Total Neoadjuvant Treatment for Esophageal Adenocarcinoma With Oligometastases: <scp>TNT</scp> ‐ <scp>OES</scp> ‐1 Trial

Chemotherapy (FLOT) and chemoradiotherapy (CROSS) are both effective as neoadjuvant regimens for esophageal/junctional cancer. Total Neoadjuvant Therapy (TNT) aims to increase efficacy by combining chemotherapy with chemoradiotherapy. This study aimed to evaluate the feasibility and safety of TNT FLOT-CROSS. Patients with histologically proven esophageal/junctional adenocarcinoma with oligometastases (maximum four lesions in maximum two organs) were included. Treatment consisted of four cycles of FLOT followed by response evaluation (CT-scan). Patients without disease progression proceeded to CROSS, followed by response evaluation (CT-scan, endoscopy with biopsies and endoscopic ultrasonography with fine-needle aspiration on indication). Primary endpoint was the safety and tolerability of TNT FLOT-CROSS. Secondary endpoints included progression-free survival (PFS), disease control rate (DCR), quality of life (QoL) using QLQ-C30 and QLQ-OG25, toxicity and the proportion of patients proceeding to local therapy. Twenty patients were included of whom 16 (80%) had a single metastatic lesion. Median follow-up was 47.9 months (95% CI 32.8-63.1). Fifteen patients (75%) completed TNT FLOT-CROSS. FLOT came with manageable, expected toxicity, and all patients without progression were able to start and complete CROSS. No grade 3-5 toxicities occurred during CROSS. After TNT FLOT-CROSS, two patients underwent surgery. The 1- and 2-year PFS were 40% and 13%, respectively. Three months after TNT FLOT-CROSS completion, DCR was 55%. Dysphagia scores significantly decreased over time, while fatigue significantly increased. Sequencing TNT FLOT-CROSS in patients with oligometastatic esophageal adenocarcinoma is feasible and comes with manageable toxicity and promising efficacy, with a 1-year progression free survival of 40%. Trial Registration: Dutch trial register, NL9269.