The Association of Incidental Radiation Dose to the Heart Base with Overall Survival and Cardiac Events after Curative-intent Radiotherapy for Non-small Cell Lung Cancer: Results from the NI-HEART Study.

AIMS: Cardiac disease is a dose-limiting toxicity in non-small cell lung cancer radiotherapy. The dose to the heart base has been associated with poor survival in multiple institutional and clinical trial datasets using unsupervised, voxel-based analysis. Validation has not been undertaken in a cohort with individual patient delineations of the cardiac base or for the endpoint of cardiac events. The purpose of this study was to assess the association of heart base radiation dose with overall survival and the risk of cardiac events with individual heart base contours. MATERIALS AND METHODS: Patients treated between 2015 and 2020 were reviewed for baseline patient, tumour and cardiac details and both cancer and cardiac outcomes as part of the NI-HEART study. Three cardiologists verified cardiac events including atrial fibrillation, heart failure and acute coronary syndrome. Cardiac substructure delineations were completed using a validated deep learning-based autosegmentation tool and a composite cardiac base structure was generated. Cox and Fine-Gray regressions were undertaken for the risk of death and cardiac events. RESULTS: Of 478 eligible patients, most received 55 Gy/20 fractions (96%) without chemotherapy (58%), planned with intensity-modulated radiotherapy (71%). Pre-existing cardiovascular morbidity was common (78% two or more risk factors, 46% one or more established disease). The median follow-up was 21.1 months. Dichotomised at the median, a higher heart base Dmax was associated with poorer survival on Kaplan-Meier analysis (20.2 months versus 28.3 months; hazard ratio 1.40, 95% confidence interval 1.14-1.75, P = 0.0017) and statistical significance was retained in multivariate analyses. Furthermore, heart base Dmax was associated with pooled cardiac events in a multivariate analysis (hazard ratio 1.75, 95% confidence interval 1.03-2.97, P = 0.04). CONCLUSIONS: Heart base Dmax was associated with the rate of death and cardiac events after adjusting for patient, tumour and cardiovascular factors in the NI-HEART study. This validates the findings from previous unsupervised analytical approaches. The heart base could be considered as a potential sub-organ at risk towards reducing radiation cardiotoxicity.

Is community treatment best? a randomised trial comparing delivery of cancer treatment in the hospital, home and GP surgery.

BACKGROUND: Care closer to home is being explored as a means of improving patient experience as well as efficiency in terms of cost savings. Evidence that community cancer services improve care quality and/or generate cost savings is currently limited. A randomised study was undertaken to compare delivery of cancer treatment in the hospital with two different community settings. METHODS: Ninety-seven patients being offered outpatient-based cancer treatment were randomised to treatment delivered in a hospital day unit, at the patient's home or in local general practice (GP) surgeries. The primary outcome was patient-perceived benefits, using the emotional function domain of the EORTC quality of life (QOL) QLQC30 questionnaire evaluated after 12 weeks. Secondary outcomes included additional QOL measures, patient satisfaction, safety and health economics. RESULTS: There was no statistically significant QOL difference between treatment in the combined community locations relative to hospital (difference of -7.2, 95% confidence interval: -19·5 to +5·2, P=0.25). There was a significant difference between the two community locations in favour of home (+15·2, 1·3 to 29·1, P=0.033). Hospital anxiety and depression scale scores were consistent with the primary outcome measure. There was no evidence that community treatment compromised patient safety and no significant difference between treatment arms in terms of overall costs or Quality Adjusted Life Year. Seventy-eight percent of patients expressed satisfaction with their treatment whatever their location, whereas 57% of patients preferred future treatment to continue at the hospital, 81% at GP surgeries and 90% at home. Although initial pre-trial interviews revealed concerns among health-care professionals and some patients regarding community treatment, opinions were largely more favourable in post-trial interviews. INTERPRETATION: Patient QOL favours delivering cancer treatment in the home rather than GP surgeries. Nevertheless, both community settings were acceptable to and preferred by patients compared with hospital, were safe, with no detrimental impact on overall health-care costs.

Radiomics for Predicting Lung Cancer Outcomes Following Radiotherapy: A Systematic Review.

Lung cancer's radiomic phenotype may potentially inform clinical decision-making with respect to radical radiotherapy. At present there are no validated biomarkers available for the individualisation of radical radiotherapy in lung cancer and the mortality rate of this disease remains the highest of all other solid tumours. MEDLINE was searched using the terms 'radiomics' and 'lung cancer' according to the Preferred Reporting Items for Systematic Reviews and Met-Analyses (PRISMA) guidance. Radiomics studies were defined as those manuscripts describing the extraction and analysis of at least 10 quantifiable imaging features. Only those studies assessing disease control, survival or toxicity outcomes for patients with lung cancer following radical radiotherapy ± chemotherapy were included. Study titles and abstracts were reviewed by two independent reviewers. The Radiomics Quality Score was applied to the full text of included papers. Of 244 returned results, 44 studies met the eligibility criteria for inclusion. End points frequently reported were local (17%), regional (17%) and distant control (31%), overall survival (79%) and pulmonary toxicity (4%). Imaging features strongly associated with clinical outcomes include texture features belonging to the subclasses Gray level run length matrix, Gray level co-occurrence matrix and kurtosis. The median cohort size for model development was 100 (15-645); in the 11 studies with external validation in a separate independent population, the median cohort size was 84 (21-295). The median number of imaging features extracted was 184 (10-6538). The median Radiomics Quality Score was 11% (0-47). Patient-reported outcomes were not incorporated within any studies identified. No studies externally validated a radiomics signature in a registered prospective study. Imaging-derived indices attained through radiomic analyses could equip thoracic oncologists with biomarkers for treatment response, patterns of failure, normal tissue toxicity and survival in lung cancer. Based on routine scans, their non-invasive nature and cost-effectiveness are major advantages over conventional pathological assessment. Improved tools are required for the appraisal of radiomics studies, as significant barriers to clinical implementation remain, such as standardisation of input scan data, quality of reporting and external validation of signatures in randomised, interventional clinical trials.

Observed high incidence of prostatic calculi with the potential to act as natural fiducials for prostate image guided radiotherapy.

PURPOSE: This study aims to quantify the incidence and distribution of prostatic calculi in a population of prostate radiotherapy patients and assess their potential role in prostate image guided radiotherapy (IGRT). METHODS & MATERIALS: A retrospective analysis of trans-rectal ultrasound (TRUS), computed tomography (CT) planning and treatment verification cone beam CT (CBCT) scans from radical prostate radiotherapy patients (external beam and brachytherapy) between 2012 and 2014 was undertaken by a single experienced observer. An internationally validated schema from the Prostate Imaging Reporting and Data system (PIRADS) was used to map the location of calculi. The association of calculi with patient and disease characteristics was explored. Data was analysed using SPSS (IBM version 22.0) using descriptive statistical methods and logistic binary regression analysis. RESULTS: 389 scan sets from 254 patients were included in the analysis. The overall incidence of calculi was 85% (n = 218) of which 79% (n = 201) were intra-prostatic calculi. The mean number of intra-prostatic calculi was 2 (range 1-10) and the mean size of calculi was 3.7 mm (range 0.5-15 mm). Calculi were most frequently observed in the posterior of the mid-gland (PI-RADs 3p, 9p) and posterior of the apex (PI-RADs 5p, 11p). 99% (n = 135) of CT planning scans with a corresponding CBCT had calculi in the same PIRADs location and all calculi were visible at the last fraction. There was no statistically significant association of calculi and N stage, M stage or Gleason score. CONCLUSIONS: A significant proportion of prostate radiotherapy patients have prostatic calculi detectable on pre radiotherapy imaging. Calculi observed on CT were also detectable on CBCT in 99% of cases and remain visible at the end of treatment. These findings add to the growing evidence base supporting the potential of calculi as an alternative to fiducial markers to aid prostate IGRT.

Erratum to "Observed high incidence of prostatic calculi with the potential to act as natural fiducials for prostate image guided radiotherapy" [Tech. Innov. Patient Support Radiat. Oncol. 9 (2019) 35-40].

[This corrects the article DOI: 10.1016/j.tipsro.2019.01.004.].

Radical radiation therapy in a patient with head and neck cancer and severe Parkinson's disease.

We report the case of a 61-year-old man with severe Parkinson's disease, who was successfully treated with postoperative radiation therapy for a T4N2cM0 transglottic squamous cell carcinoma of the larynx, with the aid of a deep brain stimulator.

Time-resolved dosimetric verification of respiratory-gated radiotherapy exposures using a high-resolution 2D ionisation chamber array.

The aim of this work was to track and verify the delivery of respiratory-gated irradiations, performed with three versions of TrueBeam linac, using a novel phantom arrangement that combined the OCTAVIUS(®) SRS 1000 array with a moving platform. The platform was programmed to generate sinusoidal motion of the array. This motion was tracked using the real-time position management (RPM) system and four amplitude gating options were employed to interrupt MV beam delivery when the platform was not located within set limits. Time-resolved spatial information extracted from analysis of x-ray fluences measured by the array was compared to the programmed motion of the platform and to the trace recorded by the RPM system during the delivery of the x-ray field. Temporal data recorded by the phantom and the RPM system were validated against trajectory log files, recorded by the linac during the irradiation, as well as oscilloscope waveforms recorded from the linac target signal. Gamma analysis was employed to compare time-integrated 2D x-ray dose fluences with theoretical fluences derived from the probability density function for each of the gating settings applied, where gamma criteria of 2%/2 mm, 1%/1 mm and 0.5%/0.5 mm were used to evaluate the limitations of the RPM system. Excellent agreement was observed in the analysis of spatial information extracted from the SRS 1000 array measurements. Comparisons of the average platform position with the expected position indicated absolute deviations of <0.5 mm for all four gating settings. Differences were observed when comparing time-resolved beam-on data stored in the RPM files and trajectory logs to the true target signal waveforms. Trajectory log files underestimated the cycle time between consecutive beam-on windows by 10.0 ± 0.8 ms. All measured fluences achieved 100% pass-rates using gamma criteria of 2%/2 mm and 50% of the fluences achieved pass-rates >90% when criteria of 0.5%/0.5 mm were used. Results using this novel phantom arrangement indicate that the RPM system is capable of accurately gating x-ray exposure during the delivery of a fixed-field treatment beam.

A review of recent advances in optical fibre sensors for in vivo dosimetry during radiotherapy.

This article presents an overview of the recent developments and requirements in radiotherapy dosimetry, with particular emphasis on the development of optical fibre dosemeters for radiotherapy applications, focusing particularly on in vivo applications. Optical fibres offer considerable advantages over conventional techniques for radiotherapy dosimetry, owing to their small size, immunity to electromagnetic interferences, and suitability for remote monitoring and multiplexing. The small dimensions of optical fibre-based dosemeters, together with being lightweight and flexible, mean that they are minimally invasive and thus particularly suited to in vivo dosimetry. This means that the sensor can be placed directly inside a patient, for example, for brachytherapy treatments, the optical fibres could be placed in the tumour itself or into nearby critical tissues requiring monitoring, via the same applicators or needles used for the treatment delivery thereby providing real-time dosimetric information. The article outlines the principal sensor design systems along with some of the main strengths and weaknesses associated with the development of these techniques. The successful demonstration of these sensors in a range of different clinical environments is also presented.

Changes to dose in the build-up region when using multi-leaf collimators in place of lead blocks supported on an accessory tray.

Doses in the build-up region have been compared for regular fields with and without a perspex accessory tray and for two irregular fields defined by either a Philips multi-leaf collimator (MLC) or lead blocks. The results show an increase in doses within the build-up region, by up to a factor of two, primarily due to the presence of the accessory tray. Fields shaped with the MLC exhibited build-up characteristics similar to those in unblocked fields and hence there will be systematic changes to the build-up dose when treatments are transferred from lead blocking techniques to those using an MLC mounted within the treatment head.

Quality control aspects of the Philips multileaf collimator.

BACKGROUND AND PURPOSE: Linear accelerators equipped with multileaf collimators (MLCs) are becoming more common and are widely available from most commercial manufacturers. There is a need to ensure they retain their commissioning specification using a preventative maintenance and quality control (QC) programme. This paper considers the design criteria of the Philips MLC which are important to the production of a comprehensive quality control programme. MATERIALS AND METHODS: The specific QC problems related to MLCs are identified as the positional accuracy of the leaves and their relationship to the back-up collimators, leakage considerations, the relationship of X-ray to light field and the influence of gravity on the positioning and leakage characteristics of the leaves. These problems are considered in relation to the general design considerations of the MLC, and methods of performing routine quality control checks are discussed. RESULTS AND CONCLUSIONS: The introduction of MLCs into clinical use results in new QC procedures being developed but it can be concluded that for the Philips MLC only an extra 30 min of QC time is needed per month and that its use has added little to the general down-time of this department.

The design and evaluation of a phantom for the audit of the treatment chain for prostate radiotherapy.

BACKGROUND AND PURPOSE: A phantom has been designed and built for a multi-institutional technique audit of the planning and delivery for radiotherapy to the prostate. The phantom was designed to test both the geometric and dosimetric accuracy of each aspect of the process. MATERIALS AND METHODS: The phantom consists of two curved water filled perspex tanks either side of a central block of solid water equivalent material. There are two options for the central section; a target defining block and a dose measurement block. The target defining block uses air holes to define a 3-D target volume for imaging via a CT scanner or a simulator. These holes can subsequently be filled with steel pins to allow megavoltage imaging. The dose measurement block allows thimble chamber measurements to be made at pre-selected points in a 5x5mm array. Five dose measurement points, typical for a prostate planning target volume (PTV) were selected. Initial evaluation of the phantom was performed by auditing the prostate radiotherapy planning and treatment chain at one institution. RESULTS: Agreement between the phantom and planned geometry confirmed that the stages of image acquisition, transfer and manipulation were accurately performed. Agreement within 0.5% was found between phantom and water tank measurements for dose calibration at a reference point. The measured dose delivered was within 2% of the dose calculated by the planning computer for all of the selected measurement points. The target volume marked by the steel pins was visible using electronic portal imaging. CONCLUSIONS: The phantom is a useful tool for the technique audit of prostate radiotherapy.

Customised compensation using intensity modulated beams delivered by dynamic multileaf collimation.

BACKGROUND AND PURPOSE: This paper describes the development of customised compensation by intensity modulated radiation therapy (IMRT), delivered by dynamic application of a multileaf collimator (MLC), in order to improve dose homogeneity in treatments of the pelvic region. The introduction of this simple IMRT procedure will help facilitate the clinical implementation of more complex 3D conformal therapy techniques. MATERIALS AND METHOD: Computer software is used to generate profiles of the intensity modulated beams which are required to deliver a uniform dose in a plane, passing through the isocentre and normal to the beam axis, under an irregular surface contour. These profiles are then operated on by interpreter software which determines the leaf trajectories that are necessary to deliver these beam profiles using a single, unidirectional sweep of the MLC leaves. A full dose calculation based on the calculated leaf positions is subsequently performed, allowing further fine adjustments to the modulation where required. RESULTS AND CONCLUSION: The compensation procedure has been successfully tested using films placed under a test phantom. The effect of the compensation procedure on dose distributions in the transverse plane has been investigated using an anthropomorphic phantom. Overall dose homogeneity has been improved through the use of customised compensation delivered by dynamic multileaf collimation.

Clinical implementation of dynamic multileaf collimation for compensated bladder treatments.

BACKGROUND AND PURPOSE: To describe the clinical implementation of dynamic multileaf collimation (DMLC). Custom compensated four-field treatments of carcinoma of the bladder have been used as a simple test site for the introduction of intensity modulated radiotherapy. MATERIALS AND METHODS: Compensating intensity modulations are calculated from computed tomography (CT) data, accounting for scattered, as well as primary radiation. Modulations are converted to multileaf collimator (MLC) leaf and jaw settings for dynamic delivery on a linear accelerator. A full dose calculation is carried out, accounting for dynamic leaf and jaw motion and transmission through these components. Before treatment, a test run of the delivery is performed and an absolute dose measurement made in a water or solid water phantom. Treatments are verified by in vivo diode measurements and real-time electronic portal imaging. RESULTS: Seven patients have been treated using DMLC. The technique improves dose homogeneity within the target volume, reducing high dose areas and compensating for loss of scatter at the beam edge. A typical total treatment time is 20 min. CONCLUSIONS: Compensated bladder treatments have proven an effective test site for DMLC in an extremely busy clinic.

High technology to simplify the planning and delivery of radiotherapy.

Two techniques for the automatic selection of individual leaf positions of a Philips multi-leaf collimator are described. Target volumes are identified either on simulator images or on cross-sectional images from CT or MR scanners. The setting of each leaf is computed to position the beam edge to cover the target with an appropriate, user defined, margin. An important consideration in the development of the system was its robustness and so the applications initially implemented have been relatively simple, comprising single field, parallel opposed fields and coplanar 4 field box techniques. Attention has been paid to the overall integrity of the planning and treatment delivery process. Before treatment commences, the beam shapes, which have been generated by the computer and transferred to the MLC control computer over a local area network, are checked against a printed template representing each beam. All data used for planning is archived and is accessible for review or, if necessary, for treatment modification.

Monitor chamber backscatter for intensity modulated radiation therapy using multileaf collimators.

Backscattered radiation into the machine monitor chamber can affect the machine output variation, with changes in field size and shape. For intensity modulated radiation therapy (IMRT) where many field, which may have small dimensions, are summed to give an intensity modulated field, the magnitude of backscatter will be different due to both the backscattering surface area changing, and the delivered monitor units being larger than for the equivalent static field. The effect of backscatter variation with field size for a Philips SL15 accelerator has been investigated at 8 MV for static and IMRT fields both in the standard clinical operating condition where an anti-backscatter plate is fitted, and also for a case where the anti-backscatter plate has been removed. The results show that in the absence of the anti-backscatter plate the variation in output between a 4 cm by 4 cm field and a 40 cm by 40 cm field size due to backscattered radiation was 5% for static fields. The anti-backscatter plate reduced this variation to less than 1%. When the accelerator operated in IMRT mode, with the backscatter plate in place, changes in the output due to additional backscattered radiation were less than 0.3%. With the backscatter plate removed, the outputs were lower, indicating the presence of additional backscattered radiation. It can be concluded that for the Philips MLC and SL accelerator with its anti-backscatter plate, the effects of backscattered radiation can be ignored for both static and IMRT fields.

Head scatter modelling for irregular field shaping and beam intensity modulation.

Scattered radiation from within the treatment head can contribute significant dose to all parts of a radiotherapy treatment field. A multileaf collimator may be used to create an arbitrarily shaped field, and may also be used, under dynamic control, to modulate the beam intensity over the field. This method of intensity modulation is effectively a superposition of a large number of fields which have the same beam direction, but different shapes, and some of these shapes may have unusually small dimensions, particularly in the direction of the leaf movement. Two models for predicting the head scatter under these conditions have been investigated. These are a first-order Compton scatter approximation from the flattening filter, and an empirical fit to measured data using an exponential function. The first model only considers scatter from the flattening filter and has been applied to field sizes between 2 cm by 2 cm and 10 cm by 10 cm, where agreements are all within 1%. However it is not satisfactory at larger field sizes where small scatter contributions, from scattering sources other than the flattening filter, are integrated over large areas. The second model uses measured data between 4 cm by 4 cm and 30 cm by 30 cm to optimize the exponential function and is used to calculate the head scatter contribution for all field sizes. In this case good agreement is achieved over the full field size range, and hence this is a more generally applicable model. Results are presented for static irregularly shaped fields and intensity modulated beams created using a Philips multileaf collimator.

The variation in output of symmetric, asymmetric and irregularly shaped wedged radiotherapy fields.

A model for calculating the variation in output of symmetric, asymmetric and irregularly shaped wedged radiotherapy fields is presented. The variation in output from the treatment head when a wedge is used is calculated by dividing the output into a primary component and one due to scattered radiation. The scatter component is then further subdivided into contributions from elements which have a 1 cm x 1 cm cross-sectional area at the isocentre. The scatter from each element is determined as the contribution from the head scatter component modified by the presence of the wedge and a contribution due to additional scattered radiation from the wedge. The relative intensity of the scattered radiation from the wedge is modelled using a simple first scatter approximation. In this approximation the magnitude of the scatter is given by a t exp(-mu t) function where t is the thickness of the wedge for the selected element. The magnitude of the primary component and the relative intensity of scatter from each element are then obtained by an iterative fit to measured data. The technique has been applied to two different internally mounted wedge designs, for a standard treatment head, two asymmetric treatment heads and two similar multileaf collimators, over a range of energies between 4 and 20 MV. Calculations agree with measured values over a range of field sizes and shapes to within 1.5%.

Electron contamination and build-up doses in conformal radiotherapy fields.

The dose in the build-up region depends upon the primary photon beam, backscattered radiation from the patient and contamination radiation from outside the patient. In this paper, a model based on measured data is proposed which allows the build-up dose for arbitrarily shaped treatment fields to be determined. The dose in the build-up region is assumed to comprise a primary photon component and a contamination component that is a function of the field size and shape. This contamination component, for modelling purposes, is subdivided into contributions that correspond to elements of 1 cm by 1 cm cross-sectional area at the plane of the isocentre. The magnitude of these components has been obtained by fitting measured data to an exponential function. The exponent was found to vary linearly with depth for energies between 4 MV and 20 MV. The coefficient decreased linearly with depth at 4, 6 and 8 MV, but exhibited a broad build-up region at 20 MV. The primary component, in the build-up region, could be approximated by a 100 - (100 - PSD) e(-mu d) function, where PSD is the primary surface dose. The values obtained during the fitting procedure were used to calculate dose in the build-up region for arbitrarily shaped fields. Good agreement was found in each case.

A macropencil beam model: clinical implementation for conformal and intensity modulated radiation therapy.

The increasing use of irregularly shaped, off-centre fields in advanced treatment techniques, particularly intensity modulated radiation therapy, has strained the limits of conventional, broad-beam dose calculation algorithms. More recent models, such as kernel-based pencil beams and Monte Carlo methods, are accurate but suffer from the time needed for calculations and from the lack of clearly established methods for determining the parameters needed to match calculations with the particular dosimetric characteristics of an individual machine. This paper presents the implementation of a model that uses an extended source model to calculate the variation of fluence at the patient surface for any arbitrarily shaped field. It uses a macropencil beam model to calculate phantom scatter. Both head scatter and phantom scatter models use exponential functions fit to a series of measurements to determine the model's parameters. The means by which the model can be implemented in a clinical setting using standard dosimetric equipment is presented. Results for two separate machines and three energies are presented. Comparisons with measurements for a set of regular and irregular fields demonstrate the accuracy of the model for conventional, conformal and intensity modulated treatments. For rectangular and irregular fields at depths up to 20 cm, the accuracy was better than < or =1.5%, compared with errors of up to 7.5% with a standard algorithm. For a 20-step intensity modulated field, the accuracy was 3.4% compared with 18% with the conventional algorithm. The advantages of this model for IMRT are discussed.

The measurement of kappach factors for application with the IPEMB very low energy dosimetry protocol.

In 1996. the IPEMB issued a new code of practice detailing the procedures by which the output of therapeutic kilovoltage x-ray devices are to be determined. For x-ray beam qualities in the range 0.035-1.0 mm Al half-value thickness (HVL), the equation for converting the instrument reading into absorbed dose to water contained a factor named kch. This was included to account for the change in response of the parallel plate chamber from its calibration conditions free in air to those in the user's measurement phantom. As no data were available with which to quantify this factor at very low energies, the code advised that the user take a value of unity until sufficient data became available upon which to base an addendum. In this work, kch values have been determined for four chambers: two PTW 23344 large volume soft x-ray chambers, one PTW 23342 small volume soft x-ray chamber and a Markus electron chamber. Variations in the value of kch were investigated for changes in FSD, applicator size and beam quality. The water equivalence of the Mix-D phantom used for these measurements was also verified. A comparison of the results for the two PTW 23344 chambers showed no significant differences for any experimental situation, indicating that kch is a factor of chamber design rather than variations in construction. No variation in kch was identified with changes in FSD. A small dependence on applicator size was identified for larger applicators, and this was found to be dependent upon chamber design. The measured values of kch were found to increase with energy and again differences were seen between chamber designs. Overall, the values of kch recorded during these measurements ranged from 1.01 to 1.08. These results highlight a significant underestimation of doses calculated using the very low energy code of practice. This supports the need for further work to confirm these results. and the production of an addendum to the code in its present form.