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Objectives: Proton therapy has a theoretical dosimetric advantage due to the Bragg peak, but the linear energy transfer (LET), and therefore the relative biological effectiveness (RBE), increase at the end of range. For patients with Hodgkin lymphoma, the distal edge of beam is often located within or close to the heart, where elevated RBE would be of potential concern. The purpose of this study was to investigate the impact of RBE and the choice of beam arrangement for adolescent patients with mediastinal Hodgkin lymphoma. Methods: For three previously treated adolescent patients, proton plans with 1–3 fields were created to a prescribed dose of 19.8 Gy (RBE) in 11 fractions (Varian Eclipse v13.7), assuming an RBE of 1.1. Plans were recalculated using Monte-Carlo (Geant4 v10.3.3/Gate v8.1) to calculate dose-averaged LET. Variable RBE-weighted dose was calculated using the McNamara model, assuming an α/β ratio of 2 Gy for organs-at-risk. Results: Although the LET decreased as the number of fields increased, the difference in RBE-weighted dose (Δdose) to organs-at-risk did not consistently decrease. Δdose values varied by patient and organ and were mostly of the order of 0–3 Gy (RBE), with a worst-case of 4.75 Gy (RBE) in near-maximum dose to the left atrium for one plan. Conclusions: RBE-weighted doses to organs-at-risk are sensitive to the choice of RBE model, which is of particular concern for the heart. Advances in knowledge: There is a need to remain cautious when evaluating proton plans for Hodgkin lymphoma, especially when near-maximum doses to organs-at-risk are considered.

Preclinical radiation research lacks standardized dosimetry procedures that provide traceability to a primary standard. Consequently, ensuring accuracy and reproducibility between studies is challenging. Using 3D printed murine phantoms we undertook a dosimetry audit of Xstrahl Small Animal Radiation Research Platforms (SARRPs) installed at 7 UK centres. The geometrically realistic phantom accommodated alanine pellets and Gafchromic EBT3 film for simultaneous measurement of the dose delivered and the dose distribution within a 2D plane, respectively. Two irradiation scenarios were developed: (1) a 10 × 10 mm

The strong in vitro evidence that proton Relative Biological Effectiveness (RBE) varies with Linear Energy Transfer (LET) has led to an interest in applying LET within treatment planning. However, there is a lack of consensus on LET definition, Monte Carlo (MC) parameters or clinical methodology. This work aims to investigate how common variations of LET definition may affect potential clinical applications. MC simulations (GATE/GEANT4) were used to calculate absorbed dose and different types of LET for a simple Spread Out Bragg Peak (SOBP) and for four clinical PBT plans covering a range of tumour sites. Variations in the following LET calculation methods were considered: (i) averaging (dose-averaged LET (LETd) & track-averaged LET); (ii) scoring (LETd to water, to medium and to mass density); (iii) particle inclusion (LETd to all protons, to primary protons and to particles); (iv) MC settings (hit type and Maximum Step Size (MSS)). LET distributions were compared using: qualitative comparison, LET Volume Histograms (LVHs), single value criteria (maximum and mean values) and optimised LET-weighted dose models. Substantial differences were found between LET values in averaging, scoring and particle type. These differences depended on the methodology, but for one patient a difference of ∼100% was observed between the maximum LETd for all particles and maximum LETd for all protons within the brainstem in the high isodose region (4 keV μm−1 and 8 keV μm−1 respectively). An RBE model using LETd including heavier ions was found to predict substantially different LET-weighted dose compared to those using other LET definitions. In conclusion, the selection of LET definition may affect the results of clinical metrics considered in treatment planning and the results of an RBE model. The authors’ advocate for the scoring of dose-averaged LET to water for primary and secondary protons using a random hit type and automated MSS.

Modeling provides an attractive approach for the design of phased array ultrasound transducers for hyperthermia. However, measurements on physical transducers reveal differences from the idealized field profiles predicted by simulation. In this paper we report a method of analyzing the origins of these differences. The measured performance of a 15-element sparse phased array is described and compared with simulated fields calculated using the point source method. It highlighted two notable differences: First, that the focal region was located closer to the surface of the physical transducer than in the simulated fields; and second, that numerous intensity maxima were present between the surface of the transducer and the focal zone in the experimental data, but not in the simulated fields. We identified six factors that could potentially affect the field but were not taken into account by the default simulations, and we performed a sensitivity analysis on these: (i) Variation in the amplitude of the output from each element, (ii) the presence of square-wave harmonics in the drive signals, (iii) nonpistonlike vibration of elements, (iv) quantization of the applied phases, (v) errors in the spatial positioning of each element; and (vi) interelement cross-coupling. Both the independent impact of each factor and the interactions between multiple factors were analyzed by using a full-factorial experimental design composed of 64 (2(6)) simulations. The results indicated that nonpistonlike motion of elements is likely to be the primary cause of differences between the measured and modelled fields. Determination of the precise vibrational modes of elements in an array is complex and would require full finite element analysis. However, the simple vibrational mode considered within the present work, corresponding to the addition of a surface Rayleigh wave originating at the element center and propagating radially, produced simulation results that were in good agreement with the measured data. (E-mail: adam.aitkenhead@physics.cr.man.ac.uk) (C) 2010 World Federation for Ultrasound in Medicine & Biology.

In this paper we describe the design and evaluation of a planar phased-array ultrasound transducer suitable for producing localized hyperthermia in solid tumors deep within the body. Simulation using a customized version of Ultrasim has been used to determine the relationship between the size and position of the focus and parameters of the array. These parameters include the overall size of the array and the size, shape and distribution of the individual elements. A 15-element prototype array has been constructed using the results of the simulation. Beam profile measurements on this transducer made in an acoustic tank were compared with the beam profile predicted by simulation. The results showed good agreement in the shape of the focal region, but with the focus closer to the surface of the physical transducer when compared with the simulation and with small high-intensity areas between the surface of the transducer and the focus in the measured profile. A sensitivity analysis using a simulated factorial experiment indicated that the presence of a secondary vibrational mode within the elements of the array was the principal cause for both the shift in the position of the focus and for the unwanted maxima close to the surface of the array. The results also showed that the array was tolerant of a large variation in output intensity of the individual elements in the array in producing a focal region. Extrapolation of the results obtained in this study indicate that an array of 60 elements, based on the design described, driven by 550 V peak-to-peak pulses would be capable of producing a peak focal intensity of 50 Wcm −2 at a depth of 60 mm in tissue, which would be appropriate for hyperthermia used as an adjunct to radiotherapy or chemotherapy. (E-mail: a.h.aitkenhead@warwick.ac.uk)

Objectives: High-energy Proton Beam Therapy (PBT) commenced in England in 2018 and NHS England commissions PBT for 1.5% of patients receiving radical radiotherapy. We sought expert opinion on the level of provision. Methods: Invitations were sent to 41 colleagues working in PBT, most at one UK centre, to contribute by completing a spreadsheet. 39 responded: 23 (59%) completed the spreadsheet; 16 (41%) declined, arguing that clinical outcome data are lacking, but joined six additional site-specialist oncologists for two consensus meetings. The spreadsheet was pre-populated with incidence data from Cancer Research UK and radiotherapy use data from the National Cancer Registration and Analysis Service. ‘Mechanisms of Benefit’ of reduced growth impairment, reduced toxicity, dose escalation and reduced second cancer risk were examined. Results: The most reliable figure for percentage of radical radiotherapy patients likely to benefit from PBT was that agreed by 95% of the 23 respondents at 4.3%, slightly larger than current provision. The median was 15% (range 4–92%) and consensus median 13%. The biggest estimated potential benefit was from reducing toxicity, median benefit to 15% (range 4–92%), followed by dose escalation median 3% (range 0 to 47%); consensus values were 12 and 3%. Reduced growth impairment and reduced second cancer risk were calculated to benefit 0.5% and 0.1%. Conclusions: The most secure estimate of percentage benefit was 4.3% but insufficient clinical outcome data exist for confident estimates. The study supports the NHS approach of using the evidence base and developing it through randomised trials, non-randomised studies and outcomes tracking. Advances in knowledge: Less is known about the percentage of patients who may benefit from PBT than is generally acknowledged. Expert opinion varies widely. Insufficient clinical outcome data exist to provide robust estimates. Considerable further work is needed to address this, including international collaboration; much is already underway but will take time to provide mature data.