Background: 

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.

Methods: 

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.

Results: 

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).

Conclusions: 

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.

中文翻译：

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食管和食管胃交界处腺癌的 CROSS 与 FLOT 方案：倾向匹配比较

背景： 

FLOT 方案和 CROSS 三联方案代表了目前治疗局部晚期食管腺癌的标准。在没有公布的随机对照试验数据的情况下，这种倾向匹配比较评估了耐受性、毒性、对肌肉减少症和肺部生理学的影响、手术并发症和肿瘤学指标。

方法： 

222 名患者，每组 111 名，来自 2 个高容量中心。对治疗前和治疗后的计算机断层扫描测量的肌肉减少和肺功能（第一秒用力呼气量/用力肺活量/一氧化碳扩散能力）进行比较。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 定义。测量肿瘤消退等级和 R 状态，并根据 Kaplan-Meier 估计生存率。

结果： 

总共 83% 为男性，FLOT 的 cT3/cN+ 为 92%/68%，CROSS 为 86%/60%。40% 的 FLOT 患者耐受完整的处方方案，而 CROSS 患者为 92%。FLOT 的肌肉减少症从 16% 增加到 33%，CROSS 的肌肉减少症从 14% 增加到 30%（两组之间P <0.01）。FLOT 的一氧化碳扩散能力下降中位数为 -8.25%（-34 至 25），而 CROSS 为 -13.8%（-38 至 29）（臂间P = 0.01）。FLOT 和 CROSS 的主要病理反应分别为 27% 和 44%（P = 0.03）。住院死亡率分别为 1% 和 2%（P = 0.9），Clavien Dindo > III 22% 和 27%（P = 0.59），但是 CROSS 增加了呼吸衰竭，分别为 13% 和 3% (磷<0.001)。三年生存率相似，分别为 63% (FLOT) 和 60% (CROSS) ( P = 0.42)。

结论： 

CROSS 和 FLOT 的存活率相当。手术结果相似，但 CROSS 方案增加了术后呼吸衰竭和心房颤动。不到一半的患者接受了规定的 FLOT 方案，尽管毒性率是可以接受的。这些数据支持临床平衡，然而，对于呼吸系统风险最大的患者，可能建议谨慎使用 CROSS。