방사선치료 시 환자의 움직임 및 setup error를 고려한 target volume은? (ICUR target volume definitions, ICRU Report 71)

방사선치료 시 환자의 움직임 및 setup error를 고려한 target volume은?

A. GTV
B. CTV
G. ITV
M. PTV

 

정답: 

 

---

The volume concepts

Several volume concepts were developed in the ICRU Reports (Fig. 1):

• gross tumour volume (GTV),
• clinical target volume (CTV),
• internal target volume (ITV),
• planning target volume (PTV),
• organ at risk (OR),
• planning organ at risk volume (PRV),
• treated volume, and
• irradiated volume.

Figure 1

Schematic illustration of the different volumes as defined in ICRU Report 50 (1993). Gross tumour volume (GTV) denotes the demonstrated tumour. Clinical target volume (CTV) denotes the demonstrated tumour (when present) and also volumes with suspected (subclinical) tumour considered to need treatment (e.g. a margin around the GTV and regional lymph nodes not invaded clinically). The CTV is thus a purely anatomical clinical concept. Planning target volume (PTV) consists of the CTV(s) and a margin to account for variations in size, shape, and position relative to the treatment beam(s). The PTV is thus a geometrical concept used to ensure that the CTV receives the prescribed dose, and it is defined in relation to a fixed coordinate system. Note that in the example shown, the magnitude of foreseen movements of the CTV is different in different directions. Treated volume is the volume that receives a dose that is considered important for local cure or palliation. The concept is useful for the evaluation of loco-regional relapses. Irradiated volume is the tissue volume which receives a dose that is considered significant in relation to normal tissue tolerance (other than those specifically defined as organs at risk) (reproduced by kind permission from the ICRU).

Only GTV, CTV, and OR represent tissues, whereas the others are geometric concepts and do not strictly represent tissue or organ volumes.

GTV (gross tumour volume)

The gross tumour volume (GTV) is the gross palpable or visible/demonstrable extent and location of the malignant growth.

The GTV may consist of primary tumour (GTV-T), metastatic lymphadenopathy (GTV-N), or other metastases (GTV-M). The GTV corresponds almost always to those parts of the malignant growth where the tumour cell density is the highest. Due to the high density of the cancer cells in the GTV, an adequate dose must be delivered to the whole GTV to obtain local tumour control in radical treatments. No GTV can be defined if the tumour has been completely removed, e.g. by previous surgery.

The shape, size, and location of a GTV may be determined by different methods such as clinical examination (e.g. inspection, palpation, endoscopy), and various imaging techniques (e.g. X-ray, computed tomography (CT), digital radiography, ultrasonography, magnetic resonance imaging (MRI), and radionuclide methods). The methods used to determine the GTV should meet the requirements for staging the tumour according to the clinical TNM[8,9] and American Joint Committee on Cancer (AJCC)[10,11] systems, and the definition of the GTV is then in full agreement with the criteria used for the TNM classification.

The GTV (primary tumour (GTV-T), metastatic lymphadenopathy (GTV-N), other metastases (GTV-M)), may be different in size and shape, sometimes significantly, depending on what examination technique is used for evaluation (e.g. palpation or mammography for breast tumours, and CT or MRI for some brain tumours). The radiation oncologists should therefore indicate in each case which methods have been used for evaluation and for the definition of the GTV. The problem has been highlighted recently[12]. The image format should make it possible to fuse information from different imaging equipments, using, e.g. DICOM format[13].

Since the description of a GTV on scans for radiation treatment planning usually is made subjectively, an interobserver variation can be expected.

The GTV should be described in standard topographical or anatomical terms, e.g. ‘tumour 18 mm in diameter in the left lobe of the prostate adjacent to but not breaching the capsule’. In many situations, a verbal description might be too cumbersome and, for the purpose of data recording and analysis, a classification system is needed. Several systems have been proposed for coding the anatomical description; some of them are mentioned in ICRU Report No. 50[4].

GTV may be confined to only part of an organ (e.g. a T1 breast cancer), or involve a whole organ (e.g. in multiple metastases to the brain). The GTV may or may not extend outside the normal borders of the organ or tissue involved.

CTV (clinical target volume)

The clinical target volume (CTV) is a tissue volume that contains a demonstrable GTV and/or is considered to contain microscopic, subclinical extensions at a certain probability level. This volume thus has to be considered for therapy and, if included, should be irradiated adequately to achieve cure.

For the treatment of subclinical disease, two situations may be defined as below, and as illustrated in Fig. 2. In this situation the prescription is based on the assumption that in some anatomically definable tissues/organs, there may be cancer cells at a given probability level, even though the cannot be detected; they are subclinical. The level of probability is based on clinical experience from adequately documented treatments and follow-up. For the purpose of prescription of treatment, it can usually be described in terms of frequency of risk for later detectable mainfestations (failure rate), when not treated adequately in the “subclinical” situation.

Figure 2

Schematic illustration of the relations between GTV-T/N(s) and CTV-T/N(s) in different clinical situations (from ICRU, Report 71, 2004[7], with kind permission of Oxford University Press). (a) Simple case with one GTV and the corresponding CTV (e.g. a skin tumour). At the level of the GTV (dark red), the cellular density is the highest (as an average, about 106 cells/mm3), but may be heterogeneous (e.g. due to necrosis). The width of the safety margin (light red) is selected so that, in principle, no cancer cells are present outside the limits of the CTV. The cancer cell density decreases between the border of the GTV and the outer limit of the CTV, but the variation of the cell density with distance is not known (‘?’ in the figure) and depends on tumour type and location. In some situations a natural anatomical border may limit subclinical extensions, e.g. pariental pleura in mediastinal lymphomas. (b) Two GTVs are present: the primary tumour, GTV-T, and a metastatic fixed lymph node, GTV-N (e.g. a tumour of the tonsil with a homolateral cervical lymph node). A safety margin for microscopic invasion has to be taken around each GTV, which may lead to the definition of two CTVs: CTV-T corresponding to the primary tumour and its safety margin, and CTV-N for the lymph node and its safety margin. Actually, since in this example, the two CTVs are close to each other and because there are certainly malignant cells between the two GTVs, only a single CTV is selected (CTV-TN), which includes the two GTVs and a common safety margin. (c) The primary tumour and its safety margin define a first CTV (CTV-T). In addition, there is a high probability of invasion of the adjacent lymph node area, which leads to the definition of a second CTV (CTV-N). It is decided to keep the two CTVs adjacent to each other as there could be cancer cells all along between them (e.g. breast cancer and adjacent lymph node area(s), or tumour of the head and neck and adjacent lymph node area(s)). (d) A similar situation to that in (c), but there is free space between the CTV containing the primary tumour and the CTVs including the lymph node areas at risk. This is the case, e.g. for a tumour of the anus and the inguinal lymphatic areas, which can be treated with electron beams.

Prescription of treatment of subclinical extensions adjacent to a GTV 

Clinical experience indicates that around a GTV (Fig. 2a,b) (primary tumour; GTV-T, or metastatic lymphadenopathy; GTV-N) there is generally subclinical involvement, i.e. individual malignant cells, small cell clusters, or microextensions, which cannot be detected by staging procedures. The GTV together with this surrounding volume of local subclinical involvement can be defined as a clinical target volume (CTV-T for primary tumour, and CTV-N for metastatic lymphadenopathy, etc.). If the same dose is prescribed for two such CTVs and if they are close to each other, they can be labelled CTV-TN. If different doses are prescribed, there will be one CTV-T and one CTV-N, respectively. If the GTV has been removed by seemingly radical surgery, but it is still felt that radiotherapy is needed for the tissues that remain close to the site of the removed GTV, this volume is also usually designated as CTV-T.

Prescription of treatment of subclinical extension at a distance from a GTV 

Additional volumes (CTVs) with presumed subclinical spread (Fig. 2c,d) (e.g. regional lymph nodes, N0) may also be considered for therapy. They are also defined as clinical target volumes, and may topographically be designated CTV-N I, CTV-N II, etc. To stress that in such cases subclinical disease is treated ‘electively’, it may be useful to add ‘E’, e.g. CTV-EN. It may also be useful to differentiate between ‘CTV-E high-risk’ and ‘CTV-E low-risk’. A precise description of the terminology used should be available in the treatment protocol[14]. The anatomical localisation of different lymph node areas has been reported[15,16].

If different doses are prescribed, different CTVs have to be defined for treatment planning. For any given situation there is often more than one CTV. One situation can be illustrated by considering a primary tumour and its regional lymphatics separately (e.g. in breast conserving procedures) where the primary tumour and its regional lymphatics are separated anatomically. In other situations the aim is to treat two or more CTVs to different dose levels. One common example of this is ‘boost’ therapy, where often the ‘high-dose’ volume (often containing the GTV or GTVs) is located inside the ‘low-dose’ volume.

The prescription of the GTV(s) and CTV(s) are based on general oncological principles, and are not specific to the field of radiation therapy. For instance, in surgery, a safety margin is taken around the gross tumour volume according to clinical judgment, and this implies the same use of the clinical target volume concept as in external beam radiation treatments.

In brachytherapy, volumes to be treated are also defined, and thus the concept of CTV is valid. The definition of GTV(s) and CTV(s) thus constitute the basic prescription of treatment for all radiation therapy techniques, and must precede the subsequent treatment planning.

ITV (internal target volume) and PTV (planning target volume)

Once the CTV(s) have been defined, in external beam radiation treatment, a suitable arrangement of radiation beam(s) must be selected to achieve an acceptable dose distribution. Today this calculation can only be done for a static representation, whereas in fact there are variations and uncertainties in the positions, sizes and shapes, and orientations of both the tissues, patient, and the beams in relation to the common coordinate system. This will be seen both during a single session and from one session to another. The variations and errors may be either random or systematic. A detailed analysis of this problem can be found in ‘Geometric uncertainties in Radiotherapy’[17]. Such variations and uncertainties may also occur when information for decision making is obtained (e.g. by CT scanning), and also between this part of the procedure and the first treatment. This creates a situation where the dose distribution is being calculated for a static situation which does not reflect the real dynamic situation. If no margins are added, some of the tissues will move out of the beam for part of the treatment resulting in underdosage. Other parts of the tissues may move around in a dose gradient, making it difficult to state the exact dose received by each tissue element. Too wide margins will result in unnecessary morbidity. There is no ideal solution, and acceptable compromises must be agreed. To assure that the CTV(s) in practice receive a dose that does not deviate significantly from the prescribed and planned dose, margins must be added to the CTV(s) for variations in tissue positions, sizes, and shapes, as well as for variations in patient position and beam geometries, both intrafractionally and interfractionally. This leads to the concept of planning target volume (PTV).

For the final treatment planning (definition of beam sizes, etc.), all the different variations and uncertainties must be considered, to define a static volume (planning target volume (PTV)) that will be used for treatment planning and for basic reporting of doses, which is considered representative of the corresponding CTV(s).

An internal margin (IM) must be added to the CTV to compensate for physiological variations in size, shape, and position of the CTV during therapy in relation to an internal reference point and its corresponding coordinate system. The IM, commonly asymmetric around the CTV, compensates for movements and variations in site, size and shape of the tissues which contain or are adjacent to the CTV, resulting from e.g.:

• respiration,
• variable filling of the bladder,
• variable filling of the rectum,
• swallowing,
• heart beat,
• movements of the bowel.

These internal variations are physiological ones, and they result in changes in site, size, and shape of the CTV. They cannot always be influenced easily. Techniques to take these into account (such as gating) are being tested. They do not depend on external uncertainties in patient day-to-day set-up or beam geometry.

The internal target volume (ITV) is the volume encompassing the CTV, which takes into account the fact that the CTV varies in position, shape and size.

The internal target volume (ITV) is defined by the internal margin (IM), as described above, and is referred to the patient coordinate system.

To account specifically for uncertainties and variability in the reproducibility of patient positioning and inaccuracies in the alignment of the therapeutic beams during treatment planning and throughout treatment, a set-up margin (SM) for each beam is needed. The uncertainties to be compensated for may vary on different anatomical directions, and thus the extent of such margins depends on the selection of beam geometries. The inaccuracies depend on factors such as:

• variations in patient positioning,
• lack of reproducibility of the equipment (worn bearings causing, e.g. sagging of gantry, collimators, and couch),
• human factors (e.g. experience and precision of the radiographers/radiotherapists).

They may also vary from machine to machine. The use of patient immobilisation devices, the application of quality assurance programs for the physical aspects of the treatment equipment, and the skill and experience of the radiographers/radiotherapists are important factors which must be taken into account. The use of different record and verify systems (in real time or not) may also be important, and may significantly reduce the size of the set-up margins needed.

Each centre should evaluate its own set-up margins, at least for frequent treatment techniques, thus allowing for potential standardisations.

The net effect of combining an internal margin (referenced in the patient coordinate system) and a set-up margin (referenced to the external coordinate system) to the CTV leads to the concept of planning target volume (PTV).

The planning target volume (PTV) is a geometric concept, used for treatment planning, and it is defined to select appropriate beam sizes and beam arrangements, to ensure that the prescribed dose is actually delivered to the CTV.

Thus the border of the PTV must be clearly defined on charts or in files for treatment planning purposes. For dose specification for reporting, the margin that defines the PTV must be a closed line/surface, even if this may not be necessary for the proper selection of beam parameters.

Reporting ITV is not considered to be compulsory in the last ICRU Report[7].

In some cases, the internal margin approaches a very low value, (e.g. with brain tumours), and in other cases the set-up margin may be very small (e.g. with on-line correction for the different set-up errors and variations).

Ideally, the size of the margins should be determined in an iterative way during the selection of an optimal beam arrangement, e.g. in beam's eye view (as when planning both co-planar and non-coplanar conformal therapy). In practice this may not always be feasible, and as a compromise one can specify the margins for uncertainty in such a way that they can be used for different types of beam arrangement (e.g. one beam, two opposed beams, box technique, orthogonal beams, moving beams). In daily clinical use, this is probably most appropriate for defining the PTV for treatment planning and for basic dose specification for reporting, and it is the approach recommended in ICRU Report No. 50, 1993[4]. Note that intensity modulated radiotherapy (IMRT) presents special difficulties for checking beam geometry.

When delineating the PTV, consideration should also be given to the presence of any radiosensitive normal tissue (see next section). This may lead to choice of alternative beam arrangements and/or shapes as part of an optimisation procedure (Fig. 3). In some cases it may be necessary to change the prescription (for volumes and/or doses), and accept a smaller benefit. If, for radical treatments, the probability of benefit approaches a low value, the aim of therapy may shift from radical to palliative.

Figure 3

Schematic illustration of the relationship between GTV-T/N(s) and CTV-T/N(s) in different clinical situations[6]. (Reproduced by kind permission from the ICRU). Scenario A. A margin is added around the gross tumour volume (GTV) to take into account potential ‘subclinical’ invasion. The GTV and this margin define the clinical target volume (CTV). In external beam therapy, to ensure that all parts of the CTV receive the prescribed dose, additional margins for geometric variations and uncertainties must be considered. An internal margin (IM) is added for the variations in position and/or shape and size of the CTV. This defines the internal target volume. A set-up margin is added to take into account all the variations/uncertainties in patient-beam positioning. CTV+IM+SM define the planning target volume (PTV) on which the selection of beam size and arrangement is based. Scenario B. The simple (linear) addition of all factors of geometric uncertainty, as indicated in scenario A, often leads to an excessively large PTV, which would be incompatible with the tolerance of the surrounding normal tissues. In such instances, instead of adding linearly the internal margin and the set up margin, compromise combinations are used, e.g., 

 formalism). This quantitative evaluation is only possible if all uncertainties and their σ are available, i.e., in a few sophisticated protocols. Scenarios C and D. In the majority of clinical situations, a ‘global’ safety margin is adopted. In some cases, the presence of an organ at risk dramatically reduces the width of the acceptable safety margin (e.g., presence of the spinal cord, optical nerve, etc.). In other situations (scenario C), larger safety margins may be accepted. Since the incidence of subclinical invasion may decrease with distance from the GTV (see Fig. 2.4), a reduction of the margin for subclinical invasion may still be compatible with chance for cure, albeit at a lower probability rate. It is important to stress that the thickness of the different safety margins may vary with the angle at which one looks at the PTV (e.g., bony structures or fibrotic tissue may prevent, at least temporarily, malignant cell dissemination). (Note that if an adequate dose cannot be given to the whole GTV, the whole aim of therapy shifts from radical to palliative).

OR (organs at risk) and PRV (planning organ at risk volume)

Organs at risk are normal tissues whose radiation sensitivity may significantly influence treatment planning and/or prescribed dose (e.g. spinal cord).

The dose–volume response of normal tissues is a complex process, which changes progressively. It has been suggested that the tissues of an organ at risk can be considered to be organised in functional sub units (FSUs), and the concepts of ‘serial’, ‘parallel’, and ‘serial-parallel’ organisation of the normal structures (Fig. 4) has been suggested. For example, the spinal cord has a high ‘relative seriality’, implying that a dose above the tolerance limit to even a small volume of the organ at risk may be deleterious, whereas the lung usually has a low ‘relative seriality’, meaning that it may be the relative size of the volume that is irradiated above tolerance level that is the most important parameter.

Figure 4

Schematic examples of tissue organisation structures in the parallel–serial model. (a) A serial string of subunits (e.g., the spinal cord), (b) a parallel string of subunits (e.g., the lungs), (c) a serial–parallel string of subunits (e.g., the heart), (d) a combination of parallel and serial structures (e.g., a nephron). Modified from Withers et al.[35] and Källman et al.[36], citied in ICRU[6] (reproduced by kind permission from the ICRU).

For example, the late effects from (partial) irradiation of the lungs (a parallel tissue) in H.D. were much less serious than those from the heart (a combined serial [coronary arteries] and parallel [myocardium] tissue)[18,19].

As is the case with the planning target volume, any movements of the organ(s) at risk during treatment, as well as uncertainties in the set-up during the whole treatment course must be considered.

An integrated margin has to be added to the OR to compensate for these variations and uncertainties, using the same principles of internal and set-up margins as for the PTV. This leads, in analogy with the PTV, to the concept of planning organ at risk volume (PRV). Note that a PTV and a PRV may overlap.

Treated volume and irradiated volume

Due to the limitations of irradiation techniques and in some specific clinical situations, the volume receiving the prescribed dose may not accurately match the PTV; it may be larger (sometimes much larger) and in general of a simpler shape. This leads to the concept of treated volume. It is defined when the treatment planning procedure is completed and the beam arrangement as well as all the other irradiation parameters have been selected.

The treated volume is the tissue volume which is planned to receive at least a dose selected and specified by the radiation oncologist as being appropriate to achieve the purpose of the treatment, e.g. tumour eradication, or palliation.

The treated volume is thus a volume enclosed by the isodose surface corresponding to that dose level. For example, if the prescribed dose is 60 Gy, and the minimum dose (considered to be adequate) was 5% below the central dose (which was normalised to 100%), the treated volume is then enclosed by the 57 Gy isodose surface.

Normally, in the patient, the tissue volume which actually receives that dose level (i.e. ‘actual’ treated volume) should match the ‘planned’ treated volume (‘conformal therapy’).

It is important to identify the treated volume and its shape, size, and position in relation to the PTV for various reasons. One is to distinguish causes of local recurrences (‘in-field’ [=too low dose] versus ‘marginal’ [=too small volume] ones). Another issue is to evaluate complications in normal tissues encountered outside the PTV but within the treated volume. These problems require imaging during the follow-up, so the relevant correlations can be made.

The irradiated volume is the tissue volume which receives a dose that is considered significant in relation to normal tissue tolerance.

If the irradiated volume is reported, the significant dose must be expressed either in absolute values (in Gy) or relative to the specified dose to the PTV. The irradiated volume depends on the treatment technique used.

Note that when the treated volume is made smaller by use of many beams (e.g. in IMRT) the irradiated volume may be larger, and the integral dose higher.

 

Article: What's new in target volume definition for radiologists in ICRU Report 71? How can the ICRU volume definitions be integrated in clinical practice? - PMC (nih.gov)