Development and optimisation of grid inserts for a preclinical radiotherapy system and corresponding Monte Carlo beam simulations.

Objective. To develop a physical grid collimator compatible with the X-RAD preclinical radiotherapy system and create a corresponding Monte Carlo (MC) model.Approach. This work presents a methodology for the fabrication of a grid collimator designed for utilisation on the X-RAD preclinical radiotherapy system. Additionally, a MC simulation of the grid is developed, which is compatible with the X-RAD treatment planning system. The grid was manufactured by casting a low melting point alloy, cerrobend, into a silicone mould. The silicone was moulded around a 3D-printed replica of the grid, enabling the production of diverging holes with precise radii and spacing. A MC simulation was conducted on an equivalent 3D grid model and validated using 11 layers of GAFChromic EBT-3 film interspersed in a 3D-printed water-equivalent phantom. A 3D dose distribution was constructed from the film layers, enabling a direct comparison with the MC Simulation.Main results. The film and the MC dose distribution demonstrated a gamma passing rate of 99% for a 1%, 0.5 mm criteria with a 10% threshold applied. The peak-to-valley dose ratio and output factor at the surface were determined to be 20.4 and 0.79, respectively.Significance. The pairing of the grid collimator with a MC simulation can significantly enhance the practicality of grid therapy on the X-RAD. This combination enables further exploration of the biological implications of grid therapy, supported by a knowledge of the complex dose distributions. Moreover, this methodology can be adapted for use in other systems and scenarios.

Comparison of the accuracy of Monte Carlo and Ray Tracing dose calculation algorithms for multiple target brain treatments on CyberKnife.

Single plan multiple brain targets (MBT) stereotactic radiosurgery dose difference between Monte Carlo (MC) and Ray Tracing (RT) algorithms has not been studied. A retrospective study and dose measurements were performed to access factors influencing dose differences. Fifty-three RT treatment plans with a total of 209 brain metastases were extracted from Precision Treatment Planning System (TPS). These plans were generated using fixed cones and were delivered using the CyberKnife M6 system. The same treatment plans were recalculated using MC algorithm and keeping the beam parameters unchanged. MC calculated plan parameters were extracted and dose differences were normalised to MC calculated dose. Correlations were investigated. RT and MC calculated off-centre-ratio (OCR) and tissue-phantom-ratio (TPRs) were exported from the TPS and compared with measured. Plans with 5 gross tumour volumes (GTVs) were created on a phantom and dose measured using a CC04 ionisation chamber and microdiamond detector for comparison with calculated doses. Calculated and measured TPR agreed within ± 1% beyond depth of maximum dose. The OCR showed differences up to 4.3% in the penumbra and out-of-field (OOF) regions. Largest RT and MC calculated GTV mean dose difference was - 5.7%. An increase in the number of GTVs and reduction in the geometric separation of metastases were associated with increased differences between RT and MC calculated doses. In conclusion, calculated dose disagreement in MBT depends on the number of GTVs per plan, number of GTVs within a certain separation distance and plan complexity. MC dose calculation is recommended for complex CyberKnife SRS of MBT.

Correction factors for commissioning and patient specific quality assurance of stereotactic fields in a Monte Carlo based treatment planning system : TPS correction factors.

Validation of small field dosimetry is crucial for stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT). Accurate and considered measurement of linear accelerator dose must be compared to precise and accurate calculation by the treatment planning system (TPS). Monte Carlo calculated distributions contain statistical noise, reducing the reliance that should be given to single voxel doses. The average dose to a small volume of interest (VOI) can minimise the influence of noise, but for small fields introduces significant volume averaging. Similar challenges present during measurement of composite dose from clinical plans when a small volume ionisation chamber is used. This study derived correction factors for VOI averaged TPS doses calculated for small fields, allowing correction to an isocentre dose following account for statistical noise. These factors were used to determine an optimal VOI to represent small volume ionisation chambers during patient specific quality assurance (PSQA). A retrospective comparison of 82 SRS and 28 SBRT PSQA measurements to TPS calculated doses from varying VOI was completed to evaluate the determined volumes. Small field commissioning correction factors of under 5% were obtained for field sizes of 8 mm and larger. Optimal spherical VOI with radius between 1.5 and 1.8 mm and 2.5 to 2.9 mm were determined for IBA CC01 and CC04 ionisation chambers respectively. Review of PSQA confirmed an optimal agreement between CC01 measured doses and a volume of 1.5 to 1.8 mm while CC04 measured doses showed no variation with VOI.

Dosimetric evaluation of an intraoperative radiotherapy system: a measurement-based and Monte-Carlo modelling investigation.

Intraoperative radiotherapy (IORT) is a specialised subset of radiotherapy, where a high radiation dose is delivered to a surgically exposed tumour bed in order to eradicate any remaining cancer cells. The aim of this study was to examine the dose characteristics of the Zeiss Intrabeam IORT device which provides near-isotropic emission of up to 50 kV X-rays. The EGSnrc Monte Carlo (MC) code system was used to simulate the device and percentage depth dose (PDD) data measured with a soft X-ray parallel-plate ionisation chamber were used for model verification. The model provided energy spectra, isodose curves and mean photon energies. In addition, EBT3 Gafchromic film was used to verify the MC model by examining PDDs and 2D dose distributions for various applicators. The differences between MC model and ionisation chamber measurements were within 3% for most points, with a maximum deviation of ~ 9%. Most of the simulated PDD points were within 5% of the film-measured data, with a maximum deviation of ~ 10%. The mean energy of the bare probe was found to be 21.19 keV. The mean photon energy from applicators ranged from 29.00 to 30.85 keV. Results of this study may be useful for future work on creating a system for treatment planning.

Matched linac stereotactic radiotherapy: An assessment of delivery similarity and distributive patient-specific quality assurance feasibility.

Matching multiple linacs to common baseline data allows patients to be treated, and patient-specific quality assurance (PSQA) to be completed on any linac. Stereotactic body radiotherapy (SBRT) requires higher levels of accuracy and quality assurance than routine radiotherapy. The achieved linac matching must therefore be evaluated before distributive treatment or PSQA models can be implemented safely. This investigation aimed to propose metrics for defining linacs to be matched for SBRT deliveries, assess 12 linacs against these criteria, and determine if a distributive PSQA model could be implemented by reviewing the rates of false PSQA results. Ten SBRT spine plans were delivered by 12 matched Elekta linacs and measured using one of seven SRS MapCHECK devices. For gamma criteria of (3%, 2 mm), 96.9% of equivalent location detectors, showed a range of gamma ≤ 1.0 and 99.9% showed a standard deviation of ≤ 0.5. For criteria of (3%,1 mm) and (2%,1 mm), these ranges decreased to 92.1% and 80.2% while the standard deviations decreased to 99.3% and 95.7%, respectively. The dose differences showed that 43.6%, 82.7%, and 91.4% of detectors had a dose range of ≤ 3.0%, ≤ 5.0%, and ≤ 6.0%, respectively. Standard deviations of dose differences were 1.5%, 2.5%, and 3.0% for 94.1%, 98.3%, and 99.5% of detectors, respectively. For the fleet of linacs, distributive PSQA yielded false results for 0.0%, 17.7%, and 33.0% of plans, equivalent to 1.2%, 3.5%, and 9.4% of detectors when using gamma criteria of (3%,2 mm), (3%,1 mm), or (2%,1 mm), respectively. These linacs could be considered matched for SBRT treatments and implement a distributive PSQA model when gamma analysis was completed with a criterion of (3%, 2 mm). For stricter criterion of (3%,1 mm) or (2%,1 mm), they did not meet the proposed metrics.

Assessment of HDR brachytherapy-replicating prostate radiotherapy planning for tomotherapy, cyberknife and VMAT.

A dosimetric study was undertaken to assess the ability of Cyberknife (CK), Volumetric Modulated Arc Therapy (VMAT), and TomoTherapy (Tomo) to generate treatment plans that mimic the dosimetry of high dose-rate brachytherapy (HDR BT) for prostate cancer. The project aimed to assess the potential of using stereotactic body radiotherapy (SBRT) for boost treatment of high-risk prostate cancer patients where HDR BT in combination with conformal external beam radiotherapy (EBRT) is the standard of care. The datasets of 6 prostate patients previously treated with HDR BT were collated. VMAT, CK, and TomoTherapy treatment plans were generated for each dataset using the target and organ-at-risk structures as defined by the Radiation Oncologist during the HDR BT treatment process. The HDR BT plan isodoses were also converted into planning structures to assist the other modalities to achieve a HDR BT-like dose distribution. CK plans were created using both the iris collimator (IC) and a multileaf collimator (MLC). Comparison of the techniques was made based on dose-volume indices. Each plan was created at centres experienced using the respective treatment planning systems (TPS). Planning target volume (PTV V100%), i.e., the volume of the planning target volume (PTV) receiving 100% of the relative dose, in VMAT and TomoTherapy SBRT plans was higher than HDR BT plans. PTV V150% and V200%, i.e., volume of the PTV receiving 150% and 200% of the relative dose, were approached on all the CK MLC and TomoTherapy SBRT plans. However, it is not presently achievable for "virtual brachytherapy" SBRT to replicate the same high intraprostatic doses as HDR BT while meeting the constraints on the organs-at-risk (OARs). Half of the CK IC plans achieved PTV V150% but this was at the expense of high rectal dose. TomoTherapy and CK MLC plans achieved PTV V150% and V200% but the bladder dose was higher compared to CK IC plans. VMAT exhibited excellent PTV coverage based on V100 and OAR sparing, but without any ability to achieve the high intra-prostatic doses of HDR (V150% and V200%). SBRT techniques can be used to deliver hypofractionated radiotherapy to the PTV V100%. Based on the comparison of "physical" dose distributions, SBRT cannot presently achieve the same high intraprostatic doses as HDR BT while respecting the OAR constraints. SBRT still remains an attractive treatment option for delivering hypofractionated treatments for prostate cancer compared to HDR BT, in particular as it is less invasive and less resource intensive. Long-term outcomes of clinical trials comparing HDR BT and SBRT "prostate boosts" may show whether the high intraprostatic doses are clinically significant and correlate with outcomes.

Repeatability of image features extracted from FET PET in application to post-surgical glioblastoma assessment.

Positron emission tomography (PET) imaging using the amino acid tracer O-[2-(18F)fluoroethyl]-L-tyrosine (FET) has gained increased popularity within the past decade in the management of glioblastoma (GBM). Radiomics features extracted from FET PET images may be sensitive to variations when imaging at multiple time points. It is therefore necessary to assess feature robustness to test-retest imaging. Eight patients with histologically confirmed GBM that had undergone post-surgical test-retest FET PET imaging were recruited. In total, 1578 radiomic features were extracted from biological tumour volumes (BTVs) delineated using a semi-automatic contouring method. Feature repeatability was assessed using the intraclass correlation coefficient (ICC). The effect of both bin width and filter choice on feature repeatability was also investigated. 59/106 (55.7%) features from the original image and 843/1472 (57.3%) features from filtered images had an ICC ≥ 0.85. Shape and first order features were most stable. Choice of bin width showed minimal impact on features defined as stable. The Laplacian of Gaussian (LoG, σ = 5 mm) and Wavelet filters (HLL and LHL) significantly improved feature repeatability (p ≪ 0.0001, p = 0.003, p = 0.002, respectively). Correlation of textural features with tumour volume was reported for transparency. FET PET radiomic features extracted from post-surgical images of GBM patients that are robust to test-retest imaging were identified. An investigation with a larger dataset is warranted to validate the findings in this study.

Recommended dose voxel size and statistical uncertainty parameters for precision of Monte Carlo dose calculation in stereotactic radiotherapy.

Monte Carlo (MC)-based treatment planning requires a choice of dose voxel size (DVS) and statistical uncertainty (SU). These parameters effect both the precision of displayed dose distribution and time taken to complete a calculation. For efficient, accurate, and precise treatment planning in a clinical setting, optimal values should be selected. In this investigation, 30 volumetric modulated arc therapy (VMAT) stereotactic radiotherapy (SRT) treatment plans, 10 brain, 10 lung, and 10 spine were calculated in the Monaco 5.11.02 treatment planning system (TPS). Each plan was calculated with a DVS of 0.1 and 0.2 cm using SU values of 0.50%, 0.75%, 1.00%, 1.50%, and 2.00%, along with a ground truth calculation using a DVS of 0.1 cm and SU of 0.15%. The variance at each relative dose level was calculated for all SU settings to assess their relationship. The variation from the ground truth calculation for each DVS and SU combination was determined for a range of DVH metrics and plan quality indices along with the time taken to complete the calculations. Finally, the effect of defining the maximum dose using a volume of 0.035 cc was compared to 0.100 cc when considering DVS and SU settings. Changes in the DVS produced greater variations from the ground truth calculation than changes in SU across the values tested. Plan quality metrics and mean dose values showed less sensitivity to changes in SU than DVH metrics. From this study, it was concluded that while maintaining an average calculation time of <10 min, 75% of plans could be calculated with variations of <2.0% from their ground truth values when using an SU setting of 1.50% and a DVS of 0.1 cm in the case of brain or spine plans, and a 0.2 cm DVS in the case of lung plans.

Evaluation of the Impact of the Linac MLC and Gantry Sag in volumetric modulated arc therapy.

PURPOSE: Mechanical sag in the radiotherapy linear accelerator gantry and multi-leaf collimator (MLC) carriage effectively causes systematic deviations in the isocenter with respect to gantry angle. To minimize the impact of this error on treatment, a tolerance value of a 1-mm mechanical isocenter shift is commonly accepted for intensity-modulated radiation therapy quality assurance (QA). However, this tolerance value has not been firmly established for volumetric modulated arc therapy (VMAT) treatments. The purpose of this study is therefore to evaluate the impact of gantry and MLC carriage sag on VMAT clinical performance. METHODS: A published dataset of Elekta and Varian sag measurements served as a starting point for the investigation. Typical sag profiles were chosen and modeled as continuous isocenter deviations in three dimensions. The data were then incorporated into existing Digital Imaging and Communications in Medicine protocol, extended for radiotherapy plans via a "beam-splitting" algorithm. Three treatment sites were investigated in parallel: head and neck, prostate, and prostate with surrounding lymph nodes. Monte Carlo-simulated dose distributions were obtained for varying magnifications of the modeled sag. The resulting dose distributions, including that for no error, were compared qualitatively and quantitatively, against multiple metrics. RESULTS: The dose-volume histograms (DVHs) for all plans exhibited a decrease in planning target volume (PTV) dose uniformity with increasing sag magnification, whereas dose to organs at risk exhibited no coherent trend. The prostate plan was shown to be the most vulnerable to mechanical sag across all considered metrics. However, all plans with peak isocenter deviation less than 1 mm were well within typical cutoff points for each metric. CONCLUSIONS: All avenues of investigation presented substantiate the commonly accepted tolerance value of a 1-mm peak isocenter shift in annual linac QA.

Using percolation networks to incorporate spatial-dose information for assessment of complication probability in radiotherapy.

This study investigates an extension of recent cluster based methods of assessing the probability of complication in normal organs following radiotherapy treatment which delivers a spatially non-uniform radiation dose distribution. Current methods of assessing this complication probability are spatially degenerate and do not adequately assess the contiguity of damage done to tissue. Therefore, new measures of assessing complication after radiation exposure have been proposed for parallel and serial type organs. In parallel organs an interaction between cells within a functional subunit is stipulated and complication is regarded as a weighted sum of all clusters in the organ. This allows the assessment to account for all damage to the tissue whilst emphasising the importance of damage that accumulates into large and connected spatial regions addressing a deficiency in the current method of calculating complication probabilities. Several spatially-varying doses were analysed and simulated in silico. The simulations produce complication risk estimates for homogeneous dose distributions that are comparable to empirical results but which deviate with any dose inhomogeneity. The simulations also show that the standard method of dose transformation to an effective uniform dose is not valid in cluster based models.

Radiation therapists' perspectives on participating in research.

INTRODUCTION: The objectives of this research were to: (1) determine the extent of Australian radiation therapists (RTs) research participation; (2) evaluate the impact of research involvement on career perceptions (3) explore which research topics require investigation and (4) identify benefits and barriers to research participation. METHODS: This study used mixed methods to collect qualitative and quantitative data using an online survey from a larger workforce study of RTs and radiation oncology medical physicists. Participants practising in Australia completed questions about their research involvement. Chi-square tests and logistic regression were used to analyse quantitative data and content analysis was used to explore qualitative data. RESULTS: Two hundred and ninety-six RTs answered the research questions. Forty-six percent had been involved in research. Of these, 91% had been involved in departmental, 28% in national, 14% in international and 29% in informal or self-directed research studies. Eleven RTs (8%) had received funding as a chief/principal investigator. Involvement in research was associated with a desire to make a career change. However, it also appeared to be associated with greater satisfaction with career progression and staying in the career. Respondents identified a range of potential research topics, benefits of participating in research and barriers which included lack of time, support and cost. CONCLUSION: Almost half of the RT participants identified that they were participating in research. Our data suggest that continued involvement in research, and opportunities to participate, improve RT job satisfaction. RTs' research activities are likely to be extended through provision of additional time and support.

An assessment of radiation oncology medical physicists' perspectives on undertaking research.

As part of a study of the radiation oncology workforce, radiation oncology medical physicists (ROMPs) who had worked in Australia were surveyed regarding their attitudes to participating in research. Responses from 88 ROMPs were available for analysis, representing a broad mix of employment situations and research experience. Greater than 70% of ROMPs described their involvement in research as "liking it" or "loving it", with associated identified benefits including skills development, job satisfaction and career progression. Over half of respondents agreed that involvement in research inspired them to stay in their profession. However, lack of time, support and motivation were all identified as barriers to participation in research. Areas of research interest were identified. This study highlights the importance of a research culture for job satisfaction and staff retention.

Theoretical versus Ex Vivo Assessment of Radiation Damage Repair: An Investigation in Normal Breast Tissue.

In vivo validation of models of DNA damage repair will enable their use for optimizing clinical radiotherapy. In this study, a theoretical assessment was made of DNA double-strand break (DSB) induction in normal breast tissue after intraoperative radiation therapy (IORT), which is now an accepted form of adjuvant radiotherapy for selected patients with early breast cancer. DSB rates and relative biological effectiveness (RBE) were calculated as a function of dose, radiation quality and dose rate, each varying based on the applicator size used during IORT. The spectra of primary electrons in breast tissue adjacent to each applicator were calculated using measured X-ray spectra and Monte Carlo methods, and were used to inform a Monte Carlo damage simulation code. In the absence of repair, asymptotic RBE values (relative to (60)Co) were approximately 1.5. Beam-quality changes led to only minor variations in RBE among applicators, though differences in dose rate and overall dose delivery time led to larger variations and a rapid decrease in RBE. An experimental assessment of DSB induction was performed ex vivo using pre- and postirradiation tissue samples from patients receiving breast intraoperative radiation therapy. Relative DSB rates were assessed via γ-H2AX immunohistochemistry using proportional staining. Maximum-likelihood parameter estimation yielded a DSB repair halftime of 25.9 min (95% CI, 21.5-30.4 min), although the resulting model was not statistically distinguishable from one where there was no change in DSB yield among patients. Although the model yielded an in vivo repair halftime of the order of previous estimates for in vitro repair halftimes, we cannot conclude that it is valid in this context. This study highlights some of the uncertainties inherent in population analysis of ex vivo samples, and of the quantitative limitations of immunohistochemistry for assessment of DSB repair.

Testing the Assessment of New Radiation Oncology Technology and Treatments framework using the evaluation of post-prostatectomy radiotherapy techniques.

INTRODUCTION: We tested the ability of the Assessment of New Radiation Oncology Technology and Treatments framework to determine the clinical efficacy and safety of intensity-modulated radiation therapy (IMRT) compared with 3-dimensional radiation therapy (3DCRT) for post-prostatectomy radiation therapy (PPRT) to support its timely health economic evaluation. METHODS: Treatment plans produced using FROGG guidelines provided dosimetry parameters for both techniques at 64 Gy and 70 Gy and were also used to model early and late outcome probabilities. Clinical parameters were derived from early toxicity and quality of life patient data, systematic literature review and expert opinion. Dosimetry parameters were correlated with the measures of clinical efficacy and safety. RESULTS: Data from two patient cohorts (29 and 27 respectively) were collected within the project timeframe, providing evidence for acute toxicity and quality of life, and dosimetric comparisons. Relative rates of tumour control probability (TCP) and normal tissue control probability (NTCP) modelling were readily derived from the planning exercise and demonstrated advantages in uncomplicated TCP for IMRT over 3DCRT, predominantly due to normal tissue sparing. The safety of IMRT delivery was demonstrated with TCP uncompromised by IMRT protocol violations, which achieved rectal sparing only by reducing minimum target dose and coverage. CONCLUSION: Sources of desk-top and patient-based evidence were successfully used to demonstrate potential improved clinical efficacy and safety of applying dose escalation using IMRT instead of 3DCRT in PPRT.

Small field in-air output factors: the role of miniphantom design and dosimeter type.

PURPOSE: The commissioning of treatment planning systems and beam modeling requires measured input parameters. The measurement of relative output in-air, Sc is particularly difficult for small fields. The purpose of this study was to investigate the influence of miniphantom design and detector selection on measured Sc values for small fields and to validate the measurements against Monte Carlo simulations. METHODS: Measurements were performed using brass caps (with sidewalls) or tops (no sidewalls) of varying heights and widths. The performance of two unshielded diodes (60012 and SFD), EBT2 radiochromic film, and a fiber optic dosimeter (FOD) were compared for fields defined by MLCs (5-100 mm) and SRS cones (4-30 mm) on a Varian Novalis linear accelerator. Monte Carlo simulations were performed to theoretically predict Sc as measured by the FOD. RESULTS: For all detectors, Sc agreed to within 1% for fields larger than 10 mm and to within 2.3% for smaller fields. Monte Carlo simulation matched the FOD measurements for all size of cone defined fields to within 0.5%. CONCLUSIONS: Miniphantom design is the most important variable for reproducible and accurate measurements of the in-air output ratio, S(c), in small photon fields (less than 30 mm). Sidewalls are not required for fields ≤ 30 mm and tops are therefore preferred over the larger caps. Unlike output measurements in water, S(cp), the selection of detector type for Sc is not critical, provided the active dosimeter volume is small relative to the field size.

Radiotherapy of abdomen with precise renal assessment with SPECT/CT imaging (RAPRASI): design and methodology of a prospective trial to improve the understanding of kidney radiation dose response.

BACKGROUND: The kidneys are a principal dose-limiting organ in radiotherapy for upper abdominal cancers. The current understanding of kidney radiation dose response is rudimentary. More precise dose-volume response models that allow direct correlation of delivered radiation dose with spatio-temporal changes in kidney function may improve radiotherapy treatment planning for upper-abdominal tumours. METHODS/DESIGN: The Radiotherapy of Abdomen with Precise Renal Assessment with SPECT/CT Imaging (RAPRASI) is an observational clinical research study with participating sites at Sir Charles Gairdner Hospital (SCGH) in Perth, Australia and the Peter MacCallum Cancer Centre (PMCC) in Melbourne, Australia. Eligible patients are those with upper gastrointestinal cancer, without metastatic disease, undergoing conformal radiotherapy that will involve incidental radiation to one or both kidneys. For each patient, total kidney function is being assessed before commencement of radiotherapy treatment and then at 4, 12, 26, 52 and 78 weeks after the first radiotherapy fraction, using two procedures: a Glomerular Filtration Rate (GFR) measurement using the 51Cr-ethylenediamine tetra-acetic acid (EDTA) clearance; and a regional kidney perfusion measurement assessing renal uptake of 99mTc-dimercaptosuccinic acid (DMSA), imaged with a Single Photon Emission Computed Tomography / Computed Tomography (SPECT/CT) system. The CT component of the SPECT/CT provides the anatomical reference of the kidney's position. The data is intended to reveal changes in regional kidney function over the study period after the radiotherapy. These SPECT/CT scans, co-registered with the radiotherapy treatment plan, will provide spatial correlation between the radiation dose and regional renal function as assessed by SPECT/CT. From this correlation, renal response patterns will likely be identified with the purpose of developing a predictive model. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12609000322235.