Peter MacCallum Cancer Centre, Melbourne, Victoria.
Image Guided Radiation Therapy refers to the concept of visualising the target or an important critical structure during radiotherapy to ensure accurate and reproducible radiation delivery throughout the course of treatment. There are many different methods for Image Guided Radiation Therapy, ranging from ultrasound to electronic portal imaging and volumetric CT scanning. In many circumstances, Image Guided Radiation Therapy can be enhanced by the use of implanted fiducial markers that are clearly visible and can make decision-making quicker and more robust. The most common application for image guidance at present is the accurate positioning of the target prior to treatment delivery. However, the availability of high quality imaging at the time of treatment delivery also facilitates management of intrafraction motion and adaptive radiotherapy. The latter encompasses a variety of methods to modify the treatment plan for individual patients in response to the images acquired during treatment. While there is still discussion as to what imaging approach is best for which purpose, there is no doubt that modern highly conformal or intensity modulated radiotherapy would not be feasible without some form of image guidance. The present article provides an overview of available techniques with the aim of illustrating their use in relevant clinical scenarios.
Radiotherapy is in most cases a local or loco-regional treatment, directing radiation to the tumour target while minimising the dose to surrounding normal structures. This requires the identification of the target and a means of delivering a high dose of radiation reliably to this target. Identification and characterisation of the target have improved significantly over years with state-of-the-art imaging technologies such as PET and MRI providing improved anatomical and functional definition of the target. This is discussed in detail in the article by Fay and Thomas in this issue of Cancer Forum.1
Once the target is identified, successful radiotherapy is based on two key tasks – the generation of a highly conformal radiation dose distribution and the ability to place this dose distribution in the correct position within the patient over the whole course of treatment, which typically lasts for 30 or more daily fractions. This is illustrated in figure 1. There have been dramatic improvements in our ability to deliver a highly conformal dose distribution, particularly through the use of Intensity Modulated Radiation Therapy (IMRT). The article by Foote in this issue highlights these developments.2
The final task is to ensure that the dose is actually delivered to the target in an accurate and reproducible fashion for every day of the treatment. This is in general associated with the term Image Guided Radiation Therapy (IGRT).
This article aims to review tools that have become available for IGRT and explore how they support the overall aim of radiotherapy. In doing this, the article first provides a working definition for IGRT and introduces methods that are available for image guidance. This is followed by trying to classify clinical applications and a discussion of adaptive radiotherapy, the logical extension of IGRT.
There is no uniformly accepted definition as to where conventional verification imaging ends and where IGRT starts. However, there is general agreement that the key features of IGRT are:3
This article is based on the following working definition: IGRT is radiotherapy based on data pertaining to the relationship between beam and patient geometry acquired at the point of treatment delivery, with the intent to ensure geometric accuracy of radiation delivery appropriate to the clinical scenario. This definition is a result of discussions at a consensus workshop on IGRT in Melbourne in 2008.
This implies that IGRT does not necessarily require an image to be taken. A system which can locate the target in three dimensions in relation to the radiation beams would suffice. Electromagnetic beacons implanted in the prostate and detected with an external antenna system (Calypso company, Seattle US) are an example.4-5
A large variety of imaging methods are now available.6 They range from optical methods,7where one or more video cameras observe the patient, to ultrasound,8 x-rays and even magnetic resonance imaging (MRI).9-10 MRI in particular would be of considerable interest as it not only provides the best soft tissue contrast, but also promises functional information. As it uses a method completely independent of the treatment delivery, MRI can also, at least in principle, be used in real time to monitor motion and changes due to treatment. As such, it is not surprising that several groups are currently working on prototype units despite the formidable challenges of combining strong magnetic fields with the electromagnetic components of a linac.11-13 For the time being, ultrasound is a soft tissue imaging method available in the clinic; the picture illustrating IGRT in figure 1 is an ultrasound image for localisation of the prostate. However, by far the most commonly used IGRT tools are x-ray based. These methods can utilise the megavoltage treatment beam, for example in electronic portal imaging,14 or a dedicated diagnostic x-ray tube and detector.15
I. Acquisition of one, two or more planar x-ray images of the target volume (typically two orthogonal images which allow localisation of an object in three dimensions). Examples for this are electronic portal imaging as shown in figure 2, or diagnostic x-rays mounted on the gantry. The advantage of electronic portal imaging is that the treatment beam is used for imaging, which also allows verification of the field shape of the treatment beam. However, the image quality of a dedicated diagnostic x-ray system is superior and most manufacturers have implemented a version of this technology. A linac with both imaging modalities, electronic portal imaging using the treatment beam and on-board imaging using a dedicated diagnostic x-ray tube, is shown in figure 3.
For IGRT with projection imaging, target visualisation is often enhanced through the implantation of fiducial markers into the target.17,18 These markers can be small gold seeds (1mm diameter) that can be easily visualised using x-ray imaging. Figure 2 shows an electronic portal image of a patient treated with radiotherapy for prostate cancer. The implantation of markers overcomes the problem that the prostate (or other soft tissue targets) cannot be identified using projection x-ray imaging. Fiducial markers in the target volume can be easily visualised and allow for easy and fast decision-making.
II. Volumetric three dimensional imaging of the target area.3,19 This is most commonly performed using x-ray CT technology such as cone beam CT (CBCT),20 or an in-room CT scanner where the linac and a CT scanner are housed in the same bunker.21Volumetric imaging provides significantly more information about the target region and the surrounding normal structures. This is illustrated in figure 4, which shows a planning CT and a CBCT of a patient treated with extracranial stereotactic radiotherapy for early stage lung cancer. On the axial and coronal images shown, the three dimensional location and shape of the target are clearly visible. As CBCT images are acquired over an extended period of time as the linac gantry rotates around the patient, the CBCT also allows some assessment of motion.22 Also, information on critical structures such as the parotid in head and neck cancer,23 or the rectum in prostate cancer,24,25 can only be obtained using volumetric imaging. Volumetric imaging therefore allows for more complex decision-making, which is accompanied by an increased need for adequate operator training.
Table 1 gives a summary of features for a variety of imaging modalities.
IGRT applications can be distinguished using several different features:
Estimates for some of the features discussed above are given in table 1 for common IGRT tools. It is the responsibility of the user to select the most appropriate technology for a particular clinical scenario. A good example for a systematic review of IGRT for rectal cancer was given recently by Gwynne et al.35
Volumetric imaging in the treatment room is the prerequisite for a logical extension of IGRT – adaptive radiotherapy.36 At present, IGRT is mostly used for repositioning of the patient to align the target with the radiation beams. In adaptive radiotherapy, the treatment plan is modified to take into account changes in patient shape, target volume or the spatial relationship between target and surrounding structures.37 This requires either the preparation of multiple treatment plans from which to choose the ‘plan of the day’,38 or the creation of a new treatment plan based on the image information from a small number of treatment fractions.39
Even one step further, biologically adaptive radiotherapy utilises functional imaging such as positron emission tomography to determine treatment response after part of the treatment and leads to modification of treatments in response to the biological changes observed.40,41 This could result for example, in a boost to metabolically active or hypoxic regions.
In the context of IGRT there is an increased number of decision-making points in the patient’s treatment. The decision-making can be on-line while the patient is on the treatment couch, or off-line when the images are reviewed after a given treatment fraction. The resulting action will then affect future treatment fractions. It is intuitive that this will improve patient management. However, it also adds new costs and work processes to the treatment:
On the other hand, it also adds to the confidence that the correct treatment is delivered to the patient. In addition to this, the increasing responsibility for treatment staff and the need to acquire new skills in respect to image acquisition, interpretation and decision-making, has the potential to improve job satisfaction.42
Figure 5 illustrates the workflow in IGRT. In practice, there are additional implications of image guidance for a radiotherapy department, which extend beyond the individual patient. The large amount of data generated in IGRT can be used to analyse departmental processes, determine the performance of equipment (eg. immobilisation devices), and decide on departmental procedures such as margins in a rationale way. Margins are placed around a target in treatment planning and allow for organ motion and daily variations in patient set-up.43,44 Appropriate choice of margins has a significant effect on treatment quality and the increasing availability of IGRT has the potential to help optimise them for different treatment scenarios and the practice in individual radiotherapy centres. This process may require additional infrastructure such as a database.45 However, the benefits from the additional information available for decision-making and departmental planning would likely be significant.
Image guidance has had profound implications for radiotherapy. Without IGRT, modern delivery techniques such as IMRT would not be possible. IGRT also has the potential to link observations made during the course of treatment back to the planning images that have defined the target in the first place. More decision-making points in the patient’s treatment course are the result. This has not only implications for staff and workflow, such as more training and quality assurance steps, but also increases confidence of all stakeholders that what was planned for management of the disease is actually happening for an individual patient. It is likely that IGRT in the future will provide more opportunities for adaptation of the treatment; why stick with the original treatment plan when one could adapt the plan to what has been seen during treatment? However, this will require communication and learning, and setting up an infrastructure that can facilitate this is essential for making optimal use of the new imaging tools available directly at the time of radiotherapy delivery. Image guidance has had profound implications for radiotherapy – and will continue to do so.
1. Fay M, Thomas P. Impact of Developments in Functional Imaging in Defining the Target for Radiotherapy. Cancer Forum. 2012;36:77-79.
2. Foote M. The Development of Advanced Radiotherapy Treatment Techniques. Cancer Forum. 2012;36:73-76.
3. Korreman S, Rasch C, McNair H, Verellen D, Oelfke U, Maingon P, et al. The European Society of Therapeutic Radiology and Oncology-European Institute of Radiotherapy (ESTRO-EIR) report on 3D CT-based in-room image guidance systems: A practical and technical review and guide. Radiother Oncol. 2010 Feb;94(2):129-44.
4. Kupelian P, Willoughby T, Mahadevan A, Djemil T, Weinstein G, Jani S, et al. Multi-institutional clinical experience with the Calypso System in localization and continuous, real-time monitoring of the prostate gland during external radiotherapy. Int J Radiat Oncol Biol Phys. 2007 Mar 15;67(4):1088-98.
5. Langen KM, Willoughby TR, Meeks SL, Santhanam A, Cunningham A, Levine L, et al. Observations on real-time prostate gland motion using electromagnetic tracking. Int J Radiat Oncol Biol Phys. 2008 Jul 15;71(4):1084-90.
6. van Herk M. Different styles of image-guided radiotherapy. Semin Radiat Oncol. 2007 Oct;17(4):258-67.
7. Tome WA, Meeks SL, Orton NP, Bouchet LG, Bova FJ. Commissioning and quality assurance of an optically guided three-dimensional ultrasound target localization system for radiotherapy. Med Phys. 2002 Aug;29(8):1781-8.
8. Cury FL, Shenouda G, Souhami L, Duclos M, Faria SL, David M, et al. Ultrasound-based image guided radiotherapy for prostate cancer: comparison of cross-modality and intramodality methods for daily localization during external beam radiotherapy. Int J Radiat Oncol Biol Phys. 2006 Dec 1;66(5):1562-7.
9. Lagendijk JJ, Raaymakers BW, Raaijmakers AJ, Overweg J, Brown KJ, Kerkhof EM, et al. MRI/linac integration. Radiother Oncol. 2008 Jan;86(1):25-9.
10. Fallone BG, Murray B, Rathee S, Stanescu T, Steciw S, Vidakovic S, et al. First MR images obtained during megavoltage photon irradiation from a prototype integrated linac-MR system. Med Phys. 2009 Jun;36(6):2084-8.
11. Raaymakers BW, Lagendijk JJ, Overweg J, Kok JG, Raaijmakers AJ, Kerkhof EM, et al. Integrating a 1.5 T MRI scanner with a 6 MV accelerator: proof of concept. Phys Med Biol. 2009 Jun 21;54(12):N229-37.
12. Kerkhof EM, van der Put RW, Raaymakers BW, van der Heide UA, Jurgenliemk-Schulz IM, Lagendijk JJ. Intrafraction motion in patients with cervical cancer: The benefit of soft tissue registration using MRI. Radiother Oncol. 2009 Oct;93(1):115-21.
13. Constantin DE, Fahrig R, Keall PJ. A study of the effect of in-line and perpendicular magnetic fields on beam characteristics of electron guns in medical linear accelerators. Med Phys. 2011 Jul;38(7):4174-85.
14. Herman MG. Clinical use of electronic portal imaging. Semin Radiat Oncol. 2005 Jul;15(3):157-67.
15. Fox T, Huntzinger C, Johnstone P, Ogunleye T, Elder E. Performance evaluation of an automated image registration algorithm using an integrated kilovoltage imaging and guidance system. J Appl Clin Med Phys. 2006 Winter;7(1):97-104.
16. Dawson LA, Jaffray DA. Advances in image-guided radiation therapy. J Clin Oncol. 2007 Mar 10;25(8):938-46.
17. Kron T, Thomas J, Fox C, Thompson A, Owen R, Herschtal A, et al. Intra-fraction prostate displacement in radiotherapy estimated from pre- and post-treatment imaging of patients with implanted fiducial markers. Radiother Oncol. 2010 May;95(2):191-7.
18. Schiffner DC, Gottschalk AR, Lometti M, Aubin M, Pouliot J, Speight J, et al. Daily electronic portal imaging of implanted gold seed fiducials in patients undergoing radiotherapy after radical prostatectomy. Int J Radiat Oncol Biol Phys. 2007 Feb 1;67(2):610-9.
19. Jaffray DA, Siewerdsen JH. Cone-beam computed tomography with a flat-panel imager: initial performance characterization. Med Phys. 2000 Jun;27(6):1311-23.
20. Jaffray DA, Siewerdsen JH, Wong JW, Martinez AA. Flat-panel cone-beam computed tomography for image-guided radiation therapy. Int J Radiat Oncol Biol Phys. 2002 Aug 1;53(5):1337-49.
21. Owen R, Foroudi F, Kron T, Milner A, Cox J, Cramb J, et al. A comparison of in-room computerized tomography options for detection of fiducial markers in prostate cancer radiotherapy. Int J Radiat Oncol Biol Phys. 2010 Jul 15;77(4):1248-56.
22. Vergalasova I, Maurer J, Yin FF. Potential underestimation of the internal target volume (ITV) from free-breathing CBCT. Med Phys. 2011 Aug;38(8):4689-99.
23. Duma MN, Kampfer S, Wilkens JJ, Schuster T, Molls M, Geinitz H. Comparative analysis of an image-guided versus a non-image-guided setup approach in terms of delivered dose to the parotid glands in head-and-neck cancer IMRT. Int J Radiat Oncol Biol Phys. 2010 Jul 15;77(4):1266-73.
24. Haworth A, Paneghel A, Herschtal A, Duchesne G, Williams S, Tai KH, et al. Verification of target position in the post-prostatectomy cancer patient using cone beam CT. J Med Imaging Radiat Oncol. 2009 Apr;53(2):212-20.
25. Showalter TN, Nawaz AO, Xiao Y, Galvin JM, Valicenti RK. A cone beam CT-Based Study for Clinical Target Definition Using Pelvic Anatomy During Postprostatectomy Radiotherapy. Int J Radiat Oncol Biol Phys. 2008 Feb 1;70(2):431-6.
26. Murphy MJ, Balter J, Balter S, BenComo JA, Jr., Das IJ, Jiang SB, et al. The management of imaging dose during image-guided radiotherapy: report of the AAPM Task Group 75. Med Phys. 2007 Oct;34(10):4041-63.
27. See A, Kron T, Johansen J, Hamilton C, Bydder SA, Hawkins J, et al. Decision-making models in the analysis of portal films: a clinical pilot study. Australas Radiol. 2000 Feb;44(1):72-83.
28. Tanyi JA, Fuss MH. Volumetric image-guidance: does routine usage prompt adaptive re-planning? An institutional review. Acta Oncol. 2008;47(7):1444-53.
29. Mageras GS, Mechalakos J. Planning in the IGRT context: closing the loop. Semin Radiat Oncol. 2007 Oct;17(4):268-77.
30. Kupelian PA, Langen KM, Willoughby TR, Zeidan OA, Meeks SL. Image-guided radiotherapy for localized prostate cancer: treating a moving target. Semin Radiat Oncol. 2008 Jan;18(1):58-66.
31. Korreman SS, Juhler-Nottrup T, Fredberg Persson G, Navrsted Pedersen A, Enmark M, Nystrom H, et al. The role of image guidance in respiratory gated radiotherapy. Acta Oncol. 2008;47(7):1390-6.
32. Keall PJ, Mageras GS, Balter JM, Emery RS, Forster KM, Jiang SB, et al. The management of respiratory motion in radiation oncology report of AAPM Task Group 76. Med Phys. 2006 Oct;33(10):3874-900.
33. Anders LC, Stieler F, Siebenlist K, Schafer J, Lohr F, Wenz F. Performance of an atlas-based autosegmentation software for delineation of target volumes for radiotherapy of breast and anorectal cancer. Radiother Oncol. 2012 Jan;102(1):68-73.
34. Thompson A, Fox C, Foroudi F, Styles C, Tai KH, Owen R, et al. Planning and implementing an implanted fiducial programme for prostate cancer radiation therapy. J Med Imaging Radiat Oncol. 2008 Aug;52(4):419-24.
35. Gwynne S, Webster R, Adams R, Mukherjee S, Coles B, Staffurth J. Image-guided Radiotherapy for Rectal Cancer – A Systematic Review. Clin Oncol (R Coll Radiol). 2012 May;24(4):250-60.
36. Yang D, Chaudhari SR, Goddu SM, Pratt D, Khullar D, Deasy JO, et al. Deformable registration of abdominal kilovoltage treatment planning CT and tomotherapy daily megavoltage CT for treatment adaptation. Med Phys. 2009 Feb;36(2):329-38.
37. Thongphiew D, Wu QJ, Lee WR, Chankong V, Yoo S, McMahon R, et al. Comparison of online IGRT techniques for prostate IMRT treatment: adaptive vs repositioning correction. Med Phys. 2009 May;36(5):1651-62.
38. Foroudi F, Wong J, Kron T, Rolfo A, Haworth A, Roxby P, et al. Online Adaptive Radiotherapy for Muscle-Invasive Bladder Cancer: Results of a Pilot Study. Int J Radiat Oncol Biol Phys. 2011 Oct 5;81:765-71.
39. Ahunbay EE, Peng C, Chen GP, Narayanan S, Yu C, Lawton C, et al. An on-line replanning scheme for interfractional variations. Med Phys. 2008 Aug;35(8):3607-15.
40. Brahme A, Nilsson J, Belkic D. Biologically optimized radiation therapy. Acta Oncol. 2001;40(6):725-34.
41. Ling CC, Humm J, Larson S, Amols H, Fuks Z, Leibel S, et al. Towards multidimensional radiotherapy (MD-CRT): biological imaging and biological conformality. Int J Radiat Oncol Biol Phys. 2000 Jun 1;47(3):551-60.
42. Kron T. Image guidance in the radiotherapy treatment room: can 10 years of rapid development prepare us for the future? J Radiother Pract. 2011;10:71-5.
43. ICRU. ICRU report 62: Prescribing, recording, and reporting photon beam therapy (Supplement to ICRU report 50). Bethesda: International Commission on Radiological Units and Measurements; 2000.
44. van Herk M. Errors and margins in radiotherapy. Semin Radiat Oncol. 2004 Jan;14(1):52-64.
45. Fox C, Fisher R, Kron T, Tai KH, Thompson A, Owen R, et al. Extraction of data for margin calculations in prostate radiotherapy from a commercial record and verify system. J Med Imaging Radiat Oncol. 2010 Apr;54(2):161-70.