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Defining the tumour and target volumes for radiotherapy

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. Keywords: Tumour volume; target volume; conformal radiotherapy; ICRU; organs at risk. Introduction The role of radiotherapy in the treatment of cancer The purpose of considering how to define tumour and Radiotherapy plays a key role in the management target volumes for radiotherapy is to optimise this of patients with cancer. After surgery, radiotherapy is treatment modality. Radiotherapy is a speciality which the most effective curative treatment for cancer. In requires attention to detail in order to achieve the best 2002, the Cancer Services Collaborative suggested that results. It is also important to place radiotherapy in the radiotherapy alone is responsible for 78% of non-surgical context of cancer treatments to fully appreciate its value. cancer cures. Between 30 and 40% of the population This paper is available online at http://www.cancerimaging.org. In the event of a change in the URL address, please use the DOI provided to locate the paper. 1470-7330/04/020153 + 09 c 2004 International Cancer Imaging Society 154 N G Burnet et al will develop cancer, and at least half require radiotherapy the side effect profile of radiotherapy, and hence the [2,3] at some time in their illness. Of patients having therapeutic ratio . Implementation of techniques to radiotherapy, about 60% are treated with curative intent, spare normal tissue, such as conformal radiotherapy (vide often in combination with surgery and chemotherapy. infra), therefore allows a choice between (i) dose increase In addition, radiotherapy has an important role in the with a consistent level of side effects, or (ii) the same dose palliation of symptoms from cancer. with reduced side effects (see Fig. 1). In fact, rather modest changes in dose both to the Increased TCP using Conformal RT tumour and normal tissue can deliver a clinical advantage. Tumour Normal tissue For tumours, the effect of a dose increase can be A B C assessed from the slope of the plot of tumour control probability (TCP) vs. radiotherapy dose. In the central part of the curve, where TCP is 50%, the curve is relatively straight. A parameter which describes the percentage increase in TCP for a 1% increase in dose, known as the Gamma-50 (γ ) factor, can be a useful way of estimating the benefit of dose escalation. There is a large amount of literature on both laboratory and clinical data suggesting that a 1% increase in dose typically delivers a 1–2% increase in TCP. Thus, a 10% Dose dose increase, which is realistically achievable in many 12 settings, could achieve an improvement in tumour control Cure with Cure with of 10–20%. This was achieved in a radiotherapy trial for conventional RT conformal RT head and neck cancer, where a 15% dose increase raised the local control from 40 to 59% at 5 years; this indicates Figure 1 Diagrammatic plot of tumour control [4] a value for γ of 1.33 . probability (TCP) or normal tissue complication For normal tissue, a difference in dose to the breast of probability (NTCP) vs. radiotherapy dose. Sparing approximately 10%, within the context of a radiotherapy normal tissues shifts the NTCP curve to the right (B dose trial, achieved a demonstrable change in the to C), allowing a lower incidence of normal tissue [5] incidence of shape change . The fact that a 10% dose damage for the same dose (dose 1) or the same level of NTCP for a higher dose (dose 2). This is the difference led to a 16% difference (24 vs. 40%) in basis for an improvement in the therapeutic ratio. the number of women exhibiting a change in breast This benefit can be the result of any measure which appearance at 5 years indicates that modest dose changes reduces the normal tissue dose, for example including produce a clinical effect. This will usually apply whether better target imaging, conformal radiotherapy, and the dose reduction is to the whole organ, such as the improved patient immobilisation. breast, or part of an organ, such as can be achieved with conformal radiotherapy. Thus, even a modest dose Technological developments in radiotherapy are con- increase to the tumour and a dose decrease to normal tinuing apace, and are likely to confer further clinical tissue achieved using advanced radiotherapy planning are benefit. For example, the Swedish Council on Technology worth pursuing. Assessment in Health Care estimated in 1996 that the However, in radiotherapy, tumour and normal tissue overall 5-year survival in patients receiving radiotherapy are inextricably linked. When delivering a tumoricidal should be increased by approximately 10% over the 10 years following their report as the result of technical dose to the tumour, some normal tissue is inevitably [1] innovation, which includes imaging . irradiated. If normal tissue is spared, in dose or volume, the incidence and severity of complications are reduced. This shifts the dose-response curve for complication to Fundamental principles of radiotherapy the right, allowing a choice between the same dose and tumour control with reduced side effects, and a higher There are three fundamental axioms of radiotherapy dose with increased tumour control and the same level of which are relevant background to this topic. Firstly, an normal tissue (see Fig. 1). increase in radiotherapy dose to the tumour normally This preamble is intended to show that quite small improves the probability of local control. Secondly, changes in radiotherapy can achieve a significant improving local control in the context of a localised alteration in clinical outcome. Therefore, attention to the tumour achieves an improvement in the overall cure detail of radiotherapy planning is central to the current rate, because metastatic spread from local recurrence is avoided. Finally, sparing normal tissues improves and improving therapeutic ratio. TCP or NTCP (%) Target volumes for radiotherapy 155 Radiotherapy as a localised cancer treatment treatment volume to the shape of the target quite simply eliminates, or at least reduces, the radiation exposure of a Radiotherapy is, by its nature, a localised treatment for large volume of normal tissue (see Fig. 2). localised tumours and in this respect is analogous to This seems to imply that the introduction of conformal surgery. Total body irradiation is an apparent exception, radiotherapy has led to a reduction in radiotherapy but it is designed to treat all bone marrow and circulating volumes, and generally this has been the case. However, blood, and is a localised treatment to this whole-body early experience with computed tomography (CT)-based target. Thus, disease staging is crucial in the decision on planning showed that in some circumstances, such as whether to employ radiotherapy as part of the treatment bladder cancer, volumes actually increased, compared to strategy. Better imaging produces better staging, and the older-style ‘square’ orthogonal localisation, because leads to stage migration which actually gives the illusion the tumour was visualised and localised better. of improving outcomes for all tumour stages. Staging is Further radiotherapy developments, such as intensity- also relevant in defining the extent of radiotherapy, for modulated radiotherapy (IMRT), are beyond the scope example whether to include loco-regional lymph nodes. of this article. However, IMRT is a form of conformal Following staging, radiotherapy planning requires very radiotherapy, so the same principles apply. specific definition of the location and extent of the primary tumour. Information is also required about the extent of spread around the tumour itself, and the location Definitions for radiotherapy planning of regional lymph node spread. Knowledge of anatomy and an understanding of the pathology of tumour spread During the 1990s, developments in radiotherapy technol- are essential. ogy, especially computer technology which introduced It is important for radiation oncologists to recognise the potential to plan radiotherapy dose in three dimen- that diagnostic radiologists and radiographers can play sions, led to the recognition that concise definitions an important role in helping to define optimum scanning of both the primary tumour and possible areas of protocols for use in radiotherapy planning. [6,7] local spread were required . As well as the obvious It is clear that diagnostic imaging guides the definition application to planning radiotherapy for individual of the tumour extent in almost all sites. However, for patients, definitions of target volumes are essential a successful outcome after radiotherapy, every single for radiotherapy protocols in multi-centre trials where tumour cell must be eradicated, including those which uniformity in planning is required, and to allow reporting have invaded beyond gross, palpable or imageable of results from different centres. disease. In radiotherapy planning, therefore, a margin Although strict definitions might have been usable with must be added to account for this microscopic spread. the older ‘square’ style of planning, in the era before This margin extends outside the gross tumour, sometimes modern imaging or radiotherapy planning systems the for a surprisingly large distance. Here is the fundamental uncertainties in target localisation and dose were so large difference between the extent of tumour assessed by that such definitions would have offered little advantage. current diagnostic cancer imaging and the final definition Now that we can use diagnostic quality imaging of a target volume for radiotherapy planning. directly in radiotherapy planning, imported electroni- cally, it is possible to treat the tumour reliably (i.e. ‘hit the target’) whilst avoiding normal tissue. To maximise the Conformal radiotherapy—a definition advantages of modern systems we must be very clear in the specification of the radiotherapy target. Sophisticated The concept of conformal therapy is to conform the planning requires robust thinking during the planning high dose volume as accurately as possible to the target process, with adherence to planning protocols, whether shape, which is an intuitively obvious concept. Broadly, local or multi-centre. conformal therapy employs geometric field shaping to Successful radiotherapy also requires the patient to follow the shape of the target. This is the obvious part. The older ‘square’ style of radiotherapy planning, which be positioned reliably and reproducibly with respect to pre-dates 3D computer systems, required the use of the treatment machine, normally a linear accelerator. orthogonal radiographs to delineate the furthest extent of Considerable effort and subtlety are needed to achieve the tumour or target in relation to the bony anatomy of the this goal. During radiotherapy planning, it is essential patient. This would produce six points, representing the to know the position of the patient in 3D space with furthest extent in each dimension. However, generally no considerable accuracy. This adds a level of difficulty and attempt could be made to shape the target, so that these is different from standard diagnostic imaging. Ultimately, six points define a cuboid structure. Since most tumours the radiotherapy plan must include information to grow with a pattern more like a sphere or spheroid, correctly locate the patient on the linac. The most the inclusion of the extra normal tissue in the corners straightforward method is to locate the patient so that the of the cube simply leads to irradiation of (much) more isocentre of the linac, i.e. its centre of rotation, lies within normal tissue to the full target dose. The conformation of the target. 156 N G Burnet et al Traditional 3D conformal ‘square’ planning planning Figure 2 The shape of the treatment volume from two techniques of radiotherapy planning. On the left is a cuboidal shape based on old-fashioned ‘square’ planning from orthogonal radiographs; on the right is a spherical shape produced from conformal planning. The two volumes are designed to treat the same tumour target, but the sphere is half the volume of the cube. Figure 3 Diagram to illustrate the main radiotherapy planning volumes, taken from ICRU Report 50. Specific target volumes for radiotherapy The original concepts of the GTV and CTV were detailed in Report 50 from The International Commission planning [6] of Radiation Units and Protection (ICRU) in 1993 . The report also described the principle of the margin There are three main volumes to be considered in needed for uncertainty in the process of planning and radiotherapy planning, though only the first two of these delivery, i.e. the PTV. The concept of the PTV was volumes are of real interest to diagnostic colleagues [7] refined in ICRU Report 62 in 1999 , and this added (see Fig. 3). The first of these two volumes is the further information about organs at risk (ORs) and the position and extent of the primary tumour; this is need, in certain specific circumstances, to add a margin known as the gross tumour volume (GTV). The second for uncertainty around an OR to produce a planning volume surrounds the GTV and describes the extent of organ at risk volume (PRV). Interestingly, Report 62 was microscopic, un-imageable tumour spread; this is known specifically triggered by the increasing availability of as the clinical target volume (CTV). Once these two conformal radiotherapy, where margins are more critical, volumes are established, the third volume, the planning target volume (PTV), which allows for uncertainties in and the need to describe normal tissue doses in more planning or delivery, must be added, and the normal tissue detail. These two reports set out an underlying philosophy structures in the vicinity of the target must be considered. for prescribing, recording and reporting radiotherapy, Target volumes for radiotherapy 157 which has been essential for the successful development spread, normally based on historical series rather than of modern radiotherapy. the extent of tumour quantified in an individual patient. The PTV was reviewed in 2003 by an expert group For example, for high-grade gliomas it is standard under the auspices of the British Institute of Radiology practice to apply a uniform margin around the gross [8] (BIR) . Their report details how to calculate the PTV tumour to account for microscopic infiltration, regardless margins required, and gives worked examples for a of individual considerations. This margin is based on number of sites. This report has been most valuable. biopsy and post-mortem series, and is large enough to These volumes are best discussed in a little more detail. encompass the maximum extent of invasion seen in (almost) any patient (see Fig. 4). The extent of the CTV margin depends upon imaging GTV techniques: as these have got more effective at localising gross tumour, so the edge of the gross tumour has This is the easiest volume to define, though not typically expanded and the CTV margin contracted, necessarily to localise. The GTV is essentially the gross though the final size of the CTV may have remained demonstrable location and extent of tumour. It is what the same. The CTV is also the biggest area in can be seen, palpated or imaged (see Fig. 4). As well as which developments in diagnostic imaging, especially a primary site, gross tumour involving lymph nodes or molecular imaging techniques, will enhance radiotherapy spread into adjacent soft tissue should be included in the planning. GTV. Typically, it is considered that the GTV corresponds Typically, the spread of tumours is restrained by to the part of the tumour where the tumour cell density is highest. This may have implications for choice of some anatomical barriers, and it is important that this radiotherapy dose, since tumour control requires a higher information is used to modify the CTV during the process dose if the initial tumour cell number is larger. of radiotherapy planning. For example, gliomas normally In the post-operative setting where the tumour has do not penetrate the skull, so the CTV can be constrained been excised, the GTV is no longer evident. Although within it (see Fig. 4). Soft tissue sarcomas of the limb are it is not necessary to attempt to outline a GTV if the restricted in their axial spread by inter-muscular septa, tumour has been resected, the position of the CTV must so the CTV does not have to extend beyond them (see be derived from the site of the original GTV. Therefore, Fig. 5). Additionally, the CTV does not have to extend some method of reconstruction of the original tumour beyond the surface of the patient. is necessary. This applies to rare tumours such as soft In some tumour sites it is a definite advantage to tissue sarcomas (Fig. 5), but also to common cancers such be able to use more than one imaging modality to as breast cancer, where localisation of the tumour bed plan radiotherapy. CT is normally used as the basis for may be important. Modern developments in imaging and radiotherapy planning for a number of reasons. Firstly, image matching are sure to be of help in the future. it contains density information which can be used to Although conceptually the GTV is usually the easiest calculate treatment beam attenuation, which improves to define, in practice the edges of the GTV are not the accuracy of dosimetry calculations. Secondly, it is necessarily always clear. Better imaging to delineate reliable in representing shape and position, including the gross tumour would be helpful. It is also clear that differ- accurate position of fiducial markers. These are used to ent imaging modalities may contribute different aspects locate the patient with respect to the treatment machine, of GTV localisation. For example, CT and magnetic are applied to the outside of the patient, and in an MRI resonance imaging (MRI) may be complimentary, and could be subject to distortion because they lie in the positron emission tomography (PET) may for example least homogeneous part of the magnetic field. Finally, the help to differentiate normal nodes from those involved by patient can usually be positioned in the CT scanner in tumour. the treatment position, which is not possible with MRI. For example, treatment of the chest typically requires the patient to be positioned with the thorax elevated on CTV a wedge-shaped board and the arms above the head, which can be accommodated in a CT. A similar argument The CTV contains the demonstrable GTV plus a margin applies to a number of other sites, including the breast. for sub-clinical disease spread. On occasion, there may Clearly, additional information may be available from be a second CTV, for example in a regional lymph node, other imaging modalities, especially MRI. The most where there is no obvious GTV present. The CTV is important because this volume must be adequately treated robust and reliable way to incorporate MRI data into if cure is to be achieved. It is assumed that the tumour the radiotherapy planning process is to electronically cell density in the CTV is lower than in the GTV and co-register the data and introduce this directly into consequently the radiotherapy dose may be lower. the planning system. An example is shown in Fig. 6. Typically, the CTV margin cannot be fully imaged. It It is likely that additional imaging will need to be is perhaps the most difficult of all the margins because introduced for direct use in planning, including newer it requires clinical assessment of risk and extent of MRI sequences, MR spectroscopy, PET imaging, and 158 N G Burnet et al (a) (b) (c) (d) Figure 4 Planning volumes for a patient with WHO Grade 4 glioma (glioblastoma). (a) Planning CT showing contrast-enhancing tumour. (b) The GTV is the visible tumour. (c) A margin for microscopic spread has been added to make the CTV; the margin is the same in all directions except that it is restricted by the skull. (d) The PTV has been added outside the CTV to account for uncertainties in planning and execution of treatment; this extends beyond the inner table of the skull. later molecular imaging. Some development in co- PTV registration techniques is likely to be needed for these. The PTV is really a geometric concept designed to ensure Occasionally, where different imaging modalities are that the radiotherapy prescription dose is actually delivery used, there may be uncertainties in the accuracy of co- to the CTV. It is a volume related to the isocentre of registration of the modalities. If one modality is displaced the linear accelerator rather than to the anatomy of the relative to the other, provided the size and direction can patient. For this reason, the PTV may extend beyond be measured or estimated, this can be corrected at this anatomical barriers such as bony margins, and may even stage, or allowed for in the CTV. However, if the size and extend outside the patient (Figs 4 and 5). direction of a discrepancy are unclear or unknown, they [7] In ICRU Report 62 , margins were suggested to should be addressed as part of the PTV (see below). This account for variations in size, shape and position of the can be summarised thus: ‘if there is certainty about the CTV in relation to anatomical reference points, perhaps uncertainty (of co-registration), it can be dealt with in the as the result of the filling of the stomach or bladder or CTV; if there is uncertainty about the certainty (of the co- movement due to respiration. This volume was called the registration), it should be addressed as part of the PTV’. internal margin. To this was to be added a set-up margin Target volumes for radiotherapy 159 (a) (b) Figure 5 CT planning scan for a patient with a soft tissue sarcoma of the (anatomical) posterior compartment of the thigh. The tumour has been resected so no GTV exists. (a) The CTV is shown, restricted anteriorly by the femur and intermuscular septa. (b) The PTV has been added outside the CTV and in places extends beyond the outside of the patient. to take into account all the uncertainties in planning, a spreadsheet in which to calculate margins, and provides patient positioning and beam positioning. These concepts site-specific recommendations. are useful in understanding the basis of the PTV margin. [7] ORs In ICRU Report 62 , it was accepted that under some circumstances, these margins need not be added ORs are normal tissues whose radiation sensitivity arithmetically, but rather in quadrature, for example influences treatment planning or the prescribed radiation where movements do not occur in the same direction on dose. Both systematic and random errors apply to ORs the same occasion. The report also acknowledged that just as much as to the CTV. In that case, a margin should under some circumstances the PTV might have to be be added to the OR, which is analogous to the PTV reduced, and very occasionally the CTV reduced as well, margin around the CTV, and generates the PRV. in order to limit dose to an adjacent critical normal tissue. However, adding a PRV around an OR will very This is an important concept, especially in circumstances substantially increase the volume of the normal tissue where higher radiotherapy doses are being attempted. structures and may present dilemmas concerning the [8] In its report of 2003 , the BIR showed how to radiotherapy dose to the target. Fortunately, this is only calculate the PTV margin in more detail. It suggested needed in certain circumstances. It is helpful to create abandoning the internal and set-up margins proposed in a PRV around an OR whose damage is especially ICRU Report 62 and replacing these with a systematic dangerous, and particularly where loss of a small amount error margin and a random error margin. The CTV plus of normal tissue from radiation damage would produce the systematic error margin gives the systematic target a severe clinical manifestation. A good example of this is volume (STV), and the addition of the random error the spinal cord, a ’serial’ tissue in organisation (analogous margin gives the PTV. The distinction between systematic to an electrical circuit), whose damage is catastrophic and random errors in the radiotherapy process is also for the patient. Around the spinal cord it is advisable very helpful. Broadly, systematic errors arise in treatment to add a PRV if doses which exceed the tolerance of preparation, whereas random errors are attributable to the spinal cord are intended. It must be accepted that errors in execution. This report shows how to deal with some interaction between the PTV and a PRV may be errors and uncertainties, and how to combine them. necessary, and may influence the prescribed radiation Typically, a larger margin is required for preparation dose and dose distribution. errors than for execution errors since some blurring of the execution errors happens over a course of treatment. Although errors in setting up the patient are always 3D, Radical and palliative radiotherapy it is extremely difficult to measure the 3D error. The BIR report provides a method in which the error in each Concepts of conformal therapy have most often been dimension can be incorporated separately. It also contains applied to radical, curative radiotherapy. However, the 160 N G Burnet et al (a) (b) (c) Figure 6 Example of the value of image co-registration for radiotherapy planning, which allows planning based directly on the MRI data. (a) Radiotherapy planning CT scan showing right acoustic schwannoma. (b) Diagnostic MRI, which shows the schwannoma clearly. (c) Electronic co-registration of the diagnostic MRI with the planning CT within the radiotherapy planning system. The intersection point can be moved as necessary. concepts of conformal radiotherapy apply equally well Conclusion to palliation, where avoidance of normal tissue side effects is intrinsic in the concept of good palliative care. The concepts of GTV, CTV and PTV have been Within the palliative setting, it may be reasonable to set a enormously helpful in allowing radiation oncologists to minimal CTV margin, or perhaps to use no CTV margin develop treatment protocols. All of these volumes are at all. Clearly, this is a clinical decision which is patient- crucially dependent on high quality imaging. Imaging to specific. define the gross tumour is essential as the starting point Target volumes for radiotherapy 161 for a radiotherapy treatment plan. Imaging of tumour • Delineation of the CTV is likely to benefit from spread, which has enormous potential for future devel- future developments in imaging, especially towards opment, is essential to contribute to the determination of the molecular level. the CTV. Further imaging of the surrounding anatomy is • The PTV allows for uncertainties in planning or necessary to define critical normal structures. Finally, in treatment delivery, and is designed to ensure that the assessing the margin required for a PTV, errors intrinsic radiotherapy dose is actually delivery to the CTV. in scanners, electronic transfer protocols, accuracy of co-registration of different imaging modalities, and the • The PTV is a geometric concept designed to ensure quality of the imaging are all factors to be considered. adequate treatment of the CTV, and can therefore Attention to the technicality of planning is important, extend outside the patient in some circumstances. and deviation from optimum protocols has been shown to reduce local control and cure. For radiotherapy, there • Normal tissue must be considered in radiotherapy is no doubt that ‘the devil is in the detail’. planning, and relevant structures are termed organs at It should be obvious that radiotherapy planning is com- risk (ORs). pletely dependent on diagnostic imaging, and benefits from the close involvement of diagnostic radiologists and radiographers. References [1] Swedish Council on Technology Assessment in Health Care (SBU). Radiotherapy for cancer. Acta Oncol 1996; 35(Suppl 6): 1–100, (Suppl 7): 1–152. Key points [2] Suit H. Contributions of L.H. Gray to radiation physics, biology, and oncology. Int J Radiat Oncol Biol Phys 2002; 53(4): 795–7. • The definition of tumour and target volumes for [3] Burnet NG, Wurm R, Nyman J, Peacock JH. Normal tissue radiotherapy is vital to the successful execution of radiosensitivity—how important is it? Clin Oncol 1996; 8: radiotherapy. 25–34. [4] Horiot JC, Le Fur R, N’Guyen T et al. Hyperfractionation • Attention to the detail of radiotherapy planning versus conventional fractionation in oropharyngeal carcinoma: final analysis of a randomised trial of the EORTC cooperative actually improves outcomes. group of radiotherapy. Radiother Oncol 1992; 25(4): 229–30. [5] Yarnold JR, Owen JR, Ashton A et al. Fractionation sensitivity • Radiotherapy requires the best possible diagnostic of change in breast appearance after radiotherapy for early breast imaging to define the location and extent of the cancer: long-term results of a randomised trial. Radiother Oncol tumour. 2002; 64(Suppl 1): S25. [6] ICRU. Prescribing, Recording and Reporting Photon Beam Ther- apy. Report 50. Bethesda, MD: International Commission • The GTV describes what can be seen, palpated or on Radiation Units and Measurements, 1999. imaged. [7] ICRU. Prescribing, Recording and Reporting Photon Beam Therapy (Supplement to ICRU Report 50). Report 62. Bethesda, • The CTV contains the GTV plus a margin for sub- MD: International Commission on Radiation Units and Measure- clinical disease spread which cannot be fully imaged. ments, 1999. [8] Geometric Uncertainties in Radiotherapy—Defining the Plan- • The CTV must be adequately treated to achieve cure. ning Target Volume, British Institute of Radiology, 2003. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cancer Imaging Pubmed Central

Defining the tumour and target volumes for radiotherapy

Cancer Imaging , Volume 4 (2) – Oct 21, 2004

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Pubmed Central
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1740-5025
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Abstract

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. Keywords: Tumour volume; target volume; conformal radiotherapy; ICRU; organs at risk. Introduction The role of radiotherapy in the treatment of cancer The purpose of considering how to define tumour and Radiotherapy plays a key role in the management target volumes for radiotherapy is to optimise this of patients with cancer. After surgery, radiotherapy is treatment modality. Radiotherapy is a speciality which the most effective curative treatment for cancer. In requires attention to detail in order to achieve the best 2002, the Cancer Services Collaborative suggested that results. It is also important to place radiotherapy in the radiotherapy alone is responsible for 78% of non-surgical context of cancer treatments to fully appreciate its value. cancer cures. Between 30 and 40% of the population This paper is available online at http://www.cancerimaging.org. In the event of a change in the URL address, please use the DOI provided to locate the paper. 1470-7330/04/020153 + 09 c 2004 International Cancer Imaging Society 154 N G Burnet et al will develop cancer, and at least half require radiotherapy the side effect profile of radiotherapy, and hence the [2,3] at some time in their illness. Of patients having therapeutic ratio . Implementation of techniques to radiotherapy, about 60% are treated with curative intent, spare normal tissue, such as conformal radiotherapy (vide often in combination with surgery and chemotherapy. infra), therefore allows a choice between (i) dose increase In addition, radiotherapy has an important role in the with a consistent level of side effects, or (ii) the same dose palliation of symptoms from cancer. with reduced side effects (see Fig. 1). In fact, rather modest changes in dose both to the Increased TCP using Conformal RT tumour and normal tissue can deliver a clinical advantage. Tumour Normal tissue For tumours, the effect of a dose increase can be A B C assessed from the slope of the plot of tumour control probability (TCP) vs. radiotherapy dose. In the central part of the curve, where TCP is 50%, the curve is relatively straight. A parameter which describes the percentage increase in TCP for a 1% increase in dose, known as the Gamma-50 (γ ) factor, can be a useful way of estimating the benefit of dose escalation. There is a large amount of literature on both laboratory and clinical data suggesting that a 1% increase in dose typically delivers a 1–2% increase in TCP. Thus, a 10% Dose dose increase, which is realistically achievable in many 12 settings, could achieve an improvement in tumour control Cure with Cure with of 10–20%. This was achieved in a radiotherapy trial for conventional RT conformal RT head and neck cancer, where a 15% dose increase raised the local control from 40 to 59% at 5 years; this indicates Figure 1 Diagrammatic plot of tumour control [4] a value for γ of 1.33 . probability (TCP) or normal tissue complication For normal tissue, a difference in dose to the breast of probability (NTCP) vs. radiotherapy dose. Sparing approximately 10%, within the context of a radiotherapy normal tissues shifts the NTCP curve to the right (B dose trial, achieved a demonstrable change in the to C), allowing a lower incidence of normal tissue [5] incidence of shape change . The fact that a 10% dose damage for the same dose (dose 1) or the same level of NTCP for a higher dose (dose 2). This is the difference led to a 16% difference (24 vs. 40%) in basis for an improvement in the therapeutic ratio. the number of women exhibiting a change in breast This benefit can be the result of any measure which appearance at 5 years indicates that modest dose changes reduces the normal tissue dose, for example including produce a clinical effect. This will usually apply whether better target imaging, conformal radiotherapy, and the dose reduction is to the whole organ, such as the improved patient immobilisation. breast, or part of an organ, such as can be achieved with conformal radiotherapy. Thus, even a modest dose Technological developments in radiotherapy are con- increase to the tumour and a dose decrease to normal tinuing apace, and are likely to confer further clinical tissue achieved using advanced radiotherapy planning are benefit. For example, the Swedish Council on Technology worth pursuing. Assessment in Health Care estimated in 1996 that the However, in radiotherapy, tumour and normal tissue overall 5-year survival in patients receiving radiotherapy are inextricably linked. When delivering a tumoricidal should be increased by approximately 10% over the 10 years following their report as the result of technical dose to the tumour, some normal tissue is inevitably [1] innovation, which includes imaging . irradiated. If normal tissue is spared, in dose or volume, the incidence and severity of complications are reduced. This shifts the dose-response curve for complication to Fundamental principles of radiotherapy the right, allowing a choice between the same dose and tumour control with reduced side effects, and a higher There are three fundamental axioms of radiotherapy dose with increased tumour control and the same level of which are relevant background to this topic. Firstly, an normal tissue (see Fig. 1). increase in radiotherapy dose to the tumour normally This preamble is intended to show that quite small improves the probability of local control. Secondly, changes in radiotherapy can achieve a significant improving local control in the context of a localised alteration in clinical outcome. Therefore, attention to the tumour achieves an improvement in the overall cure detail of radiotherapy planning is central to the current rate, because metastatic spread from local recurrence is avoided. Finally, sparing normal tissues improves and improving therapeutic ratio. TCP or NTCP (%) Target volumes for radiotherapy 155 Radiotherapy as a localised cancer treatment treatment volume to the shape of the target quite simply eliminates, or at least reduces, the radiation exposure of a Radiotherapy is, by its nature, a localised treatment for large volume of normal tissue (see Fig. 2). localised tumours and in this respect is analogous to This seems to imply that the introduction of conformal surgery. Total body irradiation is an apparent exception, radiotherapy has led to a reduction in radiotherapy but it is designed to treat all bone marrow and circulating volumes, and generally this has been the case. However, blood, and is a localised treatment to this whole-body early experience with computed tomography (CT)-based target. Thus, disease staging is crucial in the decision on planning showed that in some circumstances, such as whether to employ radiotherapy as part of the treatment bladder cancer, volumes actually increased, compared to strategy. Better imaging produces better staging, and the older-style ‘square’ orthogonal localisation, because leads to stage migration which actually gives the illusion the tumour was visualised and localised better. of improving outcomes for all tumour stages. Staging is Further radiotherapy developments, such as intensity- also relevant in defining the extent of radiotherapy, for modulated radiotherapy (IMRT), are beyond the scope example whether to include loco-regional lymph nodes. of this article. However, IMRT is a form of conformal Following staging, radiotherapy planning requires very radiotherapy, so the same principles apply. specific definition of the location and extent of the primary tumour. Information is also required about the extent of spread around the tumour itself, and the location Definitions for radiotherapy planning of regional lymph node spread. Knowledge of anatomy and an understanding of the pathology of tumour spread During the 1990s, developments in radiotherapy technol- are essential. ogy, especially computer technology which introduced It is important for radiation oncologists to recognise the potential to plan radiotherapy dose in three dimen- that diagnostic radiologists and radiographers can play sions, led to the recognition that concise definitions an important role in helping to define optimum scanning of both the primary tumour and possible areas of protocols for use in radiotherapy planning. [6,7] local spread were required . As well as the obvious It is clear that diagnostic imaging guides the definition application to planning radiotherapy for individual of the tumour extent in almost all sites. However, for patients, definitions of target volumes are essential a successful outcome after radiotherapy, every single for radiotherapy protocols in multi-centre trials where tumour cell must be eradicated, including those which uniformity in planning is required, and to allow reporting have invaded beyond gross, palpable or imageable of results from different centres. disease. In radiotherapy planning, therefore, a margin Although strict definitions might have been usable with must be added to account for this microscopic spread. the older ‘square’ style of planning, in the era before This margin extends outside the gross tumour, sometimes modern imaging or radiotherapy planning systems the for a surprisingly large distance. Here is the fundamental uncertainties in target localisation and dose were so large difference between the extent of tumour assessed by that such definitions would have offered little advantage. current diagnostic cancer imaging and the final definition Now that we can use diagnostic quality imaging of a target volume for radiotherapy planning. directly in radiotherapy planning, imported electroni- cally, it is possible to treat the tumour reliably (i.e. ‘hit the target’) whilst avoiding normal tissue. To maximise the Conformal radiotherapy—a definition advantages of modern systems we must be very clear in the specification of the radiotherapy target. Sophisticated The concept of conformal therapy is to conform the planning requires robust thinking during the planning high dose volume as accurately as possible to the target process, with adherence to planning protocols, whether shape, which is an intuitively obvious concept. Broadly, local or multi-centre. conformal therapy employs geometric field shaping to Successful radiotherapy also requires the patient to follow the shape of the target. This is the obvious part. The older ‘square’ style of radiotherapy planning, which be positioned reliably and reproducibly with respect to pre-dates 3D computer systems, required the use of the treatment machine, normally a linear accelerator. orthogonal radiographs to delineate the furthest extent of Considerable effort and subtlety are needed to achieve the tumour or target in relation to the bony anatomy of the this goal. During radiotherapy planning, it is essential patient. This would produce six points, representing the to know the position of the patient in 3D space with furthest extent in each dimension. However, generally no considerable accuracy. This adds a level of difficulty and attempt could be made to shape the target, so that these is different from standard diagnostic imaging. Ultimately, six points define a cuboid structure. Since most tumours the radiotherapy plan must include information to grow with a pattern more like a sphere or spheroid, correctly locate the patient on the linac. The most the inclusion of the extra normal tissue in the corners straightforward method is to locate the patient so that the of the cube simply leads to irradiation of (much) more isocentre of the linac, i.e. its centre of rotation, lies within normal tissue to the full target dose. The conformation of the target. 156 N G Burnet et al Traditional 3D conformal ‘square’ planning planning Figure 2 The shape of the treatment volume from two techniques of radiotherapy planning. On the left is a cuboidal shape based on old-fashioned ‘square’ planning from orthogonal radiographs; on the right is a spherical shape produced from conformal planning. The two volumes are designed to treat the same tumour target, but the sphere is half the volume of the cube. Figure 3 Diagram to illustrate the main radiotherapy planning volumes, taken from ICRU Report 50. Specific target volumes for radiotherapy The original concepts of the GTV and CTV were detailed in Report 50 from The International Commission planning [6] of Radiation Units and Protection (ICRU) in 1993 . The report also described the principle of the margin There are three main volumes to be considered in needed for uncertainty in the process of planning and radiotherapy planning, though only the first two of these delivery, i.e. the PTV. The concept of the PTV was volumes are of real interest to diagnostic colleagues [7] refined in ICRU Report 62 in 1999 , and this added (see Fig. 3). The first of these two volumes is the further information about organs at risk (ORs) and the position and extent of the primary tumour; this is need, in certain specific circumstances, to add a margin known as the gross tumour volume (GTV). The second for uncertainty around an OR to produce a planning volume surrounds the GTV and describes the extent of organ at risk volume (PRV). Interestingly, Report 62 was microscopic, un-imageable tumour spread; this is known specifically triggered by the increasing availability of as the clinical target volume (CTV). Once these two conformal radiotherapy, where margins are more critical, volumes are established, the third volume, the planning target volume (PTV), which allows for uncertainties in and the need to describe normal tissue doses in more planning or delivery, must be added, and the normal tissue detail. These two reports set out an underlying philosophy structures in the vicinity of the target must be considered. for prescribing, recording and reporting radiotherapy, Target volumes for radiotherapy 157 which has been essential for the successful development spread, normally based on historical series rather than of modern radiotherapy. the extent of tumour quantified in an individual patient. The PTV was reviewed in 2003 by an expert group For example, for high-grade gliomas it is standard under the auspices of the British Institute of Radiology practice to apply a uniform margin around the gross [8] (BIR) . Their report details how to calculate the PTV tumour to account for microscopic infiltration, regardless margins required, and gives worked examples for a of individual considerations. This margin is based on number of sites. This report has been most valuable. biopsy and post-mortem series, and is large enough to These volumes are best discussed in a little more detail. encompass the maximum extent of invasion seen in (almost) any patient (see Fig. 4). The extent of the CTV margin depends upon imaging GTV techniques: as these have got more effective at localising gross tumour, so the edge of the gross tumour has This is the easiest volume to define, though not typically expanded and the CTV margin contracted, necessarily to localise. The GTV is essentially the gross though the final size of the CTV may have remained demonstrable location and extent of tumour. It is what the same. The CTV is also the biggest area in can be seen, palpated or imaged (see Fig. 4). As well as which developments in diagnostic imaging, especially a primary site, gross tumour involving lymph nodes or molecular imaging techniques, will enhance radiotherapy spread into adjacent soft tissue should be included in the planning. GTV. Typically, it is considered that the GTV corresponds Typically, the spread of tumours is restrained by to the part of the tumour where the tumour cell density is highest. This may have implications for choice of some anatomical barriers, and it is important that this radiotherapy dose, since tumour control requires a higher information is used to modify the CTV during the process dose if the initial tumour cell number is larger. of radiotherapy planning. For example, gliomas normally In the post-operative setting where the tumour has do not penetrate the skull, so the CTV can be constrained been excised, the GTV is no longer evident. Although within it (see Fig. 4). Soft tissue sarcomas of the limb are it is not necessary to attempt to outline a GTV if the restricted in their axial spread by inter-muscular septa, tumour has been resected, the position of the CTV must so the CTV does not have to extend beyond them (see be derived from the site of the original GTV. Therefore, Fig. 5). Additionally, the CTV does not have to extend some method of reconstruction of the original tumour beyond the surface of the patient. is necessary. This applies to rare tumours such as soft In some tumour sites it is a definite advantage to tissue sarcomas (Fig. 5), but also to common cancers such be able to use more than one imaging modality to as breast cancer, where localisation of the tumour bed plan radiotherapy. CT is normally used as the basis for may be important. Modern developments in imaging and radiotherapy planning for a number of reasons. Firstly, image matching are sure to be of help in the future. it contains density information which can be used to Although conceptually the GTV is usually the easiest calculate treatment beam attenuation, which improves to define, in practice the edges of the GTV are not the accuracy of dosimetry calculations. Secondly, it is necessarily always clear. Better imaging to delineate reliable in representing shape and position, including the gross tumour would be helpful. It is also clear that differ- accurate position of fiducial markers. These are used to ent imaging modalities may contribute different aspects locate the patient with respect to the treatment machine, of GTV localisation. For example, CT and magnetic are applied to the outside of the patient, and in an MRI resonance imaging (MRI) may be complimentary, and could be subject to distortion because they lie in the positron emission tomography (PET) may for example least homogeneous part of the magnetic field. Finally, the help to differentiate normal nodes from those involved by patient can usually be positioned in the CT scanner in tumour. the treatment position, which is not possible with MRI. For example, treatment of the chest typically requires the patient to be positioned with the thorax elevated on CTV a wedge-shaped board and the arms above the head, which can be accommodated in a CT. A similar argument The CTV contains the demonstrable GTV plus a margin applies to a number of other sites, including the breast. for sub-clinical disease spread. On occasion, there may Clearly, additional information may be available from be a second CTV, for example in a regional lymph node, other imaging modalities, especially MRI. The most where there is no obvious GTV present. The CTV is important because this volume must be adequately treated robust and reliable way to incorporate MRI data into if cure is to be achieved. It is assumed that the tumour the radiotherapy planning process is to electronically cell density in the CTV is lower than in the GTV and co-register the data and introduce this directly into consequently the radiotherapy dose may be lower. the planning system. An example is shown in Fig. 6. Typically, the CTV margin cannot be fully imaged. It It is likely that additional imaging will need to be is perhaps the most difficult of all the margins because introduced for direct use in planning, including newer it requires clinical assessment of risk and extent of MRI sequences, MR spectroscopy, PET imaging, and 158 N G Burnet et al (a) (b) (c) (d) Figure 4 Planning volumes for a patient with WHO Grade 4 glioma (glioblastoma). (a) Planning CT showing contrast-enhancing tumour. (b) The GTV is the visible tumour. (c) A margin for microscopic spread has been added to make the CTV; the margin is the same in all directions except that it is restricted by the skull. (d) The PTV has been added outside the CTV to account for uncertainties in planning and execution of treatment; this extends beyond the inner table of the skull. later molecular imaging. Some development in co- PTV registration techniques is likely to be needed for these. The PTV is really a geometric concept designed to ensure Occasionally, where different imaging modalities are that the radiotherapy prescription dose is actually delivery used, there may be uncertainties in the accuracy of co- to the CTV. It is a volume related to the isocentre of registration of the modalities. If one modality is displaced the linear accelerator rather than to the anatomy of the relative to the other, provided the size and direction can patient. For this reason, the PTV may extend beyond be measured or estimated, this can be corrected at this anatomical barriers such as bony margins, and may even stage, or allowed for in the CTV. However, if the size and extend outside the patient (Figs 4 and 5). direction of a discrepancy are unclear or unknown, they [7] In ICRU Report 62 , margins were suggested to should be addressed as part of the PTV (see below). This account for variations in size, shape and position of the can be summarised thus: ‘if there is certainty about the CTV in relation to anatomical reference points, perhaps uncertainty (of co-registration), it can be dealt with in the as the result of the filling of the stomach or bladder or CTV; if there is uncertainty about the certainty (of the co- movement due to respiration. This volume was called the registration), it should be addressed as part of the PTV’. internal margin. To this was to be added a set-up margin Target volumes for radiotherapy 159 (a) (b) Figure 5 CT planning scan for a patient with a soft tissue sarcoma of the (anatomical) posterior compartment of the thigh. The tumour has been resected so no GTV exists. (a) The CTV is shown, restricted anteriorly by the femur and intermuscular septa. (b) The PTV has been added outside the CTV and in places extends beyond the outside of the patient. to take into account all the uncertainties in planning, a spreadsheet in which to calculate margins, and provides patient positioning and beam positioning. These concepts site-specific recommendations. are useful in understanding the basis of the PTV margin. [7] ORs In ICRU Report 62 , it was accepted that under some circumstances, these margins need not be added ORs are normal tissues whose radiation sensitivity arithmetically, but rather in quadrature, for example influences treatment planning or the prescribed radiation where movements do not occur in the same direction on dose. Both systematic and random errors apply to ORs the same occasion. The report also acknowledged that just as much as to the CTV. In that case, a margin should under some circumstances the PTV might have to be be added to the OR, which is analogous to the PTV reduced, and very occasionally the CTV reduced as well, margin around the CTV, and generates the PRV. in order to limit dose to an adjacent critical normal tissue. However, adding a PRV around an OR will very This is an important concept, especially in circumstances substantially increase the volume of the normal tissue where higher radiotherapy doses are being attempted. structures and may present dilemmas concerning the [8] In its report of 2003 , the BIR showed how to radiotherapy dose to the target. Fortunately, this is only calculate the PTV margin in more detail. It suggested needed in certain circumstances. It is helpful to create abandoning the internal and set-up margins proposed in a PRV around an OR whose damage is especially ICRU Report 62 and replacing these with a systematic dangerous, and particularly where loss of a small amount error margin and a random error margin. The CTV plus of normal tissue from radiation damage would produce the systematic error margin gives the systematic target a severe clinical manifestation. A good example of this is volume (STV), and the addition of the random error the spinal cord, a ’serial’ tissue in organisation (analogous margin gives the PTV. The distinction between systematic to an electrical circuit), whose damage is catastrophic and random errors in the radiotherapy process is also for the patient. Around the spinal cord it is advisable very helpful. Broadly, systematic errors arise in treatment to add a PRV if doses which exceed the tolerance of preparation, whereas random errors are attributable to the spinal cord are intended. It must be accepted that errors in execution. This report shows how to deal with some interaction between the PTV and a PRV may be errors and uncertainties, and how to combine them. necessary, and may influence the prescribed radiation Typically, a larger margin is required for preparation dose and dose distribution. errors than for execution errors since some blurring of the execution errors happens over a course of treatment. Although errors in setting up the patient are always 3D, Radical and palliative radiotherapy it is extremely difficult to measure the 3D error. The BIR report provides a method in which the error in each Concepts of conformal therapy have most often been dimension can be incorporated separately. It also contains applied to radical, curative radiotherapy. However, the 160 N G Burnet et al (a) (b) (c) Figure 6 Example of the value of image co-registration for radiotherapy planning, which allows planning based directly on the MRI data. (a) Radiotherapy planning CT scan showing right acoustic schwannoma. (b) Diagnostic MRI, which shows the schwannoma clearly. (c) Electronic co-registration of the diagnostic MRI with the planning CT within the radiotherapy planning system. The intersection point can be moved as necessary. concepts of conformal radiotherapy apply equally well Conclusion to palliation, where avoidance of normal tissue side effects is intrinsic in the concept of good palliative care. The concepts of GTV, CTV and PTV have been Within the palliative setting, it may be reasonable to set a enormously helpful in allowing radiation oncologists to minimal CTV margin, or perhaps to use no CTV margin develop treatment protocols. All of these volumes are at all. Clearly, this is a clinical decision which is patient- crucially dependent on high quality imaging. Imaging to specific. define the gross tumour is essential as the starting point Target volumes for radiotherapy 161 for a radiotherapy treatment plan. Imaging of tumour • Delineation of the CTV is likely to benefit from spread, which has enormous potential for future devel- future developments in imaging, especially towards opment, is essential to contribute to the determination of the molecular level. the CTV. Further imaging of the surrounding anatomy is • The PTV allows for uncertainties in planning or necessary to define critical normal structures. Finally, in treatment delivery, and is designed to ensure that the assessing the margin required for a PTV, errors intrinsic radiotherapy dose is actually delivery to the CTV. in scanners, electronic transfer protocols, accuracy of co-registration of different imaging modalities, and the • The PTV is a geometric concept designed to ensure quality of the imaging are all factors to be considered. adequate treatment of the CTV, and can therefore Attention to the technicality of planning is important, extend outside the patient in some circumstances. and deviation from optimum protocols has been shown to reduce local control and cure. For radiotherapy, there • Normal tissue must be considered in radiotherapy is no doubt that ‘the devil is in the detail’. planning, and relevant structures are termed organs at It should be obvious that radiotherapy planning is com- risk (ORs). pletely dependent on diagnostic imaging, and benefits from the close involvement of diagnostic radiologists and radiographers. References [1] Swedish Council on Technology Assessment in Health Care (SBU). Radiotherapy for cancer. Acta Oncol 1996; 35(Suppl 6): 1–100, (Suppl 7): 1–152. Key points [2] Suit H. Contributions of L.H. Gray to radiation physics, biology, and oncology. Int J Radiat Oncol Biol Phys 2002; 53(4): 795–7. • The definition of tumour and target volumes for [3] Burnet NG, Wurm R, Nyman J, Peacock JH. Normal tissue radiotherapy is vital to the successful execution of radiosensitivity—how important is it? Clin Oncol 1996; 8: radiotherapy. 25–34. [4] Horiot JC, Le Fur R, N’Guyen T et al. Hyperfractionation • Attention to the detail of radiotherapy planning versus conventional fractionation in oropharyngeal carcinoma: final analysis of a randomised trial of the EORTC cooperative actually improves outcomes. group of radiotherapy. Radiother Oncol 1992; 25(4): 229–30. [5] Yarnold JR, Owen JR, Ashton A et al. Fractionation sensitivity • Radiotherapy requires the best possible diagnostic of change in breast appearance after radiotherapy for early breast imaging to define the location and extent of the cancer: long-term results of a randomised trial. Radiother Oncol tumour. 2002; 64(Suppl 1): S25. [6] ICRU. Prescribing, Recording and Reporting Photon Beam Ther- apy. Report 50. Bethesda, MD: International Commission • The GTV describes what can be seen, palpated or on Radiation Units and Measurements, 1999. imaged. [7] ICRU. Prescribing, Recording and Reporting Photon Beam Therapy (Supplement to ICRU Report 50). Report 62. Bethesda, • The CTV contains the GTV plus a margin for sub- MD: International Commission on Radiation Units and Measure- clinical disease spread which cannot be fully imaged. ments, 1999. [8] Geometric Uncertainties in Radiotherapy—Defining the Plan- • The CTV must be adequately treated to achieve cure. ning Target Volume, British Institute of Radiology, 2003.

Journal

Cancer ImagingPubmed Central

Published: Oct 21, 2004

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