Date Published: June 11, 2018
Publisher: Public Library of Science
Author(s): Yoshiko Doi, Yuji Murakami, Nobuki Imano, Yuki Takeuchi, Ippei Takahashi, Ikuno Nishibuchi, Tomoki Kimura, Yasushi Nagata, Qinghui Zhang.
Cardiac toxicity after definitive chemoradiotherapy for esophageal cancer is a critical issue. To reduce irradiation doses to organs at risk, individual internal margins need to be identified and minimized. The purpose of this study was to quantify esophageal motion using fiducial makers based on four-dimensional computed tomography, and to evaluate the inter-CBCT session marker displacement using breath-hold.
Sixteen patients with early stage esophageal cancer, who received endoscopy-guided metallic marker placement for treatment planning, were included; there were 35 markers in total, with 9, 15, and 11 markers in the upper thoracic, middle thoracic, and lower thoracic/esophagogastric junction regions, respectively. We defined fiducial marker motion as motion of the centroidal point of the markers. Respiratory esophageal motion during free-breathing was defined as the amplitude of individual marker motion between the consecutive breathing and end-expiration phases, derived from four-dimensional computed tomography. The inter-CBCT session marker displacement using breath-hold was defined as the amplitudes of marker motion between the first and each cone beam computed tomography image. Marker motion was analyzed in the three regions (upper thoracic, middle thoracic, and lower thoracic/esophagogastric junction) and in three orthogonal directions (right-left; anterior-posterior; and superior-inferior).
Respiratory esophageal motion during free-breathing resulted in median absolute maximum amplitudes (interquartile range), in right-left, anterior-posterior, and superior-inferior directions, of 1.7 (1.4) mm, 2.0 (1.5) mm, and 3.6 (4.1) mm, respectively, in the upper thoracic region, 0.8 (1.1) mm, 1.4 (1.2) mm, and 4.8 (3.6) mm, respectively, in the middle thoracic region, and 1.8 (0.8) mm, 1.9 (2.0) mm, and 8.0 (4.5) mm, respectively, in the lower thoracic/esophagogastric region. The inter-CBCT session marker displacement using breath-hold resulted in median absolute maximum amplitudes (interquartile range), in right-left, anterior–posterior, and superior-inferior directions, of 1.3 (1.0) mm, 1.1 (0.7) mm, and 3.3 (1.8) mm, respectively, in the upper thoracic region, 0.7 (0.7) mm, 1.1 (0.4) mm, and 3.4 (1.4) mm, respectively, in the middle thoracic region, and 2.0 (0.8) mm, 2.6 (2.2) mm, and 3.5 (1.8) mm, respectively, in the lower thoracic/esophagogastric region.
During free-breathing, esophageal motion in the superior-inferior direction in all sites was large, compared to the other directions, and amplitudes showed substantial inter-individual variability. The breath-hold technique is feasible for minimizing esophageal displacement during radiotherapy in patients with esophageal cancer.
Recently, the efficacy of concurrent chemoradiotherapy (CCRT) for esophageal cancer has been reported [1–4]. CCRT has achieved favorable locoregional control and survival rates in early-stage esophageal cancer (EC) [3,4]. Given the progress in endoscopic diagnostic techniques, such as iodine staining and magnifying endoscopy with narrow band imaging, the screening of early-stage EC has become widespread. This trend has improved overall survival rate after definitive CCRT for EC.
Recently, serious late cardiopulmonary toxicities after CCRT in patients with EC have been reported [5–9]. Large volumes irradiated in high doses to the heart and lungs increase the risk of cardiopulmonary toxicity, and this volume is affected by tumor size and esophageal motion. Esophageal motion consists of respiratory, heart beat-related, and peristalsis-related motions. In clinic, patients with EC usually undergo RT during free-breathing; thus, it is important to measure esophageal motion during free-breathing to determine optimal internal margins. Several methods have been reported to evaluate esophageal motion, including evaluating the motion of a manually contoured target or the esophagus itself [11–15], as well as fiducial markers placed on the esophageal wall [16,17]. In this study, we wanted to evaluate physiological esophageal motion as accurately as possible. Therefore, we selected patients with early stage (T1-2N0M0) tumors with virtually no invasion or adhesion to adjacent structures. We also used 4D-CT metal marker motion data to confirm tumor position for treatment planning (i.e. fiducial markers for esophageal motion).
During free-breathing, esophageal motion in the SI direction is larger in all esophagus sites than in the other directions. Amplitudes vary substantially between individuals. The breath-hold technique is feasible for minimizing esophageal displacement during RT in patients with EC.