ANTI-TUMOUR TREATMENTNew developments in arc radiation therapy: A review
Introduction
The technologies available for delivering radiation therapy have advanced dramatically in the past few decades. In the 1980s, two-dimensional radiotherapy was the standard of care, relying on radiographs and anatomical knowledge for target localization. The advent of CT scanning for radiotherapy planning ushered in the era of 3D conformal radiotherapy (3D-CRT, Fig. 1A), in which 3D images of tumors, normal structures, and dose distributions could be constructed.1
In the 1990s, intensity-modulated radiotherapy (IMRT) was introduced. IMRT divides each large radiation beam into numerous small beamlets, and adjusts the intensity of each beamlet individually.2 With IMRT, it is much easier to achieve complex dose distributions (such as the sparing of the spinal cord and parotid shown in Fig. 1B) that are difficult to create with 3D-CRT. As a result, IMRT treatment plans are more conformal and allow for lower doses to organs at risk. Like 3D-CRT, IMRT is delivered using fixed beams that do not rotate while the beam is on, although the shape of the beam may change. IMRT generally requires more beams than 3D-CRT – often 5–9 beams are used for each fraction. Beam directions are chosen that allow the whole target to be encompassed while avoiding normal tissues as much as possible. Unfortunately the best angles for treatment are not always obvious.3
Compared to 3D-CRT, IMRT provides greater flexibility in controlling each beam, ultimately improving dose distributions and reducing toxicity.[2], [4] IMRT can also allow for dose escalation, delivering higher doses to the tumor while maintaining acceptable doses to critical organs at risk, such as the spinal cord. A systematic review of comparative clinical IMRT studies, including three randomized trials, confirmed that IMRT can reduce toxicity for various treatment sites, although effects on local control and survival outcomes are inconclusive.4
The benefits of IMRT come at a cost. Firstly, IMRT plans are more complex and take longer to deliver, prolonging the time that a patient spends on the radiotherapy machine and decreasing patient throughput. Secondly, IMRT can result in increased integral dose – a larger volume of normal tissues receives low doses of radiation. This effect can be seen in the areas around the target (where the beams enter and exit) and also in areas far from the target. This increase in integral dose with IMRT has in turn led to concerns about a potential increased risk of secondary malignancy.[5], [6] Thirdly, the increased treatment time with IMRT has led to concerns about increased tumor cell repair during the time required to deliver treatment.7
Two clinical developments in radiation oncology underscore the drawbacks of fixed-field treatments, whether delivered by IMRT or 3D-CRT: image-guided radiotherapy and hypofractionation. Image-guided radiotherapy (IGRT) refers to the use of imaging (such as X-rays or CT scans) immediately before or during treatment, to ensure that the patient and tumor are in the correct position. IGRT allows radiation oncologists to reduce the ‘safety margins’ that account for uncertainty in positioning, thereby reducing the volume of tissue that receives radiation.4 However, use of image guidance increases the time that a patient spends on the radiotherapy table and can also increase the integral radiation dose, further compounding the drawbacks of IMRT. The second development, hypofractionation, refers to the practice of delivering large daily doses, more than the conventional 2 Gy per day. With hypofractionation, fraction sizes can be very large: for stereotactic lung radiotherapy, three fractions of 20 Gy are commonly employed, and achieves excellent rates of local control.8 However, when delivered with fixed-fields using image-guidance, these treatments can require up to 45 min to deliver.
Arc therapy has emerged as a technique to address some of the limitations of fixed-field treatments. In contrast to fixed-field IMRT, arc therapy incorporates rotation of the beam relative to the patient while the beam is on. In most cases, the patient is treated from all angles, in one or more 360-degree rotations. The major conceptual advantage of arc therapy over standard fixed-field IMRT techniques is that since the radiation source is rotating around the patient, all angles are available to deliver radiation to the target while avoiding critical structures, and time is used efficiently because the radiation delivery does not stop in between different beam angles. Selection of angles for fixed-field IMRT can be difficult,3 and arc therapies can overcome this difficulty by allowing the tumor to be treated from all angles.
In essence, all modern arc therapies are a form of intensity-modulated radiation therapy (IMRT), and theoretically they retain the same advantages and disadvantages over 3D-CRT, trading off improved dosimetry for higher integral dose and in some cases increased treatment time. However, arc therapies have several potential advantages over IMRT (Table 1), most importantly improvements in dose distributions and treatment times.
Modern arc therapies can be broadly classified as one of two types: tomotherapy (Fig. 2) and volumetric arc therapy (Fig. 3). Tomotherapy was first introduced in 1993,9 and is analogous to CT imaging in that a thin beam of radiation is used to treat the patient in slices (axial tomotherapy) or in a spiral (helical tomotherapy) as the patient moves through the tomotherapy machine.10 Volumetric modulated arc therapy (VMAT) differs in that it can treat the whole tumor volume at once, rather than in slices, and is delivered using a standard linear accelerator.11 There are several variations on VMAT, with names such as RapidArc™, SmartArc™, intensity modulated arc therapy (IMAT) and arc-modulated radiation therapy (AMRT), but the general concepts of these are similar.[11], [12], [13], [14]
Section snippets
Tomotherapy
Tomotherapy is literally defined as ‘slice therapy’, and is best described as a combination of a CT scanner and a linear accelerator.[9], [15] As in CT scanning, the patient is moved through the machine as a radiation source rotates through 360° (Fig. 2A and B). The machine produces a thin fan-shaped beam of radiation, and as the beam rotates, the shape of the beam is adjusted. Axial tomotherapy involves treating a slice of the target and then translating the patient before treating the next
Volumetric modulated arc therapy (VMAT)
In 2007, a novel form of arc therapy called VMAT was introduced.11 With VMAT, the gantry is rotated while the beam is on, and three parameters can be changed as the beam is rotated: the dose rate, the shape of the beam, and the speed of rotation.11 VMAT is analogous to tomotherapy, in that radiotherapy can be delivered from up to 360° of beam angles, but differs in that it can be delivered on a conventional linear accelerator, and that the whole volume can be treated at once. VMAT can deliver a
Direct comparisons between systems
Since VMAT is a relatively new innovation, it has not yet been comprehensively compared with tomotherapy, although a few early reports have been published. For example, Fogliata et al. compared RapidArc with helical tomotherapy as components of two planning studies, and concluded no clinically significant dosimetric differences could be seen between the RapidArc and tomotherapy plans.[35], [36]
Since VMAT, tomotherapy, and fixed-field IMRT are all highly sophisticated techniques, it may be that
Efficiency and treatment time
The major difference between VMAT and the other techniques (fixed-field IMRT and tomotherapy) appears to be improved efficiency, resulting in faster treatment times. Prolonged treatment time has been identified as one of the drawbacks of standard fixed-field IMRT. In some cases, the time required to deliver a fraction of a complex IMRT plan can be in excess of 15–30 min,[38], [39], [40] whereas most fractions of 3D-CRT require only a few minutes, depending on complexity. This has been often
Versatility
Like IMRT, VMAT is delivered using a standard linear accelerator, which allows the flexibility to employ the other features of the linear accelerators (e.g. electrons, varied energies of photons) for other patients who do not require VMAT. Tomotherapy machines are constrained to deliver only tomotherapy, although a new modification is forthcoming that can allow the beam to remain stationary, for situations where fixed beams are more appropriate.52
By nature of its design, tomotherapy has the
Future directions
Tomotherapy and VMAT are still relatively new technologies in radiation oncology. They will continue to be tested and refined, and new systems and algorithms and are likely to come into clinical use in the near future.[12], [14] Recently, a new system has been introduced, named Vero, which can deliver arc therapy and may provide more flexibility in tumor tracking.53 Data on cost-effectiveness and long-term efficacy are anticipated as these treatments mature. It is likely that in the future,
Conclusions
Arc-based radiotherapy is a complex approach to IMRT made possible by advances in technology. Compared to standard fixed-field IMRT, arc-based radiotherapy allows tumors to be treated from all angles, and can provide advantages in terms of dose distribution, ease of real-time imaging, reduced treatment time, and/or reduced monitor unit requirements. Tomotherapy has the longest history of clinical experience, and can produce highly conformal dose distributions using a helical delivery analogous
Conflict of interest statement
The VUMC has a research collaboration with Varian Medical Systems, and Dr. Otto has received financial support from Varian Medical Systems.
Authors’ contributions
All authors (DP, WV, KO and SS) contributed to study conception, design, and data acquisition. DP and SS drafted the manuscript, and all authors revised it critically for important intellectual content. All have given final approval.
Acknowledgements
Dr. Palma’s work is supported by the Canadian Association of Radiation Oncologists Elekta Research Fellowship, the Royal College of Physicians and Surgeons, and the Ontario Institute for Cancer Research. No sponsor has contributed directly to this work.
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