Proton beam radiotherapy in the management of uveal melanoma: clinical experience in Scotland

<p>Aim: To evaluate proton-beam radiotherapy (PBRT) in the management of uveal melanoma in Scotland.</p> <p>Methods: A retrospective review was undertaken on all patients receiving PBRT for uveal melanoma (1994–2005). Data obtained included: gender, past ocular/medical history, age, presenting complaint(s), diagnosis, laterality, tumor location/ultrasound characteristics, visual acuity (VA) and intraocular pressure. At post-treatment reviews (3, 6, 12, and 24 months), the following data was obtained: VA, intraocular pressure, tumor appearance and ultrasound characteristics. Mean follow up was 38.8 months.</p> <p>Results: Seventy-six patients were included. Mean age was 64 years; male to female ratio was 1.1:1. Ninety-seven percent demonstrated initial treatment response; 87% had successful control of tumor growth. Mean pre-treatment tumor height was 6.2 mm v.s. 4.8 mm post-irradiation (p < 0.001). Pre-irradiation VA was <3/60 in 18.5% compared with 74% post-irradiation (p < 0.0001). There was a statistically significant association between adverse events (enucleation, metastasis) and greater maximal basal tumor diameter. Eighteen eyes were enucleated. The median survival time was estimated to be 54 months.</p> <p>Conclusion: In our experience, PBRT is a precise, reliable and effective treatment in the management of large, and previously treated uveal melanomas. It prevents enucleation in the majority at short term follow-up.</p&gt

Social Aspects of New Technologies - the CCTV and Biometric (Framing Privacy and Data Protection) in the Case of Poland

The purpose of this paper is to review the institution responsible for the protection of personal data within the European Union and national example - Polish as a country representing the new Member States. The analysis of institutional system - providing legal security of communication and information institutions, companies and citizens against the dangers arising from the ongoing development of innovative new technologies in the European Union and Poland. This article is an attempt to analyze the possibility of using security systems and Biometry CTTV in Poland in terms of legislation. The results of the analysis indicate that, in terms of institutions Poland did not do badly in relation to the risks arising from the implementation of technology. The situation is not as good when it comes to the awareness of citizens and small businesses. This requires that facilitate greater access to free security software companies from data leakage or uncontrolled cyber-terrorist attacks. With regard to the use of security systems, CCTV and biometrics, Poland in legal terms is still early in the process of adapting to EU Directive. The continuous development of technology should force the legislature to establish clear standards and regulations for the application of CCTV technology and biometrics, as it is of great importance in ensuring the fundamental rights and freedoms of every citizen of the Polish Republic.Wyniki analizy wskazują, że pod względem instytucji Polska nie wypada źle w odniesieniu do zagrożeń wynikających z wdrożenia technologii. Sytuacja nie jest tak dobra, jeśli chodzi o świadomość obywateli i mniejszych firm. Wymaga to ułatwiania szerszego dostępu do darmowych programów zabezpieczających firmy przed wyciekiem danych lub niekontrolowanych cyber-ataków terrorystycznych. W odniesieniu do stosowania systemów zabezpieczeń CCTV oraz biometrii, Polska pod względem prawnym jest wciąż na początku procesu dostosowania do dyrektywy UE. Ciągły rozwój technologii powinien zmusić ustawodawcę do stworzenia jednoznacznych standardów i przepisów obowiązujących w zakresie stosowania technologii CCTV oraz biometrii, gdyż ma to ogromne znaczenie w zapewnieniu podstawowych praw i wolności każdego obywatela Rzeczypospolitej Polskiej

Range verification for eye proton therapy based on proton-induced x-ray emissions from implanted metal markers.

Metal fiducial markers are often implanted on the back of the eye before proton therapy to improve target localization and reduce patient setup errors. We aim to detect characteristic x-ray emissions from metal targets during proton therapy to verify the treatment range accuracy. Initially gold was chosen for its biocompatibility properties. Proton-induced x-ray emissions (PIXE) from a 15 mm diameter gold marker were detected at different penetration depths of a 59 MeV proton beam at the CATANA proton facility at INFN-LNS (Italy). The Monte Carlo code Geant4 was used to reproduce the experiment and to investigate the effect of different size markers, materials, and the response to both mono-energetic and fully modulated beams. The intensity of the emitted x-rays decreases with decreasing proton energy and thus decreases with depth. If we assume the range to be the depth at which the dose is reduced to 10% of its maximum value and we define the residual range as the distance between the marker and the range of the beam, then the minimum residual range which can be detected with 95% confidence level is the depth at which the PIXE peak is equal to 1.96 σbkg, which is the standard variation of the background noise. With our system and experimental setup this value is 3 mm, when 20 GyE are delivered to a gold marker of 15 mm diameter. Results from silver are more promising. Even when a 5 mm diameter silver marker is placed at a depth equal to the range, the PIXE peak is 2.1 σbkg. Although these quantitative results are dependent on the experimental setup used in this research study, they demonstrate that the real-time analysis of the PIXE emitted by fiducial metal markers can be used to derive beam range. Further analysis are needed to demonstrate the feasibility of the technique in a clinical setup

Quality assurance in proton beam therapy using a plastic scintillator and a commercially available digital camera

PURPOSE: In this article, we evaluate a plastic scintillation detector system for quality assurance in proton therapy using a BC-408 plastic scintillator, a commercial camera, and a computer. METHODS: The basic characteristics of the system were assessed in a series of proton irradiations. The reproducibility and response to changes of dose, dose-rate, and proton energy were determined. Photographs of the scintillation light distributions were acquired, and compared with Geant4 Monte Carlo simulations and with depth-dose curves measured with an ionization chamber. A quenching effect was observed at the Bragg peak of the 60 MeV proton beam where less light was produced than expected. We developed an approach using Birks equation to correct for this quenching. We simulated the linear energy transfer (LET) as a function of depth in Geant4 and found Birks constant by comparing the calculated LET and measured scintillation light distribution. We then used the derived value of Birks constant to correct the measured scintillation light distribution for quenching using Geant4. RESULTS: The corrected light output from the scintillator increased linearly with dose. The system is stable and offers short-term reproducibility to within 0.80%. No dose rate dependency was observed in this work. CONCLUSIONS: This approach offers an effective way to correct for quenching, and could provide a method for rapid, convenient, routine quality assurance for clinical proton beams. Furthermore, the system has the advantage of providing 2D visualization of individual radiation fields, with potential application for quality assurance of complex, time-varying fields

Optimisation of pulse shape discrimination using EJ299-33 for high energy neutron detection in proton beam therapy

It is widely understood that proton beam therapy has considerable clinical benefits over photon therapy for treating certain types of tumours. Protons deposit most of their energy in a very localised area, the so-called Bragg peak, sparing surrounding healthy tissue and critical organs from radiation. However, secondary neutrons and gamma rays are generated in the beam nozzle and inside the patient. Clinically, it is highly desirable to monitor the neutron dose the patient is exposed to, and this requires a neutron detector sensitive to high energies. EJ299-33 is a solid plastic scintillator capable of discriminating neutrons from gamma rays using pulse shape analysis of scintillation light. EJ299-33 has the potential to detect neutrons with energies up to 100 MeV and does not present leakage and flammability hazards generally associated with liquid scintillators. Experimental measurements with 60Co, 137Cs and 241AmBe sources were performed to calibrate and optimise pulse shape discrimination parameters. We also performed experimental measurements at the Clatterbridge Cancer Centre in a 60 MeV passive scattered beam to detect high energy neutrons

Medipix3 for dosimetry and real-time beam monitoring: first tests at a 60 MeV proton therapy facility

Charged particle therapy (CPT) is an advanced modality of radiation therapy which has grown rapidly worldwide, driven by recent developments in technology and methods of delivery. To ensure safe and high quality treatments, various instruments are used for a range of different measurements such as for quality assurance, monitoring and dosimetry purposes. With the emergence of new and enhanced delivery techniques, systems with improved capabilities are needed to exceed existing performance limitations of conventional tools. The Medipix3 is a hybrid pixel detector able to count individual protons with millisecond time resolution at clinical flux with near instant readout and count rate linearity. The system has previously demonstrated use in medical and other applications, showing wide versatility and potential for particle therapy. In this work we present measurements of the Medipix3 detector in the 60 MeV ocular proton therapy beamline at the Clatterbridge Cancer Centre, UK. The beam current and lateral beam profiles were evaluated at multiple positions in the treatment line and compared with EBT3 Gafchromic film. The recorded count rate linearity and temporal analysis of the beam structure was measured with Medipix3 across the full range of available beam intensities, up to $3.12 \times 10^{10}$ protons/s. We explore the capacity of Medipix3 to provide non-reference measurements and its applicability as a tool for dosimetry and beam monitoring for CPT. This is the first known time the performance of the Medipix3 detector technology has been tested within a clinical, high proton flux environment.Comment: Revised. Prepared for submission to JINST as a Tech Report, 22 pages, 12 figure

Targeting OGG1 and PARG radiosensitises head and neck cancer cells to high-LET protons through complex DNA damage persistence

Complex DNA damage (CDD), containing two or more DNA lesions within one or two DNA helical turns, is a signature of ionising radiation (IR) and contributes significantly to the therapeutic effect through cell killing. The levels and complexity of CDD increases with linear energy transfer (LET), however, the specific cellular response to this type of DNA damage and the critical proteins essential for repair of CDD is currently unclear. We performed an siRNA screen of ~240 DNA damage response proteins to identify those specifically involved in controlling cell survival in response to high-LET protons at the Bragg peak, compared to low-LET entrance dose protons which differ in the amount of CDD produced. From this, we subsequently validated that depletion of 8-oxoguanine DNA glycosylase (OGG1) and poly(ADP-ribose) glycohydrolase (PARG) in HeLa and head and neck cancer cells leads to significantly increased cellular radiosensitivity specifically following high-LET protons, whilst no effect was observed after low-LET protons and X-rays. We subsequently confirmed that OGG1 and PARG are both required for efficient CDD repair post-irradiation with high-LET protons. Importantly, these results were also recapitulated using specific inhibitors for OGG1 (TH5487) and PARG (PDD00017273). Our results suggest OGG1 and PARG play a fundamental role in the cellular response to CDD and indicate that targeting these enzymes could represent a promising therapeutic strategy for the treatment of head and neck cancers following high-LET radiation

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

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 90 Sr source in the laboratory and a 60 MeV proton beam at the Clatterbridge Cancer Centre

Progress towards a semiconductor Compton camera for prompt gamma imaging during proton beam therapy for range and dose verification

The main objective of this work is to test a new semiconductor Compton camera for prompt gamma imaging. Our device is composed of three active layers: a Si(Li) detector as a scatterer and two high purity Germanium detectors as absorbers of high-energy gamma rays. We performed Monte Carlo simulations using the Geant4 toolkit to characterise the expected gamma field during proton beam therapy and have made experimental measurements of the gamma spectrum with a 60 MeV passive scattering beam irradiating a phantom. In this proceeding, we describe the status of the Compton camera and present the first preliminary measurements with radioactive sources and their corresponding reconstructed images