During neoadjuvant radiotherapy, gross tumours in the GEJ may move significantly due to many reasons. Although the movement of GEJ tumours may influence the accuracy of the dose delivery to the GTV, few studies have focused on the IGTV margin for GEJ cancer. In this study, GEJ cancer was divided into different regions, and the IGTV margin was assessed by 4DCT technology. In addition, we enrolled a separate group to validate the accuracy of the IGTV margin. Our studies offer a reference for IGTV margin expansion, especially during SIB intensity-modulated radiotherapy (IMRT) or for institutions lacking image-guided radiotherapy technology.
We delineated the outline of markers under the bone window, which may reduce the uncertainties of contouring the GTV. Moreover, compared to traditional CT simulations, 4DCT technology records temporal and spatial organ motion[13], improving the reliability of the data in our study. When discussing intrafractional motion, Peng Jin et al. enrolled twenty oesophageal cancer patients, and sixty markers were implanted in the proximal, middle, distal oesophagus and proximal stomach of these patients, including seventeen markers located in the proximal stomach. The study found that the intrafractional motion of the proximal stomach in LR, AP and CC directions was 3.7 cm, 5.3 cm, and 8.2 cm, respectively. They also discovered that the closer the oesophageal cancer is to the mediastinum, the larger the tumour movement in all directions[14] which is similar to ours. In addition, Lever et al. calculated oesophageal cancer motion by cine-magnetic resonance imaging and found that the tumour motion in the CC direction was larger than that in the AP and LR directions[15], which is consistent with our study. In our study, regardless of the marker position, the intrafractional displacement in the CC direction was always moves greatest, which is largely attributed to respiration[16].
In regard to interfractional motion, wang et al. discovered that the difference in interfractional motion in different directions was not significant for thoracic oesophageal cancer[17]. However, wang et al. found that the interfractional motion of oesophageal cancer was larger in the CC direction than other directions[18], which is similar to the data from the proximal marker in our study. However, the distal marker showed larger interfractional motion in the AP and LR directions in our study. On the one hand, it is likely that changes in stomach volume and shape during each fraction may be more affected in the AP and LR directions when the tumour is closer to the stomach. Studies have proven that respiratory gating[19], abdominal compression[20], and active breath control[21] technologies may reduce the errors caused by respiration; however, these methods are complicated and time consuming and require specific technology and cooperation from patients.
We calculated the IGTV margins in the proximal and distal regions within GEJ tumours. For tumour centres closer to the GEJ, we can refer to the proximal IGTV margin, and for tumours near the lesser curvature of the stomach, the distal IGTV margin can be referenced. Furthermore, we verified that the IGTV margin was appropriate in nine patients. Peng Jin et al. enrolled eleven patients diagnosed with proximal gastric cancer, and the recommended IGTVs in the LR, AP and CC directions were 16.4 mm, 6.4 mm, and 14.6 mm, respectively[22]; however, their data were merely calculated based on interfractional motion and did not account for gastric fasting or filling. Watanabe et al. analysed six gastric lymphoma patients by using repeated CT scans and suggested that to avoid missing the radiotherapy target, the expansion margins from the whole stomach in the LR, AP and CC directions should be 31 mm, 29.6 mm, and 15.9 mm, respectively[10]. Similar to our study, the closer the tumour is to the gastric body, the larger the IGTV margin in the LR and AP directions. The European Organisation for Research and Treatment of Cancer (EORTC) guidelines recommended that the IGTV margin of GEJ cancer in LR, AP and superior direction should be 10 mm and that in the inferior direction should be 15 mm. For gastric cancer, the recommended margin in three dimensions was 15 mm[23]. The expansion margin in our study was based on advanced 4DCT technology, which is more accurate in these directions. The application of these margins is expected to reduce side effects during radiotherapy.
GEJ cancer lacks IGTV recommendations during neoadjuvant radiotherapy. Our study not only assessed the IGTV margin in different regions within GEJ tumours but also verified its accuracy for the first time. The IGTV margin is vital when using SIB IMRT to treat GEJ cancer. However, this study had some limitations that should be emphasize. First, our sample size was limited in groups A and B. Second, the 4DCT and CBCT images represent only a short time of tumour displacement and cannot represent the real-time displacement during radiotherapy. Future work may focus on prospective clinical trials and measure radiotherapy target accuracy and toxicity based on the IGTV margin determined in this study.