Endosonographic radial tumor thickness after neoadjuvant chemoradiation therapy to predict response and survival in patients with locally advanced esophageal cancer: a prospective multicenter phase ll study by the Swiss Group for Clinical Cancer Research (SAKK 75/02)

Background EUS response assessment in patients with locally advanced esophageal cancer undergoing neoadjuvant chemoradiation therapy (CRT) is limited by disintegration of the involved anatomic structures. Objective Predictive and prognostic values of a prospectively defined maximum tumor thickness (MTT). Design Prospective open-label phase ll study (SAKK 75/02). Setting Multicenter, nationwide. Patients Of 66 patients with primary CRT, 56 underwent en bloc esophagectomy. Interventions EUS-measured MTT before and 2-5 weeks after CRT (yMTT). Main Outcome Measurements Cutoffs: (1) absolute thickness (yMTT) after CRT ≤6 mm; (2) relative reduction compared with baseline (ratio yMTT/MTT) ≤50%. Correlation between EUS measurements and histopathologic tumor regression grade (TRG) and overall survival (OS). Results Sixteen of 56 patients were not included for EUS evaluation (10 severe stenosis, 5 MTT not measured, 1 intolerance to second EUS). Characteristics (n = 40) were as follow: median age, 60 years; squamous cell carcinoma, 42%; and adenocarcinoma (AC), 58%. Initial stage was: 10 T2N1, 3 T3N0, 26 T3N1, 1 T3Nx; 14 of 23 AC Siewert type 1. Wilcoxon rank sum test showed significant correlation of TRG1 with yMTT ≤6 mm ( P = .008) and yMTT/MTT ≤50% ( P = .003). The effect of yMTT on TRG1 was significant ( P = .0193; odds ratio, 0.687 [95% CI, 0.502-0.941]). The predefined cutoff of ≤6 mm for yMTT was predictive for TRG1 ( P = .0037; Fisher exact test). After a median follow-up of 28.6 months, there was a clear trend for benefit in OS with yMTT ≤6 mm and yMTT/MTT ≤50%. Limitations Small sample size. Conclusion In a multicenter setting, MTT measured by EUS after CRT was highly predictive for response and showed a clear trend for predicting survival. (Clinical trial registration number: NCT00072033.)