Title: Respiratory gating for radiation therapy is not ready for prime time
Abstract: Arguing against the Proposition is Paul J. Keall, Ph.D. Dr. Keall is Associate Professor and Director of the Division of Radiation Physics in the Department of Radiation Oncology, Stanford School of Medicine, CA. He obtained his M.S. in Health Physics and Ph.D. in Physics degrees from the University of Adelaide, Australia. He serves the AAPM as a member of the Editorial Board for Medical Physics and is a member of the Therapy Research Subcommittee, the Stereotactic Body Radiotherapy TG102, the Monte Carlo in Treatment Planning TG105, and the Summer Undergraduate Fellowship Program Subcommittee. His major research interests are 4-D imaging, planning, and treatment, adaptive radiotherapy, respiratory gating, image-guided radiotherapy, and biological models in radiotherapy. Respiratory organ motion, which can be up to , reduces the effectiveness of radiation therapy (RT) for thoracic and abdominal tumor targets. This motion degrades anatomic position reproducibility during imaging, demands larger margins during RT planning, and causes errors during RT delivery. In recent years, a variety of methods and techniques have been proposed or developed to explicitly account for respiratory motion in RT. These include respiratory gating, breath holding, and respiration synchronization. The gating method, including internal and external gating systems, is the most widely discussed method so far. It has been well documented that gated RT, if carried out carefully, can significantly reduce margins and, thus, improve sparing of normal tissues.1 Currently, the only internal gating system used in the clinic is fluoroscopic tumor tracking based on implanted markers.2 For external gating technology, at least two systems are commercially available for both CT and linear accelerators: the Siemens Anzai pressure belt3 and the Varian RPM optical system.4 In my view, gated radiation delivery, although promising, is not yet ready for prime time. Generally speaking, respiration is an active and vital process not easily lending itself to manipulation. The unpredictable variation in respiratory patterns during and between image acquisition and day-to-day treatment delivery is the most challenging problem for all of the techniques developed for managing respiratory motion. For a gated procedure, this variation can result in inaccurate and/or inefficient dose delivery, and even geographic misses. Although much effort has been expended in searching for effective methods to improve breathing reproducibility, progress has not been remarkable. For example, one method to reduce breathing irregularity is to train patients with audio prompting and/or visual feedback.5,6 It has been reported, however, that about 50% of patients could not follow both audio and video instructions simultaneously.7 So far, no reliable training method is available. For external gating systems, the use of an abdominal motion signal as a surrogate for internal tumor motion is not reliable because of variations in the correlation and phase shifts between the surrogate and internal structure motion.8,9 In addition, the currently available systems are limited to one-dimensional motion. Although respiratory motion is predominantly in the superior-inferior direction, there are exceptions.10 These problems can result in significant errors in dose delivery. Furthermore, a robust treatment verification system capable of documenting the dose actually delivered and preventing geographic misses is not available for gated delivery. For internal gating systems, the high risk of pneumothorax due to the percutaneous insertion of fiducial markers in the lung is a problem, as is also the high imaging dose required for fluoroscopic tracking. These problems make internal gating impractical at the moment. Respiratory motion is complex and patient specific, and it depends on location. It cannot be predicted by any known medical/physiological models.10 In addition, clinical parameters to identify suitable patients for gating have not been defined. So far, the data acquired in the clinic for gated radiation therapy have been mostly limited to demonstration of dosimetric benefits. Whether these benefits transfer to outcome gain is unknown. In conclusion, respiration gating, although very promising, is not mature and can be risky. Its clinical benefits have not been documented. Therefore, for the moment, gated radiation therapy should be performed with caution only for selected groups of patients. The recently published AAPM Task Group Report on respiratory motion management recommended that “If target motion is greater than , a method of respiratory motion management is available; and if the patient can tolerate the procedure, respiratory motion management technology is appropriate.”1 Respiratory gating is one technique for respiratory motion management that has been seamlessly integrated into the clinical process. Does respiratory gating solve all of the motion issues? Definitely not! But the debate is not “Is respiratory gating with current technology perfect?” The question is “Is respiratory gating better than not accounting for motion at all?” By disputing three fallacies I will argue that respiratory gating is well established and widely available, and that there is strong clinical evidence that it will result in improved patient outcomes. Fallacy #1: Respiratory gating is not an established technology The first published article on respiratory gating in radiotherapy was that of O'Hara et al.11 in 1989 in which they described seven patient treatments. Technologies that are now considered mainstream but were actually first clinically used after respiratory gating include IMRT, superposition and Monte Carlo-based treatment planning, multi-slice CT scanning, and cone beam CT imaging. Respiratory gating is an established technology and it has been commercially available in the US since 1999. Fallacy #2: Not many sites have or use respiratory gating Respiratory gating is the most widely available method of respiratory motion management with several vendors offering respiratory gating products. Over 1000 respiratory gating systems have been sold worldwide. In a recent RTOG IGRT survey, 26 out of 91 sites surveyed were performing respiratory gating (J. Bradley M.D., ASTRO 2006), and the trend is toward increased use. At Stanford, respiratory gating is performed on three linear accelerators with an additional two performing respiratory tracking. Fallacy #3: There are no clinical data to support the use of gating The proof is in the pudding as the saying goes—is respiratory gating better for patients? A seminal paper by Fang et al.12 demonstrated that 3D radiotherapy has statistically significant survival advantage over 2D radiotherapy, with 27% (3D) vs. 6% (2D) overall survival. A compelling piece of data in that study was that patients treated with respiratory gating had a hazard ratio of 0.25 , indicating that patients are four times more likely to survive than those not treated with gating. In multivariate analysis gating was not significant—the study was not powered to address this question—but there is a strong suggestion that respiratory gating does, indeed, improve survival in lung cancer patients. Wagman et al.13 in a liver cancer study found that using respiratory gating reduced fluoroscopically visible motion from . The use of gating, in combination with a rigorous portal imaging protocol, allowed the CTV-PTV margin to be reduced from . This margin reduction allowed dose increases from 7% to 27%, and also allowed radiotherapy to be given to patients for whom the treatment would otherwise have been too toxic. Several treatment planning studies have reinforced these clinical findings.14–19 Perhaps the most accurate form of respiratory gating has been implemented by the Hokkaido group,20,21 where implanted markers are tracked in real-time using fluoroscopy, and the treatment beam gated on when the markers are within predetermined positions. This active program has treated many liver and lung cancer patients with gated stereotactic radiotherapy. In summary, if respiratory motion management systems are available, and have shown clinical benefit, we are ethically bound to use them. Today at Stanford we are routinely treating the following abdominal and thoracic sites with respiratory gating and IMRT/conformal radiotherapy: lung, breast, esophagus, pancreas, and lymphoma. Respiratory gating is beyond prime time, it is routine. Respiratory gating, which associates with tight margins, is better than not accounting for motion at all only if it is carried out properly. Tight margins, which increase the risk of geometric misses, require accurate treatment delivery. However, such accurate delivery is not trivial during a course of multi-fractionated radiotherapy because of inter- and intrafractional variations. I agree with Dr. Keall that the technology for respiratory gating is reasonably established and the technical implementation of commercial gating systems can be seamless. However, the clinical use of these technologies is not yet mature. The fact that only 26 out of 91 RTOG members are performing respiratory gating reflects the hesitation of using these technologies for patients on a large scale. Gating technology has been commercially available since 1999 and most RTOG members are academic centers that would be expected to have the resources needed to perform respiratory gating, but only a few are actually using it. Issues that contribute to this hesitation include (1) more effective prediction techniques and/or training methods for patient breathing are needed to reduce inter- and intrafractional variations in breathing patterns; (2) more reliable mechanisms are required to correlate external surrogates with internal tumor motions; and (3) proper clinical parameters are needed to identify suitable patients. Until these issues have been fully addressed, respiratory gating should be carried out only in those clinical settings that can provide the considerable resources needed to carefully select suitable patients, cautiously design treatment plans, and extensively validate treatment delivery. I concur with Dr. Li's statements that, if used appropriately in conjunction with methods to manage interfraction variations, respiratory gating allows safe margin reduction. I also agree with the statement that respiratory motion is complex, multidimensional, and patient specific. However, it is precisely for these reasons that we want to manage motion with technologies such as respiratory gating. Ignoring the problem does not make it go away—respiratory gating can reduce the apparent motion by over a factor of 4 (Ref. 13) and can minimize deleterious effects. Following are my responses to the statements of Dr. Li: High imaging dose for internal gating: The dose for fluoroscopy-based gating has been estimated to be 1% of the treatment dose.20 Unacceptable risk of pneumothorax for marker implantation: Percutaneous22 and bronchoscopic23 lung implantation have shown pneumothorax rates of 19% and 2%, respectively. The increased accuracy offered by marker implantation outweighs the associated morbidity. 50% success rate of audio-visual biofeedback: A 24-patient repeat session study found a 100% success rate, reducing the residual motion by an average of 20% at exhale and 25% at inhale.5 Lack of verification: The same verification methods used without gating can be used with gating, e.g., portal images. However, as respiratory motion affects many of the landmarks used for planar imaging, such as the diaphragm, chest wall, and carina, verification is even more effective with respiratory gating than without. To conclude, respiratory gating is at its prime time now. It represents an intermediate step towards the widespread implementation of target tracking technology.
Publication Year: 2007
Publication Date: 2007-02-07
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 27
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