Intensity Modulated Arc Therapy: Technology and Clinical Implementation

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1 Intensity Modulated Arc Therapy: Technology and Clinical Implementation Cedric X. Yu University of Maryland School of Medicine

2 Abstract Intensity modulated arc therapy (IMAT) was proposed by Yu as an alternative to Tomotherapy. Over more than a decade, many progresses have been made. The advantages and limitations of IMAT technique have also been better understood. In recent years, single arc forms of IMAT has emerged and commercially adopted. The leading example was the Volumetric Modulated Art Therapy, a single arc form of IMAT that delivers apertures of varying weightings with a single arc rotation using dose rate variation of the treatment machine. With the commercial implementation of VMAT, wide clinical adoption is quickly taken root. However, there is a lack of a general understanding of how such arc treatments are planned, and what delivery limitations and compromises are made. Commercial promotions and competitions added further confusion for the end users. It is therefore necessary to provide a summary of this technology and some guidelines on its clinical implementation and quality assurance. The purpose of this review is to provide a summary of the works from the community leading to the wide clinical adaptation, and point to the issues still remaining, provide some perspectives on its further development in the context of increased clinical use of image guidance. Because there has been vast experience in IMRT using multiple intensity modulated fields, comparisons between IMAT and IMRT are also made in the review in the areas of planning, delivery and quality assurance.

3 I. HISTORICAL REVIEW 1, Early development leading to IMAT Although arc therapy can be traced back to the dawn of the 20 th century, arc therapy involving dynamic field shaping using a multileaf collimator was first described by Takahashi in 1965 [1]. He described a method of rotational therapy, which we now referred to as conformal arc therapy the beam aperture shaped by a multiple leaf collimator (MLC) dynamically varies to match the beam s-eye-view of the target. In 1982, Brahme et al solved an integral equation for a hypothetical target wrapped around a critical structure and treated with arc therapy [2]. They demonstrated that to deliver a uniform dose to the target while sparing the critical structure, the beam intensities have to be modulated. In 1983, Chin et al proposed and demonstrated that with computer optimization and the freedom of computer-controlled gantry rotation, collimator motion and dose-rate variation, highly conformal dose distribution can be achieved [3]. These initial developments on arc therapy were accompanied and followed by the development and wide adoption of three-dimensional radiation therapy (3DCRT) in the 1980s [4]. The need for more convenient field shaping brought the multileaf collimator (MLC) to radiotherapy practice. In 1985, Brahme et al published a paper which showed that if the intensities of radiation can be modulated across a radiation field, the increased freedom would afford a greater ability to shape the volume of high doses to better conform to the target than 3DCRT [5]. The motorized field shaping capabilities of MLC was quickly explored to modulate the intensities within a radiation field. Intensitymodulated radiation therapy (IMRT) aims to deliver a highly conformal dose to a tumor while sparing the surrounding normal tissues and sensitive structures. In 1992, Convery

4 and Rosenbloom derived the mathematical formula for realizing intensity modulation with the dynamic movement of collimator [6]. In 1994, more works were published to demonstrate the feasibility of using MLCs for intensity modulation [7-10]. The amount of work on this emerging technology quickly mushroomed, and clinical implementations of the IMRT technique immediately followed [11]. In 1993, another form of IMRT using rotational fan beams, called Tomotherapy, was proposed by Mackie et al [12]. The idea was quickly commercialized as the Peacock device by NOMOS Corporation [N/A]. Intensity modulation was achieved with a binary collimator, which opens and closes under computer control. As the fan beam continuously rotates around the patient, the exposure time of a small width of the fan beam, or a beamlet, can be adjusted with the opening and closing of the binary collimator, allowing the radiation to be delivered to the tumor through the most preferred directions and locations of the patient. The initial commercial system by NOMOS Corporation added the binary collimator on to a linear accelerator and delivered radiation treatments one slice at a time, and the treatment table had to be precisely indexed from one slice to the next. Helical tomotherapy was then developed by Tomotherapy, Inc. as a dedicated rotational IMRT system with a slip-ring rotating gantry. More automated delivery was achieved by continuous gantry rotation and treatment couch translation [same as 12]. The dosimetric advantages of rotational treatments are illustrated by Shepard et al [13], which summarizes results from an optimization series performed for a C-shaped target with a sensitive structure in the concavity of the C. For these simulations, all planning parameters such as percent dose constraints were held constant except for the number of beam angles. It was shown that each increase in the number of beam angles led to a more homogeneous dose in the tumor and a

5 lower dose to the sensitive structure. Significant dosimetric improvements continued well beyond the number of beam angles typically used for fixed field IMRT. It is also noteworthy that the total integral dose is nearly independent of the number of beam angles. # Angles Obj. Funct. Value Std. Dev. in target dose d 95 Mean dose to RAR Total integral dose Table 1: Impact of number of beam angles on plan quality. permission from [13] Reproduced with Intensity modulated arc therapy (IMAT) was introduced by the author in 1995[14]. Like tomotherapy, IMAT is delivered in an arc manner. Instead of using rotating fan beams as in tomotherapy, IMAT uses rotational cone beams of varying shapes to achieve intensity modulation. Starting from the same tomotherapy plan, which approximates the full arc with evenly spaced fixed fields, the strategy was to convert the intensity patterns into multiple segments and deliver with overlapping arcs. Based on the fact that numerous segment configurations can yield the same intensity pattern, it is possible to find such a segment configuration at each beam angle such that segments at successive angles are connected geometrically. The stacks of overlapping beam apertures can then be delivered with multiple overlapping arcs. Through the initial proof-of-principle study, it was shown that IMAT could be a valid alternative to tomotherapy in terms of treatment delivery. However, unlike tomotherapy, IMAT must account for restrictions on MLC movement as the gantry moves from one beam angle to the next. Because deliverability must take priority, an optimal field shape may have to be altered in order to have smooth delivery. As the result, plan quality should be adversely affected for some cases. This restriction does not apply to tomotherapy due to the use of a binary MLC. As the result,

6 tomotherapy should theoretically have the best plan quality. As compared with tomotherapy, IMAT also has some advantages: (1) IMAT does not need to move the patient during treatment and avoids abutment issues seen with serial tomotherapy; (2) IMAT retains the ability of using non-coplanar beams and arcs, which has great value for brain and head/neck tumors; (3) IMAT uses a conventional linac, thus complex rotational IMRT treatments and simple palliative treatments can be delivered with the same treatment unit. 2. Continued Efforts in Planning and Clinical Implementation The wide availability of linear accelerators and the advantages if IMAT propelled continued progress of the IMAT technique. In 2000, a Phase I clinical trial of IMAT using forward planning was conducted at the University of Maryland Error! Reference source not found., to test the safety and feasibility of changing the field shape during gantry rotation. Fifty patients with cancers of various sites were treated using IMAT. Due to the lack of an IMAT inverse planning system, forward planning was used for determining the arc range and aperture shapes. Arcs were approximated as multiple shaped fields spaced every 5 to 10 degrees around the patient. Multiple coplanar or non-coplanar arcs were allowed. At each beam angle, irregular field shapes were defined based on the beams-eye-view (BEV) of the planning target volume and normal critical structures. Typically, at a given angle, one field shape conformed to the beam seye-view of the target, and additional field shapes were set to shield individual critical structures that overlap the target in the BEV. Because beam rotation and irradiation are concurrent, the delivery is very efficient. A typical treatment with 3 to 5 arcs takes less than 10 minutes from start to finish, comparable to conventional techniques. As is the case with most forward planning techniques, these approaches rely heavily on the experience of the planner and could result in sub-optimal plans and prolonged planning times. Another clinical study was conducted at Ghent University Hospital. The aperture shapes were first determined based on the BEV of the target and critical structures similar to the

7 approach adopted by University of Maryland. However, the anatomy based apertures were further refined by allowing the leaves to move slightly using a greedy search optimization scheme (DeGersem 2004). Treatment planning studies were published for rectal cancer and whole abdominopelvic radiation therapy [17-18]. Wong et al formulated the forward planning into a practical approach which they termed Simplified Intensity Modulated Arc Therapy (SIMAT) [19]. SIMAT starts by creating multiple arcs based on the BEV of the anatomy with each arc serving a distinct planning goal, such as covering the whole target, or protecting one critical structure. The weightings of the arcs were subsequently optimized assuming a constant dose rate delivery. The SIMAT strategy was applied to various sites including prostate and highrisk endometrial cancer [20-21]. Cortutz et al also demonstrated that IMAT strategy could be used to treat a target that wrapped around a critical structure [22]. Under the assumption that arcs can only be delivered with constant dose rates, the author also proposed hybrid IMRT and IMAT to purther increase efficiency [] 3, Works Led to Single Arc IMAT In proposing IMAT as an alternative to tomotherapy, Yu predicted that with the increase in the number of gantry angles, the number of intensity levels at each gantry angle can be reduced without degrading plan quality [14]. He argued that the plan quality is a function of the total number of quanta defined as the product of the number of beam angles and the number of intensity levels. In another word, it is the total number of aperture shape variations that determines the plan quality. If this is true, a single arc with sufficient number of aperture shape variations would be able to create the optimal treatment plans.

8 Many works that followed have attempted to use a single arc for IMAT. Because linear accelerators at the time cannot vary the dose rate dynamicaaly during gantry rotation. Most previous works on single arc IMAT was under the assumption that the machine dose rate has to be constant during arc rotation. As illustrated by Jiang et al [], a single arc with 36 beam aperture variations under constant dose rate cannot realize the optimal plan quality. To reach the desired plan quality, one must increase the number of field segments or apertures, or allow the dose rate to vary during gantry rotation, or both. MacKenzie et al proposed a technique whereby 24 equally spaced beam orientations are optimized for sliding window IMRT and arc delivery is performed by allowing the gantry of the linear accelerator to rotate to static gantry orientations and deliver the optimized sliding window IMRT deliveries [27]. Crooks et al developed an IMAT planning algorithm that is based on the observation that the dose error for beam apertures being off by a small angular deviation is very small [28]. In their algorithm, IMRT fields were created approximately 30 apart with segments per beam direction. The segments were spread out with the previous observation regarding angular deviations and the plan was simulated and delivered in a single arc with deviations from the original IMRT plan on the order of 5-10%. Cameron developed a technique that uses a sweeping window arc therapy (SWAT) technique that initialized the collimator to 90 so that the leaf positions are normal to the axial plane of the patient [29]. Shapes of the MLC apertures prior to optimization are initialized so that the MLC leaf positions sweep across the PTV with rotation. Optimization of MLC leaf positions is then performed by simulated annealing and arc weight optimization that can be performed for a constant or variable angular dose rate.

9 Ulrich et al developed an optimization technique whereby arc therapy plans are optimized for a single arc delivery [30]. In their algorithm, arc shapes are optimized by a tabu search optimization algorithm and arc weights are optimized by a gradient search. The algorithm demonstrates better treatment plans than an in-house IMRT optimization technique and requires a variable dose rate delivery with gantry rotation. By assuming that the machine dose rate can vary as needed, Otto developed a single arc IMAT algorithm that he referred to as Volumetric Modulated Arc Therapy (VMAT) [31]. In addition to allowing dose rate variation, VMAT algorithm uses progressive beam angle sampling to optimize large number (> 100) of apertures using direct aperture optimization. The apertures shapes and weights are optimized initially for a number of coarsely spaced gantry angles with little consideration of aperture connectivity. Once the solution converges, additional gantry angles are inserted. As the angular spacing becomes smaller, the optimizer considers aperture shape connectivity both in the initialization of aperture shapes and during the optimization. The shapes of the newly inserted apertures are linearly interpolated from their angular neighbors. Such coarse-tofine sampling has been termed progressive sampling, and allows the optimization to converge faster. Because the aperture shape connectivity is ignored initially, the optimizer is give the freedom to aim for optimal dose distribution. Because the final plan ensures aperture connectivity, the optimized single arc can be delivered within 2 minutes. 4. Commercial Development and nomenclatures Although IMAT has been proposed since 1995 and many researchers have developed different planning methods and demonstrate that IMAT is capable of creating highly

10 conformal treatment plans that can be efficient delivered, large scale clinical implementation did not start until Varian adopted Otto s VMAT algorithm and marketed with the trade name of RapidArc TM in The linac control also updated to allow the dose rate variation during gantry rotation. Not long after Varian s announcement, Elekta also started to market their IMAT solution with the trade name VMAT TM. Recently, Philips Medical Systems, Inc. has announced plans to provide a rotational IMRT solution with the trade name of SmartArc TM. In describing their two-step planning method for single arc IMAT, Wang et al named their method as arc-modulated radiation therapy or AMRT [32]. Since all these variations subscribe to the same principle of intensity modulated arc therapy, they are just different implementations of IMAT. Therefore, in this review, no different trade names will be used. Instead, the original acronym IMAT will be used throughout this paper. Conclusion Rotational IMRT using conventional linear accelerators has after 12 years since the initially proposed in Significant technological developments in treatment planning by numerous researchers and in linear accelerator design led to its eventual clinical adoption. With on-board CT capabilities now available with linear accelerators from all 3 major vendors, IMAT promises a great potential for widespread clinical application.. With on-board CT capabilities now available with linear accelerators from all 3 major vendors, IMAT promises a great potential for widespread clinical application. References 1. Takahashi S Conformation radiotherapy. Rotation techniques as applied to radiography and radiotherapy of cancer. Acta Radiol Diagn (Stockh). Suppl

11 2. Brahme A, Roos JE and Lax I Solution of an integral equation encountered in radiation therapy Phys. Med. Biol Chin LM, Kijewski PK, Svensson GK, Bjärngard BE.1983 Dose optimization with computer-controlled gantry rotation, collimator motion and dose-rate variation. Int J Radiat Oncol Biol Phys Perez CA, Purdy JA, Harms W, Gerber R, Graham MV, Matthews JW, Bosch W, Drzymala R, Emami B, Fox S, et al. Three-dimensional treatment planning and conformal radiation therapy: preliminary evaluation, Radiother Oncol (1): A Brahme, Optimization of stationary and moving beam radiation therapy techniques, Radiother Oncol. 12, (1988). 6. Convery DJ and Rosenbloom ME The generation of intensity-modulated fields for conformal radiotherapy by dynamic collimation Phys. Med. Biol Bortfeld T, Boyer A L, Schlegel W, Kahler D L and Waldron T J 1994a Realization and verification of three-dimensional conformal radiotherapy with modulated fields Int. J. Radiat. Oncol. Biol. Phys Bortfeld T, Kahler D L, Waldron T J and Boyer A L 1994b X-ray field compensation with multileaf collimators Int. J. Radiat. Oncol. Biol. Phys C.X. Yu, M.J. Symons, M.N. Du et al : A method for implementing dynamic photon beam intensity modulation using independent jaws and multileaf collimator, Phys. Med. Biol. 40, (1995). 10. Spirou S V and Chui C S 1994 Generation of arbitrary fluence profiles by dynamic jaws or multileaf collimators Med. Phys Stein J, Bortfeld T, Doerschel B and Schlegel W 1994 Dynamic x-ray compensation for conformal radiotherapy by means of multi-leaf collimation Radiother. Oncol Ling C C et al 1996 Conformal radiation treatment of prostate cancer using inversely-planned intensity-modulated photon beams produced with dynamic multileaf collimation Int. J. Radiat. Oncol. Biol. Phys

12 13. C. Burman, C. Chui, G. Kutcher, S. Leibel, M. Zelefsky, T. LoSasso, S. Spirou, Q. Wu, J. Yang, J. Stein, R. Mohan, Z. Fuks, C. Ling Planning, delivery, and quality assurance of intensity-modulated radiotherapy using dynamic multileaf collimator: a strategy for large-scale implementation for the treatment of carcinoma of the prostate, Int J Radiat Oncol Biol Phys., 39(4), (1997). 14. Mackie TR, Holmes T, Swerdloff S, Reckwerdt P, Deasy JO, Yang J, Paliwal B, Kinsella T.1993 Tomotherapy: a new concept for the delivery of conformal radiotherapy Med. Phys M. Carol Integrated 3D conformal planning/multivane intensity modulating delivery system for radiotherapy, in 3D Radiation Treatment Planning and Conformal Therapy, edited by J.A. Purdy and B. Emami (Medical Physics Publishing, Madison, WI), pp (1995) 16. Shepard D M, Olivera G, Angelos L, Sauer O, Reckwerdt P and Mackie T R 1999 A simple model for examining issues in radiotherapy optimization Med. Phys Yu CX 1995 Intensity-modulated arc therapy with dynamic multileaf collimation: an alternative to tomotherapy Phys. Med. Biol Yu CX, Li XA, Ma L, Chen D, Naqvi SA, Shepard DM, Sarfaraz M, Holmes TW, Suntharalingam M and Mansfield CM 2002 Clinical implementation of intensitymodulated arc therapy. Int J Radiat Oncol Biol Phys Claus F, De Gersem W, Vanhoutte I, Duthoy W, Remouchamps V, De Wagter C, De Neve W Evaluation of a leaf position optimization tool for intensity modulated radiation therapy of head and neck cancer. Radiother Oncol DeGersem W. Intensity Modulated Arc Therapy. Proc of ICCR, Duthoy W, De Gersem W, Vergote K, Coghe M, Boterberg T, De Deene Y, De Wagter C, Van Belle S, De Neve W Whole abdominopelvic radiotherapy (WAPRT) using intensity-modulated arc therapy (IMAT): first clinical experience. Int J Radiat Oncol Biol Phys Duthoy W, De Gersem W, Vergote K, Boterberg T, Derie C, Smeets P, De Wagter C, De Neve W 2004 Clinical implementation of intensity-modulated arc therapy (IMAT) for rectal cancer. Int J Radiat Oncol Biol Phys

13 23. Wong E, Chen JZ, Greenland J 2002 Intensity-modulated arc therapy simplified. Int J Radiat Oncol Biol Phys Bauman G, Gete E, Chen JZ and Wong E Simplified intensity-modulated arc therapy for dose escalated prostate cancer radiotherapy. Med Dosim Wong E, D'Souza DP, Chen JZ, Lock M, Rodrigues G, Coad T, Trenka K, Mulligan M, Bauman GS 2005 Intensity-modulated arc therapy for treatment of high-risk endometrial malignancies. Int J Radiat Oncol Biol Phys Cotrutz C, Kappas C, Webb S 2000 Intensity modulated arc therapy (IMAT) with centrally blocked rotational fields. Phys. Med. Biol G. Tang, M. Earl, S. Luan, S. Naqvi and C.X. Yu, Converting multiple-arc Intensitymodulated Arc Therapy into a single arc for efficient delivery, Int. J. Rad. Oncol. Biol. Phys 69(3,) Supplement, S673 (2007). 28. Ma L, Yu CX, Earl M, Holmes T, Sarfaraz M, Li XA, Shepard D, Amin P, DiBiase S, Suntharalingam M and Mansfield C Optimized intensitymodulated arc therapy for prostate cancer treatment. Int J Cancer Li XA, Ma L, Naqvi SA, Shih R, Yu CX 2004 Monte Carlo dose verification for intensity-modulated arc therapy. Phys. Med. Biol Tang G, Earl MA, Luan S, Wang C, Cao D, Yu CX, Naqvi SA 2008 Stochastic versus deterministic kernel-based superposition approaches for dose calculation of intensity-modulated arcs. Phys. Med. Biol MacKenzie MA, Robinson DM Intensity modulated arc deliveries approximated by a large number of fixed gantry position sliding window dynamic multileaf collimator fields. Med Phys Crooks SM, Wu X, Takita C, Watzich M, Xing L 2003 Aperture modulated arc therapy. Phys. Med. Biol Cameron C Sweeping-window arc therapy: an implementation of rotational IMRT with automatic beam-weight calculation. Phys Med Biol Ulrich S, Nill S, and Oelfke U 2007 Development of an optimization concept for arc-modulated cone beam therapy. Phys. Med. Biol Otto K 2008 Volumetric modulated arc therapy: IMRT in a single gantry arc. Med Phys Wang C, Luan S, Tang G, Chen DZ, Earl MA, Yu CX 2008 Arc-Modulated Radiation Therapy (AMRT): A Single-Arc Form of Intensity-Modulated Arc Therapy. Phys. Med. Biol

14 37. Earl MA, Shepard DM, Naqvi S, Li XA, and Yu CX, 2003 Inverse planning for intensity-modulated arc therapy using direct aperture optimization Phys. Med. Biol. 48, Shepard DM, Cao D, Afghan MK, Earl MA 2007 An arc-sequencing algorithm for intensity modulated arc therapy. Med Phys Gladwish A, Oliver M, Craig J, Chen J, Bauman G, Fisher B and Wong E Segmentation and leaf sequencing for intensity modulated arc therapy. Med Phys Luan S, Wang C, Cao D, Chen DZ, Shepard DM, Yu CX Leaf-sequencing for intensity-modulated arc therapy using graph algorithms. Med Phys Cao D, Earl MA, Luan S, Shepard DM 2006 Continuous intensity map optimization (CIMO): a novel approach to leaf sequencing in step and shoot IMRT. Med Phys Shepard DM, Earl MA, Li XA, Naqvi SA and Yu CX 2002 Direct aperture optimization: a turnkey solution for step-and-shoot IMRT. Med Phys Tang G, Earl MA, Luan S, Naqvi SA and Yu CX 2007 Converting multiple-arc Intensity-modulated Arc Therapy into a single arc for efficient delivery. Int. J. Rad. Oncol. Biol. Phys 69 S673.

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