Proton beam radiotherapy for choroidal and ciliary body melanoma in the UK-national audit of referral patterns of 1084 cases.

INTRODUCTION: Proton beam therapy has been utilised for the treatment of uveal melanoma in the UK for over 30 years, undertaken under a single centre. In the UK, all ocular tumours are treated at one of four centres. We aimed to understand the variation in referral patterns to the UK proton service, capturing all uveal melanoma patients treated with this modality. METHODS: Retrospective analysis of data regarding all patients treated at the Clatterbridge Proton service between January 2004 and December 2014. RESULTS: A total of 1084 patients with uveal melanoma were treated. The mean age was 57 years (range 9-90 years), basal diameter of 11.5 mm (range 2.0-23.4 mm) and tumour thickness of 3.9 mm (range 0.1-15.4 mm). The majority were TNM stage I (39%) or II (36%). The distance to the optic nerve varied from 0 to 24.5 mm with 148 (14%) of patients having ciliary body involvement. There were variations in the phenotypic characteristic of the tumours treated with protons from different centres, with London referring predominantly small tumours at the posterior pole, Glasgow referring large tumours often at the ciliary body and Liverpool sending a mix of these groups. DISCUSSION: In the UK, common indications for the use of proton treatment in uveal melanoma include small tumours in the posterior pole poorly accessible for plaque treatment (adjacent to the disc), tumours at the posterior pole affecting the fovea and large anterior tumours traditionally too large for brachytherapy. This is the first UK-wide audit enabling the capture of all patients treated at the single proton centre.

Application of a portable primary standard level graphite calorimeter for absolute dosimetry in a clinical low-energy passively scattered proton beam.

Objective. A calibration service based on a primary standard calorimeter for the direct determination of absorbed dose for proton beams does not exist. A new Code of Practice (CoP) for reference dosimetry of proton beams is being developed by a working party of the UK Institute of Physics and Engineering in Medicine (IPEM), which will recommend that ionisation chambers are calibrated directly in their clinical beams against the proposed Primary Standard Proton Calorimeter (PSPC) developed at the National Physical Laboratory (NPL). The aim of this work is to report on the use of the NPL PSPC to directly calibrate ionisation chambers in a low-energy passively scattered proton beam following recommendations of the upcoming IPEM CoP.Approach. A comparison between the dose derived using the proposed IPEM CoP and the IAEA TRS-398 protocol was performed, andkQvalues were determined experimentally for three types of chambers. In total, 9 plane-parallel and 3 cylindrical chambers were calibrated using the two protocols for two separate visits.Main results. The ratio of absorbed dose to water obtained with the PSPC and with ionisation chambers applying TRS-398 varied between 0.98 and 1.00, depending on the chamber type. The new procedure based on the PSPC provides a significant improvement in uncertainty where absorbed dose to water measured with a user chamber is reported with an uncertainty of 0.9% (1σ), whereas the TRS-398 protocol reports an uncertainty of 2.0% and 2.3% (1σ) for cylindrical and plane-parallel chambers, respectively. ThekQvalues found agree within uncertainties with those from TRS-398 and Monte Carlo calculations.Significance. The establishment of a primary standard calorimeter for the determination of absorbed dose in proton beams combined with the introduction of the associated calibration service following the IPEM recommendations will reduce the uncertainty and improve consistency in the dose delivered to patients.

A high-resolution anthropomorphic voxel-based tomographic phantom for proton therapy of the eye.

Proton therapy is increasingly used in medical treatments for cancer patients due to the sharp dose conformity offered by the characteristic Bragg peak. Proton beam interactions with the eye will be simulated using the MCNPX Monte Carlo code and available nuclear cross-section data to calculate the dose distribution in the eye gel and surrounding organs. A high-resolution eye model will be employed using a 3D geometrical voxel-based anthropomorphic head phantom obtained from the Visible Human Project (female data). Manual segmentation of the eye, carried out by the Medical Physics group at the University of Surrey resulted in 15 identified structures. This work emphasizes the use of a realistic phantom for accurately predicting dose deposition by protons.

Evaluation of the water-equivalence of plastic materials in low- and high-energy clinical proton beams.

The aim of this work was to evaluate the water-equivalence of new trial plastics designed specifically for light-ion beam dosimetry as well as commercially available plastics in clinical proton beams. The water-equivalence of materials was tested by computing a plastic-to-water conversion factor, [Formula: see text]. Trial materials were characterized experimentally in 60 MeV and 226 MeV un-modulated proton beams and the results were compared with Monte Carlo simulations using the FLUKA code. For the high-energy beam, a comparison between the trial plastics and various commercial plastics was also performed using FLUKA and Geant4 Monte Carlo codes. Experimental information was obtained from laterally integrated depth-dose ionization chamber measurements in water, with and without plastic slabs with variable thicknesses in front of the water phantom. Fluence correction factors, [Formula: see text], between water and various materials were also derived using the Monte Carlo method. For the 60 MeV proton beam, [Formula: see text] and [Formula: see text] factors were within 1% from unity for all trial plastics. For the 226 MeV proton beam, experimental [Formula: see text] values deviated from unity by a maximum of about 1% for the three trial plastics and experimental results showed no advantage regarding which of the plastics was the most equivalent to water. Different magnitudes of corrections were found between Geant4 and FLUKA for the various materials due mainly to the use of different nonelastic nuclear data. Nevertheless, for the 226 MeV proton beam, [Formula: see text] correction factors were within 2% from unity for all the materials. Considering the results from the two Monte Carlo codes, PMMA and trial plastic #3 had the smallest [Formula: see text] values, where maximum deviations from unity were 1%, however, PMMA range differed by 16% from that of water. Overall, [Formula: see text] factors were deviating more from unity than [Formula: see text] factors and could amount to a few percent for some materials.

Development and application of a water calorimeter for the absolute dosimetry of short-range particle beams.

In this work, we describe a new design of water calorimeter built to measure absorbed dose in non-standard radiation fields with reference depths in the range of 6-20 mm, and its initial testing in clinical electron and proton beams. A functioning calorimeter prototype with a total water equivalent thickness of less than 30 mm was constructed in-house and used to obtain measurements in clinical accelerator-based 6 MeV and 8 MeV electron beams and cyclotron-based 60 MeV monoenergetic and modulated proton beams. Corrections for the conductive heat transfer due to dose gradients and non-water materials was also accounted for using a commercial finite element method software package. Absorbed dose to water was measured with an associated type A standard uncertainty of approximately 0.4% and 0.2% for the electron and proton beam experiments, respectively. In terms of thermal stability, drifts were on the order of a couple of hundred µK min-1, with a short-term variation of 5-10 µK. Heat transfer correction factors ranged between 1.021 and 1.049. The overall combined standard uncertainty on the absorbed dose to water was estimated to be 0.6% for the 6 MeV and 8 MeV electron beams, as well as for the 60 MeV monoenergetic protons, and 0.7% for the modulated 60 MeV proton beam. This study establishes the feasibility of developing an absorbed dose transfer standard for short-range clinical electrons and protons and forms the basis for a transportable dose standard for direct calibration of ionization chambers in the user's beam. The largest contributions to the combined standard uncertainty were the positioning (⩽0.5%) and the correction due to conductive heat transfer (⩽0.4%). This is the first time that water calorimetry has been used in such a low energy proton beam.

A new silicon tracker for proton imaging and dosimetry.

For many years, silicon micro-strip detectors have been successfully used as tracking detectors for particle and nuclear physics experiments. A new application of this technology is to the field of particle therapy where radiotherapy is carried out by use of charged particles such as protons or carbon ions. Such a treatment has been shown to have advantages over standard x-ray radiotherapy and as a result of this, many new centres offering particle therapy are currently under construction around the world today. The Proton Radiotherapy, Verification and Dosimetry Applications (PRaVDA) consortium are developing instrumentation for particle therapy based upon technology from high-energy physics. The characteristics of a new silicon micro-strip tracker for particle therapy will be presented. The array uses specifically designed, large area sensors with technology choices that follow closely those taken for the ATLAS experiment at the HL-LHC. These detectors will be arranged into four units each with three layers in an x-u-v configuration to be suitable for fast proton tracking with minimal ambiguities. The sensors will form a tracker capable of tracing the path of ~200 MeV protons entering and exiting a patient allowing a new mode of imaging known as proton computed tomography (pCT). This will aid the accurate delivery of treatment doses and in addition, the tracker will also be used to monitor the beam profile and total dose delivered during the high fluences used for treatment. We present here details of the design, construction and assembly of one of the four units that will make up the complete tracker along with its characterisation using radiation tests carried out using a 90Sr source in the laboratory and a 60 MeV proton beam at the Clatterbridge Cancer Centre.

An approach to 3D dose mapping using Gafchromic film.

The tissue equivalent composition of the Gafchromic films makes them particularly suitable for the mapping of 2D and 3D treatment fields. This paper presents the results obtained using MD-55 film for the verification of real radiotherapy treatments through proton beam irradiation of suitable phantoms at the Clatterbridge Centre for Oncology (CCO) in Bebington (UK). After exposure, the variation in optical density of the films was measured using a CCD100 Microdensitometer (source at 665 nm). Holes of calibrated diameter, made during the assembly phase of the phantom, are identified by the MIRA software, used for data analysis, and allow the rendering of the films. The surface dose distributions were obtained from the variation in optical density of each of the films making up the phantom. Their elaboration to duplicate their position within the phantom, performed by 3D-doctor software, allows the volumetric reconstruction of the dose distribution.

Outcomes of treatment with stereotactic radiosurgery or proton beam therapy for choroidal melanoma.

AIM: To present our experience of the use of stereotactic radiosurgery and proton beam therapy to treat posterior uveal melanoma over a 10 year period. METHODS AND MATERIALS: Case notes of patients treated with stereotactic radiosurgery (SRS), or Proton beam therapy (PBT) for posterior uveal melanoma were reviewed. Data collected included visual acuity at presentation and final review, local control rates, globe retention and complications. We analysed post-operative visual outcomes and if visual outcomes varied with proximity to the optic nerve or fovea. RESULTS: 191 patients were included in the study; 85 and 106 patients received Stereotactic radiosurgery and Proton beam therapy, respectively. Mean follow up period was 39 months in the SRS group and 34 months in the PBT group. Both treatments achieved excellent local control rates with eye retention in 98% of the SRS group and 95% in the PBT group. The stereotactic radiosurgery group showed a poorer visual prognosis with 65% losing more than 3 lines of Snellen acuity compared to 45% in the PBT group. 33% of the SRS group and 54% of proton beam patients had a visual acuity of 6/60 or better. CONCLUSIONS: Stereotactic radiosurgery and proton beam therapy are effective treatments for larger choroidal melanomas or tumours unsuitable for plaque radiotherapy. Our results suggest that patients treated with proton beam therapy retain better vision post-operatively; however, possible confounding factors include age, tumour location and systemic co-morbidities. These factors as well as the patient's preference should be considered when deciding between these two therapies.

Proton tracking for medical imaging and dosimetry.

For many years, silicon micro-strip detectors have been successfully used as tracking detectors for particle and nuclear physics experiments. A new application of this technology is to the field of particle therapy, where radiotherapy is carried out by use of charged particles such as protons or carbon ions. Such a treatment has been shown to have advantages over standard x-ray radiotherapy and as a result of this, many new centres offering particle therapy are currently under construction - including two in the U.K.. The characteristics of a new silicon micro-strip detector based system for this application will be presented. The array uses specifically designed large area sensors in several stations in an x-u-v co-ordinate configuration suitable for very fast proton tracking with minimal ambiguities. The sensors will form a tracker capable of giving information on the path of high energy protons entering and exiting a patient. This will allow proton computed tomography (pCT) to aid the accurate delivery of treatment dose with tuned beam profile and energy. The tracker will also be capable of proton counting and position measurement at the higher fluences and full range of energies used during treatment allowing monitoring of the beam profile and total dose. Results and initial characterisation of sensors will be presented along with details of the proposed readout electronics. Radiation tests and studies with different electronics at the Clatterbridge Cancer Centre and the higher energy proton therapy facility of iThemba LABS in South Africa will also be shown.

Proton dosimetry comparison involving ionometry and calorimetry.

A comparison of the absorbed dose to tissue determined by various ionization chambers, Faraday cups, and an A-150 plastic calorimeter was performed in the 200 MeV proton beam of Orsay, France. Four European proton-therapy centers (Clatterbridge, UK, Louvain la Neuve, Belgium, and Nice and Orsay, France) participated in the comparison. An agreement of better than 1% was observed in the absorbed dose to A-150 measured with the different chambers of the participating groups. The mean ratio of the absorbed dose to A-150 determined with the calorimeter to that determined by the different ionization chambers in the different irradiation conditions was found to be 0.952 +/- 0.007 [1 standard deviation (SD)] according to the code of practice used by all the participating centers, based on Janni's tables of stopping powers and a value of 35.2 J/Coulomb for (W(air)/e)p. A better agreement in the mean ratio calorimeter/chamber, 0.985 +/- 0.007 (1 SD) is observed when using the proton stopping power ratio values recently published by the International Commission on Radiation Units and Measurements in Report no. 49. The mean ratio of these doses determined in accordance with the American Association of Physicists in Medicine protocol and using the new recommended stopping power tables becomes 1.002 +/- 0.007 (1 SD). Two Faraday cups agree in measured charge to within 0.8%; however, the calculation of dose is underestimated by up to 17%; compared with ion chamber measurements and seems to be very sensitive to measurement conditions, particularly to the distance to the collimator.

Proton dosimetry intercomparison.

BACKGROUND AND PURPOSE: Methods for determining absorbed dose in clinical proton beams are based on dosimetry protocols provided by the AAPM and the ECHED. Both groups recommend the use of air-filled ionization chambers calibrated in terms of exposure or air kerma in a 60Co beam when a calorimeter or Faraday cup dosimeter is not available. The set of input data used in the AAPM and the ECHED protocols, especially proton stopping powers and w-value is different. In order to verify inter-institutional uniformity of proton beam calibration, the AAPM and the ECHED recommend periodic dosimetry intercomparisons. In this paper we report the results of an international proton dosimetry intercomparison which was held at Loma Linda University Medical Center. The goal of the intercomparison was two-fold: first, to estimate the consistency of absorbed dose delivered to patients among the participating facilities, and second, to evaluate the differences in absorbed dose determination due to differences in 60Co-based ionization chamber calibration protocols. MATERIALS AND METHODS: Thirteen institutions participated in an international proton dosimetry intercomparison. The measurements were performed in a 15-cm square field at a depth of 10 cm in both an unmodulated beam (nominal accelerator energy of 250 MeV) and a 6-cm modulated beam (nominal accelerator energy of 155 MeV), and also in a circular field of diameter 2.6 cm at a depth of 1.14 cm in a beam with 2.4 cm modulation (nominal accelerator energy of 100 MeV). RESULTS: The results of the intercomparison have shown that using ionization chambers with 60Co calibration factors traceable to standard laboratories, and institution-specific conversion factors and dose protocols, the absorbed dose specified to the patient would fall within 3% of the mean value. A single measurement using an ionization chamber with a proton chamber factor determined with a Faraday cup calibration differed from the mean by 8%. CONCLUSION: The adoption of a single ionization chamber dosimetry protocol and uniform conversion factors will establish agreement on proton absorbed dose to approximately 1.5%, consistent with that which has been observed in high-energy photon and electron dosimetry.

A correction method for diamond detector signal dependence with proton energy.

Small dosimeters as solid state detectors can be useful for the dosimetric characterization and periodic quality control of radiotherapy proton beams. The calibration of solid state detectors for proton beams is not a solved problem especially for ophthalmologic proton beams, where these detectors present a LET-dependent signal. In this work a PTW diamond detector has been selected because of its good signal reproducibility (0.3%) and stable response with accumulated dose. A method that takes into account the LET dependence of the diamond detector signal, at 62 MeV proton beam, is here proposed. In particular an empirical correction factor, kDD(Eo) (Rres), has been determined as a function of the residual range quality index, to correct the diamond detector signal for a proton beam of incident effective energy E0= 62 MeV. A dedicated software allows us to use the diamond detector as an on-line reference dosimeter, where an ionization chamber may be difficult to use, or for periodic quality control procedures. The article also reports a comparison between the signal dependence on proton energy of silicon, diamond, and radiochromic film detectors.

Predictive factors for the development of rubeosis following proton beam radiotherapy for uveal melanoma.

AIMS/BACKGROUND: Proton beam radiotherapy can effectively treat primary uveal melanomas of any size. Some patients, however, develop adverse late effects following treatment and the purpose of this study was to determine which factors give rise to a poor local outcome. METHODS: The hospital records from a first cohort of 127 patients treated by protons from 1989 to 1992 were reviewed retrospectively. The presence of rubeosis was selected as a measure of significant ocular damage. Split file analysis was performed with 73 cases forming a test group with the remaining 54 cases acting as a validation group. RESULTS: Large tumour size and the presence of retinal detachment were significant, independent risk factors for developing rubeosis for both the test and validation groups. These factors also predicted subsequent enucleation for uncontrolled ocular pain. Patients with tumours too large to plaque and with an associated retinal detachment had a 90% chance of developing rubeosis within 4 years of proton beam radiotherapy. CONCLUSIONS: Patients with a uveal melanoma too large for plaque therapy and an associated retinal detachment run a very high risk of developing rubeosis after proton beam radiotherapy and one third of individuals developing rubeosis required enucleation for pain even if local tumour control was satisfactory.

The measurement of silicon in a lung phantom--a comparison of two nuclear reactions for in vivo activation analysis.

The amount of silica in the human lung may be estimated by measurement of silicon using in vivo neutron activation analysis. A pulsed, fast neutron beam, produced with a 2 MV Van de Graaff generator using the 2H + 2H reaction, was used to irradiate a Si-doped chest phantom in order to determine minimum detection limits (MDL). Two 'in-beam' nuclear reactions on Si were studied; prompt fast neutron inelastic scatter 28Si (n,n' gamma)28Si reaction was measured during the beam burst and the slow neutron prompt capture reaction was measured between the fast neutron bursts. Although the latter reaction appeared less favourable due to neutron cross section and measurement efficiency considerations, it yielded an MDL of 1.8 g compared with 2.3 g for the 28Si(n,n' gamma)28Si reaction. A comparison was made with a 252Cf neutron irradiation system where a Si MDL of 6.3 g was obtained using the slow neutron capture reaction. The Van de Graaff system permits 'exposed' Si lung burdens to be measured but not normal levels. Improved measurement sensitivity may be achieved by reduction of high counting-rate losses and high background radiation.

Characteristics of silicon and diamond detectors in a 60 MeV proton beam.

The calibration factor variation for a PTW natural diamond detector and a Scanditronix p-type stereotactic silicon diode (designed for use in photon beams) was studied in the 10-59 MeV range. Irradiations were performed in a water phantom with the 60 MeV ocular therapy beam at the CCO (UK). The diamond detector showed a sensitivity increase with energy, underestimating the dose by about 18% at the Bragg peak, by 7% at the centre and by 17% at the distal end of the SOBP region. The silicon diode did not show any significant sensitivity change with energy. However, a decrease in response of 24% was observed for an accumulated dose of 300 Gy.

The 62 MeV proton beam for the treatment of ocular melanoma at Clatterbridge.

A second treatment room and beam line has been constructed at the Cyclotron Unit at Clatterbridge for the purpose of using 62 MeV protons for the treatment of ocular melanoma. A uniform beam is produced by a double foil scattering system. The initial Bragg peak is spread across the target volume by the use of beam modulators. These are rotating four-vaned stepped absorbers made from Perspex. Two beam lines can be configured with different positions of modulators and range limiters. The first has a maximum penetration of 31.9 +/- 0.2 mm in water and the second a penetration of 31.2 +/- 0.2 mm. The second configuration has the advantage of less variation in beam penumbra, with a typical value of 1.7 +/- 0.1 mm for the 90% to 10% decrement lines. The patients are treated with individually shaped collimators. Beam output varies by less than 2% over the range of collimator areas used. The resulting whole-body dose equivalent to patient has also been assessed. In the first three years of operation over 250 patients have been treated.

Modelling concepts of proton eye radiotherapy.

Information concerning the application of proton beams in radiotherapy of ocular tumours is provided using conventional website technology by a number of treatment facilities around the world. We hypothesized, however, that many of the key concepts would be better conveyed by an interactive computer model utilizing virtual reality technology. We describe the implementation, using Virtual Reality Modelling Language (VRML), of such a model, the Proton Therapy Concepts Demonstrator (PTCD). The World-Wide-Web-accessible PTCD is intended to provide information useful both to trainee and to qualified clinical staff and also to patients. A model was created of the radiotherapy room that was linked to an interactive model depicting a simple explanation of the process of proton eye radiotherapy. This model also allows the user to explore specific elements of the treatment planning and delivery process, such as beam collimation and range modulation. A further level of detail has been provided by a dynamic model demonstrating how a specific modulated dose distribution is achieved as the time integration of discrete modulated Bragg peaks. We believe this VR-based model has the potential of enabling users to gain more rapid insight into the proton therapy process. Its development as an educational tool is continuing, following feedback collected from clinical staff and patients.

2D and 3D dose distribution determination in proton beam radiotherapy with GafChromic film detectors.

This paper presents the results obtained using radiochromic (MD-55 GafChromic) film for the 2D and 3D dosimetric reconstruction of the dose delivered by a proton beam under the real conditions of a programme of radiotherapy treatment for ocular tumours. Standard microdensitometric measurements were used to determine the variation in film optical density (O.D.) vs dose. Calibration curves were obtained by least-square fitting of the experimental OD values using a second order polynomial. This allows conversion of O.D. to dose. With this procedure it was possible to determine the distribution of the dose delivered by the proton beam in a phantom composed of layers of GafChromic film, with high surface spatial resolution and, through sections, the complete mapping of the dose delivered to a volume subjected to irradiation, as in a course of radiotherapy treatment.

The physics of Cerenkov light production during proton therapy.

There is increasing interest in using Cerenkov emissions for quality assurance and in vivo dosimetry in photon and electron therapy. Here, we investigate the production of Cerenkov light during proton therapy and its potential applications in proton therapy. A primary proton beam does not have sufficient energy to generate Cerenkov emissions directly, but we have demonstrated two mechanisms by which such emissions may occur indirectly: (1) a fast component from fast electrons liberated by prompt gamma (99.13%) and neutron (0.87%) emission; and (2) a slow component from the decay of radioactive positron emitters. The fast component is linear with dose and doserate but carries little spatial information; the slow component is non-linear but may be localised. The properties of the two types of emission are explored using Monte Carlo modelling in GEANT4 with some experimental verification. We propose that Cerenkov emissions could contribute to the visual sensation reported by some patients undergoing proton therapy of the eye and we discuss the feasibility of some potential applications of Cerenkov imaging in proton therapy.

Evaluation of Gafchromic® EBT3 films characteristics in therapy photon, electron and proton beams.

PURPOSE: To evaluate the uncertainties and characteristics of radiochromic film-based dosimetry system using the EBT3 model Gafchromic(®) film in therapy photon, electron and proton beams. MATERIAL AND METHODS: EBT3 films were read using an EPSON Expression 10000XL/PRO scanner. They were irradiated in five beams, an Elekta SL25 6 MV and 18 MV photon beam, an IBA 100 MeV 5 × 5 cm(2) proton beam delivered by pencil-beam scanning, a 60 MeV fixed proton beam and an Elekta SL25 6 MeV electron beam. Reference dosimetry was performed using a FC65-G chamber (Elekta beam), a PPC05 (IBA beam) and both Markus 1916 and PPC40 Roos ion-chambers (60 MeV proton beam). Calibration curves of the radiochromic film dosimetry system were acquired and compared within a dose range of 0.4-10 Gy. An uncertainty budget was estimated on films irradiated by Elekta SL25 by measuring intra-film and inter-film reproducibility and uniformity; scanner uniformity and reproducibility; room light and film reading delay influences. RESULTS: The global uncertainty on acquired optical densities was within 0.55% and could be reduced to 0.1% by placing films consistently at the center of the scanner. For all beam types, the calibration curves are within uncertainties of measured dose and optical densities. The total uncertainties on calibration curve due to film reading and fitting were within 1.5% for photon and proton beams. For electrons, the uncertainty was within 2% for dose superior to 0.8 Gy. CONCLUSIONS: The low combined uncertainty observed and low beam and energy-dependence make EBT3 suitable for dosimetry in various applications.