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With more patients receiving external beam radiation therapy with protons, it becomes increasingly important to refine the clinical understanding of the relative biological effectiveness (RBE) for dose delivered during treatment. Treatment planning systems used in clinics typically implement a constant RBE of 1.1 for proton fields irrespective of their highly heterogeneous linear energy transfer (LET). Quality assurance tools that can measure beam characteristics and quantify or be indicative of biological outcomes become necessary in the transition towards more sophisticated RBE weighted treatment planning and for verification of the Monte Carlo and analytical based models they use. In this study the RBE for the CHO-K1 cell line in a passively delivered clinical proton spread out Bragg peak (SOBP) is determined both in vitro and using a silicon-on-insulator (SOI) microdosimetry method paired with the modified microdosimetric kinetic model. The RBE along the central axis of a SOBP with 2 Gy delivered at the middle of the treatment field was found to vary between 1.11–1.98 and the RBE for 10% cell survival between 1.07–1.58 with a 250 kVp x-ray reference radiation and between 1.19–2.34 and 0.95–1.41, respectively, for a Co60 reference. Good agreement was found between RBE values calculated from the SOI-microdosimetry-MKM approach and in vitro. A strong correlation between proton lineal energy and RBE was observed particularly in the distal end and falloff of the SOBP. [ABSTRACT FROM AUTHOR]

Background: This paper describes the protocol for the Nano X Image Guidance (Nano X IG) trial, a single-institution, clinical imaging study. The Nano X is a prototype fixed-beam radiotherapy system developed to investigate the feasibility of a low-cost, compact radiotherapy system to increase global access to radiation therapy. This study aims to assess the feasibility of volumetric image guidance with cone beam computed tomography (CBCT) acquired during horizontal patient rotation on the Nano X radiotherapy system., Methods: In the Nano X IG study, we will determine whether radiotherapy image guidance can be performed with the Nano X radiotherapy system where the patient is horizontally rotated while scan projections are acquired. We will acquire both conventional CBCT scans and Nano X CBCT scans for 30 patients aged 18 and above and receiving radiotherapy for head/neck or upper abdomen cancers. For each patient, a panel of experts will assess the image quality of Nano X CBCT scans against conventional CBCT scans. Each patient will receive two Nano X CBCT scans to determine the image quality reproducibility, the extent and reproducibility of patient motion and assess patient tolerance., Discussion: Fixed-beam radiotherapy systems have the potential to help ease the current shortfall and increase global access to radiotherapy treatment. Advances in image guidance could facilitate fixed-beam radiotherapy using horizontal patient rotation. The efficacy of this radiotherapy approach is dependent on our ability to image and adapt to motion due to rotation and for patients to tolerate rotation during treatment., Trial Registration: ClinicalTrials.gov, NCT04488224. Registered on 27 July 2020., (© 2023. The Author(s).)

Fixed-gantry radiation therapy has been proposed as a low-cost alternative to the conventional rotating-gantry radiation therapy, that may help meet the rising global treatment demand. Fixed-gantry systems require gravitational motion compensated reconstruction algorithms to produce cone-beam CT (CBCT) images of sufficient quality for image guidance. The aim of this work was to adapt and investigate five CBCT reconstruction algorithms for fixed-gantry CBCT images. The five algorithms investigated were Feldkamp-Davis-Kress (FDK), prior image constrained compressed sensing (PICCS), gravitational motion compensated FDK (GMCFDK), motion compensated PICCS (MCPICCS) (a novel CBCT reconstruction algorithm) and simultaneous motion estimation and iterative reconstruction (SMEIR). Fixed-gantry and rotating-gantry CBCT scans were acquired of 3 rabbits, with the rotating-gantry scans used as a reference. Projections were sorted into rotation bins, based on the angle of rotation of the rabbit during image acquisition. The algorithms were compared using the structural similarity index measure root mean square error, and reconstruction time. Evaluation of the reconstructed volumes showed that, when compared with the reference rotating-gantry volume, the conventional FDK algorithm did not accurately reconstruct fixed-gantry CBCT scans. Whilst the PICCS reconstruction algorithm reduced some motion artefacts, the motion estimation reconstruction methods (GMCFDK, MCPICCS and SMEIR) were able to greatly reduce the effect of motion artefacts on the reconstructed volumes. This finding was verified quantitatively, with GMCFDK, MCPICCS and SMEIR reconstructions having RMSE 17%-19% lower and SSIM 1% higher than a conventional FDK. However, all motion compensated fixed-gantry CBCT reconstructions had a 56%-61% higher RMSE and 1.5% lower SSIM than FDK reconstructions of conventional rotating-gantry CBCT scans. The results show that motion compensation is required to reduce motion artefacts for fixed-gantry CBCT reconstructions. This paper further demonstrates the feasibility of fixed-gantry CBCT scans, and the ability of CBCT reconstruction algorithms to compensate for motion due to horizontal rotation., (© 2021 Institute of Physics and Engineering in Medicine.)

Proton therapy has a distinct dosimetric advantage over conventional photon therapy due to its Bragg peak profile. This allows greater accuracy in dose delivery and dose conformation to the target, however it requires greater precision in setup, delivery and for quality assurance (QA) procedures. The AAPM TG 224 report recommends daily range and spot position checks with tolerance on the order of a millimetre. Daily QA systems must therefore be efficient for daily use and be capable of sub-millimetre precision however few suitable commercial systems are available. In this work, a compact, real-time daily QA system is optimised and characterised for proton range verification using an ad-hoc Geant4 simulation. The system is comprised of a monolithic silicon diode array detector embedded in a perspex phantom. The detector is orientated at an angular offset to the incident proton beam to allow range in perspex to be determined for flat proton fields. The accuracy of the system for proton range in perspex measurements was experimentally evaluated over the full range of clinical proton energies. The mean R 100 , R 90 and R 80 ranges measured with the system were accurate within ±0.6 mm of simulated ranges in a perspex phantom for all energies assessed. This system allows real-time read-out of individual detector channels also making it appropriate for temporal beam delivery diagnostics and for spot position monitoring along one axis. The system presented provides a suitable, economical and efficient alternative for daily QA in proton therapy., (© 2021 Institute of Physics and Engineering in Medicine.)

Purpose: A radiotherapy system with a fixed treatment beam and a rotating patient positioning system could be smaller, more robust and more cost effective compared to conventional rotating gantry systems. However, patient rotation could cause anatomical deformation and compromise treatment delivery. In this work, we demonstrate an image-guided treatment workflow with a fixed beam prototype system that accounts for deformation during rotation to maintain dosimetric accuracy., Methods: The prototype system consists of an Elekta Synergy linac with the therapy beam orientated downward and a custom-built patient rotation system (PRS). A phantom that deforms with rotation was constructed and rotated within the PRS to quantify the performance of two image guidance techniques: motion compensated cone-beam CT (CBCT) for pre-treatment volumetric imaging and kilovoltage infraction monitoring (KIM) for real-time image guidance. The phantom was irradiated with a 3D conformal beam to evaluate the dosimetric accuracy of the workflow., Results: The motion compensated CBCT was used to verify pre-treatment position and the average calculated position was within -0.3 ± 1.1 mm of the phantom's ground truth position at 0°. KIM tracked the position of the target in real-time as the phantom was rotated and the average calculated position was within -0.2 ± 0.8 mm of the phantom's ground truth position. A 3D conformal treatment delivered on the prototype system with image guidance had a 3%/2 mm gamma pass rate of 96.3% compared to 98.6% delivered using a conventional rotating gantry linac., Conclusions: In this work, we have shown that image guidance can be used with fixed-beam treatment systems to measure and account for changes in target position in order to maintain dosimetric coverage during horizontal rotation. This treatment modality could provide a viable treatment option when there insufficient space for a conventional linear accelerator or where the cost is prohibitive.

An experimental and simulation-based study was performed on a 12C ion minibeam radiation therapy (MBRT) field produced with a clinical broad beam and a brass multi-slit collimator (MSC). Silicon-on-insulator (SOI) microdosimeters developed at the Centre for Medical Radiation Physics (CMRP) with micron sized sensitive volumes were used to measure the microdosimetric spectra at varying positions throughout the MBRT field and the corresponding dose-mean lineal energies and RBE for 10% cell survival (RBE10) were calculated using the modified Microdosimetric Kinetic Model (MKM). An increase in the average RBE10 of ∼30% and 10% was observed in the plateau region compared to broad beam for experimental and simulation values, respectively. The experimental collimator misalignment was determined to be 0.7° by comparison between measured and simulated microdosimetric spectra at varying collimator angles. The simulated dose-mean lineal energies in the valley region between minibeams were found to be higher on average than in the minibeams due to higher LET particles being produced in these regions from the MSC. This work presents the first experimental microdosimetry measurements and characterisation of the local biological effectiveness in a MBRT field., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

A new methodology for assessing linear energy transfer (LET) and relative biological effectiveness (RBE) in proton therapy beams using thermoluminescent detectors is presented. The method is based on the different LET response of two different lithium fluoride thermoluminescent detectors (LiF:Mg,Ti and LiF:Mg,Cu,P) for measuring charged particles. The relative efficiency of the two detector types was predicted using the recently developed Microdosimetric d(z) Model in combination with the Monte Carlo code PHITS. Afterwards, the calculated ratio of the expected response of the two detector types was correlated with the fluence- and dose- mean values of the unrestricted proton LET. Using the obtained proton dose mean LET as input, the RBE was assessed using a phenomenological biophysical model of cell survival. The aforementioned methodology was benchmarked by exposing the detectors at different depths within the spread out Bragg peak (SOBP) of a clinical proton beam at iThemba LABS. The assessed LET values were found to be in good agreement with the results of radiation transport computer simulations performed using the Monte Carlo code GEANT4. Furthermore, the estimated RBE values were compared with the RBE values experimentally determined by performing colony survival measurements with Chinese Hamster Ovary (CHO) cells during the same experimental run. A very good agreement was found between the results of the proposed methodology and the results of the in vitro study.

With more patients receiving external beam radiation therapy with protons, it becomes increasingly important to refine the clinical understanding of the relative biological effectiveness (RBE) for dose delivered during treatment. Treatment planning systems used in clinics typically implement a constant RBE of 1.1 for proton fields irrespective of their highly heterogeneous linear energy transfer (LET). Quality assurance tools that can measure beam characteristics and quantify or be indicative of biological outcomes become necessary in the transition towards more sophisticated RBE weighted treatment planning and for verification of the Monte Carlo and analytical based models they use. In this study the RBE for the CHO-K1 cell line in a passively delivered clinical proton spread out Bragg peak (SOBP) is determined both in vitro and using a silicon-on-insulator (SOI) microdosimetry method paired with the modified microdosimetric kinetic model. The RBE along the central axis of a SOBP with 2 Gy delivered at the middle of the treatment field was found to vary between 1.11-1.98 and the RBE for 10% cell survival between 1.07-1.58 with a 250 kVp x-ray reference radiation and between 1.19-2.34 and 0.95-1.41, respectively, for a Co60 reference. Good agreement was found between RBE values calculated from the SOI-microdosimetry-MKM approach and in vitro. A strong correlation between proton lineal energy and RBE was observed particularly in the distal end and falloff of the SOBP.

Purpose: The measurement of depth dose profiles for range and energy verification of heavy ion beams is an important aspect of quality assurance procedures for heavy ion therapy facilities. The steep dose gradients in the Bragg peak region of these profiles require the use of detectors with high spatial resolution. The aim of this work is to characterize a one dimensional monolithic silicon detector array called the "serial Dose Magnifying Glass" (sDMG) as an independent ion beam energy and range verification system used for quality assurance conducted for ion beams used in heavy ion therapy., Methods: The sDMG detector consists of two linear arrays of 128 silicon sensitive volumes each with an effective size of 2mm × 50μm × 100μm fabricated on a p-type substrate at a pitch of 200 μm along a single axis of detection. The detector was characterized for beam energy and range verification by measuring the response of the detector when irradiated with a 290 MeV/u 12 C ion broad beam incident along the single axis of the detector embedded in a PMMA phantom. The energy of the 12 C ion beam incident on the detector and the residual energy of an ion beam incident on the phantom was determined from the measured Bragg peak position in the sDMG. Ad hoc Monte Carlo simulations of the experimental setup were also performed to give further insight into the detector response., Results: The relative response profiles along the single axis measured with the sDMG detector were found to have good agreement between experiment and simulation with the position of the Bragg peak determined to fall within 0.2 mm or 1.1% of the range in the detector for the two cases. The energy of the beam incident on the detector was found to vary less than 1% between experiment and simulation. The beam energy incident on the phantom was determined to be (280.9 ± 0.8) MeV/u from the experimental and (280.9 ± 0.2) MeV/u from the simulated profiles. These values coincide with the expected energy of 281 MeV/u., Conclusions: The sDMG detector response was studied experimentally and characterized using a Monte Carlo simulation. The sDMG detector was found to accurately determine the 12 C beam energy and is suited for fast energy and range verification quality assurance. It is proposed that the sDMG is also applicable for verification of treatment planning systems that rely on particle range., (© 2017 American Association of Physicists in Medicine.)