factor were assessed as a function of both lateral displacement from the treatment field edge and distance downstream of the beam's distal edge., Results: Dose-equivalent value range was 8.3-0.3 mSv/Gy (2.5-60-cm lateral displacement) for a typical prostate cancer field, 10.8-0.58 mSv/Gy (2.5-40-cm lateral displacement) for the cranial medulloblastoma field, 2.5-0.58 mSv/Gy (5-20-cm lateral displacement) for the spinal medulloblastoma field, and 0.5-0.08 mSv/Gy (2.5-10-cm lateral displacement) for the ocular melanoma field. Measurements of external field dose equivalent for the stereotactic field case showed differences as high as 50% depending on the modality of beam collimation. Average quality factors derived from this work ranged from 2-7, with the value dependent on the position within the phantom in relation to the primary beam., Conclusions: This work provides a valuable and clinically relevant comparison of the external field dose equivalents for various passively scattered proton treatment fields.

Measurements were performed to assess the dose equivalent outside a primary proton treatment field, using a silicon-on-insulator (SOI) microdosimeter. The SOI microdosimeter was placed on the surface of an anthropomorphic phantom and dose equivalents were determined as a function of lateral distance from a typical passively scattered and modulated prostate treatment field. Measurements were also completed within a polystyrene plate phantom as a function of depth for a distance of 5 cm from the field edge, as function of lateral distance from field edge at two different depths, and as a function of distance from the distal edge on the central beam axis. The dose equivalent at the surface of the anthropomorphic phantom decreases from 3.9 to 0.18 mSv/Gy when the lateral distance from the proton field edge increases from 2.5 to 60 cm. Measurements along the proton depth dose distribution at a constant distance of 5 cm from the primary field edge indicate a decrease in dose equivalent as a function of depth, with a 38% decrease relative to the surface dose at a depth of 5 cm in polystyrene. Measurements completed as a function of lateral distance from the primary field at two separate depths within polystyrene illustrate a convergence of the dose equivalent at approximately 20 cm from the primary field edge. Past the distal edge of the spread-out Bragg peak dose equivalents decrease exponentially for increasing distance, with an initial value of 1.6 mSv/Gy at 0.6 cm from the distal edge. Silicon microdosimetry measurements were also compared with published results obtained utilizing different measurement techniques. This study demonstrates the applicability of SOI microdosimetry in determining the dose equivalent outside proton treatment fields, and provides valuable information on the dose equivalent both at the surface and at depth experienced by prostate cancer patients treated with protons.

The problem of the lateral containment of a 160 MeV proton beam interacting with a medium simulating biological material was studied. The confining action of a longitudinal magnetic field was calculated by means of Monte Carlo simulation, where scattering and motion in the magnetic field were treated simultaneously. Appreciable compression of the beam could only be achieved using fields of the order at least 50 T, much beyond the realm of practical feasibility.

Background: This review article will focus on clinical results and limitations of proton beam irradiation. Possible technological, biological and medical perspectives will be addressed., Patients and Methods: A total of 911 patients with limited stage prostate cancer were treated with proton beam irradiation at Loma Linda University between 1991 and 1996. Endpoints of this evaluation were biochemically no evidence of disease survival (bNED) as well as acute and late treatment-related toxicity., Results: The bNED survival rate was 82% at 5 years. Among 870 patients evaluable for late toxicity the following late effects were observed: Grade 3/4: 0%, Grade 2 rectal: 3.5% and bladder: 5.4%., Conclusions: Despite relatively short follow-up times it seems justified to conclude that proton beam irradiation of prostate cancer can improve bNED rates by 10% and decrease Grade 2 late effects by more than 10%. There were no Grade 3 and 4 late effects.

Background: The role and optimum dose of radiation to eradicate prostate cancer continues to be evaluated. Protons offer an opportunity to increase the radiation dose to the prostate while minimizing treatment toxicity., Methods: Six hundred forty-three patients with localized prostate cancer were treated with protons, with or without photons. Treatments were planned with a 3D planning system; patients received 74-75 CGE (Cobalt Gray Equivalent) at 1.8-2.0 CGE per fraction. Patients were evaluated for response to therapy and treatment-related toxicity., Results: The overall clinical disease-free survival rate was 89% at 5 years. When post-treatment prostate-specific antigen (PSA) was used as an endpoint for disease control, the 4.5-year disease-free survival rate was 100% for patients with an initial PSA of < 4.0 ng/ml, and 89%, 72%, and 53% for patients with initial PSA levels of 4.1-10.0, 10.1-20.0, and > 20.0, respectively. Patients in whom the post-treatment PSA nadir was below 0.5 ng/ml did significantly better than those whose nadir values were between 0.51-1.0 or > 1.0 ng/ml: the corresponding 5-year disease-free survival rates were 91%, 79%, and 40%, respectively. Minimal radiation proctitis was seen in 21% of patients; toxicity of greater severity was seen in less than 1%., Conclusion: Proton therapy to 74-75 CGE produced minimal treatment-related toxicity and excellent PSA normalization and disease-free survival in patients with low initial PSA levels. A prospective randomized dose-escalation trial is now underway to help define the optimum dose of radiation for patients with early stage prostate cancer.

Purpose: Accelerated protons were used in an attempt to limit treatment-related morbidity in children with tumors in or near the developing brain, by reducing the integral dose to adjacent normal tissues., Methods and Materials: Children treated with protons at Loma Linda University Medical Center between August 1991 and December 1994 were analyzed retrospectively. Twenty-eight children, aged 1 to 18 years, were identified as at risk for brain injury from treatment. Medical records, physical examinations, and correspondence with patients, their parents, and referring physicians were analyzed. The investigators tabulated post-treatment changes in pre-treatment signs and symptoms and made judgments as to whether improvement, no change, or worsening related to disease or treatment had supervened. Magnetic resonance images were correlated with clinical findings and radiographic impressions were tabulated., Results: Follow-up ranged from 7 to 49 months (median 25 months). Four instances of treatment-related morbidity were identified. Forty-one instances of site-specific, disease-related morbidity were identified: 15 improved or resolved and 26 remained unchanged after treatment. Four patients had radiographic evidence of local failure. Three of these patients, including two with high-grade glioma, have died., Conclusion: Early treatment-related morbidity associated with proton therapy is low. Tumor progression remains a problem when treating certain histologies such as high-grade glioma. Escalating the dose delivered to target volumes may benefit children with tumors associated with poor rates of local control. Long-term follow-up, including neurocognitive testing, is in progress to assess integral-dose effects on cognitive, behavioral and developmental outcomes in children with cranial tumors.

Purpose: A study was developed to evaluate the use of combined photons and protons for the treatment of locally advanced carcinoma of the prostate. This report is a preliminary assessment of treatment-related morbidity and tumor response., Methods and Materials: One hundred and six patients in stages T2b (B2), T2c (B2), and T3 (C) were treated with 45 Gy photon-beam irradiation to the pelvis and an additional 30 Cobalt Gray Equivalent (CGE) to the prostate with 250-MeV protons, yielding a total prostate dose of 75 CGE in 40 fractions. Median follow-up time was 20.2 months (range: 10-30 months). Toxicity was scored according to the Radiation Therapy Oncology Group (RTOG) grading system; local control was evaluated by serial digital rectal examination (DRE) and prostate specific antigen (PSA) measurements., Results: Morbidity evaluation was available on 104 patients. The actuarial 2-year rate of Grade 1 or 2 late morbidity was 12% (8% rectal, 4% urinary). No patients demonstrated Grade 3 or 4 late morbidity. Treatment response was evaluated on 100 patients with elevated pretreatment serum PSA levels. The actuarial 2-year rate of PSA normalization was 96%, 97%, and 63% for pretreatment PSAs of > 4-10, > 10-20, and > 20, respectively. The 13 patients with rising PSA demonstrated local recurrence (3 patients), distant metastasis (8 patients), or no evidence of disease except increasing PSA (2 patients)., Conclusions: The low incidence of side effects, despite the tumor dose of 75 CGE, demonstrates that conformal protons can deliver higher doses of radiation to target tissues without increasing complications to surrounding normal tissues. The initial tumor response, as assessed by the high actuarial rate of normalization with pretreatment PSA < or = 20, and the low rate of recurrences within the treatment field (2.8%), are encouraging.

Purpose: Fluence‐modulated proton computed tomography (FMpCT) using pencil beam scanning aims at achieving task‐specific image noise distributions by modulating the imaging proton fluence spot‐by‐spot based on an object‐specific noise model. In this work, we present a method for fluence field optimization and investigate its performance in dose reduction for various phantoms and image variance targets. Methods: The proposed method uses Monte Carlo simulations of a proton CT (pCT) prototype scanner to estimate expected variance levels at uniform fluence. Using an iterative approach, we calculate a stack of target variance projections that are required to achieve the prescribed image variance, assuming a reconstruction using filtered backprojection. By fitting a pencil beam model to the ratio of uniform fluence variance and target variance, relative weights for each pencil beam can be calculated. The quality of the resulting fluence modulations is evaluated by scoring imaging doses and comparing them to those at uniform fluence, as well as evaluating conformity of the achieved variance with the prescription. For three different phantoms, we prescribed constant image variance as well as two regions‐of‐interest (ROI) imaging tasks with inhomogeneous image variance. The shape of the ROIs followed typical beam profiles for proton therapy. Results: Prescription of constant image variance resulted in a dose reduction of 8.9% for a homogeneous water phantom compared to a uniform fluence scan at equal peak variance level. For a more heterogeneous head phantom, dose reduction increased to 16.0% for the same task. Prescribing two different ROIs resulted in dose reductions between 25.7% and 40.5% outside of the ROI at equal peak variance levels inside the ROI. Imaging doses inside the ROI were increased by 9.2% to 19.2% compared to the uniform fluence scan, but can be neglected assuming that the ROI agrees with the therapeutic dose region. Agreement of resulting variance maps with the prescriptions was satisfactory. Conclusions: We developed a method for fluence field optimization based on a noise model for a real scanner used in pCT. We demonstrated that it can achieve prescribed image variance targets. A uniform fluence field was shown not to be dose optimal and dose reductions achievable with the proposed method for FMpCT were considerable, opening an interesting perspective for image guidance and adaptive therapy. [ABSTRACT FROM AUTHOR]

Purpose: Proton computed tomography (pCT) will enable accurate prediction of proton and ion range in a patient while providing the benefit of lower radiation exposure than in x-ray CT. The accuracy of the range prediction is essential for treatment planning in proton or ion therapy and depends upon the detector used to evaluate the water-equivalent path length (WEPL) of a proton passing through the object. A novel approach is presented for an inexpensive WEPL detector for pCT and proton radiography. Methods: A novel multistage detector with an aperture of 10?Ñ37.5 cm was designed to optimize the accuracy of the WEPL measurements while simplifying detector construction and the performance requirements of its components. The design of the five-stage detector was optimized through simulations based on the GEANT4 detector simulation toolkit, and the fabricated prototype was calibrated in water-equivalent millimeters with 200 MeV protons in the research beam line of the clinical proton synchrotron at Loma Linda University Medical Center. A special polystyrene step phantom was designed and built to speed up and simplify the calibration procedure. The calibrated five-stage detector was tested in the 200 MeV proton beam as part of the pCT head scanner, using a water phantom and polystyrene slabs to verify the WEPL reconstruction accuracy. Results: The beam-test results demonstrated excellent performance of the new detector, in good agreement with the simulation results. The WEPL measurement accuracy is about 3.0 mm per proton in the 0-260 mm WEPL range required for a pCT head scan with a 200 MeV proton beam. Conclusions: The new multistage design approach to WEPL measurements for proton CT and radiography has been prototyped and tested. The test results show that the design is competitive with much more expensive calorimeter and range-counter designs. [ABSTRACT FROM AUTHOR]

Proton radiography has applications in patient alignment and verification procedures for proton beam radiation therapy. In this paper, we report an experiment which used 200 MeV protons to generate proton energy-loss and scattering radiographs of a hand phantom. The experiment used the first-generation proton computed tomography (CT) scanner prototype, which was installed on the research beam line of the clinical proton synchrotron at Loma Linda University Medical Center. It was found that while both radiographs displayed anatomical details of the hand phantom, the energy-loss radiograph had a noticeably higher resolution. Nonetheless, scattering radiography may yield more contrast between soft and bone tissue than energy-loss radiography, however, this requires further study. This study contributes to the optimization of the performance of the next-generation of clinical proton CT scanners. Furthermore, it demonstrates the potential of proton imaging (proton radiography and CT), which is now within reach of becoming available as a new, potentially low-dose medical imaging modality. [ABSTRACT FROM AUTHOR]

Poster: Physics track: Intra-fraction motion management PO-1615: Detection and analysis of scattered protons for verification of FLASH lung tumor proton therapy M. Garbacz, R. Schulte, V. Bashkirov, M. Gao, M. Pankuch, C. Sarosiek, R.P. Johnson, J. Ramos Mendez, A. Rucinski, P. Olko. [Extracted from the article]