J. Radiat. Res., 48: Suppl., A55-A59 (2007)
Assessing Residual Motion for Gated Proton-Beam Radiotherapy Gregory C. SHARP1,2*, Hsiao Ming LU1,2 , Alexei TROFIMOV1,2, Xiaoli TANG1,2, Steve B. JIANG1,2, Julie TURCOTTE1, David P. GIERGA1,2, George T. Y. CHEN1,2 and Theodore S. HONG1,2 Liver cancer/Organ motion/Proton radiotherapy. Gated radiation therapy is a promising method for improving the dose conformality of treatments to moving targets and reducing the total volume of irradiated tissue. Target motion is of particular concern in proton beam radiotherapy, due to the finite range of proton dose deposition in tissue. Gating allows one to reduce the extent of variation, due to respiration, of the radiological depth to target during treatment delivery. However, respiratory surrogates typically used for gating do not always accurately reflect the position of the internal target. For instance, a phase delay often exists between the internal motion and the motion of the surrogate. Another phenomenon, baseline drifting refers to a gradual change in the exhale position over time, which generally affects the external and internal markers differently. This study examines the influence of these two physiological phenomena on gated radiotherapy using an external surrogate.
INTRODUCTION
MATERIALS AND METHODS
Because organs in the thorax and abdomen exhibit considerable motion during respiration,1) large margins are required to ensure adequate coverage of the clinical target volume (CTV). One alternative to large treatment margins is respiratory-gated treatment, whereby treatment delivery is synchronized with respiratory motion.2) The applicability of respiratory gating is well established for photons,3–6) protons,7) and heavy ion treatments.8) In the absence of direct fluoroscopic imaging during treatment,5) most systems that use respiratory gating rely on an external surrogate to monitor respiration and trigger the beam. The use of an indirect signal, such as an optical marker, requires consideration of the correlation and calibration between the surrogate signal and the true, internal position.9) Previous studies have established that a correlation exists, and have measured the correlation coefficients, phase delays, and residual motion.10–14) However, the degree of correlation presented in these studies varies. For example residual motion, within the gating window, can range from a few mm to 1 cm. Therefore, it is important to assess the quality and applicability of the respiratory surrogate within the context of its use for gated treatment.
Gated proton-beam radiotherapy has been used clinically at MGH since 2005, for treatments in the thorax and abdomen. The Varian Real-time Position Management system (RPM, Varian Inc, Palo Alto, CA) is used to monitor the patient's breathing cycle and to provide the gating signal. The gating signal is used in combination with the range modulation signal to control the beam current of the cyclotron. During each breathing period, the exhale phase is identified based on the marker position, and a sequence of beam pulses are delivered within the gating window. A gating circuit has been designed to ensure delivery over complete modulation cycles so that for any beam-on segment (beam pulse), the delivered dose has the exact planned spread-out Bragg peak (SOBP) distribution. An example of the beam delivery dynamics is illustrated in Fig. 1. To assess the use of RPM as a surrogate for intrafractional motion, four patients with hepatocellular carcinoma were studied. All patients had large tumor motion (peakto-peak > 1.0 cm), and therefore were candidates for gated proton beam radiotherapy in a phase I clinical trial. Between 3 and 5 gold fiducial markers were implanted in or near the site by interventional radiology to serve as internal surrogates for the treatment target. The motion of a marker placed on patient’s abdominal surface was recorded by the RPM system and used as an external surrogate for respiration. The RPM was synchronized to an orthogonal bi-plane fluoroscopic imaging system with an accuracy of +/– 20 ms. Simulation sessions were conducted under free breathing to
*Corresponding author: Phone: +1-617-724-3866, Fax: +1-617-726-3603, E-mail:
[email protected] 1 Department of Radiation Oncology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, United States; 2Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, United States.
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Fig. 1.
Fig. 2.
Beam delivery dynamics of a gated proton therapy treatment.
Fluoroscopy is synchronized with RPM, and implanted markers are tracked in 3D.
Fig. 3. Phase delay between external surrogate (RPM) and internal marker. J. Radiat. Res., Vol. 48, Suppl. A (2007); http://jrr.jstage.jst.go.jp
Residual Motion in Gated Proton Therapy
assess the correlation between the gold markers and the RPM system. Each session consisted of between 4 and 6 bursts of fluoroscopic video over a period of about 4 to 6 minutes. The three-dimensional coordinates of each marker location were tracked retrospectively, and compared with the synchronized RPM signal. An example of this is shown in Fig. 2, where the 3D motion of a marker is plotted against the surrogate signal. The phase delay from internal to external was computed by comparing fluoro and RPM signals. In addition, the baseline drifting of the exhale position over the course of several minutes was computed for both internal and external signals. The impact of these phenomena on the residual motion within the gating window during treatment was assessed for the techniques of amplitude-based gating, phase-based gating, and gating using internal markers.
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from inferior to superior approximately 5 mm for patient 1, 6 mm for patient 2, and 2 mm for patient 3. Patient 4 had a small drift from superior to inferior. Baseline drifting was greatest in the superior-inferior direction, but was also
Table 1. Summary of phase delay and exhale baseline drift measurements. ID Peak-to-peak Phase delay External drift Internal drift Motion Int->Ext A→P I→S 1
1.8 cm
30 ms
Not measured
5 mm
2
1.2 cm
140 ms
6 mm
6 mm
3
2.0 cm
220 ms
0 mm
3 mm
4
1.9 cm
–20 ms
–2 mm
–1 mm
RESULTS Phase delays were detected, indicating that motion inside the liver may not be seen simultaneously on the external surface. The average phase delays were 0.03 sec for patient 1, 0.14 sec for patient 2, 0.22 sec for patient 3, and –0.02 sec for patient 4. For each patient, the phase delay varied from marker to marker, and also over time during the course of 4 to 6 minutes. For patient 3, phase delay varied between 0.17 and 0.29 seconds. The phase delay in patient 4 was negligible, as it was within the synchronization accuracy of our equipment. Examples of phase delay are shown in Fig. 3, where arrows are used to indicate the direction of motion. Overall results are tabulated in Table 1. Baseline drifting was present in two of the four patients, indicating that the exhale position of the liver may not be stable within the first several minutes after lying on the treatment couch. The exhale position of the internal target drifted
Fig. 4. Drifting of SI position as a function of RPM marker height for patient 2.
Fig. 5. Residual motion within the gating window for different gating duty cycles, using internal markers (left), and external surrogate amplitude (right). J. Radiat. Res., Vol. 48, Suppl. A (2007); http://jrr.jstage.jst.go.jp
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observed in the anterior-posterior and left-right directions. For patient 2, the superior-inferior drift of the internal target was associated with a corresponding anterior-posterior drift of the RPM surrogate. An example of this baseline drifting is shown in Fig. 4, with the exhale baseline position moving from inferior to superior. The presence of phase delays and baseline drifting has considerable impact on residual motion for gated treatments using external surrogates. Patient 2, who exhibited baseline drifting, had residual motion (90% motion range) of 5.0 mm, 4.0 mm, and 2.7 mm respectively for phase-gated, amplitude-gated, and internal-gated plans at 30% duty cycle. Patient 3, who exhibited phase delay, had residual motion (90% motion range) of 9.3 mm, 7.4 mm, and 3.0 mm for phase-gated, amplitude-gated, and internal-gated plans at 30% duty cycle. In fact, because of the phase delay, the best amplitude-gated plan was at inhale rather than exhale. The residual motion computed as a function of duty cycle is shown in Fig. 5. These results as shown do not include the effects of electrical and mechanical delays in beam triggering.
DISCUSSION Various methods have been employed to collapse the planning target volume (PTV), which accounts for daily setup variation and internal organ motion, on to the clinical target volume (CTV), which includes the gross tumor volume as well as presumed microscopic extension. Collapsing the PTV is desirable as the PTV margin often includes a significant amount of normal tissue. In parallel organs such as liver and lung, the volume of normal tissue irradiated can have a strong association with toxicity. Typically, a PTV expansion consists of two components. One component is daily set-up variation. This component of geometric positional uncertainty has been addressed with a
variety of technologies including cone-beam CT, megavoltage CT, daily orthogonal portal imaging, among others. However, the second, and potentially more challenging component to address is the position target uncertainty due to motion. Two approaches to this problem involve limiting intra-fraction movement with stereotactic body systems and respiratory gating, seeks to have the treatment beam turned on only during certain respiratory phases. Respiratory gating requires an object that can be tracked in real-time. This can be an internal radio-opaque fiducial, as used in this study. However, drawbacks of the implanted fiducials include the invasive nature of placement as well as the imaging artifact that can obscure follow-up, especially in the liver. Hence external surrogates for respiratory motion are desirable. The use of an external surrogate complicates geometric targeting, however, because motion in the surrogate is only loosely related to internal motion. In principle, the effect of phase delay can be corrected through the use of phase-based gating. However, all four patients in this study were found to have higher residual motion with phase-based gating than with amplitude-based gating. Similarly, baseline drifting can in principle be corrected through the strict use of amplitudebased gating. Figure 4 suggests that periodic intra-fractional drifting of the respiratory baseline should not be corrected by adjusting the gating window. However, the generality of this effect is not known. The performance of surrogates can be improved to some degree through the use of multiple markers. This technique has been demonstrated previously for deep-inspiration breath hold,15–16) but is also appropriate for gated treatment. It is likely that multiple markers can be at least partly effective in correcting phase delays, because early indications of breathing transitions will be seen in some of the markers. It is well known that breathing patterns change both intraand inter-fractionally, and it has been suggested that the cor-
Fig. 6. Inter-fractional variations in breathing amplitude and period. J. Radiat. Res., Vol. 48, Suppl. A (2007); http://jrr.jstage.jst.go.jp
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relation function may undergo similar changes.9,12) Interfractional changes in amplitude and period are seen in the surrogate signal during proton treatment, and are shown in Fig. 6. The overall trend is faster and shallower breathing over the course of treatment. For patient 3, the variance in amplitude is reduced over time, suggesting that this patient’s breathing was more stable during later treatment fractions.
8.
CONCLUSION
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Gated proton therapy has been implemented at MGH, and the correlation of the RPM surrogate signal with internal motion has been performed. We observed phase delays of more than 100 ms in two of four patients, and baseline drifting of 5 mm or more in two of four patients. The presence of these phenomena may affect the quality of gated treatment using external surrogates, by increasing the residual motion within the gating window. The utility of external surrogates for gating should be studied in more detail. REFERENCES 1. Langen, K. M. and Jones, D. T. (2001) Organ motion and its management. Int J Radiat Oncol Biol Phys. 50: 265–278. 2. Mageras, G. S. and Yorke, E. (2004) Deep inspiration breath hold and respiratory gating strategies for reducing organ motion in radiation treatment. Sem Rad Onc. 14: 65–75. 3. Ohara, K. et al. (1989) Irradiation synchronized with respiration gate. Int J Radiat Oncol Biol Phys. 17: 853–857. 4. Kubo, H. D. and Hill, B. C. (1996) Respiration gated radiotherapy treatment: A technical study. Phys Med Biol. 41: 83– 91. 5. Shirato, H., Shimizu, S., Kitamura, K., Nishioka, T., Kagei, K., Hashimoto, S., Aoyama, H., Kunieda, T., Shinohara, N., Dosaka-Akita, H. and Miyasaka, K. (2000) Four-dimensional treatment planning and fluoroscopic real-time tumor tracking radiotherapy for moving tumor. Int J Radiat Oncol Biol Phys. 48: 435–442. 6. Wagman, R., Yorke, E., Ford, E., Giraud, P., Mageras, G., Minsky, B. and Rosenzweig, K. (2003) Respiratory gating for liver tumors: Use in dose escalation. Int J Radiat Oncol Biol Phys. 55: 659–668. 7. Okumura, T., Tsuji, H., Hayakawa, Y., Maruhashi, A., Inada,
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J. Radiat. Res., Vol. 48, Suppl. A (2007); http://jrr.jstage.jst.go.jp
Received on February 1, 2007 Revision received on February 24, 2007 Accepted on February 24, 2007
