Role of clip markers placed by endoscopic ultrasonography in contouring gross tumor volume for thoracic esophageal squamous cell carcinoma: one prospective study

Background: We aimed to analyze the value of metal clip markers guided and placed by endoscopic ultrasonography (EUS) in the delineation of gross tumor volume (GTV) for thoracic esophageal squamous cell carcinoma. Methods: From September 2016 to September 2018, patients with thoracic esophageal squamous cell carcinoma in Tianjin Medical University Cancer Institute and Hospital were recruited in the prospective trial, NCT02959385. They underwent titanium clips placement on tumor superior and inferior boundaries under EUS by a single expert endosonographer before radiotherapy computed tomography (CT) simulation. According to the clip markers, the reference GTVs were contoured by one experienced radiation oncologist. With the help of the Eclipse treatment planning system, clip markers on CT were concealed. Afterward, two other radiation oncologists with expertise in esophageal cancer delineated GTVs, defined as conventional GTVs, based on endoscopy and barium radiography findings. The two GTVs were compared and analyzed. Subgroup analysis was conducted in different T stage [early (T1 + T2) vs. advanced (T3 + T4)], focus location (upper vs. middle vs. lower segment), and tumor length (<5 vs. >5 cm) groups. Results: The trial recruited 55 patients with 60 thoracic esophageal cancer foci. A total of 111 titanium clips were guided and implanted by EUS. Before CT simulation, two titanium clips at two foci fell off. After the procedure, no case of intolerable esophageal pain, hemorrhage, or perforation occurred. Compared to reference GTVs, discrepancies of conventional GTVs superior borders were 0.91 +/- 0.82 cm (P<0.001), while differences of inferior borders were 0.74 +/- 0.63 cm (P<0.001). On the contrary, conventional GTVs lengths were not significantly different from reference GTVs with discrepancies 0.08 +/- 1.30 cm (P=0.64). Regardless of T stage, tumor location, and tumor length, conventional GTVs superior and inferior borders were significantly different from reference GTVs, while GTVs lengths differed insignificantly. Conclusions: This study confirmed that EUS-placed titanium clips could correct contouring of GTVs in thoracic esophageal cancer in different T stages, tumor locations, and lengths.