Cedric X. YDepartment of Radiation Oncology, University of Maryland School of Medicine, 22 South Greene Street,Baltimore, Maryland 21201 Christopher J. AmiesSiemens Medical Solutions USA, Inc., Oncology Care Systems Group, 4040 Nelson Avenue, Concord,California 94520 Michelle SvatosTranslational Research, Varian Medical Systems, 3100 Hansen Way M/S E263 Palo Alto,California 94304-1038 ͑Received 9 May 2008; revised 11 August 2008; accepted for publication 18 September 2008;published 6 November 2008͒ Intensity modulated radiation therapy ͑IMRT͒ is an advanced form of external beam radiationtherapy. IMRT offers an additional dimension of freedom as compared with field shaping in three-dimensional conformal radiation therapy because the radiation intensities within a radiation fieldcan be varied according to the preferences of locations within a given beam direction from whichthe radiation is directed to the tumor. This added freedom allows the treatment planning system tobetter shape the radiation doses to conform to the target volume while sparing surrounding normalstructures. The resulting dosimetric advantage has shown to translate into clinical advantages ofimproving local and regional tumor control. It also offers a valuable mechanism for dose escalationto tumors while simultaneously reducing radiation toxicities to the surrounding normal tissue andsensitive structures. In less than a decade, IMRT has become common practice in radiation oncol-ogy. Looking forward, the authors wonder if IMRT has matured to such a point that the room forfurther improvement has diminished and so it is pertinent to ask what the future will hold for IMRT.
This article attempts to look from the perspective of the current state of the technology to predictthe immediate trends and the future directions. This article will ͑1͒ review the clinical experience ofIMRT; ͑2͒ review what we learned in IMRT planning; ͑3͒ review different treatment deliverytechniques; and finally, ͑4͒ predict the areas of advancements in the years to come. 2008 Ameri-can Association of Physicists in Medicine. ͓DOI: Key words: radiation therapy, intensity modulation, treatment planning, radiotherapy delivery,IMRT I. OVERVIEW
therapy. The use of overlapping cone-beam arcstodeliver modulated beam intensities around the patient, re- Intensity modulated radiation therapy ͑IMRT͒ has been ferred to as intensity modulated arc therapy ͑IMAT͒, was widely adopted as a new tool in radiation therapy to deliver also proposed but has not been widely adopted for clinical high doses of radiation to the tumor while providing maxi- mal sparing of surrounding critical structures. What facili- With nearly 10 years of clinical application, both short- tated the quick dissemination of IMRT technology was not term and long-term clinical results of IMRT treatments are hard clinical evidence but rather the individually calculatedand visually illustrated dosimetric advantages. Because such emerging. Its ability to shape the high dose volume to con- dosimetric advantage was obvious, wide clinical adoption of form to the shape of the target tissues allows the decrease of IMRT preceded any randomized clinical trials. In the U.S., irradiation related sequelae by limiting the dose delivered to the increased reimbursement for the technology also fueled the surrounding normal tissues. The same dose shaping ca- the speed of clinical dissemination. Early studies indicated pability also allows the physicians to escalate doses to cer- that with IMRT, radiation doses to sensitive structures could tain tumors to enhance local control. Both dosimetric and be reduced significantly while maintaining sufficient dose clinical advantages have been demonstrated for almost all coverage to the targeted tumorous tissues.Both rotational common anatomical though the largest number of and gantry-fixed IMRT techniques have been implemented applications has been for prostate cancer and cancers of the head and neck IMRT has allowed the physicians to ͑DMLC͒In gantry-fixed IMRT, multiple coplanar escalate the dose to the prostate while reducing the toxicities and noncoplanar beams at different orientations, each with to the rectum and bladder, resulting in improved local control spatially modulated beam intensities, are Rota- and reduced complications as compared with conventional tional IMRT, as it is practiced today, mainly employs tempo- three-dimensional ͑3D͒ conformal therapy.IMRT has rally modulated fan commonly known as tomo- also shown greater capability in sparing salivary functions in Med. Phys. 35 12, December 2008
2008 Am. Assoc. Phys. Med.
Yu, Amies, and Svatos: IMRT planning and delivery
patients receiving radiation therapy for head and neck further advancement in the near future. IMRT technology Rather than delivering the prescribed dose to consists of planning methods and delivery technologies. If the entire pelvis, IMRT was able to spare the small bowel, IMRT continues to advance, improvements must be made in the bladder and the rectum, resulting in significantly lower these two areas. It is therefore crucial to summarize what we GI The use of IMRT instead of wedge pairs have learned in these two key aspects of the technology.
for tangential whole breast irradiation has resulted in im-proved dose uniformitywhich in turn resulted in signifi-cantly reduced acute and chronic IMRT has also II. IMRT TREATMENT PLANNING
been combined with stereotactic localization for deliveringradiosurgery treatments to intracranial and extracranial sites The key technology for IMRT planning is computer opti- using linear Other sites of application in- mization. Although relatively new in radiation oncology, computer optimization is not new and has been used for operations research and other fields of theoretical and applied These data indicate that for certain clinical cases, there is research. Almost all the algorithms that have been used in a direct translation between dosimetric advantage and im- other fields, including simulated annealing,gradient proved clinical outcome. With more emerging clinical data search,genetic algorithms,and linear and nonlinear pointing to the same conclusion, IMRT as a technology will programming,have been applied to plan IMRT treat- continue to be an important technique in external beam ra- There have also been significant efforts on how the opti- The way IMRT spares critical structures is by redistribut- mization problem is formulated. Universal to all the optimi- ing the normal tissue dose to less critical regions and to zation methods, the objectives of each treatment plan are reducing the high dose volume to just cover the target. For a reduced to a single value by the objective function or cost given integral dose to the target, the integral dose to the function. The objectives of the treatment can be expressed surrounding structures is roughly constant as dictated by the according to the desired dose distributionsor in terms physics of dose deposition.In many cases, the use of IMRT of biological objectives.Essentially, when the objective results in a greater volume of surrounding normal tissues function is formulated to closely depict the desirable features receiving a lower dose as compared with traditional three- of the radiation dose distribution, the quality of the candidate dimensional conformal therapy. This phenomenon raises sig- plans is judged more accurately during the optimization pro- nificant concerns for pediatric applications of IMRT cess. Therefore, as long as the objectives are defined to ap- While the long term clinical results of using IMRT for inop- propriately reflect what is really clinically optimal, the re- erable nonsmall lung cancer are its use for me- sults are generally clinically meaningful and acceptable.
sothelioma following extrapleural pneumonectomy showed a Different commercial treatment planning systems use differ- high rate of fatal pulmonary toxicityA high mean lung ent optimization algorithms, and slightly different dose or dose and a higher percentage of lung volume receiving biological dose, in the form of equivalent uniform dose, ob- 20 Gy were clear predictors of fatal pulmonary toxicity.
jectives. In general and except for certain limitations in the Another issue of using IMRT for treating tumors in the implementation and planner experience, there is no clinically thorax and abdominal regions is the breathing induced target meaningful difference in plan quality when using different motion. As illustrated by Yu et al.the interplay between the target motion and the movement of the beam to achieve Complex treatment planning problems often involve mul- intensity modulation could cause unintended hot and cold tiple targets with many surrounding normal structures. The spots in excess of 100% in a given fraction of treatment.
objectives specified for these structures are often in conflict.
Different motion management strategies have been proposed In such complex situations, it is hard if not impossible to or applied clinically, including gating the radiation beam optimally describe what is truly desired before a plan is op- and dynamically tracking the tumor with DMLCor with timized. In the situation where one cannot achieve optimality for all the objectives simultaneously, the optimal solution Clinical use of IMRT has also brought many changes in becomes the optimal trade-off among these objectives. There clinical practice. Owing to its ability to reduce dose to sur- have been several approaches proposed by different re- rounding structures, IMRT has allowed physicians to escalate searchers for dealing with such conflicting objectives. One of dose to the prostate gland to improve local control.The the approaches is to specify the treatment objective as a reduced toxicity also encouraged the use of hypofraction- probability density function rather than as a rigid dose ation schemes.The ability of IMRT to paint more com- objective.If the most desired dose is not attainable by the plex dose distributions also allowed the increased use of con- optimizer, other doses are acceptable but less preferred. Con- comitant boost and the treatment of target within tar sequently, during the optimization process, the prescription The purpose of this article is not to provide an extensive dose is allowed to deviate, with a certain preference level, review of IMRT technology. Such reviews can be found in from the most desired dose. Another approach is to build a database of plans by varying the emphasis of different objec- dict from what we learned in the last 10 years of develop- tives. Using an interactive plan navigation tool, the trade-offs ment and clinical practice of IMRT the potential direction of between different objectives can be made explicitly based on Medical Physics, Vol. 35, No. 12, December 2008
Yu, Amies, and Svatos: IMRT planning and delivery
the user’s clinical goals.The resultant plans from this ap- a result, the residual room for improvements in plan quality proach are also called Pareto-optimal plans.
under existing delivery systems has diminished over the One of the tasks in treatment planning for external beam years of refinements in treatment planning algorithms and radiation therapy is to determine the number of beams to use and their orientations. For conventional treatments, beamangles used for different treatment sites are well established.
With IMRT, the task of beam angle selection is more com- III. IMRT TREATMENT DELIVERY
plicated and less intuitive because of more complex interac-tions and mutual compensations among the different beam Most IMRT treatment deliveries require the use of the angles as the result of computer optimized beam intensities.
multileaf collimator ͑MLC͒, which was originally developed As the result, beam angle optimization has been one of the for shaping radiation fields. The ability of the MLC to easily areas of intensive investigation. Haas et employed ge- change and dynamically vary the field shapes was quickly netic algorithms to search for the best beam orientations.
explored for IMRT delivery. Over the years, linear accelera- Rowbottom et al.and Stein et al.used simulated anneal- tor vendors have not only improved the reliability of MLCs ing algorithms to perform beam angle optimization by com- but also made the leaf width smaller. Smaller leaf widths paring thousands of sets of fixed number of beams sampled allow the treatment planning system to use finer beamlet size from a constrained or unconstrained space of beam orienta- during optimization for achieving better plan quality.
tions. Pugachev et al.also reported different schemes of IMRT treatments are delivered using either fixed beam beam angle optimization with the simulated annealing algo- angles or rotational beams. Both forms of delivery were pro- rithm. Although all these studies demonstrated some effects posed and developed at the start of the IMRT technology.
of beam angle selection on plan quality, the degree of im- Although the technology is termed “intensity modulation,” provements has been small. It is thus reasonable to conclude the intensity variation is actually achieved by temporal that the mutual interactions and compensations among the modulation, allowing different beamlets to be irradiated for beams under intensity optimization also made beam angle selection less influential on plan quality as compared with Most of the IMRT treatments delivered today use a few three-dimensional conformal therapy.
fixed beam directions. The treatment planning system has In spite of years of refinements in IMRT planning, argu- converted the optimal intensity distributions into deliverable ably, the quality of treatment plans has not improved much overlapping field segments. Because the conversion is not from that of the early days. The explanation may be rooted in within the optimization process and MLC motion constraints the basic principles of inverse planning. For each patient, the have to be considered during such conversion, it may intro- anatomy dictates a unique set of preferred beam orientations duce differences between the treatment plans using the opti- and, in each beam orientation and radiation field, the pre- mal intensity distributions and that achievable with overlap- ferred locations through which radiation is directed to the ping field These field segments, also called tumor. If more freedom is given to make use of these intrin- subfields, can be delivered dynamically, i.e., MLC transition- sic preferences in treatment planning, either performed by a ing through the shapes of the subfields dynamically when the human planner or by a computer optimization system, better beam is on. They can also be delivered one segment at a time plans can be generated. IMRT provides an additional free- such that the MLC is not moving during irradiation.
dom as compared with 3D conformal radiation therapy be- Up to now, rotational IMRT treatments have primarily cause the radiation intensities within a radiation field can be been delivered using tomotherapy,an approach where a varied according to the location preferences. However, there binary collimator ͑open/close͒ is used to control the amount is a fundamental limit to which the quality of treatment plans of exposure time of a small width of the fan beam, or a can be improved. This limit is defined by the physics of the beamlet. The fraction of time a leaf is in the “open” position radiation dose deposition and by the degrees of freedom that at a given beam angle determines the relative “intensity” of are given to the computer optimization routine. There are radiation at that angle. Because the fan beam can only irra- indications that the required degree of intensity variation for diate a slice of the patient at a given time, larger tumors are achieving the optimal plan quality for a large majority of treated by either stepping the table one slice at a timeor cases is relatively small. For example, Ludlum et al.opti- continuously.The latter is called helical tomotherapy be- mized IMRT plans for different challenging cancer sites us- cause the trajectory of the radiation source relative to the ing different number of intensity levels. They found that re- patient is a helix. Tomotherapy™ ͑Madision, WI͒ offers a ducing the number of intensity levels from 10 to 3 only cause “turn-key” approach to IMRT implementation with the plan- minor degradations in dose distribution. Comparisons among ning system specifically designed for the delivery unit. To- different treatment planning and delivery motherapy utilizes all coplanar beam angles and the intensity have not yield any approach with clinically meaningful su- variations of the beamlets are not constrained by the me- periority. These studies and our own experience led us to chanical limits of the binary MLC. Therefore, theoretically believe that with the current state of the radiation delivery speaking, tomotherapy provides a planning system with the systems and without new advances to provide additional de- freedom to use highly modulated beams to create more con- grees of freedom, IMRT has approached its limits in the formal treatment plans then MLC delivery with fixed cone quality of treatment plans that can be physically achieved. As Medical Physics, Vol. 35, No. 12, December 2008
Yu, Amies, and Svatos: IMRT planning and delivery
Another rotational IMRT approach, called IMAT, was proaches to metabolic imaging, and the emergence of a new suggested by YuInstead of rotating fan beams around the generation of radiation treatment delivery systems.
patient, IMAT uses cone beams shaped with conventionalMLCs. IMAT delivers optimized intensity distributions for IV.A. Quality improvements
large number of beams spaced every 5 – 10 deg around the Based on 10 years of experience with IMRT, we have patient. Optimized intensity distributions are translated into a learned that the opportunities in improving plan quality are stack of superimposed irregular fields of uniform beam in- limited within the constraint of present linac/MLC delivery.
tensities and delivered by overlapping arcs with synchro- To improve the quality of IMRT treatment plans, we must nized gantry rotation and field shape variations. As the gan- inject new degrees of freedom. This may require an overhaul try is rotating around the patient and the radiation beam is of existing technologies. A new generation of treatment de- on, it is important that the subfields of adjacent beam angles livery systems is emerging. One of such machines is pro- do not require the MLC leaves to travel very long distances.
posed by Kamino et Besides the IMRT capability and Ensuring such connectedness of adjacent subfields for improved image guidance features, a notable feature is that smooth leaf motion is of great concern in the leaf sequencing the linear accelerator head can be pivoted. By offering non- algorithm for IMAT.Effective planning tools for IMAT coplanar beams easily without couch rotations, such machine provides new degrees of freedom into the solutions, and, Comparisons between IMRT plans for different delivery therefore, has the potential of improving the qualities of methods have been conducted. In a comparison of tomo- therapy and MLC delivery, Mavroidis et al. found that linear Several new machines currently under development incor- accelerator delivery with a MLC has slight advantage over porate image guidance from Magnetic resonance imaging tomotherapy for most sites other than head and neck.Simi- ͑MRI͒. The design of the Renaissance™ ͑ViewRay, Inc., lar results have been found by Muzik et al.Cao et al. Cleveland, OH͒ incorporates real-time MR imaging and mul- compared the treatment plan quality of IMAT plans and to- tihead Co-60 rotational delivery. The use of MRI for image motherapy plans for ten cases including head and neck, lung, guidance may provide improved soft tissue contrast for im- brain, and prostate. It was found that these two kinds of rotational delivery methods are also equivalent for most These new technologies are aimed for delivering radiation cases. For cases where noncoplanar beams are desirable, treatments to all sites. As the room for quality improvements such as for intracranial tumors and some head and neck is further squeezed, technologies specific for particular treat- cases, the use of partial noncoplanar arcs in IMAT was found ment sites may also emerge to take advantage of the anatomy to be more Shepard et al. compared IMAT plans with IMRT 84 and found that the employment of rota- As machines increase in complexity, it becomes harder for tional IMRT is advantageous for most of the cases.
a generic treatment planning system to fully utilize the ma- It is important to note that there are many other issues chines capabilities. Diversity in delivery systems forces the besides plan quality that are associated with different deliv- planning system to be more specifically tailored to the treat- ery techniques. These include the efficiency of planning, de- ment machine. Treatment planning systems designed specifi- livery, and quality assurance, the complexity and reliability cally for a delivery device as a turn-key solution will become of delivery, and the total monitor units required to deliver the IMRT is not limited to the use of photons. It has been demonstrated that the IMRT principle can also be applied to IV. FUTURE DIRECTIONS OF ADVANCEMENTS
electronsand protons.The fast introduction of proton beams in radiation therapy would allow us to push the limitof achievable plan quality higher than using only photons.
Revolutionary advances in biology and genomics have brought a wave of new molecular therapeutic agents for IV.B. Efficiency improvements
fighting cancer and the continued acceleration in the direc-tion will mark a new era of cancer therapies. However, mo- The fact that treatment plans of different complexity de- lecular agents have not been shown to eliminate local thera- signed for different delivery methods can achieve similar pies. Therefore, we do not see that the role of radiation quality of treatments suggest that there is substantial room therapy will diminish in this new era. The dose shaping ca- for improving the workflow and efficiency. Past attempts in pabilities of IMRT make it an essential tool for better inte- improving treatment efficiency include the use of direct ap- gration of radiation with chemotherapy and molecular thera- erture optimizationand the development of single arc The areas in which IMRT technology can be improved Instead of optimizing intensity maps and then translating include ͑1͒ the quality of treatment plans, ͑2͒ the accuracy of the intensity maps into deliverable segments, Shepard et treatment delivery, and ͑3͒ the efficiency of both planning proposed and developed a method called “direct aperture op- and delivery of IMRT treatments. We predict that the ad- timization” ͑DAO͒ that directly optimizes the shapes and vances in these areas will be driven by factors including weights of MLC segments simultaneously in one step. The on-line and real-time image guidance, individualized ap- planner determines the number of beams to use and the num- Medical Physics, Vol. 35, No. 12, December 2008
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ber of apertures desired at each of the beams. The planning IV.C. Improving the accuracy of IMRT delivery with
system optimizes the aperture shape and aperture weights image guidance
simultaneously. Physical constraints of the MLC are consid- Besides improving efficiency, great opportunities also ex- ered in the optimization process. With a small number of ist for improving the accuracy of treatment delivered by us- apertures, the resulting plan quality generally rivals that ing on-board image guidance. The advent of on-board cone based on intensity optimization which requires large number beam computed tomography ͑CBCT͒ and in-room CT with of apertures. Earl et al.and Kim et al.also demon- high soft tissue contrast opens new opportunities for high- strated that even with overlapping rectangular fields formed precision radiation therapyThe success of the image by independent jaws, IMRT type of dose distribution can be guided radiation therapy ͑IGRT͒ lies not only in the ability to achieved for prostate, breast, and even head and neck cases, acquire the images but largely in how we use the images to if the aperture shapes and weights are optimized with DAO.
achieve our goal of controlling more cancers while decreas- Earl et al. illustrated that DAO can also be applied for the ing the normal tissue toxicities. In many cases, the tumor not optimization of IMAT plans.The possibility of varying only changes its location but also its shape and the relative dose rates during gantry rotation and irradiation also opens geometrical relationship with its surrounding normal struc- the opportunity for delivering IMRT-like plans with a single tures. Consequently, simply shifting the patient does not arc rotation. In proposing the IMAT idea, Yhas predicted guarantee optimal treatments. Therefore, reoptimizing the that, with reasonable number of beam angles, the quality of IMRT plan or adapting an existing plan to the “anatomy of an IMRT or IMAT plan depends on the number of total seg- the day” will increasingly become an active area of research.
ments, or aperture variations. Given enough aperture varia- Recognizing the impracticality of a full-fledged daily re- tions, a single arc should be able to achieve IMRT-like plan planning with current technology, several researchers have quality. Beam intensity modulation is not a fundamental re- recently proposed methods for incorporating the deformable quirement for achieving optimal treatment plans. The ability component into an online correction strategy. Wu et al.have shown that for tomotherapy delivery, intensities can be to take advantage of the preferred angles and locations, modified online with given transformation parameters or through which the radiation is directed to the tumor, is the with a quick reoptimization. Mohan et proposed to de- key to achieve optimal dose distributions. For example, the form the intensity patterns as an online correction strategy.
CyberKnife™ system͑Accuray, Sunnyvale, CA͒, which Feng et have proposed a scheme that deforms the ap- uses small circular x-ray beams generated by an x-band lin- erture shapes of the IMRT segments by using the deforma- ear accelerator mounted on a robot to deliver the radiation to tion matrix derived from the planning image set and the im- the target, does not explicitly modulate the intensity of a ages of the day. Ahunbay et developed a similar beam, but is able to deliver highly conformal treatments.
scheme but added aperture weight optimization after aperture The feasibility of delivering IMRT with a single arc was deformation. These schemes have shown to be able to ap- first demonstrated by Cameron et al.Using a DAO scheme proach the plan quality resulting from reoptimization using as Earl et al. but employing a more efficient way for select- ing the initial aperture shapes, Ulrich et al. also showed that As computer technology continue to advance, such short IMRT-like dose distributions can be achieved with a single cuts as described above may no longer be needed. Replan- When optimizing a large number of beam apertures ning using the images of the day will become a reality. The from large number of beam angles, the scheme by Ulrich and advance of IGRT will make imaging, planning and treatment Earl can take a long time for the optimization to converge.
delivery all performed in a single session. Under the new Otto devised a coarse-to-fine optimization scheme that starts “image-plan-treat” process, initial imaging and planning will with a small number of beams with large angular spacing and become merely a first look into what degree of dose confor- gradually inserts new beam angles to be optimized.The mity is achievable. With experience and confidence, the ini- computer optimizes the aperture shapes and weights simul- tial planning may even be eliminated. Such a procedure, taneously as in DAO. Tang et al.illustrated that a single arc which has been the norm for radiosurgery, will allow further IMAT plan can be derived from a multiarc IMAT plan by shrinkage of PTV margins and encourage radiation oncolo- spacing the stacked apertures to the neighboring angles. Us- gists to revise the current dose fractionation schemes. There ing graph algorithms, Wang et al.have shown that IMRT are three technologies that will enable for this image-plan- plans optimized with 36 fields can be sequenced into and delivered with a single arc. The pressure for more efficient ͑1͒ Imaging systems integrated with delivery machines will IMRT delivery will encourage linear accelerator vendors to be faster and provide greater image quality before and offer different single arc IMAT solutions.
during treatment. Currently, the gantry speed is setting In addition to rotational delivery, the use of higher dose the limit on the speed of image acquisition for imaging rates, either by the improvements in acceleration technology systems mounted on the treatment gantry. The image or by eliminating the flattening filter, could also be explored quality achievable with CBCT also does not match that for efficiency As IMRT becomes easier to plan and of fan beam CT units because of the limitations of the to deliver, the need for traditional beam modifiers such as the reconstruction algorithms for CBCT and the added ra- use of physical wedges will diminish.
diation scatter contributions. These limitations will be Medical Physics, Vol. 35, No. 12, December 2008
Yu, Amies, and Svatos: IMRT planning and delivery
corrected in the long-term by the emergence of new de- such as DAO and single arc IMAT. The rapid adaptation of signs of on-line imaging systems, new imaging recon- IGRT will encourage the integration of IMRT planning and struction and scatter subtraction algorithms, and/or new delivery with on-line imaging. Strategies of on-line plan ad- aptation and on-line replanning will be the emphasis in the ͑2͒ Dose calculation and optimization can be performed near future. The adoption of biology and molecular imaging within a couple of minutes. Computational speeds have guidance will push IMRT into dose painting paradigm in the been increasing rapidly according to Moore’s law. Other innovations, such as the use of special hardware for dose Author to whom correspondence should be addressed. Electronic mail: A. Brahme, “Optimization of stationary and moving beam radiation 3͒ Fast image registration will allow the structures delin- therapy techniques,” 12, 129–140 ͑1988͒.
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