Federated Learning Survival Model and Potential Radiotherapy Decision Support Impact Assessment for Non-small Cell Lung Cancer Using Real-World Data.

AIMS: The objective of this study was to develop a two-year overall survival model for inoperable stage I-III non-small cell lung cancer (NSCLC) patients using routine radiation oncology data over a federated (distributed) learning network and evaluate the potential of decision support for curative versus palliative radiotherapy. METHODS: A federated infrastructure of data extraction, de-identification, standardisation, image analysis, and modelling was installed for seven clinics to obtain clinical and imaging features and survival information for patients treated in 2011-2019. A logistic regression model was trained for the 2011-2016 curative patient cohort and validated for the 2017-2019 cohort. Features were selected with univariate and model-based analysis and optimised using bootstrapping. System performance was assessed by the receiver operating characteristic (ROC) and corresponding area under curve (AUC), C-index, calibration metrics and Kaplan-Meier survival curves, with risk groups defined by model probability quartiles. Decision support was evaluated using a case-control analysis using propensity matching between treatment groups. RESULTS: 1655 patient datasets were included. The overall model AUC was 0.68. Fifty-eight percent of patients treated with palliative radiotherapy had a low-to-moderate risk prediction according to the model, with survival times not significantly different (p = 0.87 and 0.061) from patients treated with curative radiotherapy classified as high-risk by the model. When survival was simulated by risk group and model-indicated treatment, there was an estimated 11% increase in survival rate at two years (p < 0.01). CONCLUSION: Federated learning over multiple institution data can be used to develop and validate decision support systems for lung cancer while quantifying the potential impact of their use in practice. This paves the way for personalised medicine, where decisions can be based more closely on individual patient details from routine care.

Dosimetric Impact of Delineation and Motion Uncertainties on the Heart and Substructures in Lung Cancer Radiotherapy.

AIMS: Delineation variations and organ motion produce difficult-to-quantify uncertainties in planned radiation doses to targets and organs at risk. Similar to manual contouring, most automatic segmentation tools generate single delineations per structure; however, this does not indicate the range of clinically acceptable delineations. This study develops a method to generate a range of automatic cardiac structure segmentations, incorporating motion and delineation uncertainty, and evaluates the dosimetric impact in lung cancer. MATERIALS AND METHODS: Eighteen cardiac structures were delineated using a locally developed auto-segmentation tool. It was applied to lung cancer planning CTs for 27 curative (planned dose ≥50 Gy) cases, and delineation variations were estimated by using ten mapping-atlases to provide separate substructure segmentations. Motion-related cardiac segmentation variations were estimated by auto-contouring structures on ten respiratory phases for 9/27 cases that had 4D-planning CTs. Dose volume histograms (DVHs) incorporating these variations were generated for comparison. RESULTS: Variations in mean doses (Dmean), defined as the range in values across ten feasible auto-segmentations, were calculated for each cardiac substructure. Over the study cohort the median variations for delineation uncertainty and motion were 2.20-11.09 Gy and 0.72-4.06 Gy, respectively. As relative values, variations in Dmean were between 18.7%-65.3% and 7.8%-32.5% for delineation uncertainty and motion, respectively. Doses vary depending on the individual planned dose distribution, not simply on segmentation differences, with larger dose variations to cardiac structures lying within areas of steep dose gradient. CONCLUSION: Radiotherapy dose uncertainties from delineation variations and respiratory-related heart motion were quantified using a cardiac substructure automatic segmentation tool. This predicts the 'dose range' where doses to structures are most likely to fall, rather than single DVH curves. This enables consideration of these uncertainties in cardiotoxicity research and for future plan optimisation. The tool was designed for cardiac structures, but similar methods are potentially applicable to other OARs.

Validation of a Fully Automated Hybrid Deep Learning Cardiac Substructure Segmentation Tool for Contouring and Dose Evaluation in Lung Cancer Radiotherapy.

BACKGROUND AND PURPOSE: Accurate and consistent delineation of cardiac substructures is challenging. The aim of this work was to validate a novel segmentation tool for automatic delineation of cardiac structures and subsequent dose evaluation, with potential application in clinical settings and large-scale radiation-related cardiotoxicity studies. MATERIALS AND METHODS: A recently developed hybrid method for automatic segmentation of 18 cardiac structures, combining deep learning, multi-atlas mapping and geometric segmentation of small challenging substructures, was independently validated on 30 lung cancer cases. These included anatomical and imaging variations, such as tumour abutting heart, lung collapse and metal artefacts. Automatic segmentations were compared with manual contours of the 18 structures using quantitative metrics, including Dice similarity coefficient (DSC), mean distance to agreement (MDA) and dose comparisons. RESULTS: A comparison of manual and automatic contours across all cases showed a median DSC of 0.75-0.93 and a median MDA of 2.09-3.34 mm for whole heart and chambers. The median MDA for great vessels, coronary arteries, cardiac valves, sinoatrial and atrioventricular conduction nodes was 3.01-8.54 mm. For the 27 cases treated with curative intent (planned target volume dose ≥50 Gy), the median dose difference was -1.12 to 0.57 Gy (absolute difference of 1.13-3.25%) for the mean dose to heart and chambers; and -2.25 to 4.45 Gy (absolute difference of 0.94-6.79%) for the mean dose to substructures. CONCLUSION: The novel hybrid automatic segmentation tool reported high accuracy and consistency over a validation set with challenging anatomical and imaging variations. This has promising applications in substructure dose calculations of large-scale datasets and for future studies on long-term cardiac toxicity.

Outcomes of Patients Treated in the UK Proton Overseas Programme: Non-central Nervous System Group.

AIMS: The UK Proton Overseas Programme (POP) was launched in 2008. The Proton Clinical Outcomes Unit (PCOU) warehouses a centralised registry for collection, curation and analysis of all outcomes data for all National Health Service-funded UK patients referred and treated abroad with proton beam therapy (PBT) via the POP. Outcomes are reported and analysed here for patients diagnosed with non-central nervous system tumours treated from 2008 to September 2020 via the POP. MATERIALS AND METHODS: All non-central nervous system tumour files for treatments as of 30 September 2020 were interrogated for follow-up information, and type (following CTCAE v4) and time of onset of any late (>90 days post-PBT completion) grade 3-5 toxicities. RESULTS: Four hundred and ninety-five patients were analysed. The median follow-up was 2.1 years (0-9.3 years). The median age was 11 years (0-69 years). 70.3% of patients were paediatric (<16 years). Rhabdomyosarcoma (RMS) and Ewing sarcoma were the most common diagnoses (42.6% and 34.1%). 51.3% of treated patients were for head and neck (H&N) tumours. At last known follow-up, 86.1% of all patients were alive, with a 2-year survival rate of 88.3% and 2-year local control of 90.3%. Mortality and local control were worse for adults (≥25 years) than for the younger groups. The grade 3 toxicity rate was 12.6%, with a median onset of 2.3 years. Most were in the H&N region in paediatric patients with RMS. Cataracts (30.5%) were the most common, then musculoskeletal deformity (10.1%) and premature menopause (10.1%). Three paediatric patients (1-3 years at treatment) experienced secondary malignancy. Seven grade 4 toxicities occurred (1.6%), all in the H&N region and most in paediatric patients with RMS. Six related to eyes (cataracts, retinopathy, scleral disorder) or ears (hearing impairment). CONCLUSIONS: This study is the largest to date for RMS and Ewing sarcoma, undergoing multimodality therapy including PBT. It demonstrates good local control, survival and acceptable toxicity rates.

A Novel Model and Infrastructure for Clinical Outcomes Data Collection and Their Systematic Evaluation for UK Patients Receiving Proton Beam Therapy.

AIMS: To establish an infrastructure for sustainable, comprehensive data collection and systematic outcomes evaluation for UK patients receiving proton beam therapy (PBT). MATERIALS AND METHODS: A Proton Outcomes Working Group was formed in 2014 to develop a national minimum dataset for PBT patients and to define a clinically integrated informatics solution for data collection. The Christie Proton Beam Therapy Centre formed its Proton Clinical Outcomes Unit in 2018 to collect, curate and analyse outcomes data prospectively for UK-treated patients and retrospectively for UK patients referred abroad for PBT since 2008 via the Proton Overseas Programme (POP). RESULTS: A single electronic form (eForm) was developed to capture the agreed data, using a data tree approach including conditional logic: data items are requested once, further questions depend on previous answers and are sensitive to tumour site and patient pathway time point. Relevant data automatically populate other forms, saving time, prompting completeness of clinical assessments and ensuring data consistency. Completed eForm data populate the electronic patient record and generate individualised outputs, including consultation letters, treatment summary and surveillance plans, based on organs at risk irradiated, age and sex. All data regarding POP-treated patients are verified and migrated into the system, ensuring that patient data, whether overseas or UK treated, are consistently recorded. The eForm utilises a 'user friendly' web portal interface, the Clinical Web Portal, including clickable tables and infographics. Data items are coded to a universally recognised standard comparable with other data systems. Patient-reported outcomes are also integrated, highlighting significant toxicities and prompting a response. Outcomes data can be correlated with dosimetric DICOM data to support radiation dose modelling. CONCLUSION: Outcomes data from both POP-treated and The Christie-treated patients support long-term care, allow evaluation of PBT efficacy and safety, assist future selection of PBT patients and support hypothesis generation for future clinical trials.

Prediction of radiation-induced mucositis of H&N cancer patients based on a large patient cohort.

PURPOSE/OBJECTIVE: Radiation-induced mucositis is a severe acute side effect, which can jeopardize treatment compliance and cause weight loss during treatment. The study aimed to develop robust models to predict the risk of severe mucositis. MATERIALS/METHODS: Mucosal toxicity scores were prospectively recorded for 802 consecutive Head and Neck (H&N) cancer patients and dichotomised into non-severe event (grade 0-2) and severe event (grade 3+) groups. Two different model approaches were utilised to evaluate the robustness of the models. These used LASSO and Best Subset selection combined with 10-fold cross-validation performed on two-thirds of the patient cohort using principal component analysis of DVHs. The remaining one-third of the patients were used for validation. Model performance was tested through calibration plot and model performance metrics. RESULTS: The main predicted risk factors were treatment acceleration and the first two principal dose components, which reflect the mean dose and the balance between high and low doses to the oral cavity. For the LASSO model, gender and current smoker status were also included in the model. The AUC values of the two models on the validation cohort were 0.797 (95%CI: 0.741-0.857) and 0.808 (95%CI: 0.749-0.859), respectively. The two models predicted very similar risk values with an internal Pearson coefficient of 0.954, indicating their robustness. CONCLUSIONS: Robust prediction models of the risk of severe mucositis have been developed based on information from the entire dose distribution for a large cohort of patients consisting of all patients treated H&N for within our institution over a five year period.

Comparison of multi-institutional pre-treatment verification for VMAT of nasopharynx with delivery errors.

PURPOSE: Measurement-based pre-treatment verification with phantoms frequently uses gamma analysis to assess acceptable delivery accuracy. This study evaluates the sensitivity of a commercial system to simulated machine errors for three different institutions' Volumetric Modulated Arc Therapy (VMAT) planning approaches. METHODS: VMAT plans were generated for ten patients at three institutions using each institution's own protocol (manually-planned at institution 1; auto-planned at institutions 2 and 3). Errors in Multi-Leaf Collimator (MLC) field size (FS), MLC shift (S), and collimator angle (C) of -5, -2, -1, 1, 2 and 5 mm or degrees were introduced. Dose metric constraints discriminated which error magnitudes were considered unacceptable. The smallest magnitude error treatment plans deemed clinically unacceptable (typically for a 5% dose change) were delivered to the ArcCHECK for all institutions, and with a high-dose point ion chamber measurement in 2 institutions. Error detection for different gamma analysis criteria was compared. RESULTS: Not all deliberately introduced VMAT plan errors were detected using a typical 3D 3%/3 mm global gamma pass rate of 95%. Considering all institutions, gamma analysis was least sensitive to negative FS errors. The most sensitive was a 2%/2 mm global analysis for institution 1, whilst for institution 2 it was 3%/3 mm global analysis. The majority of errors (58/59 for institution 1, 54/60 for institution 3) were detected using ArcCHECK and ion chamber measurements combined. CONCLUSIONS: Not all clinically unacceptable errors are detected. Combining ion chamber measurements with gamma analysis improved sensitivity and is recommended. Optimum gamma settings varied across institutions.

Characterisation of flattening filter free (FFF) beam properties for initial beam set-up and routine QA, independent of flattened beams.

Flattening filter free (FFF) beams have reached widespread use for clinical treatment deliveries. The usual methods for FFF beam characterisation for their quality assurance (QA) require the use of associated conventional flattened beams (cFF). Methods for QA of FFF without the need to use associated cFF beams are presented and evaluated against current methods for both FFF and cFF beams. Inflection point normalisation is evaluated against conventional methods for the determination of field size and penumbra for field sizes from 3 cm × 3 cm to 40 cm × 40cm at depths from dmax to 20 cm in water for matched and unmatched FFF beams and for cFF beams. A method for measuring symmetry in the cross plane direction is suggested and evaluated as FFF beams are insensitive to symmetry changes in this direction. Methods for characterising beam energy are evaluated and the impact of beam energy on profile shape compared to that of cFF beams. In-plane symmetry can be measured, as can cFF beams, using observed changes in profile, whereas cross-plane symmetry can be measured by acquiring profiles at collimator angles 0 and 180. Beam energy and 'unflatness' can be measured as with cFF beams from observed shifts in profile with changing beam energy. Normalising the inflection points of FFF beams to 55% results in an equivalent penumbra and field size measurement within 0.5 mm of conventional methods with the exception of 40 cm × 40 cm fields at a depth of 20 cm. New proposed methods are presented that make it possible to independently carry out set up and QA measurements on beam energy, flatness, symmetry and field size of an FFF beam without the need to reference to an equivalent flattened beam of the same energy. The methods proposed can also be used to carry out this QA for flattened beams, resulting in universal definitions and methods for MV beams. This is presented for beams produced by an Elekta linear accelerator, but is anticipated to also apply to other manufacturers' beams.

Deformable image registration for cervical cancer brachytherapy dose accumulation: Organ at risk dose-volume histogram parameter reproducibility and anatomic position stability.

PURPOSE: The purpose of this study was to determine the effect of deformable image registration (DIR) on cumulative organ at risk dose-volume histogram (DVH) parameter summation for more than three brachytherapy fractions. The reproducibility of different methods of DIR was tested. DIR was then used to assess the stability of the anatomic position of the DVH parameters within the bladder and rectum. METHODS AND MATERIALS: DIR was completed for 39 consecutive cervical cancer brachytherapy patients' planning CTs. Accumulated DVH parameters (D2cc and D0.1cc) for bladder and rectum were compared with dose summation without DIR. Reproducibility of DIR results was assessed for different methods of implementation based on adding contour biases added to the DIR algorithm. VolD2cc and VolD0.1cc structures were created from the overlap of the D2cc and D0.1cc isodose and the bladder or rectum, respectively. The overlap of VolD2cc and VolD0.1cc structures was calculated using the Dice similarity coefficient. RESULTS: DIR accumulated D2cc and D0.1cc decreased by an average of 2.9% and 4.2% for bladder and 5.08% and 2.8% for rectum compared with no DIR. DIR was most reproducible when the bladder or rectum contour was masked. The average Dice similarity coefficient was 0.78 and 0.61 for the bladder D2cc and D0.1cc as well as 0.83 and 0.62 for rectal D2cc and D0.1cc, respectively. CONCLUSIONS: Dose decreases were observed for accumulated DVH parameters using DIR. Adding contour-based biases to the algorithm increases the reproducibility of D2cc and D0.1cc accumulation. The anatomic position of VolD2cc was more stable than VolD0.1cc.

Does a too risk-averse approach to the implementation of new radiotherapy technologies delay their clinical use?

Radiotherapy is a generally safe treatment modality in practice; nevertheless, recent well-reported accidents also confirm its potential risks. However, this may obstruct or delay the introduction of new technologies and treatment strategies/techniques into clinical practice. Risks must be addressed and judged in a realistic context: risks must be assessed realistically. Introducing new technology may introduce new possibilities of errors. However, delaying the introduction of such new technology therefore means that patients are denied the potentially better treatment opportunities. Despite the difficulty in quantitatively assessing the risks on both sides of the possible choice of actions, including the "lost opportunity", the best estimates should be included in the overall risk-benefit and cost-benefit analysis. Radiotherapy requires a sufficiently high level of support for the safety, precision and accuracy required: radiotherapy development and implementation is exciting. However, it has been anxious with a constant awareness of the consequences of mistakes or misunderstandings. Recent history can be used to show that for introduction of advanced radiotherapy, the risk-averse medical physicist can act as an electrical fuse in a complex circuit. The lack of sufficient medical physics resource or expertise can short out this fuse and leave systems unsafe. Future technological developments will continue to present further safety and risk challenges. The important evolution of radiotherapy brings different management opinions and strategies. Advanced radiotherapy technologies can and should be safely implemented in as timely a manner as possible for the patient groups where clinical benefit is indicated.

Clinical use of diodes and micro-chambers to obtain accurate small field output factor measurements.

There have been substantial advances in small field dosimetry techniques and technologies, over the last decade, which have dramatically improved the achievable accuracy of small field dose measurements. This educational note aims to help radiation oncology medical physicists to apply some of these advances in clinical practice. The evaluation of a set of small field output factors (total scatter factors) is used to exemplify a detailed measurement and simulation procedure and as a basis for discussing the possible effects of simplifying that procedure. Field output factors were measured with an unshielded diode and a micro-ionisation chamber, at the centre of a set of square fields defined by a micro-multileaf collimator. Nominal field sizes investigated ranged from 6 × 6 to 98 × 98 mm(2). Diode measurements in fields smaller than 30 mm across were corrected using response factors calculated using Monte Carlo simulations of the diode geometry and daisy-chained to match micro-chamber measurements at intermediate field sizes. Diode measurements in fields smaller than 15 mm across were repeated twelve times over three separate measurement sessions, to evaluate the reproducibility of the radiation field size and its correspondence with the nominal field size. The five readings that contributed to each measurement on each day varied by up to 0.26  %, for the "very small" fields smaller than 15 mm, and 0.18 % for the fields larger than 15 mm. The diode response factors calculated for the unshielded diode agreed with previously published results, within uncertainties. The measured dimensions of the very small fields differed by up to 0.3 mm, across the different measurement sessions, contributing an uncertainty of up to 1.2 % to the very small field output factors. The overall uncertainties in the field output factors were 1.8 % for the very small fields and 1.1 % for the fields larger than 15 mm across. Recommended steps for acquiring small field output factor measurements for use in radiotherapy treatment planning system beam configuration data are provided.

Benchmarking of a treatment planning system for spot scanning proton therapy: comparison and analysis of robustness to setup errors of photon IMRT and proton SFUD treatment plans of base of skull meningioma.

PURPOSE: Base of skull meningioma can be treated with both intensity modulated radiation therapy (IMRT) and spot scanned proton therapy (PT). One of the main benefits of PT is better sparing of organs at risk, but due to the physical and dosimetric characteristics of protons, spot scanned PT can be more sensitive to the uncertainties encountered in the treatment process compared with photon treatment. Therefore, robustness analysis should be part of a comprehensive comparison between these two treatment methods in order to quantify and understand the sensitivity of the treatment techniques to uncertainties. The aim of this work was to benchmark a spot scanning treatment planning system for planning of base of skull meningioma and to compare the created plans and analyze their robustness to setup errors against the IMRT technique. METHODS: Plans were produced for three base of skull meningioma cases: IMRT planned with a commercial TPS [Monaco (Elekta AB, Sweden)]; single field uniform dose (SFUD) spot scanning PT produced with an in-house TPS (PSI-plan); and SFUD spot scanning PT plan created with a commercial TPS [XiO (Elekta AB, Sweden)]. A tool for evaluating robustness to random setup errors was created and, for each plan, both a dosimetric evaluation and a robustness analysis to setup errors were performed. RESULTS: It was possible to create clinically acceptable treatment plans for spot scanning proton therapy of meningioma with a commercially available TPS. However, since each treatment planning system uses different methods, this comparison showed different dosimetric results as well as different sensitivities to setup uncertainties. The results confirmed the necessity of an analysis tool for assessing plan robustness to provide a fair comparison of photon and proton plans. CONCLUSIONS: Robustness analysis is a critical part of plan evaluation when comparing IMRT plans with spot scanned proton therapy plans.

Design and experimental testing of air slab caps which convert commercial electron diodes into dual purpose, correction-free diodes for small field dosimetry.

PURPOSE: Two diodes which do not require correction factors for small field relative output measurements are designed and validated using experimental methodology. This was achieved by adding an air layer above the active volume of the diode detectors, which canceled out the increase in response of the diodes in small fields relative to standard field sizes. METHODS: Due to the increased density of silicon and other components within a diode, additional electrons are created. In very small fields, a very small air gap acts as an effective filter of electrons with a high angle of incidence. The aim was to design a diode that balanced these perturbations to give a response similar to a water-only geometry. Three thicknesses of air were placed at the proximal end of a PTW 60017 electron diode (PTWe) using an adjustable "air cap". A set of output ratios (ORDet (fclin) ) for square field sizes of side length down to 5 mm was measured using each air thickness and compared to ORDet (fclin) measured using an IBA stereotactic field diode (SFD). kQclin,Qmsr (fclin,fmsr) was transferred from the SFD to the PTWe diode and plotted as a function of air gap thickness for each field size. This enabled the optimal air gap thickness to be obtained by observing which thickness of air was required such that kQclin,Qmsr (fclin,fmsr) was equal to 1.00 at all field sizes. A similar procedure was used to find the optimal air thickness required to make a modified Sun Nuclear EDGE detector (EDGEe) which is "correction-free" in small field relative dosimetry. In addition, the feasibility of experimentally transferring kQclin,Qmsr (fclin,fmsr) values from the SFD to unknown diodes was tested by comparing the experimentally transferred kQclin,Qmsr (fclin,fmsr) values for unmodified PTWe and EDGEe diodes to Monte Carlo simulated values. RESULTS: 1.0 mm of air was required to make the PTWe diode correction-free. This modified diode (PTWeair) produced output factors equivalent to those in water at all field sizes (5-50 mm). The optimal air thickness required for the EDGEe diode was found to be 0.6 mm. The modified diode (EDGEeair) produced output factors equivalent to those in water, except at field sizes of 8 and 10 mm where it measured approximately 2% greater than the relative dose to water. The experimentally calculated kQclin,Qmsr (fclin,fmsr) for both the PTWe and the EDGEe diodes (without air) matched Monte Carlo simulated results, thus proving that it is feasible to transfer kQclin,Qmsr (fclin,fmsr) from one commercially available detector to another using experimental methods and the recommended experimental setup. CONCLUSIONS: It is possible to create a diode which does not require corrections for small field output factor measurements. This has been performed and verified experimentally. The ability of a detector to be "correction-free" depends strongly on its design and composition. A nonwater-equivalent detector can only be "correction-free" if competing perturbations of the beam cancel out at all field sizes. This should not be confused with true water equivalency of a detector.

Beam characteristics of energy-matched flattening filter free beams.

PURPOSE: Flattening filter free (FFF) linear accelerators can increase treatment efficiency and plan quality. There are multiple methods of defining a FFF beam. The Elekta control system supports tuning of the delivered FFF beam energy to enable matching of the percentage depth-dose (PDD) of the flattened beam at 10 cm depth. This is compared to FFF beams where the linac control parameters are identical to those for the flattened beam. All beams were delivered on an Elekta Synergy accelerator with an Agility multi-leaf collimator installed and compared to the standard, flattened beam. The aim of this study is to compare "matched" FFF beams to both "unmatched" FFF beams and flattened beams to determine the benefits of matching beams. METHODS: For the three modes of operation 6 MV flattened, 6 MV matched FFF, 6 MV unmatched FFF, 10 MV flattened, 10 MV matched FFF, and 10 MV unmatched FFF beam profiles were obtained using a plotting tank and were measured in steps of 0.1 mm in the penumbral region. Beam penumbra was defined as the distance between the 80% and 20% of the normalized dose when the inflection points of the unflattened and flattened profiles were normalized with the central axis dose of the flattened field set as 100%. PDD data was obtained at field sizes ranging from 3 cm × 3 cm to 40 cm × 40 cm. Radiation protection measurements were additionally performed to determine the head leakage and environmental monitoring through the maze and primary barriers. RESULTS: No significant change is made to the beam penumbra for FFF beams with and without PDD matching, the maximum change in penumbra for a 10 cm × 10 cm field was within the experimental error of the study. The changes in the profile shape with increasing field size are most significant for the matched FFF beam, and both FFF beams showed less profile shape variation with increasing depth when compared to flattened beams, due to consistency in beam energy spectra across the radiation field. The PDDs of the FFF beams showed less variation with field size, the d(max) value was deeper for the matched FFF beam than the FFF beam and deeper than the flattened beam for field sizes greater than 5 cm × 5 cm. The head leakage when using the machine in FFF mode is less than half that for a flattened beam, but comparable for both FFF modes. The radiation protection dose-rate measurements show an increase of instantaneous dose-rates when operating the machines in FFF mode but that increase is less than the ratio of MU/min produced by the machine. CONCLUSIONS: The matching of a FFF beam to a flattened beam at a depth of 10 cm in water by increasing the FFF beam energy does not reduce any of the reported benefits of FFF beams. Conversely, there are a number of potential benefits resulting from matching the FFF beam; the depth of maximum dose is deeper, the out of field dose is potentially reduced, and the beam quality and penetration more closely resembles the flattened beams currently used in clinical practice, making dose distributions in water more alike. Highlighted in this work is the fact that some conventional specifications and methods for measurement of beam parameters such as penumbra are not relevant and further work is required to address this situation with respect to "matched" FFF beams and to determine methods of measurement that are not reliant on an associated flattened beam.

A practical and theoretical definition of very small field size for radiotherapy output factor measurements.

PURPOSE: This work introduces the concept of very small field size. Output factor (OPF) measurements at these field sizes require extremely careful experimental methodology including the measurement of dosimetric field size at the same time as each OPF measurement. Two quantifiable scientific definitions of the threshold of very small field size are presented. METHODS: A practical definition was established by quantifying the effect that a 1 mm error in field size or detector position had on OPFs and setting acceptable uncertainties on OPF at 1%. Alternatively, for a theoretical definition of very small field size, the OPFs were separated into additional factors to investigate the specific effects of lateral electronic disequilibrium, photon scatter in the phantom, and source occlusion. The dominant effect was established and formed the basis of a theoretical definition of very small fields. Each factor was obtained using Monte Carlo simulations of a Varian iX linear accelerator for various square field sizes of side length from 4 to 100 mm, using a nominal photon energy of 6 MV. RESULTS: According to the practical definition established in this project, field sizes ≤ 15 mm were considered to be very small for 6 MV beams for maximal field size uncertainties of 1 mm. If the acceptable uncertainty in the OPF was increased from 1.0% to 2.0%, or field size uncertainties are 0.5 mm, field sizes ≤ 12 mm were considered to be very small. Lateral electronic disequilibrium in the phantom was the dominant cause of change in OPF at very small field sizes. Thus the theoretical definition of very small field size coincided to the field size at which lateral electronic disequilibrium clearly caused a greater change in OPF than any other effects. This was found to occur at field sizes ≤ 12 mm. Source occlusion also caused a large change in OPF for field sizes ≤ 8 mm. Based on the results of this study, field sizes ≤ 12 mm were considered to be theoretically very small for 6 MV beams. CONCLUSIONS: Extremely careful experimental methodology including the measurement of dosimetric field size at the same time as output factor measurement for each field size setting and also very precise detector alignment is required at field sizes at least ≤ 12 mm and more conservatively ≤ 15 mm for 6 MV beams. These recommendations should be applied in addition to all the usual considerations for small field dosimetry, including careful detector selection.

A dosimetric characterization of a novel linear accelerator collimator.

PURPOSE: The aim of this work is to characterize a new linear accelerator collimator which contains a single pair of sculpted diaphragms mounted orthogonally to a 160 leaf multileaf collimator (MLC). The diaphragms have "thick" regions providing full attenuation and "thin" regions where attenuation is provided by both the leaves and the diaphragm. The leaves are mounted on a dynamic leaf guide allowing rapid leaf motion and leaf travel over 350 mm. METHODS: Dosimetric characterization, including assessment of leaf transmission, leaf tip transmission, penumbral width, was performed in a plotting tank. Head scatter factor was measured using a mini-phantom and the effect of leaf guide position on output was assessed using a water phantom. The tongue and groove effect was assessed using multiple exposures on radiochromic film. Leaf reproducibility was assessed from portal images of multiple abutting fields. RESULTS: The maximum transmission through the multileaf collimator is 0.44% at 6 MV and 0.52% at 10 MV. This reduced to 0.22% and 0.27%, respectively, when the beam passes through the dynamic leaf guide in addition to the MLC. The maximum transmission through the thick part of the diaphragm is 0.32% and 0.36% at 6 and 10 MV. The combination of leaf and diaphragm transmission ranges from 0.08% to 0.010% at 6 MV and 0.10% to 0.14% depending on whether the shielding is through the thick or thin part of the diaphragm. The off-axis intertip transmission for a zero leaf gap is 2.2% at 6 and 10 MV. The leaf tip penumbra for a 100 × 100 mm field ranges from 5.4 to 4.3 mm at 6 and 10 MV across the full range of leaf motion when measured in the AB direction, which reduces to 4.0-3.4 mm at 6 MV and 4.5-3.8 mm at 10 MV when measured in the GT direction. For a 50 × 50 mm field, the diaphragm penumbra ranges from 4.3 to 3.7 mm at 6 MV and 4.5 to 4.1 mm at 10 MV in the AB direction and 3.7 to 3.2 mm at 6 MV and 4.2 to 3.7 mm when measured in the GT direction. The tongue and groove effect observed from exposure of a radiochromic film to two abutting fields is an underdose of 25%. The head scatter factor at both 6 and 10 MV is similar to that from the MLCi2 collimator to within 0.8%. The uncertainty in the leaf position reproducibility is 0.05 mm (2σ). CONCLUSIONS: The Agility collimator is a low leakage, high definition collimator where both the MLC and the sculpted diaphragm have been optimized for dynamic treatments.

Small field dosimetric characterization of a new 160-leaf MLC.

The goal of this work was to perform a 6 MV small field characterization of the new Agility 160-leaf multi-leaf collimator (MLC) from Elekta. This included profile measurement analysis and central axis relative output measurements using various diode detectors and an air-core fiber optic scintillation dosimeter (FOD). Data was acquired at a depth of 10.0 cm for field sizes of 1.0, 0.9, 0.8, 0.7, 0.6 and 0.5 cm. Three experimental data sets, comprised of five readings, were made for both the relative output and profile measurements. Average detector-specific output ratios (OR[overline](f(clin))(det))) were calculated with respect to a field size of 3.0 cm and small field replacement correction factors (k(f(clin),f(msr))(Q(clin),Q(msr))) derived for the diodes using the scintillation dosimeter readings as the baseline. The standard experimental uncertainty on OR[overline](f(clin))(det)) was calculated at a 90% confidence interval and the coefficient of variation (CV) used to characterize the detector-specific measurement precision. The positional accuracy of the collimation system was also investigated by analyzing the repeated profile measurements and field width constancy investigated as a function of collimator rotation. For comparison the output and profile measurements were repeated using the Elekta 80-leaf MLCi2 on a beam matched linac at 6 MV. The measured OR[overline](f(clin))(det)) varied as a function of detector and MLC design. At the smallest field size the standard experimental uncertainty on OR[overline](f(clin))(det)) was consistent across all detectors at approximately 0.5% and 1.0% for Agility and MLCi2 collimators respectively. The CV associated with the FOD measurements were greater than that of the diodes but did not translate into increased measurement uncertainty. At the smallest field size, the diode detector correction factors were approximately 2% greater for MLCi2 than that required for the Agility. Profile data revealed the Agility MLC to have a greater positional reproducibility than both the MLCi2 and the linac diaphragms (jaws), as also reflected in the experimental uncertainties on OR[overline](f(clin))(det)). The relative output, profile widths and associated uncertainties were all found to differ between the two MLC systems investigated, as were the field size specific diode detector replacement correction factors. The data also clearly showed that the Agility 160-leaf MLC performs to a tighter positional tolerance than the MLCi2.

Monte Carlo investigation of I-125 interseed attenuation for standard and thinner seeds in prostate brachytherapy with phantom validation using a MOSFET.

PURPOSE: In permanent seed implant prostate brachytherapy the actual dose delivered to the patient may be less than that calculated by TG-43U1 due to interseed attenuation (ISA) and differences between prostate tissue composition and water. In this study the magnitude of the ISA effect is assessed in a phantom and in clinical prostate postimplant cases. Results are compared for seed models 6711 and 9011 with 0.8 and 0.5 mm diameters, respectively. METHODS: A polymethyl methacrylate (PMMA) phantom was designed to perform ISA measurements in a simple eight-seed arrangement and at the center of an implant of 36 seeds. Monte Carlo (MC) simulation and experimental measurements using a MOSFET dosimeter were used to measure dose rate and the ISA effect. MC simulations of 15 CT-based postimplant prostate treatment plans were performed to compare the clinical impact of ISA on dose to prostate, urethra, rectum, and the volume enclosed by the 100% isodose, for 6711 and 9011 seed models. RESULTS: In the phantom, ISA reduced the dose rate at the MOSFET position by 8.6%-18.3% (6711) and 7.8%-16.7% (9011) depending on the measurement configuration. MOSFET measured dose rates agreed with MC simulation predictions within the MOSFET measurement uncertainty, which ranged from 5.5% to 7.2% depending on the measurement configuration (k = 1, for the mean of four measurements). For 15 clinical implants, the mean ISA effect for 6711 was to reduce prostate D90 by 4.2 Gy (3%), prostate V100 by 0.5 cc (1.4%), urethra D10 by 11.3 Gy (4.4%), rectal D2cc by 5.5 Gy (4.6%), and the 100% isodose volume by 2.3 cc. For the 9011 seed the mean ISA effect reduced prostate D90 by 2.2 Gy (1.6%), prostate V100 by 0.3 cc (0.7%), urethra D10 by 8.0 Gy (3.2%), rectal D2cc by 3.1 Gy (2.7%), and the 100% isodose volume by 1.2 cc. Differences between the MC simulation and TG-43U1 consensus data for the 6711 seed model had a similar impact, reducing mean prostate D90 by 6 Gy (4.2%) and V100 by 0.6 cc (1.8%). CONCLUSIONS: ISA causes the delivered dose in prostate seed implant brachytherapy to be lower than the dose calculated by TG-43U1. MC simulation of phantom seed arrangements show that dose at a point can be reduced by up to 18% and this has been validated using a MOSFET dosimeter. Clinical simulations show that ISA reduces DVH parameter values, but the reduction is less for thinner seeds.

Monte Carlo modelling of diode detectors for small field MV photon dosimetry: detector model simplification and the sensitivity of correction factors to source parameterization.

The goal of this work was to examine the use of simplified diode detector models within a recently proposed Monte Carlo (MC) based small field dosimetry formalism and to investigate the influence of electron source parameterization has on MC calculated correction factors. BEAMnrc was used to model Varian 6 MV jaw-collimated square field sizes down to 0.5 cm. The IBA stereotactic field diode (SFD), PTW T60016 (shielded) and PTW T60017 (un-shielded) diodes were modelled in DOSRZnrc and isocentric output ratios (OR(fclin)(detMC)) calculated at depths of d = 1.5, 5.0 and 10.0 cm. Simplified detector models were then tested by evaluating the percent difference in (OR(fclin)(detMC)) between the simplified and complete detector models. The influence of active volume dimension on simulated output ratio and response factor was also investigated. The sensitivity of each MC calculated replacement correction factor (k(fclin,fmsr)(Qclin,Qmsr)), as a function of electron FWHM between 0.100 and 0.150 cm and energy between 5.5 and 6.5 MeV, was investigated for the same set of small field sizes using the simplified detector models. The SFD diode can be approximated simply as a silicon chip in water, the T60016 shielded diode can be modelled as a chip in water plus the entire shielding geometry and the T60017 unshielded diode as a chip in water plus the filter plate located upstream. The detector-specific (k(fclin,fmsr)(Qclin,Qmsr)), required to correct measured output ratios using the SFD, T60016 and T60017 diode detectors are insensitive to incident electron energy between 5.5 and 6.5 MeV and spot size variation between FWHM = 0.100 and 0.150 cm. Three general conclusions come out of this work: (1) detector models can be simplified to produce OR(fclin)(detMC) to within 1.0% of those calculated using the complete geometry, where typically not only the silicon chip, but also any high density components close to the chip, such as scattering plates or shielding material is necessary to be included in the model, (2) diode detectors of smaller active radius require less of a correction and (3) (k(fclin,fmsr)(Qclin,Qmsr)) is insensitive to the incident the electron energy and spot size variations investigated. Therefore, simplified detector models can be used with acceptable accuracy within the recently proposed small field dosimetry formalism.

An evaluation of four CT-MRI co-registration techniques for radiotherapy treatment planning of prone rectal cancer patients.

OBJECTIVES: MRI is the preferred staging modality for rectal carcinoma patients. This work assesses the CT-MRI co-registration accuracy of four commercial rigid-body techniques for external beam radiotherapy treatment planning for patients treated in the prone position without fiducial markers. METHODS: 17 patients with biopsy-proven rectal carcinoma were scanned with CT and MRI in the prone position without the use of fiducial markers. A reference co-registration was performed by consensus of a radiologist and two physicists. This was compared with two automated and two manual techniques on two separate treatment planning systems. Accuracy and reproducibility were analysed using a measure of target registration error (TRE) that was based on the average distance of the mis-registration between vertices of the clinically relevant gross tumour volume as delineated on the CT image. RESULTS: An automated technique achieved the greatest accuracy, with a TRE of 2.3 mm. Both automated techniques demonstrated perfect reproducibility and were significantly faster than their manual counterparts. There was a significant difference in TRE between registrations performed on the two planning systems, but there were no significant differences between the manual and automated techniques. CONCLUSION: For patients with rectal cancer, MRI acquired in the prone treatment position without fiducial markers can be accurately registered with planning CT. An automated registration technique offered a fast and accurate solution with associated uncertainties within acceptable treatment planning limits.