Donlon Noel E, Moran Brendan, Kamilli Anitha, Davern Maria, Sheppard Andrew, King Sinead, Donohoe Claire L, Lowery Maeve, Cunningham Moya, Ravi Narayanasamy, Mueller Carmen, Cools-Lartigue Jonathan, Ferri Lorenzo, Reynolds John V
Trinity St. James's Cancer Institute, Dublin, Ireland.
Division of Thoracic Surgery, Montreal General Hospital, Montreal, QC, Canada.
Ann Surg. 2022 Nov 1;276(5):792-798. doi: 10.1097/SLA.0000000000005617. Epub 2022 Jul 25.
The FLOT protocol and the CROSS trimodality regimen represent current standards in the management of locally advanced esophageal adenocarcinoma. In the absence of published Randomised Controlled Trial data, this propensity-matched comparison evaluated tolerance, toxicity, impact on sarcopenia and pulmonary physiology, operative complications, and oncologic metrics.
Two hundred and twenty-two patients, 111 in each arm, were included from 2 high-volume centers. Computed tomography-measured sarcopenia, and pulmonary function (forced expiratory volume in first second/forced vital capacity/diffusion capacity for carbon monoxide) were compared pretherapy and posttherapy. Operative complications were defined as per the Esophageal Complications Consensus Group (ECCG) criteria, and severity per Clavien-Dindo. Tumor regression grade and R status were measured, and survival estimated per Kaplan-Meier.
A total of 83% were male, cT3/cN+ was 92%/68% for FLOT, and 86%/60% for CROSS. The full prescribed regimen was tolerated in 40% of FLOT patients versus 92% for CROSS. Sarcopenia increased from 16% to 33% for FLOT, and 14% to 30% in CROSS ( P <0.01 between arms). Median decrease in diffusion capacity for carbon monoxide was -8.25% (-34 to 25) for FLOT, compared with -13.8%(-38 to 29), for CROSS ( P =0.01 between arms). Major pathologic response was 27% versus 44% for FLOT and CROSS, respectively ( P =0.03). In-hospital mortality, respectively, was 1% versus 2% ( P =0.9), and Clavien Dindo >III 22% versus 27% ( P =0.59), however, respiratory failure was increased by CROSS, at 13% versus 3% ( P <0.001). Three-year survival was similar at 63% (FLOT) and 60% (CROSS) ( P =0.42).
Both CROSS and FLOT resulted in equivalent survival. Operative outcomes were similar, however, the CROSS regimen increased postoperative respiratory failure and atrial fibrillation. Less than half of patients received the prescribed FLOT regimen, although toxicity rates were acceptable. These data support clinical equipoise, caution, however, may be advised with CROSS in patients with greatest respiratory risk.
FLOT方案和CROSS三联疗法是目前局部晚期食管腺癌治疗的标准方案。在缺乏已发表的随机对照试验数据的情况下，这项倾向匹配比较评估了耐受性、毒性、对肌肉减少症和肺生理学的影响、手术并发症和肿瘤学指标。
从2个高容量中心纳入222例患者，每组111例。在治疗前和治疗后比较计算机断层扫描测量的肌肉减少症和肺功能（第1秒用力呼气量/用力肺活量/一氧化碳弥散量）。手术并发症根据食管并发症共识组（ECCG）标准定义，严重程度根据Clavien-Dindo分级。测量肿瘤退缩分级和R状态，并根据Kaplan-Meier法估计生存率。
共83%为男性，FLOT组cT3/cN+分别为92%/68%，CROSS组为86%/60%。40%的FLOT患者耐受了完整的规定方案，而CROSS组为92%。FLOT组肌肉减少症从16%增加到33%，CROSS组从14%增加到30%（两组间P<0.01）。FLOT组一氧化碳弥散量的中位数下降为-8.25%（-34至25），而CROSS组为-13.8%（-38至29）（两组间P=0.01）。主要病理反应分别为FLOT组27%和CROSS组44%（P=0.03）。住院死亡率分别为1%和2%（P=0.9），Clavien Dindo>III级分别为22%和27%（P=0.59），然而，CROSS组呼吸衰竭增加，分别为13%和3%（P<0.001）。三年生存率相似，FLOT组为63%，CROSS组为60%（P=0.42）。
CROSS和FLOT方案的生存率相当。手术结果相似，然而，CROSS方案增加了术后呼吸衰竭和心房颤动的发生率。不到一半的患者接受了规定的FLOT方案，尽管毒性率是可接受的。这些数据支持临床 equipoise，然而，对于呼吸风险最高的患者，使用CROSS方案时可能需要谨慎。
