FLOT-regimen Chemotherapy and Transthoracic en bloc Resection for Esophageal and Junctional Adenocarcinoma.

Abstract

BACKGROUND AND AIMS\nThe FLOT4-AIO trial established the FLOT regimen (Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel) as a compelling option for gastric, junctional and esophageal adenocarcinoma. Data on FLOT with en-bloc transthoracic esophagectomy (TTE) are limited. This study explored operative complications, tolerance, toxicity, physiological impact, and oncologic outcomes.\n\n\nSTUDY DESIGN\nAn observational cohort study on consecutive patients at 3 tertiary centers undergoing FLOT and TTE. Toxicity, operative complications (per ECCG definitions), tumor regression grade (TRG), recurrences and survival were documented, as well as pre- and post FLOT assessment of sarcopenia and pulmonary physiology.\n\n\nRESULTS\n175 patients (cT2-4a, Nany) commenced treatment, 84% male, median age 65, 94% cT3/T4a, 73% cN+. 89% completed 4 preoperative cycles, and 35% all cycles. Grade 3/4 toxicities included neutropenia (12%), diarrhoea (13%), and infection (15%). Sarcopenia increased from 18% to 37% (p = 0.020), and diffusion capacity (DLCO) decreased by 8% (-34%+25%; p < 0.010). On pathology, ypT3/4 was 59%, and ypN+54%, with 10% TRG 1, 14% TRG 2, and 76% TRG3-5, and R0 95%. 161 underwent TTE, with an in-hospital mortality of 0.6%, 24%-pneumonia, 11%-anastomotic leak, and Clavien Dindo ≥III in 27%. At a median follow up of 12\u200amonths (1-85), 33 relapsed, 8 (5%) locally, and 3yr survival was 60%.\n\n\nCONCLUSION\nFLOT and en bloc TTE was safe, with no discernible impact on operative complications, with 24% having a major pathologic response. Caveats include a limited pathologic response in the majority, and negative impact on muscle mass and lung physiology, and low use of adjuvant cycles. These data may provide a real-world benchmark for this complex care pathway.