Clinical Oncology 27 (2015) 495e497 Contents lists available at ScienceDirect
Clinical Oncology journal homepage: www.clinicaloncologyonline.net
Editorial
Magnetic Resonance Imaging-guided Radiation Therapy: Technological Innovation Provides a New Vision of Radiation Oncology Practice U. Oelfke Joint Department of Physics at the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, London, UK Received 17 March 2015; accepted 15 April 2015
Technological innovations have been the driving force behind step changes in radiation oncology practice in recent decades. About 20 years ago, the introduction of intensitymodulated radiation therapy (IMRT) substantially broadened the spectrum of treatment options for a range of tumour sites [1]. The innovative cornerstones of IMRT e the technical perfection of dose delivery concepts and the introduction of inverse treatment planning e led to fascinating new opportunities conforming doses tightly, even to concave radiation targets encompassing organs at risk. However, it was evident that the full exploitation of this improved dose-shaping potential critically required an accurate and reliable knowledge of the patient’s anatomy at the time of treatment. The approach to solving this problem involved the introduction of a hybrid technology integrating a kilovoltage X-ray source and a flat-panel imager with state of the art dose delivery equipment [2], leading to the development of X-ray-based image-guided radiation therapy (IGRTx). This technology has been available for routine clinical application for more than a decade and is increasingly viewed as a routine means of facilitating therapy adaptation for a substantial proportion of radiation therapy patients [3]. However, despite its success, the day to day practice of IGRTx revealed two major limitations inherent to this technology. First, the most severe limitation of IGRTx is its poor softtissue contrast, making it impossible to discriminate between tumour targets and adjacent healthy tissues for most clinical indications. Second, the detection and continuous monitoring of intrafraction organ motion is extremely difficult. The acquisition of three-dimensional images during treatment is impossible due to the acquisition time that is required. Fluoroscopic two-dimensional projection
Author for correspondence: U. Oelfke, Royal Marsden Hospital, Downs Road, Sutton SM2 5PT, UK. Tel: þ44-208-915-6221. E-mail address: [email protected]
imaging only allows for a direct assessment of one of the relevant translational coordinates of organ motion at a time. Furthermore, continuous X-ray imaging only enables visualisation of high-contrast objects and is generally associated with an unacceptable accumulation of imaging doses within healthy tissues. Therefore, X-ray-based image guidance is usually used sparingly during conventionally fractionated courses of radiation therapy. An obvious solution to these shortcomings of IGRTx would be the integration of magnetic resonance imaging (MRI) within modern radiation therapy treatment machines. Diagnostic MRI is well known for its superb soft-tissue contrast, and the fact that it can be used continuously without any extra radiation burden to the patient. Additionally, it can provide functional tissue characterisation to further improve radiation therapy by enabling the development of dose-painting strategies [4]. However, the design, realisation and subsequent operation of the required hybrid technology, consisting of an MRI scanner directly integrated with a modern linear accelerator (linac), was considered to be extremely challenging. Two major problems had to be solved. First, the technological challenge of achieving an ‘electromagnetic decoupling’ between the MRI scanner and the linac of the dose delivery system had to be addressed. There were concerns that the strong magnetic field of the MRI scanner would interfere with the correct operation of the linac and that an operating linac would degrade the quality of the MRI images. Second, the practice of MRI-guided radiation therapy in patients located within a magnetic field demands a range of new radiation therapy procedures and concepts. Dose distributions and their verification are influenced by the extra Lorentz force acting on every dose-depositing electron moving within the magnetic field of the MRI scanner. This requires the development of new dose calculation algorithms, dosimetry protocols, quality assurance measures and treatment planning strategies. In particular, the use of MRI images for radiation therapy treatment planning
http://dx.doi.org/10.1016/j.clon.2015.04.004 0936-6555/Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
496
U. Oelfke / Clinical Oncology 27 (2015) 495e497
demands dedicated calibration and quality assurance procedures to ensure the geometrical accuracy of the acquired images [5]. Pioneering work to solve these problems started about a decade ago at the University Medical Centre (UMC) in Utrecht [6] and the University of Florida (UOF) [7]. Currently, there are five different types of system either under development or in clinical practice worldwide. A comprehensive overview of their basic features can be found in [8]. The MRI-on-rails solution installed at Princess Margaret Hospital in Toronto sidesteps most of the challenges discussed above by locating the MRI scanner outside the treatment room during radiation delivery. Consequently, the system lacks the ability to perform real-time imaging during treatment [9]. The device developed at UOF is the commercially available MRIdian system (Viewray, Ohio, USA). It achieves the ‘electromagnetic decoupling’ of the MRI scanner and the dose delivery system by replacing the linac with three 60Co sources. This arrangement requires the use of a split magnet, with the resulting compromise of a relatively low magnetic field of 0.35 T for MRI. The first patient treatments with the MRIdian system were carried out in January 2014 [10]. The full complexity of a hybrid MRIelinac device, in which an MRI scanner and a 6 MV linac can operate simultaneously, was addressed by ground-breaking investigations of the groups at UMC Utrecht [11] and the University of Edmonton [12]. The most ambitious approach, based on combining a 1.5 T MRI scanner with a 6 MV treatment machine e aiming for exquisite image quality to drive high performance dose adaptation in real-time e was developed in a collaboration between UMC Utrecht, Elekta and Philips [13]. Elekta has announced that it expects to achieve regulatory approval for this system (called Atlantic) in 2017. Atlantic consists of a newly designed 1.5 T MRI scanner (Philips) combined with a newly designed linac radiation therapy system (Elekta) that can rotate continuously around the MRI scanner. Dose delivery is accomplished by irradiating patients through the magnet with a 1.5 m distance between the radiation source and the isocentre. Dose shaping and imaging can be carried out simultaneously in real-time. The anticipated benefits of this new technology are enormous. Short-term clinical applications will exploit the superior ability of the MRIelinac to image the patient’s anatomy. By seeing what to treat, at the time of treatment, and by being able to adapt the treatment in real-time, we will be able to escalate therapeutic doses to the tumour and/ or improve dose sparing of radio-sensitive organs for a number of treatment sites. Specifically, treatments in the areas of the pelvis (prostate, bladder, cervix, rectal) and head and neck will probably benefit from MRI-guided radiation therapy. There are real opportunities to develop MRI-guided radiation therapy of lung cancer with benefits in terms of more accurate and continuous quantification of breathing-induced organ motion. In turn, this will allow reductions in planning target volume margins and facilitate dynamic tumour tracking. Other clinical indications that
will be targeted in the first wave of translational studies will be brain tumours (primary and metastatic) and oesophageal cancers. Furthermore, treatment-integrated MRI is expected to open up new horizons for radiation therapy as a treatment option for clinical indications such as cancer of the kidney, pancreas or liver metastasis. Apart from the considerable clinical benefits discussed above, the availability of MRI images acquired in the treatment position creates opportunities to streamline and automate a number of our standard manually driven radiation therapy procedures, especially for the practice of adaptive radiation therapy. High-quality MRI images enhance our capabilities to identify crucial volumes of interest (both tumour and organs at risk) automatically. This will drive the development of cost-saving, automated treatment planning procedures, quality assurance concepts and real-time therapy adaptation strategies. In the long-term, treatment-integrated MRI will be a key technology to develop high-precision personalised adaptive radiation therapy. The initial focus on using MRI for guiding radiation therapy adaptations is to visualise the patient’s anatomy. However, advanced diagnostic MRI techniques can provide much more information for radiation therapy. MRI visualisation of the micro-environment and metabolism of irradiated tissues during the course of treatment will enable us to use radiation more effectively. We will probably be able to target dominant tumour lesions specifically for dose-escalation. There is also the prospect that we will be able to assess and predict the treatment response of the individual patient to radiation therapy at an early time point during the course of treatment [14]. By realising this possibility, we would be able to adapt and personalise therapy in a clinically meaningful way e for example, by identifying patients with highly hypoxic tumours that might benefit from hypoxic cell sensitisers. In recognition of the practice-changing potential of MRIguided radiation therapy, in 2013 the Institute of Cancer Research (ICR)/Royal Marsden Hospital (RMH) decided to make MRI-guided radiation therapy a major focus of its translational research programme in medical physics and clinical oncology. Therefore, ICR/RMH joined Elekta’s International Atlantic consortium in 2014 and aims to deliver the UK’s first MRI-guided radiation therapy treatments with the Atlantic system by 2017. The Christie Hospital in Manchester has also recently entered the consortium and the presence of two UK centres of excellence means that UK radiation oncology will be at the cutting edge of developing this transformative technology. Before MRI-guided radiation therapy becomes a clinical reality, a number of challenges remain to be addressed. Research topics range from the optimisation of MRI sequences, the development of dosimetry standards in magnetic fields, the implementation of fast Monte-Carlo dose algorithms and treatment planning strategies through to the design of clinical studies suited to show the clinical benefits of this exciting technology. After the introduction of IMRT in the mid-1990s and IGRTx around 2005, it is now time to launch MRI-guided radiation therapy e the technological advance that will
U. Oelfke / Clinical Oncology 27 (2015) 495e497
drive a step change in the practice of high-precision radiation therapy. The development and design of the MRIelinac hybrid technology is at its final stage and its first translation into clinical practice is imminent. Leaving the shadows of IGRTx behind, for the first time, we will be able to see the patient’s anatomy clearly during treatment and will be able to characterise biological processes that determine outcomes in tumours and organs at risks. This change will literally provide us with a new vision for the practice of radiation therapy in the future.
Acknowledgements This work was supported by the Cancer Research UK programme grant C33589/A19727. The MRIelinac programme at RMH/ICR is supported by an infrastructure award from the Medical Research Council (Clinical research capabilities and technologies initiative (MR/M009068/1)) and research funding from the Oracle Cancer Trust. The author also acknowledges the support of the National Institute for Health Research RMH/ICR Biomedical Research Centre.
References [1] Bortfeld T. IMRT: a review and preview. Phys Med Biol 2006;51(13):R363eR379. [2] 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;53(5): 1337e1349. [3] Simpson DR, Lawson JD, Nath SK, et al. A survey of IGRT use in the United States. Cancer 2010;116:3953e3960.
497
[4] van der Heide UA, Houweling AC, Groenendaal G, BeetsTan RG, Lambin P. Functional MRI for radiotherapy dose painting. Magn Reson Imaging 2012;30(9):1216e1223. [5] Crijns S, Raaymakers B. From static to dynamic 1.5T MRI-linac prototype: impact of gantry position related magnetic field variation on image fidelity. Phys Med Biol 2014;59(13): 3241e3247. [6] Lagendijk JJ, Raaymakers BW, Raaijmakers AJ, et al. MRI/linac integration. Radiother Oncol 2008;86(1):25e29. [7] Dempsey JF, Benoit D, Fitzsimmons JR, et al. A device for realtime 3d image guided IMRT. Radiat Oncol Biol Phys 2005;63(2):S202. [8] Lagendijk JJ, Raaymakers BW, Van den Berg CA, Moerland MA, Philippens ME, van Vulpen M. MR guidance in radiotherapy. Phys Med Biol 2014;59(21):R349eR369. [9] Jaffray DA, Carlone MC, Milosevic MF, et al. A facility for magnetic resonance-guided radiation therapy. Semin Radiat Oncol 2014;24(3):193e195. [10] Mutic S, Dempsey JF. The ViewRay system: magnetic resonance-guided and controlled radiotherapy. Semin Radiat Oncol 2014;24(3):196e199. [11] Raaymakers BW, Lagendijk JJ, Overweg J, et al. Integrating a 1.5 T MRI scanner with a 6 MV accelerator: proof of concept. Phys Med Biol 2009;54(12):N229eN337. [12] Fallone BG, Murray B, Rathee S, et al. First MR images obtained during megavoltage photon irradiation from a prototype integrated linac-MR system. Med Phys 2009;36(6): 2084e2088. [13] Lagendijk JJ, Raaymakers BW, van Vulpen M. The magnetic resonance imaging-linac system. Semin Radiat Oncol 2014;24(3):207e209. [14] Richter C, Seco J, Hong TS, Duda DG, Bortfeld T. Radiationinduced changes in hepatocyte-specific Gd-EOB-DTPA enhanced MRI: potential mechanism. Med Hypotheses 2014;83(4):477e481.
Clinical Oncology journal homepage: www.clinicaloncologyonline.net
Editorial
Magnetic Resonance Imaging-guided Radiation Therapy: Technological Innovation Provides a New Vision of Radiation Oncology Practice U. Oelfke Joint Department of Physics at the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, London, UK Received 17 March 2015; accepted 15 April 2015
Technological innovations have been the driving force behind step changes in radiation oncology practice in recent decades. About 20 years ago, the introduction of intensitymodulated radiation therapy (IMRT) substantially broadened the spectrum of treatment options for a range of tumour sites [1]. The innovative cornerstones of IMRT e the technical perfection of dose delivery concepts and the introduction of inverse treatment planning e led to fascinating new opportunities conforming doses tightly, even to concave radiation targets encompassing organs at risk. However, it was evident that the full exploitation of this improved dose-shaping potential critically required an accurate and reliable knowledge of the patient’s anatomy at the time of treatment. The approach to solving this problem involved the introduction of a hybrid technology integrating a kilovoltage X-ray source and a flat-panel imager with state of the art dose delivery equipment [2], leading to the development of X-ray-based image-guided radiation therapy (IGRTx). This technology has been available for routine clinical application for more than a decade and is increasingly viewed as a routine means of facilitating therapy adaptation for a substantial proportion of radiation therapy patients [3]. However, despite its success, the day to day practice of IGRTx revealed two major limitations inherent to this technology. First, the most severe limitation of IGRTx is its poor softtissue contrast, making it impossible to discriminate between tumour targets and adjacent healthy tissues for most clinical indications. Second, the detection and continuous monitoring of intrafraction organ motion is extremely difficult. The acquisition of three-dimensional images during treatment is impossible due to the acquisition time that is required. Fluoroscopic two-dimensional projection
Author for correspondence: U. Oelfke, Royal Marsden Hospital, Downs Road, Sutton SM2 5PT, UK. Tel: þ44-208-915-6221. E-mail address: [email protected]
imaging only allows for a direct assessment of one of the relevant translational coordinates of organ motion at a time. Furthermore, continuous X-ray imaging only enables visualisation of high-contrast objects and is generally associated with an unacceptable accumulation of imaging doses within healthy tissues. Therefore, X-ray-based image guidance is usually used sparingly during conventionally fractionated courses of radiation therapy. An obvious solution to these shortcomings of IGRTx would be the integration of magnetic resonance imaging (MRI) within modern radiation therapy treatment machines. Diagnostic MRI is well known for its superb soft-tissue contrast, and the fact that it can be used continuously without any extra radiation burden to the patient. Additionally, it can provide functional tissue characterisation to further improve radiation therapy by enabling the development of dose-painting strategies [4]. However, the design, realisation and subsequent operation of the required hybrid technology, consisting of an MRI scanner directly integrated with a modern linear accelerator (linac), was considered to be extremely challenging. Two major problems had to be solved. First, the technological challenge of achieving an ‘electromagnetic decoupling’ between the MRI scanner and the linac of the dose delivery system had to be addressed. There were concerns that the strong magnetic field of the MRI scanner would interfere with the correct operation of the linac and that an operating linac would degrade the quality of the MRI images. Second, the practice of MRI-guided radiation therapy in patients located within a magnetic field demands a range of new radiation therapy procedures and concepts. Dose distributions and their verification are influenced by the extra Lorentz force acting on every dose-depositing electron moving within the magnetic field of the MRI scanner. This requires the development of new dose calculation algorithms, dosimetry protocols, quality assurance measures and treatment planning strategies. In particular, the use of MRI images for radiation therapy treatment planning
http://dx.doi.org/10.1016/j.clon.2015.04.004 0936-6555/Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
496
U. Oelfke / Clinical Oncology 27 (2015) 495e497
demands dedicated calibration and quality assurance procedures to ensure the geometrical accuracy of the acquired images [5]. Pioneering work to solve these problems started about a decade ago at the University Medical Centre (UMC) in Utrecht [6] and the University of Florida (UOF) [7]. Currently, there are five different types of system either under development or in clinical practice worldwide. A comprehensive overview of their basic features can be found in [8]. The MRI-on-rails solution installed at Princess Margaret Hospital in Toronto sidesteps most of the challenges discussed above by locating the MRI scanner outside the treatment room during radiation delivery. Consequently, the system lacks the ability to perform real-time imaging during treatment [9]. The device developed at UOF is the commercially available MRIdian system (Viewray, Ohio, USA). It achieves the ‘electromagnetic decoupling’ of the MRI scanner and the dose delivery system by replacing the linac with three 60Co sources. This arrangement requires the use of a split magnet, with the resulting compromise of a relatively low magnetic field of 0.35 T for MRI. The first patient treatments with the MRIdian system were carried out in January 2014 [10]. The full complexity of a hybrid MRIelinac device, in which an MRI scanner and a 6 MV linac can operate simultaneously, was addressed by ground-breaking investigations of the groups at UMC Utrecht [11] and the University of Edmonton [12]. The most ambitious approach, based on combining a 1.5 T MRI scanner with a 6 MV treatment machine e aiming for exquisite image quality to drive high performance dose adaptation in real-time e was developed in a collaboration between UMC Utrecht, Elekta and Philips [13]. Elekta has announced that it expects to achieve regulatory approval for this system (called Atlantic) in 2017. Atlantic consists of a newly designed 1.5 T MRI scanner (Philips) combined with a newly designed linac radiation therapy system (Elekta) that can rotate continuously around the MRI scanner. Dose delivery is accomplished by irradiating patients through the magnet with a 1.5 m distance between the radiation source and the isocentre. Dose shaping and imaging can be carried out simultaneously in real-time. The anticipated benefits of this new technology are enormous. Short-term clinical applications will exploit the superior ability of the MRIelinac to image the patient’s anatomy. By seeing what to treat, at the time of treatment, and by being able to adapt the treatment in real-time, we will be able to escalate therapeutic doses to the tumour and/ or improve dose sparing of radio-sensitive organs for a number of treatment sites. Specifically, treatments in the areas of the pelvis (prostate, bladder, cervix, rectal) and head and neck will probably benefit from MRI-guided radiation therapy. There are real opportunities to develop MRI-guided radiation therapy of lung cancer with benefits in terms of more accurate and continuous quantification of breathing-induced organ motion. In turn, this will allow reductions in planning target volume margins and facilitate dynamic tumour tracking. Other clinical indications that
will be targeted in the first wave of translational studies will be brain tumours (primary and metastatic) and oesophageal cancers. Furthermore, treatment-integrated MRI is expected to open up new horizons for radiation therapy as a treatment option for clinical indications such as cancer of the kidney, pancreas or liver metastasis. Apart from the considerable clinical benefits discussed above, the availability of MRI images acquired in the treatment position creates opportunities to streamline and automate a number of our standard manually driven radiation therapy procedures, especially for the practice of adaptive radiation therapy. High-quality MRI images enhance our capabilities to identify crucial volumes of interest (both tumour and organs at risk) automatically. This will drive the development of cost-saving, automated treatment planning procedures, quality assurance concepts and real-time therapy adaptation strategies. In the long-term, treatment-integrated MRI will be a key technology to develop high-precision personalised adaptive radiation therapy. The initial focus on using MRI for guiding radiation therapy adaptations is to visualise the patient’s anatomy. However, advanced diagnostic MRI techniques can provide much more information for radiation therapy. MRI visualisation of the micro-environment and metabolism of irradiated tissues during the course of treatment will enable us to use radiation more effectively. We will probably be able to target dominant tumour lesions specifically for dose-escalation. There is also the prospect that we will be able to assess and predict the treatment response of the individual patient to radiation therapy at an early time point during the course of treatment [14]. By realising this possibility, we would be able to adapt and personalise therapy in a clinically meaningful way e for example, by identifying patients with highly hypoxic tumours that might benefit from hypoxic cell sensitisers. In recognition of the practice-changing potential of MRIguided radiation therapy, in 2013 the Institute of Cancer Research (ICR)/Royal Marsden Hospital (RMH) decided to make MRI-guided radiation therapy a major focus of its translational research programme in medical physics and clinical oncology. Therefore, ICR/RMH joined Elekta’s International Atlantic consortium in 2014 and aims to deliver the UK’s first MRI-guided radiation therapy treatments with the Atlantic system by 2017. The Christie Hospital in Manchester has also recently entered the consortium and the presence of two UK centres of excellence means that UK radiation oncology will be at the cutting edge of developing this transformative technology. Before MRI-guided radiation therapy becomes a clinical reality, a number of challenges remain to be addressed. Research topics range from the optimisation of MRI sequences, the development of dosimetry standards in magnetic fields, the implementation of fast Monte-Carlo dose algorithms and treatment planning strategies through to the design of clinical studies suited to show the clinical benefits of this exciting technology. After the introduction of IMRT in the mid-1990s and IGRTx around 2005, it is now time to launch MRI-guided radiation therapy e the technological advance that will
U. Oelfke / Clinical Oncology 27 (2015) 495e497
drive a step change in the practice of high-precision radiation therapy. The development and design of the MRIelinac hybrid technology is at its final stage and its first translation into clinical practice is imminent. Leaving the shadows of IGRTx behind, for the first time, we will be able to see the patient’s anatomy clearly during treatment and will be able to characterise biological processes that determine outcomes in tumours and organs at risks. This change will literally provide us with a new vision for the practice of radiation therapy in the future.
Acknowledgements This work was supported by the Cancer Research UK programme grant C33589/A19727. The MRIelinac programme at RMH/ICR is supported by an infrastructure award from the Medical Research Council (Clinical research capabilities and technologies initiative (MR/M009068/1)) and research funding from the Oracle Cancer Trust. The author also acknowledges the support of the National Institute for Health Research RMH/ICR Biomedical Research Centre.
References [1] Bortfeld T. IMRT: a review and preview. Phys Med Biol 2006;51(13):R363eR379. [2] 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;53(5): 1337e1349. [3] Simpson DR, Lawson JD, Nath SK, et al. A survey of IGRT use in the United States. Cancer 2010;116:3953e3960.
497
[4] van der Heide UA, Houweling AC, Groenendaal G, BeetsTan RG, Lambin P. Functional MRI for radiotherapy dose painting. Magn Reson Imaging 2012;30(9):1216e1223. [5] Crijns S, Raaymakers B. From static to dynamic 1.5T MRI-linac prototype: impact of gantry position related magnetic field variation on image fidelity. Phys Med Biol 2014;59(13): 3241e3247. [6] Lagendijk JJ, Raaymakers BW, Raaijmakers AJ, et al. MRI/linac integration. Radiother Oncol 2008;86(1):25e29. [7] Dempsey JF, Benoit D, Fitzsimmons JR, et al. A device for realtime 3d image guided IMRT. Radiat Oncol Biol Phys 2005;63(2):S202. [8] Lagendijk JJ, Raaymakers BW, Van den Berg CA, Moerland MA, Philippens ME, van Vulpen M. MR guidance in radiotherapy. Phys Med Biol 2014;59(21):R349eR369. [9] Jaffray DA, Carlone MC, Milosevic MF, et al. A facility for magnetic resonance-guided radiation therapy. Semin Radiat Oncol 2014;24(3):193e195. [10] Mutic S, Dempsey JF. The ViewRay system: magnetic resonance-guided and controlled radiotherapy. Semin Radiat Oncol 2014;24(3):196e199. [11] Raaymakers BW, Lagendijk JJ, Overweg J, et al. Integrating a 1.5 T MRI scanner with a 6 MV accelerator: proof of concept. Phys Med Biol 2009;54(12):N229eN337. [12] Fallone BG, Murray B, Rathee S, et al. First MR images obtained during megavoltage photon irradiation from a prototype integrated linac-MR system. Med Phys 2009;36(6): 2084e2088. [13] Lagendijk JJ, Raaymakers BW, van Vulpen M. The magnetic resonance imaging-linac system. Semin Radiat Oncol 2014;24(3):207e209. [14] Richter C, Seco J, Hong TS, Duda DG, Bortfeld T. Radiationinduced changes in hepatocyte-specific Gd-EOB-DTPA enhanced MRI: potential mechanism. Med Hypotheses 2014;83(4):477e481.
