Department of Surgery, Trinity St. James's Cancer Institute, Dublin, Ireland.
Division of Thoracic and Upper Gastrointestinal Surgery, Montreal General Hospital - McGill University Health Centre, Montreal, Quebec, Canada.
Ann Surg. 2021 Nov 1;274(5):814-820. doi: 10.1097/SLA.0000000000005097.
The FLOT4-AIO trial established the FLOT regimen 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.
An 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.
175 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 months (1-85), 33 relapsed, 8 (5%) locally, and 3yr survival was 60%.
FLOT 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.
FLOT4-AIO 试验确立了 FLOT 方案作为胃、交界性和食管腺癌的一种有吸引力的选择。关于联合胸内食管切除术（TTE）的 FLOT 数据有限。本研究探讨了手术并发症、耐受性、毒性、生理影响和肿瘤学结果。
这是一项在 3 家三级中心进行的连续患者的观察性队列研究，他们接受了 FLOT 和 TTE 治疗。记录了毒性、手术并发症（按 ECCG 定义）、肿瘤退缩分级（TRG）、复发和生存情况，以及在 FLOT 前后评估肌肉减少症和肺生理学。
175 名患者（cT2-4a，Nany）开始接受治疗，84%为男性，中位年龄为 65 岁，94%为 cT3/T4a，73%为 cN+。89%的患者完成了 4 个术前周期，35%的患者完成了所有周期。3/4 级毒性包括中性粒细胞减少症（12%）、腹泻（13%）和感染（15%）。肌肉减少症从 18%增加到 37%（P = 0.020），弥散能力（DLCO）下降了 8%（-34%+25%；P < 0.010）。病理上，ypT3/4 为 59%，ypN+为 54%，TRG1 为 10%，TRG2 为 14%，TRG3-5 为 76%，R0 为 95%。161 例行 TTE，院内死亡率为 0.6%，24%为肺炎，11%为吻合口漏，Clavien Dindo ≥III 级为 27%。在中位随访 12 个月（1-85 个月）时，33 例患者复发，8 例（5%）为局部复发，3 年生存率为 60%。
FLOT 和联合 TTE 是安全的，对手术并发症没有明显影响，24%的患者有明显的病理反应。需要注意的是，大多数患者的病理反应有限，对肌肉质量和肺生理学有负面影响，且辅助周期的应用率较低。这些数据可能为这一复杂的治疗途径提供了一个真实世界的基准。
