德国比勒菲尔德大学Jens Hoeppner团队比较了食管癌围手术期化疗或术前放化疗对患者预后的影响。2025年1月23日出版的《新英格兰医学杂志》发表了这项成果。

可切除局部晚期食管腺癌的最佳多模式策略尚不清楚。一个重要的问题是围手术期化疗是否优于术前放化疗。

在这项临床3期、多中心、随机试验中，研究组以1：1的比例将可切除食管腺癌患者分配给FLOT（氟尿嘧啶、甲酰四氢叶酸、奥沙利铂和多西他赛）加手术的围手术期化疗组或术前放化疗（41.4 Gy剂量的放疗，卡铂和紫杉醇）加手术组。合格标准包括临床分期为cT1 cN+、cT2–4a cN+或cT2–4a-cN0疾病的原发性肿瘤，其中T表示肿瘤的大小和程度（数字越大表示肿瘤越晚期），N表示癌症是否存在（N+）或不存在（N0）扩散到淋巴结，没有转移扩散的证据。主要终点是总生存期。

2016年2月到2020年4月，研究组将221名患者分配到FLOT组，217名患者分配给术前放化疗组。中位随访时间为55个月，FLOT组3年总生存率为57.4%（95%置信区间[CI]，50.1至64.0），术前放化疗组为50.7%（95%CI，43.5至57.5）（死亡风险比为0.70；95%CI为0.53至0.92；P=0.01）。FLOT组3年无进展生存率为51.6%（95%CI，44.3至58.4），术前放化疗组为35.0%（95%CI28.4至41.7）（疾病进展或死亡的风险比为0.66；95%CI为0.51至0.85）。

在开始指定治疗的患者中，FLOT组207名患者中有120名（58.0%）出现了3级或更高的不良事件，术前放化疗组196名患者中也有98名（50.0%）出现了不良事件。在FLOT组的207名患者中，有98名（47.3%）出现了严重不良事件，在术前放化疗组的196名患者中有82名（41.8%）。术后90天，FLOT组和术前放化疗组的死亡率分别为3.1%和5.6%。

研究结果表明，与术前放化疗相比，围手术期使用FLOT的化疗提高了可切除食管腺癌患者的生存率。

附：英文原文

Title: Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer

Author: Jens Hoeppner, Thomas Brunner, Claudia Schmoor, Peter Bronsert, Birte Kulemann, Rainer Claus, Stefan Utzolino, Jakob Robert Izbicki, Ines Gockel, Berthold Gerdes, Michael Ghadimi, Benedikt Reichert, Johan F. Lock, Christiane Bruns, Ernst Reitsamer, Maximillian Schmeding, Frank Benedix, Tobias Keck, Gunnar Folprecht, Peter Thuss-Patience, Ulf Peter Neumann, Andreas Pascher, Detlef Imhof, Severin Daum, Tanja Strieder, Christian Krautz, Simone Zimmermann, Jens Werner, Rolf Mahlberg, Gerald Illerhaus, Peter Grimminger, Florian Lordick

Issue&Volume: 2025-01-23

Abstract:

BACKGROUND

The best multimodal approach for resectable locally advanced esophageal adenocarcinoma is unclear. An important question is whether perioperative chemotherapy is preferable to preoperative chemoradiotherapy.

METHODS

In this phase 3, multicenter, randomized trial, we assigned in a 1:1 ratio patients with resectable esophageal adenocarcinoma to receive perioperative chemotherapy with FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) plus surgery or preoperative chemoradiotherapy (radiotherapy at a dose of 41.4 Gy and carboplatin and paclitaxel) plus surgery. Eligibility criteria included a primary tumor with a clinical stage of cT1 cN+, cT2–4a cN+, or cT2–4a cN0 disease, in which T indicates the size and extent of the tumor (higher numbers indicate a more advanced tumor), and N indicates the presence (N+) or absence (N0) of cancer spread to the lymph nodes, without evidence of metastatic spread. The primary end point was overall survival.

RESULTS

From February 2016 through April 2020, we assigned 221 patients to the FLOT group and 217 patients to the preoperative-chemoradiotherapy group. With a median follow-up of 55 months, overall survival at 3 years was 57.4% (95% confidence interval [CI], 50.1 to 64.0) in the FLOT group and 50.7% (95% CI, 43.5 to 57.5) in the preoperative-chemoradiotherapy group (hazard ratio for death, 0.70; 95% CI, 0.53 to 0.92; P=0.01). Progression-free survival at 3 years was 51.6% (95% CI, 44.3 to 58.4) in the FLOT group and 35.0% (95% CI, 28.4 to 41.7) in the preoperative-chemoradiotherapy group (hazard ratio for disease progression or death, 0.66; 95% CI, 0.51 to 0.85). Among the patients who started the assigned treatment, grade 3 or higher adverse events were observed in 120 of 207 patients (58.0%) in the FLOT group and in 98 of 196 patients (50.0%) in the preoperative-chemoradiotherapy group. Serious adverse events were observed in 98 of 207 patients (47.3%) in the FLOT group and in 82 of 196 patients (41.8%) in the preoperative-chemoradiotherapy group. Mortality at 90 days after surgery was 3.1% in the FLOT group and 5.6% in the preoperative-chemoradiotherapy group.

CONCLUSIONS

Perioperative chemotherapy with FLOT led to improved survival among patients with resectable esophageal adenocarcinoma as compared with preoperative chemoradiotherapy.

DOI: NJ202501233920406

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2409408