Clinical investigation: lung
Precise and real-time measurement of 3D tumor motion in lung due to breathing and heartbeat, measured during radiotherapy

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Abstract

Purpose: In this work, three-dimensional (3D) motion of lung tumors during radiotherapy in real time was investigated. Understanding the behavior of tumor motion in lung tissue to model tumor movement is necessary for accurate (gated or breath-hold) radiotherapy or CT scanning.

Methods: Twenty patients were included in this study. Before treatment, a 2-mm gold marker was implanted in or near the tumor. A real-time tumor tracking system using two fluoroscopy image processor units was installed in the treatment room. The 3D position of the implanted gold marker was determined by using real-time pattern recognition and a calibrated projection geometry. The linear accelerator was triggered to irradiate the tumor only when the gold marker was located within a certain volume. The system provided the coordinates of the gold marker during beam-on and beam-off time in all directions simultaneously, at a sample rate of 30 images per second. The recorded tumor motion was analyzed in terms of the amplitude and curvature of the tumor motion in three directions, the differences in breathing level during treatment, hysteresis (the difference between the inhalation and exhalation trajectory of the tumor), and the amplitude of tumor motion induced by cardiac motion.

Results: The average amplitude of the tumor motion was greatest (12 ± 2 mm [SD]) in the cranial-caudal direction for tumors situated in the lower lobes and not attached to rigid structures such as the chest wall or vertebrae. For the lateral and anterior-posterior directions, tumor motion was small both for upper- and lower-lobe tumors (2 ± 1 mm). The time-averaged tumor position was closer to the exhale position, because the tumor spent more time in the exhalation than in the inhalation phase. The tumor motion was modeled as a sinusoidal movement with varying asymmetry. The tumor position in the exhale phase was more stable than the tumor position in the inhale phase during individual treatment fields. However, in many patients, shifts in the exhale tumor position were observed intra- and interfractionally. These shifts are the result of patient relaxation, gravity (posterior direction), setup errors, and/or patient movement.

The 3D trajectory of the tumor showed hysteresis for 10 of the 21 tumors, which ranged from 1 to 5 mm. The extent of hysteresis and the amplitude of the tumor motion remained fairly constant during the entire treatment. Changes in shape of the trajectory of the tumor were observed between subsequent treatment days for only one patient. Fourier analysis revealed that for 7 of the 21 tumors, a measurable motion in the range 1–4 mm was caused by the cardiac beat. These tumors were located near the heart or attached to the aortic arch. The motion due to the heartbeat was greatest in the lateral direction. Tumor motion due to hysteresis and heartbeat can lower treatment efficiency in real-time tumor tracking-gated treatments or lead to a geographic miss in conventional or active breathing controlled treatments.

Conclusion: The real-time tumor tracking system measured the tumor position in all three directions simultaneously, at a sampling rate that enabled detection of tumor motion due to heartbeat as well as hysteresis. Tumor motion and hysteresis could be modeled with an asymmetric function with varying asymmetry. Tumor motion due to breathing was greatest in the cranial-caudal direction for lower-lobe unfixed tumors.

Introduction

Recent developments in radiotherapy such as intensity-modulated radiotherapy, noncoplanar conformal radiotherapy 1, 2, 3, 4, 5, and active breathing controlled-gated treatments (6) are all aimed at increasing the tumor dose and reducing the dose to normal tissue. Discrepancies in tumor position between treatment and a planning computed tomography (CT) scan can be caused by setup errors and organ motion 7, 8, 9. To account for these errors, a safety margin is added to the clinical target volume to obtain the planning target volume. Reducing setup error and understanding organ motion are essential in designing the tightest possible safety margin without compromising the tumor coverage. To examine the motion of lung tumors during respiration, Ekberg et al. (10) used fluoroscopy at the time of simulation. They demonstrated an average movement of 3.9 mm (range: 0–12 mm) in the cranial-caudal direction, 2.4 mm (range: 0–5 mm) in the mediolateral direction, and 2.4 mm (range: 0–5 mm) in the dorsoventral direction. Breath-hold 6, 11 or gated 12, 13 radiotherapy is designed to reduce tumor motion due to breathing. A novel method of accurate dose delivery to moving tumors with small margins is the real-time tumor tracking radiotherapy (RTRT) system 14, 15, 16.

Three-dimensional (3D) treatment planning is often performed on a CT scan made while the patient breathes freely, under the assumption that the CT image represents the average position of the tumor. However, breathing motion can cause misdetection of the tumor during CT scanning, especially for small tumors, resulting in a smaller planning volume or a distorted tumor shape (17). To obtain an accurate tumor image, a breath-hold CT is preferable. The ideal breathing phase in which the breath-hold CT is taken must correspond to the average tumor position. When the breathing motion of the tumor is not symmetric, the average tumor location is no longer midway between the inhale and exhale tumor position.

In this study, precise 3D recordings of tumor position were made during RTRT treatment, both beam-on and beam-off periods, at a high sampling rate to determine and model tumor motion due to breathing, heartbeat, and patient motion.

Section snippets

Patients and methods

Twenty patients with tumors at different sites in the lung (One patient had two tumors) were included in the analysis (Table 1). Seventeen patients had non-small-cell primary lung cancer, and three had metastatic lung tumors. A typical treatment schedule consisted of 4 × 10 Gy with a four-field noncoplanar conformal technique using multiple static beams (4 MV) shaped with a multileaf collimator.

A 2.0-mm gold marker was implanted into or near the tumor mass using bronchial endoscopy or, when

Amplitude

For each patient, the average amplitude of the tumor motion was assessed in all three directions (Table 2). In the cranial-caudal (y) direction, tumors situated in the lower lobes and not attached to rigid structures, such as the chest wall or vertebrae, move more than upper-lobe tumors or tumors attached to rigid structures: 12 ± 6 and 2 ± 2 mm (SD), respectively, (p = 0.005, two-tailed, unequal variances). For tumors attached to rigid structures and for the LR and AP directions, there was no

Discussion

The RTRT system is unique in recording the tumor position in all three directions simultaneously at a high sampling rate. This enabled us to detect tumor motion due to the heartbeat, as well as hysteresis. The system measures the position of a gold marker implanted in or near the tumor. In some studies 11, 12, 19, 20, 21, the position of the chest wall or diaphragm is used to monitor breath-holding or to trigger the linear accelerator. However, the position of the tumor can be different from

Conclusion

In conclusion, the RTRT system has been used to measure tumor position in all three orthogonal directions simultaneously, at a high sampling rate that enabled the detection of tumor motion due to heartbeat, as well as hysteresis. Tumor motion and hysteresis could be modeled with an asymmetric trigonometric function. Tumor motion due to breathing was greatest in the cranial-caudal direction for lower-lobe unfixed tumors.

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