Associations between voxel-level accumulated dose and rectal toxicity in prostate radiotherapy.

BACKGROUND AND PURPOSE: Associations between dose and rectal toxicity in prostate radiotherapy are generally poorly understood. Evaluating spatial dose distributions to the rectal wall (RW) may lead to improvements in dose-toxicity modelling by incorporating geometric information, masked by dose-volume histograms. Furthermore, predictive power may be strengthened by incorporating the effects of interfraction motion into delivered dose calculations.Here we interrogate 3D dose distributions for patients with and without toxicity to identify rectal subregions at risk (SRR), and compare the discriminatory ability of planned and delivered dose. MATERIAL AND METHODS: Daily delivered dose to the rectum was calculated using image guidance scans, and accumulated at the voxel level using biomechanical finite element modelling. SRRs were statistically determined for rectal bleeding, proctitis, faecal incontinence and stool frequency from a training set (n = 139), and tested on a validation set (n = 47). RESULTS: SRR patterns differed per endpoint. Analysing dose to SRRs improved discriminative ability with respect to the full RW for three of four endpoints. Training set AUC and OR analysis produced stronger toxicity associations from accumulated dose than planned dose. For rectal bleeding in particular, accumulated dose to the SRR (AUC 0.76) improved upon dose-toxicity associations derived from planned dose to the RW (AUC 0.63). However, validation results could not be considered significant. CONCLUSIONS: Voxel-level analysis of dose to the RW revealed SRRs associated with rectal toxicity, suggesting non-homogeneous intra-organ radiosensitivity. Incorporating spatial features of accumulated delivered dose improved dose-toxicity associations. This may be an important tool for adaptive radiotherapy in the future.

An evaluation of the mid-ventilation method for the planning of stereotactic lung plans.

BACKGROUND AND PURPOSE: Stereotactic ablative body radiotherapy for lung plans requires 4DCT. Most radiotherapy centres use this to determine an internal target volume (ITV), despite studies suggesting that planning on a mid-ventilation (Mid-V) phase can reduce target volumes. The purpose of this study is two-fold: to determine whether the Mid-V approach provides adequate coverage and to discuss methods to enable the Mid-V approach to be applied more widely. METHOD: 4D scans of 79 patients were outlined on every phase. The mid-V phase was identified. Margins were determined from the range of motion, and plans generated with a 55 Gy prescription. A grid-based method was used to get the probability of tumour coverage in the presence of systematic and random uncertainties, with and without blurring for breathing motion. RESULTS: For the Mid-V plans with the margins calculated from the van-Herk formula, after blurring doses for breathing, the coverage (dose covering 95% of the CTV 95% of the time) was greater than for plans with isotropic 5 mm margins uncorrected for breathing (58.2 Gy v 57.3 Gy). Similar results were obtained for a linear margin chosen as 0.15 of the breathing range. Deformable contour propagation in a commercial outlining system (ProSoma) identified the same mid-V phase in the majority of cases. CONCLUSION: Our results confirm that a mid-V approach can be used to reduce the PTV size, with no loss of tumour coverage. We propose the use of a simplified margin formula equal to the margin ignoring breathing plus 0.15 of the range of motion.

Anatomical change during radiotherapy for head and neck cancer, and its effect on delivered dose to the spinal cord.

BACKGROUND AND PURPOSE: The impact of weight loss and anatomical change during head and neck (H&N) radiotherapy on spinal cord dosimetry is poorly understood, limiting evidence-based adaptive management strategies. MATERIALS AND METHODS: 133 H&N patients treated with daily mega-voltage CT image-guidance (MVCT-IG) on TomoTherapy, were selected. Elastix software was used to deform planning scan SC contours to MVCT-IG scans, and accumulate dose. Planned (DP) and delivered (DA) spinal cord D2% (SCD2%) were compared. Univariate relationships between neck irradiation strategy (unilateral vs bilateral), T-stage, N-stage, weight loss, and changes in lateral separation (LND) and CT slice surface area (SSA) at C1 and the superior thyroid notch (TN), and ΔSCD2% [(DA - DP) D2%] were examined. RESULTS: The mean value for (DA - DP) D2% was -0.07 Gy (95%CI -0.28 to 0.14, range -5.7 Gy to 3.8 Gy), and the mean absolute difference between DP and DA (independent of difference direction) was 0.9 Gy (95%CI 0.76-1.04 Gy). Neck treatment strategy (p = 0.39) and T-stage (p = 0.56) did not affect ΔSCD2%. Borderline significance (p = 0.09) was seen for higher N-stage (N2-3) and higher ΔSCD2%. Mean reductions in anatomical metrics were substantial: weight loss 6.8 kg; C1LND 12.9 mm; C1SSA 12.1 cm2; TNLND 5.3 mm; TNSSA 11.2 cm2, but no relationship between weight loss or anatomical change and ΔSCD2% was observed (all r2 < 0.1). CONCLUSIONS: Differences between delivered and planned spinal cord D2% are small in patients treated with daily IG. Even patients experiencing substantial weight loss or anatomical change during treatment do not require adaptive replanning for spinal cord safety.

Unintended doses in radiotherapy-over, under and outside?

Radiotherapy is a safe treatment; nevertheless, national reporting of serious incidents allows investigation of potential harm to individuals and failing safety culture. UK guidance has previously been limited to overexposures, but underexposures will be included in the new legislation, and positioning errors have also been explicitly included in recent guidance. This commentary reviews current guidance and suggests practical approaches to the additional categories, including the definition of a local error margin.

Applying physical science techniques and CERN technology to an unsolved problem in radiation treatment for cancer: the multidisciplinary 'VoxTox' research programme.

The VoxTox research programme has applied expertise from the physical sciences to the problem of radiotherapy toxicity, bringing together expertise from engineering, mathematics, high energy physics (including the Large Hadron Collider), medical physics and radiation oncology. In our initial cohort of 109 men treated with curative radiotherapy for prostate cancer, daily image guidance computed tomography (CT) scans have been used to calculate delivered dose to the rectum, as distinct from planned dose, using an automated approach. Clinical toxicity data have been collected, allowing us to address the hypothesis that delivered dose provides a better predictor of toxicity than planned dose.

Implementation of TomoEDGE in the independent dose calculator CheckTomo.

PURPOSE: CheckTomo is an independent dose calculation software for tomotherapy. Recently, Accuray (Accuray Inc., Sunnyvale, CA, USA) released an upgrade of its tomotherapy treatment device, called TomoEDGE Dynamic Jaws, which improves the quality of treatment plans by enhancing the dose delivery with the help of jaws motion. This study describes the upgrade of CheckTomo to that new feature. METHODS: To account for the varying width and off-axis shift of dynamic jaws fields, the calculation engine of CheckTomo multiplies the treatment field profile by a penumbral filter and shifts the dose calculation grid. Penumbral filters were obtained by dividing the edge field profiles by that of the corresponding nominal field. They were sampled at widths 1.0, 1.8, and 2.5 cm at isocenter in the edges of the 2.5 and 5 cm treatment field. RESULTS: The upgrade of CheckTomo was tested on 30 patient treatments planned with dynamic jaws. The gamma pass rate averaged over 10 abdomen plans was 95.9%, with tolerances of 3 mm/3%. For 10 head and neck plans, the mean pass rate was 95.9% for tolerances of 4 mm/4%. Finally, misplacement and overdosage errors were simulated. In each tested cases, the 2 mm/3% gamma pass rate fell below 95% when a 4 mm shift or 3% dose difference was applied. CONCLUSIONS: These results are equivalent to what CheckTomo achieves in static jaws cases. So, in terms of dose calculation accuracy and errors detection, the upgraded version of CheckTomo is as reliable for dynamic jaws plans as the former release was for static cases.

Recalculation of dose for each fraction of treatment on TomoTherapy.

OBJECTIVE: The VoxTox study, linking delivered dose to toxicity requires recalculation of typically 20-37 fractions per patient, for nearly 2000 patients. This requires a non-interactive interface permitting batch calculation with multiple computers. METHODS: Data are extracted from the TomoTherapy(®) archive and processed using the computational task-management system GANGA. Doses are calculated for each fraction of radiotherapy using the daily megavoltage (MV) CT images. The calculated dose cube is saved as a digital imaging and communications in medicine RTDOSE object, which can then be read by utilities that calculate dose-volume histograms or dose surface maps. The rectum is delineated on daily MV images using an implementation of the Chan-Vese algorithm. RESULTS: On a cluster of up to 117 central processing units, dose cubes for all fractions of 151 patients took 12 days to calculate. Outlining the rectum on all slices and fractions on 151 patients took 7 h. We also present results of the Hounsfield unit (HU) calibration of TomoTherapy MV images, measured over an 8-year period, showing that the HU calibration has become less variable over time, with no large changes observed after 2011. CONCLUSION: We have developed a system for automatic dose recalculation of TomoTherapy dose distributions. This does not tie up the clinically needed planning system but can be run on a cluster of independent machines, enabling recalculation of delivered dose without user intervention. ADVANCES IN KNOWLEDGE: The use of a task management system for automation of dose calculation and outlining enables work to be scaled up to the level required for large studies.

Accumulated dose to the rectum, measured using dose-volume histograms and dose-surface maps, is different from planned dose in all patients treated with radiotherapy for prostate cancer.

OBJECTIVE: We sought to calculate accumulated dose (DA) to the rectum in patients treated with radiotherapy for prostate cancer. We were particularly interested in whether dose-surface maps (DSMs) provide additional information to dose-volume histograms (DVHs). METHODS: Manual rectal contours were obtained for kilovoltage and daily megavoltage CT scans for 10 participants from the VoxTox study (380 scans). Daily delivered dose recalculation was performed using a ray-tracing algorithm. Delivered DVHs were summated to create accumulated DVHs. The rectum was considered as a cylinder, cut and unfolded to produce daily delivered DSMs; these were summated to produce accumulated DSMs. RESULTS: Accumulated dose-volumes were different from planned in all participants. For one participant, all DA levels were higher and all volumes were larger than planned. For four participants, all DA levels were lower and all volumes were smaller than planned. For each of these four participants, ≥1% of pixels on the accumulated DSM received ≥5 Gy more than had been planned. CONCLUSION: Differences between accumulated and planned dose-volumes were seen in all participants. DSMs were able to identify differences between DA and planned dose that could not be appreciated from the DVHs. Further work is needed to extract the dose data embedded in the DSMs. These will be correlated with toxicity as part of the VoxTox Programme. ADVANCES IN KNOWLEDGE: DSMs are able to identify differences between DA and planned dose that cannot be appreciated from DVHs alone and should be incorporated into future studies investigating links between DA and toxicity.

Three-dimensional analysis of the respiratory interplay effect in helical tomotherapy: Baseline variations cause the greater part of dose inhomogeneities seen.

PURPOSE: Dose differences from those planned can occur due to the respiratory interplay effect on helical tomotherapy. The authors present a technique to calculate single-fraction doses in three-dimensions resulting from craniocaudal motion applied to a patient CT set. The technique is applied to phantom and patient plans using patient respiratory traces. An additional purpose of the work is to determine the contribution toward the interplay effect of different components of the respiratory trace. METHODS: MATLAB code used to calculate doses to a CT dataset from a helical tomotherapy plan has been modified to permit craniocaudal motion and improved temporal resolution. Real patient traces from seven patients were applied to ten phantom plans of differing field width, modulation factor, pitch and fraction dose, and simulations made with peak-to-peak amplitudes ranging from 0 to 2.5 cm. PTV voxels near the superior or inferior limits of the PTV are excluded from the analysis. The maximum dose discrepancy compared with the static case recorded along with the proportion of voxels receiving more than 10% and 20% different from prescription dose. The analysis was repeated with the baseline variation of the respiratory trace removed, leaving the cyclic component of motion only. Radiochromic film was used on one plan-trace combination and compared with the software simulation. For one case, filtered traces were generated and used in simulations which consisted only of frequencies near to particular characteristic frequencies of the treatment delivery. Intraslice standard deviation of dose differences was used to identify potential MLC interplay, which was confirmed using nonmodulated simulations. Software calculations were also conducted for four realistic patient plans and modeling movement of a patient CT set with amplitudes informed by the observed motion of the GTV on 4DCT. RESULTS: The maximum magnitude of dose difference to a PTV voxel due to the interplay effect within a particular plan-trace combination for peak-to-peak amplitudes of up to 2.5 cm ranged from 4.5% to 51.6% (mean: 23.8%) of the dose delivered in the absence of respiratory motion. For cyclic motion only, the maximum dose differences in each combination ranged from 2.1% to 26.2% (mean: 9.2%). There is reasonable correspondence between an example of the phantom plan simulations and radiochromic film measurement. The filtered trace simulations revealed that frequencies close to the characteristic frequency of the jaw motion across the target were found to generate greater interplay effect than frequencies close to the gantry frequency or MLC motion. There was evidence of interplay between respiratory motion and MLC modulation, but this is small compared with the interplay between respiratory motion and jaw motion. For patient-plan simulations, dose discrepancies are seen of up to 9.0% for a patient with 0.3 cm peak-to-peak respiratory amplitude and up to 17.7% for a patient with 0.9 cm peak-to-peak amplitude. These values reduced to 1.3% and 6.5%, respectively, when only cyclic motion was considered. CONCLUSIONS: Software has been developed to simulate craniocaudal respiratory motion in phantom and patient plans using real patient respiratory traces. Decomposition of the traces into baseline andcyclic components reveals that the large majority of the interplay effect seen with the full trace is due to baseline variation during treatment.

Intra-fraction motion of the prostate during treatment with helical tomotherapy.

BACKGROUND AND PURPOSE: To measure the geometric uncertainty resulting from intra-fraction motion and intra-observer image matching, for patients having image-guided prostate radiotherapy on TomoTherapy. MATERIAL AND METHODS: All patients had already been selected for prostate radiotherapy on TomoTherapy, with daily MV-CT imaging. The study involved performing an additional MV-CT image at the end of treatment, on 5 occasions during the course of 37 treatments. 54 patients were recruited to the study. A new formula was derived to calculate the PTV margin for intra-fraction motion. RESULTS: The mean values of the intra-fraction differences were 0.0mm, 0.5mm, 0.5mm and 0.0° for LR, SI, AP and roll, respectively. The corresponding standard deviations were 1.1mm, 0.8mm, 0.8mm and 0.6° for systematic uncertainties (Σ), 1.3mm, 2.0mm, 2.2mm and 0.3° for random uncertainties (σ). This intra-fraction motion requires margins of 2.2mm in LR, 2.1mm in SI and 2.1mm in AP directions. Inclusion of estimates of the effect of rotations and matching errors increases these margins to approximately 4mm in LR and 5mm in SI and AP directions. CONCLUSIONS: A new margin recipe has been developed to calculate margins for intra-fraction motion. This recipe is applicable to any measurement technique that is based on the difference between images taken before and after treatment.

Impact of the fixed gantry angle approximation on dosimetric accuracy for helical tomotherapy plans.

PURPOSE: The purpose of the work was to determine the accuracy of the dose calculation of off-axis, small target helical tomotherapy treatments using 51 calculation angles, and to determine the increase in calculation angles required to improve the accuracy to acceptable standards. METHODS: A previously described dose calculation program [S. J. Thomas, K. R. Eyre, G. S. J. Tudor, and J. Fairfoul, "Dose calculation software for helical tomotherapy, utilizing patient CT data to calculate an independent three-dimensional dose cube," Med. Phys. 39, 160-167 (2012)] was modified to permit decomposition of each projection into several subprojections, allowing more accurate modeling of the temporal distribution of fluence within each beamlet. Four plans of small off-axis spherical targets were recalculated several times with different numbers of subprojections, with the minimum dose to 95% of the PTV (D(95%)) and the minimum dose to 2% of the PTV (D(2%)) calculated for each, in order to determine the minimum number of subprojections required for accurate dose statistics. A further nine plans were used to determine the effect on conventional calculation accuracy of varying target size, target position, modulation factor, and pitch. For this analysis, the mean dose and equivalent uniform dose were considered in addition to D(95%) and D(2%). RESULTS: The differences between calculations made using the 51 angle approximation and using the closest approximation to real treatment delivery were notable, with up to 11.0% overestimate of D(95%) for the cases studied. A previously unreported underestimate of dose to parts of the PTV was observed due to this effect, with D(2%) being underestimated by up to 3.3%. The effect is dependent on target size, position, modulation factor, and the angular distribution of fluence within the sinogram but not pitch. Decomposing each projection into three subprojections left differences in dose statistics that were of reduced magnitude but still appreciable. The effect of increasing the number of subprojections beyond five had little effect. CONCLUSIONS: When applied to small, off-axis targets, the limitations of the 51 calculation angle model can substantially affect the veracity of PTV dose statistics, including both underestimation and overestimation of dose depending on position within the PTV. Increasing the number of calculation angles by a factor of 5 reduces the effect to insignificant levels. While the latest release of TomoTherapy planning software will ameliorate the problem, the studied effect is best avoided by positioning small targets near to the bore center. Where this is not possible, it is recommended to ensure a high actual modulation factor and to use an unscaled delivery for patient-specific quality assurance.

A comparison of four indices for combining distance and dose differences.

PURPOSE: When one is comparing two dose distributions, a number of methods have been published to combine dose difference and distance to agreement into a single measure. Some have been defined as pass/fail indices and some as numeric indices. We show that the pass/fail indices can all be used to derive numeric indices, and we compare the results of using these indices to evaluate one-dimensional (1D) and three-dimensional (3D) dose distributions, with the aim of selecting the most appropriate index for use in different circumstances. METHODS AND MATERIALS: The indices compared are the gamma index, the kappa index, the index in International Commission on Radiation Units & Measurements Report 83, and a box index. Comparisons are made for 1D and 3D distributions. The 1D distribution is chosen to have a variety of dose gradients. The 3D distribution is taken from a clinical treatment plan. The effect of offsetting distributions by known distances and doses is studied. RESULTS: The International Commission on Radiation Units & Measurements Report 83 index causes large discontinuities unless the dose gradient cutoff is set to equal the ratio of the dose tolerance to the distance tolerance. If it is so set, it returns identical results to the kappa index. Where the gradient is very high or very low, all the indices studied in this article give similar results for the same tolerance values. For moderate gradients, they differ, with the box index being the least strict, followed by the gamma index, and with the kappa index being the most strict. CONCLUSIONS: If the clinical tolerances are much greater than the uncertainties of the measuring system, the kappa index should be used, with tolerance values determined by the clinical tolerances. In cases where the uncertainties of the measuring system dominate, the box index will be best able to determine errors in the delivery system.

Dose calculation software for helical tomotherapy, utilizing patient CT data to calculate an independent three-dimensional dose cube.

PURPOSE: Treatment plans for the TomoTherapy unit are produced with a planning system that is integral to the unit. The authors have produced an independent dose calculation system, to enable plans to be recalculated in three dimensions, using the patient's CT data. METHODS: Software has been written using MATLAB. The DICOM-RT plan object is used to determine the treatment parameters used, including the treatment sinogram. Each projection of the sinogram is segmented and used to calculate dose at multiple calculation points in a three-dimensional grid using tables of measured beam data. A fast ray-trace algorithm is used to determine effective depth for each projection angle at each calculation point. Calculations were performed on a standard desktop personal computer, with a 2.6 GHz Pentium, running Windows XP. RESULTS: The time to perform a calculation, for 3375 points averaged 1 min 23 s for prostate plans and 3 min 40 s for head and neck plans. The mean dose within the 50% isodose was calculated and compared with the predictions of the TomoTherapy planning system. When the modified CT (which includes the TomoTherapy couch) was used, the mean difference for ten prostate patients, was -0.4% (range -0.9% to +0.3%). With the original CT (which included the CT couch), the mean difference was -1.0% (range -1.7% to 0.0%). The number of points agreeing with a gamma 3%∕3 mm averaged 99.2% with the modified CT, 96.3% with the original CT. For ten head and neck patients, for the modified and original CT, respectively, the mean difference was +1.1% (range -0.4% to +3.1%) and 1.1% (range -0.4% to +3.0%) with 94.4% and 95.4% passing a gamma 4%∕4 mm. The ability of the program to detect a variety of simulated errors has been tested. CONCLUSIONS: By using the patient's CT data, the independent dose calculation performs checks that are not performed by a measurement in a cylindrical phantom. This enables it to be used either as an additional check or to replace phantom measurements for some patients. The software has potential to be used in any application where one wishes to model changes to patient conditions.

Prevalence of symptoms and signs of shoulder problems in people with diabetes mellitus.

Diabetes mellitus is a known risk factor for frozen shoulder. This study was performed to quantify this association and test any relationship with other risk factors for diabetic complications. Patients attending diabetic (n = 865) and general medical (n = 202) clinics were interviewed and examined. External rotation was measured in both shoulders. Glycated hemoglobin A(1c) was measured in all diabetic patients. Frozen shoulder was defined as pain for more than 3 months and external rotation of less than 50% of the unaffected shoulder. Bilateral frozen shoulder was defined as external rotation of less than 30 degrees in both shoulders. Shoulder pain was present in 25.7% of diabetic patients compared with 5.0% of general medical patients. The criteria for frozen shoulder were fulfilled in 4.3% of diabetic patients and in 0.5% of the general medical patients. Only duration of diabetes had a positive association. The prevalence of painful or stiff shoulder was greater in diabetic patients than general medical patients. The prevalence of frozen shoulder is less than previously reported but still greater in diabetic patients.

Margins for treatment planning of proton therapy.

For protons and other charged particles, the effect of set-up errors on the position of isodoses is considerably less in the direction of the incident beam than it is laterally. Therefore, the margins required between the clinical target volume (CTV) and planning target volume (PTV) can be less in the direction of the incident beam than laterally. Margins have been calculated for a typical head plan and a typical prostate plan, for a single field, a parallel opposed and a four-field arrangement of protons, and compared with margins calculated for photons, assuming identical geometrical uncertainties for each modality. In the head plan, where internal motion was assumed negligible, the CTV-PTV margin reduced from approximately 10 mm to 3 mm in the axial direction for the single field and parallel opposed plans. For a prostate plan, where internal motion cannot be ignored, the corresponding reduction in margin was from 11 mm to 7 mm. The planning organ at risk (PRV) margin in the axial direction reduced from 6 mm to 2 mm for the head plan, and from 7 mm to 4 mm for the prostate plan. No reduction was seen on the other axes, or for any axis of the four-field plans. Owing to the shape of proton dose distributions, there are many clinical cases in which good dose distributions can be obtained with one or two fields. When this is done, it is possible to use smaller PTV and PRV margins. This has the potential to convert untreatable cases, in which the PTV and PRV overlap, into cases with a gap between PTV and PRV of adequate size for treatment planning.

The effect of optimization on surface dose in intensity modulated radiotherapy (IMRT).

Although IMRT has been shown clinically to increase skin doses for some patients, it has also been shown that intensity modulated delivery does not, of itself, increase skin doses. The reason for this apparent difference is that inverse planning can result in solutions that give high fluence to tangential beam segments near the skin surface, in an attempt to counter the build-up region. In cases where the clinical target volume (CTV) stops short of the skin surface, but the planning target volume (PTV) does not, there is no clinical reason to treat the skin. The CTV-PTV margin exists purely to ensure that fields are large enough to allow for geometrical uncertainties. With an objective function based on the doses to the PTV, it is possible for a plan that gives excess fluence to the skin to have a lower objective function, and hence to be preferred in an optimization. We describe a technique of plan evaluation, based on analysis of a plan by recalculating several plans in which the isocentre has been offset by a distance equal to the CTV-PTV margin. We demonstrate that changes to a plan that reduce a PTV-based objective can give a worse dose distribution to the CTV when systematic and random set-up errors are accounted for, and increase skin dose. Several possible strategies for avoiding this problem are discussed, including the use of the skin as an organ at risk, modification of the PTV to avoid the skin, and the use of 'pretend bolus' applied in planning but not in treatment. The latter gave the best results. The possibility of using the evaluation method itself, as the basis of an objective function for optimization, is discussed.

Defining the tumour and target volumes for radiotherapy.

Radiotherapy is a localised treatment. The definition of tumour and target volumes for radiotherapy is vital to its successful execution. This requires the best possible characterisation of the location and extent of tumour. Diagnostic imaging, including help and advice from diagnostic specialists, is therefore essential for radiotherapy planning. There are three main volumes in radiotherapy planning. The first is the position and extent of gross tumour, i.e. what can be seen, palpated or imaged; this is known as the gross tumour volume (GTV). Developments in imaging have contributed to the definition of the GTV. The second volume contains the GTV, plus a margin for sub-clinical disease spread which therefore cannot be fully imaged; this is known as the clinical target volume (CTV). It is the most difficult because it cannot be accurately defined for an individual patient, but future developments in imaging, especially towards the molecular level, should allow more specific delineation of the CTV. The CTV is important because this volume must be adequately treated to achieve cure. The third volume, the planning target volume (PTV), allows for uncertainties in planning or treatment delivery. It is a geometric concept designed to ensure that the radiotherapy dose is actually delivered to the CTV. Radiotherapy planning must always consider critical normal tissue structures, known as organs at risk (ORs). In some specific circumstances, it is necessary to add a margin analogous to the PTV margin around an OR to ensure that the organ cannot receive a higher-than-safe dose; this gives a planning organ at risk volume. This applies to an organ such as the spinal cord, where damage to a small amount of normal tissue would produce a severe clinical manifestation. The concepts of GTV, CTV and PTV have been enormously helpful in developing modern radiotherapy. Attention to detail in radiotherapy planning is vital, and does affect outcomes: 'the devil is in the detail'. Radiotherapy planning is also dependent on high quality imaging, and the better the imaging the better will be the outcomes from radiotherapy.