Infrastructure platform for privacy-preserving distributed machine learning development of computer-assisted theragnostics in cancer.

INTRODUCTION: Emerging evidence suggests that data-driven support tools have found their way into clinical decision-making in a number of areas, including cancer care. Improving them and widening their scope of availability in various differing clinical scenarios, including for prognostic models derived from retrospective data, requires co-ordinated data sharing between clinical centres, secondary analyses of large multi-institutional clinical trial data, or distributed (federated) learning infrastructures. A systematic approach to utilizing routinely collected data across cancer care clinics remains a significant challenge due to privacy, administrative and political barriers. METHODS: An information technology infrastructure and web service software was developed and implemented which uses machine learning to construct clinical decision support systems in a privacy-preserving manner across datasets geographically distributed in different hospitals. The infrastructure was deployed in a network of Australian hospitals. A harmonized, international ontology-linked, set of lung cancer databases were built with the routine clinical and imaging data at each centre. The infrastructure was demonstrated with the development of logistic regression models to predict major cardiovascular events following radiation therapy. RESULTS: The infrastructure implemented forms the basis of the Australian computer-assisted theragnostics (AusCAT) network for radiation oncology data extraction, reporting and distributed learning. Four radiation oncology departments (across seven hospitals) in New South Wales (NSW) participated in this demonstration study. Infrastructure was deployed at each centre and used to develop a model predicting for cardiovascular admission within a year of receiving curative radiotherapy for non-small cell lung cancer. A total of 10,417 lung cancer patients were identified with 802 being eligible for the model. Twenty features were chosen for analysis from the clinical record and linked registries. After selection, 8 features were included and a logistic regression model achieved an area under the receiver operating characteristic (AUROC) curve of 0.70 and C-index of 0.65 on out-of-sample data. CONCLUSION: The infrastructure developed was demonstrated to be usable in practice between clinical centres to harmonize routinely collected oncology data and develop models with federated learning. It provides a promising approach to enable further research studies in radiation oncology using real world clinical data.

A novel method to determine linac mechanical isocenter position and size and examples of specific QA applications.

The most important geometric characteristic of stereotactic treatment is the accuracy of positioning the target at the treatment isocenter and the accuracy of directing the radiation beam at the treatment isocenter. Commonly, the radiation isocenter is used as the reference for the treatment isocenter, but its method of localization is not strictly defined, and it depends on the linac-specific beam steering parameters. A novel method is presented for determining the linac mechanical isocenter position and size based on the localization of the collimator axis of rotation at arbitrary gantry angle. The collimator axis of rotation position is determined from the radiation beam center position corrected for the focal spot offset. The focal spot offset is determined using the image center shift method with a custom-design rigid phantom with two sets of ball-bearings. Three specific quality assurance (QA) applications and assessment methods are also presented to demonstrate the functionality of linac mechanical isocenter position and size determination in clinical practice. The first is a mechanical and radiation isocenters coincidence test suitable for quick congruence assessment of these two isocenters for a selected energy, usually required after a nonroutine linac repair and/or energy adjustment. The second is a stereotactic beam isocentricity assessment suitable for pretreatment stereotactic QA. The third is a comprehensive linac geometrical performance test suitable for routine linac QA. The uncertainties of the method for determining mechanical isocenter position and size were measured to be 0.05 mm and 0.04 mm, respectively, using four available photon energies, and were significantly smaller than those of determining the radiation isocenter position and size, which were 0.36 mm and 0.12 mm respectively. It is therefore recommended that the mechanical isocenter position and size be used as the reference linac treatment isocenter and a linac mechanical characteristic parameter respectively.

Assessment of error in the MV radiation isocenter position calculated with the Elekta XVI software.

The assessment of the coincidence of imaging and radiation isocenters is an important task of regular quality assurance of medical linear accelerators (linacs) as recommended in national and international quality assurance guidelines. A previously reported investigation of the accuracy of the Elekta XVI software to localize the linac radiation isocenter, by comparing statistically with other independent software, has shown some discrepancies at the sub-mm level. A further investigation is carried out here using a set of reference images and mathematical operations to observe how the Elekta XVI software analyses them. Symmetric mathematical operations on reference images should result in symmetrical outcomes. Three different rotation functions are used in increasing degree of complexity to characterize the Elekta XVI software error in the linac radiation isocenter position. No independent algorithms or phantoms are used in this methodology. The magnitude and direction of the radiation isocenter localization error has been determined to be consistently 0.13 mm or 0.14 mm in the longitudinal direction towards the target depending on the case. The radiation isocenter localization error comprises two separated errors of the Ball Bearing Center by 0.13 mm and MV Field Center by either 0.00 mm or -0.01 mm in the longitudinal direction towards the target. The calculation of the MV Field Center is influenced by the polymethyl methacrylate rod supporting the ball-bearing. The precise value and the root cause of the error cannot be assessed due to the rounding effect of the results reported by the Elekta XVI software and lack of access to the source code.

Testing the methodology for a dosimetric end-to-end audit of IMRT/VMAT: results of IAEA multicentre and national studies.

Introduction: Within an International Atomic Energy Agency (IAEA) co-ordinated research project (CRP), a remote end-to-end dosimetric quality audit for intensity modulated radiation therapy (IMRT)/ volumetric arc therapy (VMAT) was developed to verify the radiotherapy chain including imaging, treatment planning and dose delivery. The methodology as well as the results obtained in a multicentre pilot study and national trial runs conducted in close cooperation with dosimetry audit networks (DANs) of IAEA Member States are presented.Material and methods: A solid polystyrene phantom containing a dosimetry insert with an irregular solid water planning target volume (PTV) and organ at risk (OAR) was designed for this audit. The insert can be preloaded with radiochromic film and four thermoluminescent dosimeters (TLDs). For the audit, radiotherapy centres were asked to scan the phantom, contour the structures, create an IMRT/VMAT treatment plan and irradiate the phantom. The dose prescription was to deliver 4 Gy to the PTV in two fractions and to limit the OAR dose to a maximum of 2.8 Gy. The TLD measured doses and film measured dose distributions were compared with the TPS calculations.Results: Sixteen hospitals from 13 countries and 64 hospitals from 6 countries participated in the multicenter pilot study and in the national runs, respectively. The TLD results for the PTV were all within ±5% acceptance limit for the multicentre pilot study, whereas for national runs, 17 participants failed to meet this criterion. All measured doses in the OAR were below the treatment planning constraint. The film analysis identified seven plans in national runs below the 90% passing rate gamma criteria.Conclusion: The results proved that the methodology of the IMRT/VMAT dosimetric end-to-end audit was feasible for its intended purpose, i.e., the phantom design and materials were suitable; the phantom was easy to use and it was robust enough for shipment. Most importantly the audit methodology was capable of identifying suboptimal IMRT/VMAT delivery.

Patient education using virtual reality increases knowledge and positive experience for breast cancer patients undergoing radiation therapy.

PURPOSE: Improved access to technology in the radiation therapy (RT) workforce education has resulted in opportunities for innovative patient education methods. This study investigated the impact of a newly developed education tool using the Virtual Environment for Radiotherapy Training (VERT) system on patients' RT knowledge and anxiety. METHOD: Breast cancer patients were recruited into a control group (CG) (n = 18) who underwent the standard pre-RT education package at a targeted cancer therapy centre, followed by a VERT group (VG) (n = 19). VG patients attended a VERT-based education session detailing RT immobilisation, planning and treatment. All patients completed questionnaires at four time points throughout their treatment, with survey sub-sections on RT knowledge, experience and anxiety. RESULTS: For both groups, anxiety levels were highest at time point 1(T1 after initial radiation oncologist consultation) (CG, 41.2; VG, 43.1), with a gradual decrease observed thereafter at time points before simulation, at the beginning of treatment and at the end of treatment (p > 0.05). The VG's RT knowledge scores were statistically significantly higher than those of the CG scores at all time points following VERT education (p < 0.05). CONCLUSION: This study reports the high value of VERT breast cancer-targeted education programs in improving RT knowledge and perhaps decreasing patient anxiety. Continued efforts are required to improve patients' accessibility to VERT in Australia, and to better understand the effect of VERT's unique educational features on patients' emotional and physical needs throughout their RT.

Beam focal spot position determination for an Elekta linac with the Agility® head; practical guide with a ready-to-go procedure.

A novel phantomless, EPID-based method of measuring the beam focal spot offset of a linear accelerator was proposed and validated for Varian machines. In this method, one set of jaws and the MLC were utilized to form a symmetric field and then a 180o collimator rotation was utilized to determine the radiation isocenter defined by the jaws and the MLC, respectively. The difference between these two isocentres is directly correlated with the beam focal spot offset of the linear accelerator. In the current work, the method has been considered for Elekta linacs. An Elekta linac with the Agility® head does not have two set of jaws, therefore, a modified method is presented making use of one set of diaphragms, the MLC and a full 360o collimator rotation. The modified method has been tested on two Elekta Synergy® linacs with Agility® heads and independently validated. A practical guide with instructions and a MATLAB® code is attached for easy implementation.

Beam focal spot position: The forgotten linac QA parameter. An EPID-based phantomless method for routine Stereotactic linac QA.

Modern day Stereotactic treatments require high geometric accuracy of the delivered treatment. To achieve the required accuracy the IGRT imaging isocenter needs to closely coincide with the treatment beam isocenter. An influence on this isocenter coincidence and on the spatial positioning of the beam itself is the alignment of the treatment beam focal spot with collimator rotation axis. The positioning of the focal spot is dependent on the linac beam steering and on the stability of the monitor chamber and beam steering servo system. As such, there is the potential for focal spot misalignment and this should be checked on a regular basis. Traditional methods for measuring focal spot position are either indirect, inaccurate, or time consuming and hence impractical for routine use. In this study a novel, phantomless method has been developed using the EPID (Electronic Portal Imaging Device) that utilizes the different heights of the MLC and jaws. The method has been performed on four linear accelerators and benchmarked against an alternate ion chamber-based method. The method has been found to be reproducible to within ±0.012 mm (1 SD) and in agreement with the ion chamber-based method to within 0.001 ± 0.015 mm (1 SD). The method could easily be incorporated into a departmental routine linac QA (Quality Assurance) program.

Testing the methodology for dosimetry audit of heterogeneity corrections and small MLC-shaped fields: Results of IAEA multi-center studies.

UNLABELLED: The International Atomic Energy Agency (IAEA) has a long tradition of supporting development of methodologies for national networks providing quality audits in radiotherapy. A series of co-ordinated research projects (CRPs) has been conducted by the IAEA since 1995 assisting national external audit groups developing national audit programs. The CRP 'Development of Quality Audits for Radiotherapy Dosimetry for Complex Treatment Techniques' was conducted in 2009-2012 as an extension of previously developed audit programs. MATERIAL AND METHODS: The CRP work described in this paper focused on developing and testing two steps of dosimetry audit: verification of heterogeneity corrections, and treatment planning system (TPS) modeling of small MLC fields, which are important for the initial stages of complex radiation treatments, such as IMRT. The project involved development of a new solid slab phantom with heterogeneities containing special measurement inserts for thermoluminescent dosimeters (TLD) and radiochromic films. The phantom and the audit methodology has been developed at the IAEA and tested in multi-center studies involving the CRP participants. RESULTS: The results of multi-center testing of methodology for two steps of dosimetry audit show that the design of audit procedures is adequate and the methodology is feasible for meeting the audit objectives. A total of 97% TLD results in heterogeneity situations obtained in the study were within 3% and all results within 5% agreement with the TPS predicted doses. In contrast, only 64% small beam profiles were within 3 mm agreement between the TPS calculated and film measured doses. Film dosimetry results have highlighted some limitations in TPS modeling of small beam profiles in the direction of MLC leave movements. DISCUSSION: Through multi-center testing, any challenges or difficulties in the proposed audit methodology were identified, and the methodology improved. Using the experience of these studies, the participants could incorporate the auditing procedures in their national programs.

Comparison of automatic image registration uncertainty for three IGRT systems using a male pelvis phantom.

A series of phantom images using the CIRS Virtual Human Male Pelvis was acquired across available dose ranges for three image-guided radiotherapy (IGRT) imaging systems: Elekta XVI CBCT, Varian TrueBeam CBCT, and TomoTherapy MV CT. Each image was registered to a fan-beam CT within the XVI software 100 times with random initial offsets. The residual registration error was analyzed to assess the role of imaging hardware and reconstruction in the uncertainty of the IGRT process. Residual translation errors were similar for all systems and < 0.5 mm. Over the clinical dose range for prostate IGRT images (10-25 mGy), all imaging systems provided acceptable matches in > 90% of registrations when incorporating residual rotational error using a dual quaternion derived distance metric. Outside normal dose settings, large uncertainties were observed at very low and very high dose levels. No trend between initial offset and residual registration error was observed. Patient images may incur higher uncertainties than this phantom study; however, these results encourage automatic matching for standard dose settings with review by treatment staff.

A simple model for predicting the signal for a head-mounted transmission chamber system, allowing IMRT in-vivo dosimetry without pretreatment linac time.

The DAVID is a transparent, multi-wire transmission-style detector that attaches to a linear accelerator (linac) collimator for use as an in vivo detector. Currently, the normal method for using the DAVID is to measure a signal at the time of phantom-based pretreatment verification and use that signal as a baseline to compare with in vivo measurements for subsequent treatment fractions. The device has previously been shown to be both stable and accurate.(1,2) This work presents the development of a predictive algorithm for the expected signal, eradicating the need to spend time on the linac prior to treatment, and thereby making the process more efficient. The DAVID response at each wire is a consequence of both primary radiation, from the leaf pair associated with the wire, and scatter radiation as a result of radiation incident on other parts of the detector scattering in the Perspex plate. The primary radiation was shown to be linearly proportional to both leaf separation and delivered monitor units (MU). The scatter signal dropped off exponentially with regard to distance. Both of these effects were modeled; the resulting algorithm was used to predict the response from ten five-field IMRT head and neck plans. The system predicted all DAVID signals to within 5%, and was able to detect artificially generated changes in linac output. Having shown that the algorithm works, a new working paradigm is suggested, and the errors that can be detected are outlined.

The rationale for a carbon ion radiation therapy facility in Australia.

Australia has taken a collaborative nationally networked approach to achieve particle therapy capability. This supports the under-construction proton therapy facility in Adelaide, other potential proton centres and an under-evaluation proposal for a hybrid carbon ion and proton centre in western Sydney. A wide-ranging overview is presented of the rationale for carbon ion radiation therapy, applying observations to the case for an Australian facility and to the clinical and research potential from such a national centre.

Cardiac substructure delineation in radiation therapy - A state-of-the-art review.

Delineation of cardiac substructures is crucial for a better understanding of radiation-related cardiotoxicities and to facilitate accurate and precise cardiac dose calculation for developing and applying risk models. This review examines recent advancements in cardiac substructure delineation in the radiation therapy (RT) context, aiming to provide a comprehensive overview of the current level of knowledge, challenges and future directions in this evolving field. Imaging used for RT planning presents challenges in reliably visualising cardiac anatomy. Although cardiac atlases and contouring guidelines aid in standardisation and reduction of variability, significant uncertainties remain in defining cardiac anatomy. Coupled with the inherent complexity of the heart, this necessitates auto-contouring for consistent large-scale data analysis and improved efficiency in prospective applications. Auto-contouring models, developed primarily for breast and lung cancer RT, have demonstrated performance comparable to manual contouring, marking a significant milestone in the evolution of cardiac delineation practices. Nevertheless, several key concerns require further investigation. There is an unmet need for expanding cardiac auto-contouring models to encompass a broader range of cancer sites. A shift in focus is needed from ensuring accuracy to enhancing the robustness and accessibility of auto-contouring models. Addressing these challenges is paramount for the integration of cardiac substructure delineation and associated risk models into routine clinical practice, thereby improving the safety of RT for future cancer patients.

Open-source, fully-automated hybrid cardiac substructure segmentation: development and optimisation.

Radiotherapy for thoracic and breast tumours is associated with a range of cardiotoxicities. Emerging evidence suggests cardiac substructure doses may be more predictive of specific outcomes, however, quantitative data necessary to develop clinical planning constraints is lacking. Retrospective analysis of patient data is required, which relies on accurate segmentation of cardiac substructures. In this study, a novel model was designed to deliver reliable, accurate, and anatomically consistent segmentation of 18 cardiac substructures on computed tomography (CT) scans. Thirty manually contoured CT scans were included. The proposed multi-stage method leverages deep learning (DL), multi-atlas mapping, and geometric modelling to automatically segment the whole heart, cardiac chambers, great vessels, heart valves, coronary arteries, and conduction nodes. Segmentation performance was evaluated using the Dice similarity coefficient (DSC), mean distance to agreement (MDA), Hausdorff distance (HD), and volume ratio. Performance was reliable, with no errors observed and acceptable variation in accuracy between cases, including in challenging cases with imaging artefacts and atypical patient anatomy. The median DSC range was 0.81-0.93 for whole heart and cardiac chambers, 0.43-0.76 for great vessels and conduction nodes, and 0.22-0.53 for heart valves. For all structures the median MDA was below 6 mm, median HD ranged 7.7-19.7 mm, and median volume ratio was close to one (0.95-1.49) for all structures except the left main coronary artery (2.07). The fully automatic algorithm takes between 9 and 23 min per case. The proposed fully-automatic method accurately delineates cardiac substructures on radiotherapy planning CT scans. Robust and anatomically consistent segmentations, particularly for smaller structures, represents a major advantage of the proposed segmentation approach. The open-source software will facilitate more precise evaluation of cardiac doses and risks from available clinical datasets.

Towards zero radiation isocentre size: minimising radiation beam isocentricity on Elekta linear accelerators by means of optimising look-up tables.

The most important geometric characteristics of SRS/SBRT treatments are precise target localisation and precise aiming of the radiation beam at the target. The AAPM-RSS Medical Physics Practice Guideline 9.a. for SRS/SBRT recommends that the radiation isocentricity (i.e. beam deviation from the isocentre) should not exceed 1 mm for SRS and 1.5 mm for SBRT. Minimising the beam deviations from the treatment target, largely due to the gantry sag, can improve the accuracy of radiosurgery and stereotactic treatments and commonly beam steering parameters are optimised to achieve this objective. This study aims to investigate, as a proof of concept, if it is possible to eliminate the beam deviations on Elekta linear accelerators altogether by optimising gantry angle dependent beam steering parameters, as stored in look-up tables. The investigation used the EPID-based Winston-Lutz test at 13 gantry angles separated every 30° (from - 180° to + 180°). Elekta linacs have two look-up tables that can be customised explicitly for radial beam angle and transverse beam position. Modifications of the radial look-up table were limited by the radial beam asymmetry inhibit of more than 5%, as measured by the linac in-built ionisation chamber. Therefore, only small radial beam deviation reductions of 0.1 mm were achieved (on average from 0.37 to 0.26 mm) while radial beam symmetry changed significantly by up to ± 7%, depending on the gantry angle as measured by the IC Profiler™. The optimised transverse look-up table resulted in reduction of transverse beam deviations to almost zero (on average from 0.20 to 0.03 mm), however, that changed the transverse beam symmetry by almost a constant value of 1%, as measured by the IC Profiler™. Ideally, two additional look-up tables are needed for effective beam steering, one for radial beam position and one for transverse beam angle. Four look-up tables in total would enable customising beam centre position and beam symmetry at any gantry angle that would minimize radiation isocentre size without compromising beam symmetry.

Practical beam steering of X-ray beams on Elekta accelerators: The effect of focal spot alignment on beam (symmetry and position) and radiation isocentre (size and position).

Acceptance and commissioning of a linear accelerator is the process of preparing it for clinical use. One of the initial important dosimetric tasks for X-ray beam set-up and use is to optimise the trajectory of the electron beam before it hits the target (focal spot). The main purpose of this study is to characterise the effect of the focal spot position (offset) on the photon beam symmetry and centre position, as well as on linac radiation isocentre size and position for an Elekta Synergy® linac. For this machine, the initial electron beam steering control items 2T and Bending F were altered to steer the beam in both transverse and radial directions respectively. The IC Profiler™ was utilised to measure the photon beam symmetry and centre position; the electronic portal imaging device (EPID) and the authors' published ready-to-go procedure were used to measure the focal spot offset; and the radiation isocentre size and position were measured using the EPID, the Elekta ball-bearing phantom and in-house software. It was observed that for the 6MV beam investigated, beam symmetry shows a high dependency on the focal spot position, with correlation coefficients of 8.6%/mm and 5.6%/mm in transverse and radial directions respectively. The radiation isocentre size shows dependency of 1.7 mm/mm on focal spot position in the transverse direction only. The radiation isocentre longitudinal position shows dependency of - 1.8 mm/mm on the focal spot position in the radial direction only. The beam centre position is directly correlated with the focal spot position in both directions, but the correlation coefficient depends on the collimation used in a given direction i.e. MLC (- 1.5 mm/mm) or diaphragms (- 0.8 mm/mm). Based on the results, a fast beam steering method was proposed and used successfully on an Elekta Versa HD™ linac, utilizing the IC Profiler™ and its associated Gantry Mounting Fixture™ (GMF) to efficiently and effectively optimise beam steering parameters for clinical use. Independent validation of the method showed that focal spot offsets and beam symmetries in terms of absolute deviations were on average 0.08 ± 0.05 mm (1SD) and 0.70 ± 0.27% (1SD) respectively.

Assessing the dependency of the uncertainties in the Elekta Agility MLC calibration procedure on the focal spot position.

The effectiveness of radiotherapy treatments depends on the accuracy of the dose delivery process. The majority of radiotherapy courses are delivered on linear accelerators with a Multi Leaf Collimator (MLC) in 3D conformal Radiation Therapy, Intensity Modulated Radiation Therapy (IMRT) or Volumetric Modulated Arc Therapy (VMAT) modes that require accurate MLC positioning. This study investigates the MLC calibration accuracy, following manufacturer procedures for an Elekta Synergy linac with the Agility head, against the radiation focal spot offset (alignment with the collimator axis of rotation). If the radiation focal spot is not aligned ideally with the collimator axis of rotation then a systematic error can be introduced into the calibration procedure affecting absolute MLC leaf positions. Calibration of diaphrams is equally affected; however they are not investigated here. The results indicate that an estimated 0.15 mm MLC uncertainty in all MLC leaves positions can be introduced due to uncertainty of the radiation focal spot position of 0.21 mm.

Phantom scatter factors for small MV photon fields.

BACKGROUND AND PURPOSE: A table of small field (<4 cm width) S(p) values was created from measured S(cp) and S(c) data and compared with other authors' work. METHODS AND MATERIALS: S(cp) and S(c) values measured with three types of diode and a diamond were used to calculate S(p). RESULTS: The results from measurements with different detectors were examined to determine the reasons for the differences and these were found to be due to detector and phantom-specific problems in the experimental determination of S(cp) and S(c). Small field S(p) were shown to be independent of beam defining system and linac design and dependent only on measurement depth and beam area irradiated. S(p) values obtained from S(cp) and S(c) measurements with a photon diode were found to be unreliable, due to problems with S(cp) measurements. CONCLUSION: Although the electron and stereotactic diodes and the diamond are suitable detectors for S(cp) and S(c) measurements, the differences between S(p) values calculated from diamond measurements and those calculated from measurements with unshielded diodes still require clarification through Monte Carlo modelling. A final table of S(p) was produced, for fields >0.5 cm width.

Clinical implications of the implementation of advanced treatment planning algorithms for thoracic treatments.

BACKGROUND AND PURPOSE: Radiotherapy treatment planning algorithms continue to develop and current planning systems typically offer simpler, but faster, algorithms, which may be 2, 2.5 or 3D in modelling scatter, but which do not model electron transport (type a) and more accurate algorithms which aim to be fully 3D, i.e. which model 3D scatter and also model electron transport (type b). A range of comparative planning studies and experiments indicate that the main situation where the changes are significant between the two types of algorithm is where lung tissue is involved. However, more generally, interface areas between materials of different electron density and composition are expected to show differences between the two types of algorithms. These are likely to pose potentially significant clinical consequences when a centre changes from using older simpler algorithms to more accurate fully 3D ones and require careful consideration. MATERIALS AND METHODS: Some modelling is presented using the different type algorithms for a recently available novel design of linear accelerator treatment head, as part of the commissioning of that machine and in preparing for a change in TPS algorithm. The TPS data are compared to measurements and to Monte Carlo calculations. RESULTS AND DISCUSSION: The results add to the evidence of other studies that 3D planning techniques and type b dose calculation algorithms lead to systematic changes in computation and delivery of radiotherapy dose and in dose distributions, as compared to simpler methods, and that these changes are more pronounced in treatments involving lung tissue. The type b algorithms agree well with Monte Carlo modelling. CONCLUSIONS: Careful analysis of the changes is required before adopting new algorithms into clinical treatment planning practice. Discussion is needed between physicists and oncologists to fully understand the effects and potential consequences. These include changes in delivered dose to the reference point, to coverage of the PTV and to the dose distribution and also to dosimetric parameters used to constrain toxicity for lung, e.g. V20, and other tissues. There are consequences for assessment of dose-effect relationships and of parameters used in treatment planning decisions and this is an opportune time to re-evaluate this information.