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.

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.

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.

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.

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.

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.

Fluence correction factors for graphite calorimetry in a low-energy clinical proton beam: I. Analytical and Monte Carlo simulations.

The conversion of absorbed dose-to-graphite in a graphite phantom to absorbed dose-to-water in a water phantom is performed by water to graphite stopping power ratios. If, however, the charged particle fluence is not equal at equivalent depths in graphite and water, a fluence correction factor, kfl, is required as well. This is particularly relevant to the derivation of absorbed dose-to-water, the quantity of interest in radiotherapy, from a measurement of absorbed dose-to-graphite obtained with a graphite calorimeter. In this work, fluence correction factors for the conversion from dose-to-graphite in a graphite phantom to dose-to-water in a water phantom for 60 MeV mono-energetic protons were calculated using an analytical model and five different Monte Carlo codes (Geant4, FLUKA, MCNPX, SHIELD-HIT and McPTRAN.MEDIA). In general the fluence correction factors are found to be close to unity and the analytical and Monte Carlo codes give consistent values when considering the differences in secondary particle transport. When considering only protons the fluence correction factors are unity at the surface and increase with depth by 0.5% to 1.5% depending on the code. When the fluence of all charged particles is considered, the fluence correction factor is about 0.5% lower than unity at shallow depths predominantly due to the contributions from alpha particles and increases to values above unity near the Bragg peak. Fluence correction factors directly derived from the fluence distributions differential in energy at equivalent depths in water and graphite can be described by kfl = 0.9964 + 0.0024·zw-eq with a relative standard uncertainty of 0.2%. Fluence correction factors derived from a ratio of calculated doses at equivalent depths in water and graphite can be described by kfl = 0.9947 + 0.0024·zw-eq with a relative standard uncertainty of 0.3%. These results are of direct relevance to graphite calorimetry in low-energy protons but given that the fluence correction factor is almost solely influenced by non-elastic nuclear interactions the results are also relevant for plastic phantoms that consist of carbon, oxygen and hydrogen atoms as well as for soft tissues.

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.

Water equivalence of some plastic-water phantom materials for clinical proton beam dosimetry.

Plastic-water phantom materials are not exactly water equivalent since they have a different elemental composition and different interaction cross sections for protons than water. Several studies of the water equivalence of plastic-water phantom materials have been reported for photon and electron beams, but none for clinical proton beams. In proton beams, the difference between non-elastic nuclear interactions in plastic-water phantom materials compared to those in water should be considered. In this work, the water equivalence of Plastic Water® (PW)1, Plastic Water® Diagnostic Therapy (PWDT)1 and solid water (WT1)2 phantoms was studied for clinical proton energies of 60 MeV and 200 MeV. This was done by evaluating the fluence correction factor at equivalent depths; first with respect to water and then with respect to graphite by experiment and Monte Carlo (MC) simulations using FLUKA. MC simulations showed that the fluence correction with respect to water was less than 0.5% up to the entire penetration depth of the protons at 60 MeV and less than 1% at 200 MeV up to 20 cm depth for PWDT, PW and WT1. With respect to graphite the fluence correction was about 0.5% for 60 MeV and about 4% for 200 MeV. The experimental results for modulated and un-modulated 60 MeV proton beams showed good agreement with the MC simulated fluence correction factors with respect to graphite deviating less than 1% from unity for the three plastic-water phantoms.

SU-E-T-118: Characterization of EBT3 Films in Photon and Proton Beams.

PURPOSE: To measure the calibration curves of EBT3 dosimetry films in photon and proton beams and to quantify the related uncertainties from one beam type to another. METHODS: EBT3 Gafchromic films have similar properties than EBT2 with a symmetric construction and a matte polyester substrate to prevent Newton's ring artefacts. Films from a same batch were exposed in three different beam qualities, an Elekta SL25 6 MV photon beam, a 100 MeV 5×5cm2 proton beam delivered by pencil-beam scanning dedicated system from IBA and a 60 MeV fixed proton beam (2.5cm in diameter) at Clatterbridge Center for Oncology (CCO), UK. The films were read using an EPSON 10000 XL/PRO scanner. Film calibration curves were acquired for all modalities within a range of 0.05 to 20 Gy. Influence of increasing linear-energy transfer (LET) on film response was investigated by comparing dose measured by EBT3 to a silicon diode detector in depth for a fully-modulated beam using the CCO beam line (homogeneous dose with distal end at 3.1cm in water). A comprehensive uncertainty budget (reproducibility, uniformity'¦) was estimated on films irradiated by Elekta SL25. RESULTS: The main source of uncertainty was the non-uniformity of the scanner response. By placing all the irradiated films at the center of the scanner, the uncertainty could be reduced from 5.8% to 1.9% (1 sigma). For all beams and energies, the calibration curves were matched within uncertainties. Along the fully-modulated depth dose curve, diode and EBT3 measurement were in a 4% agreement point-to-point, indicating films weak dependence with LET. CONCLUSIONS: The weak influence of LET, beam type and energy on film response as well as its small uncertainty make EBT3 suitable for relative dosimetry and a promising candidate for measuring correction factors (quality, recombination,'¦) for reference dosimetry with ion chambers of non-standard beams (e.g pencil-beam scanning proton-therapy). â€Å“This work is supported by the Walloon Region under the project name InVivoIGT, convention number 1017266.â€.

SU-E-T-146: Reference Dosimetry for Protons and Light-Ion Beams Based on Graphite Calorimetry.

PURPOSE: The IAEA TRS-398 code of practice can be applied for the measurement of absorbed dose to water under reference conditions with an ionization chamber. For protons, the combined relative standard uncertainty on those measurements is less than 2% while for light-ion beams, it is considerably larger, i.e. 3.2%, mainly due to the higher uncertainty contributions for the water to air stopping power ration and the W air-value on the beam quality correction factors kQ,Q0 . To decrease this uncertainty, a quantification of kQ,Q0 is proposed using a primary standard level graphite calorimeter. This work includes numerical and experimental determinations of dose conversion factors to derive dose to water from graphite calorimetry. It also reports on the first experimental data obtained with the graphite calorimeter in proton, alpha and carbon ion beams. METHODS: Firstly, the dose conversion has been calculated with by Geant4 Monte-Carlo simulations through the determination of the water to graphite stopping power ratio and the fluence correction factor. The latter factor was also derived by comparison of measured ionization curves in graphite and water. Secondly, kQ,Q0 was obtained by comparison of the dose response of ionization chambers with that of the calorimeter. RESULTS: Stopping power ratios are found to vary by no more than 0.35% up to the Bragg peak, while fluence correction factors are shown to increase slightly above unity close to the Bragg peak. The comparison of the calorimeter with ionization chambers is currently under analysis. For the modulated proton beam, preliminary results on W air confirm the value recommended in TRS-398. Data in both the non-modulated proton and light-ion beams indicate higher values but further investigation of heat loss corrections is needed. CONCLUSIONS: The application of graphite calorimetry to proton, alpha and carbon ion beams has been demonstrated successfully. Other experimental campaigns will be held in 2012. This work is supported by the BioWin program of the Wallon Government.

A preliminary analysis of LET effects in the dosimetry of proton beams using PRESAGE and optical CT.

PRESAGE is a solid dosimeter based on a clear polyurethane matrix doped with radiochromic components (leuco dyes). On exposure to ionizing radiation a colour change is generated in the dosimeter, and hence an optical absorption or optical density change that can be read out by optical CT. The main focus of present investigations has been to investigate the possible LET dependence of PRESAGE to the dose deposited at the Bragg maxima using proton beam absorbed dose measurements, and the linearity of response of the dosimeter. Proton irradiations were performed using the proton beam facility at the Douglas Cyclotron, Clatterbridge Centre for Oncology (CCO) using a configuration that approximates the one routinely used in treatment of patients with ocular tumours. The samples were irradiated with both monoenergetic and modulated proton beams. Optical tomography measurements were carried out with our in-house CCD-based optical-CT system. Initial results for monoenergetic beams show that in PRESAGE the measured ratio of the Bragg peak dose to entrance dose is approximately 2:1 whereas the true value measured at CCO is approximately 5:1. For range-modulated proton beams, the absorbed dose close to the end of the proton range, i.e. at the Bragg peak, is underestimated by approximately 20% compared to the corresponding diode measurement. Further investigations are necessary to understand and quantify the effect of LET on PRESAGE, and to measure the uncertainties related to our optical CT.

Monte Carlo simulation and polymer gel dosimetry of 60 MeV clinical proton beams for the treatment of ocular tumours.

Monte Carlo (MCNPX) simulations of a clinical proton beam-line under a range of beam conditions have been compared with MR analysis of irradiated polymer gel (BANG-1). Gel results were found to under-estimate the height of the full energy Bragg peak relative to simulation by the order of 30%, due to increased LET in this region, which has been reported elsewhere. Comparison of narrow-beam lateral profiles suggests a slight over-prediction of lateral proton scatter in MCNPX, which has been reported previously.

Protontherapy of eye tumours in the UK: a review of treatment at Clatterbridge.

The Scanditronix MC-60 PF cyclotron at Clatterbridge was commissioned in 1984 for fast neutrontherapy trials. It also produced a 60.0 MeV clinical beam suitable for treating ocular tumours with a maximum penetration of 31 mm (water) and a 0.9 mm fall-off. An additional treatment room was built with an ocular beamline constructed in-house. The first group of eye patients was treated in June 1989, making this the first hospital-based proton facility. More than 1700 eye patients have been treated by the only UK proton service.

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.

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.