Hoeppner Jens, Brunner Thomas, Schmoor Claudia, Bronsert Peter, Kulemann Birte, Claus Rainer, Utzolino Stefan, Izbicki Jakob Robert, Gockel Ines, Gerdes Berthold, Ghadimi Michael, Reichert Benedikt, Lock Johan F, Bruns Christiane, Reitsamer Ernst, Schmeding Maximillian, Benedix Frank, Keck Tobias, Folprecht Gunnar, Thuss-Patience Peter, Neumann Ulf Peter, Pascher Andreas, Imhof Detlef, Daum Severin, Strieder Tanja, Krautz Christian, Zimmermann Simone, Werner Jens, Mahlberg Rolf, Illerhaus Gerald, Grimminger Peter, Lordick Florian
From Bielefeld University, Medical School and University Medical Center Ostwestfalen-Lippe, Campus Hospital Lippe, Detmold, Germany (J.H.); the Department of Radiation Oncology, Medical University of Graz, Graz, Austria (T.B.); the Clinical Trials Unit, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany (C.S.); the Institute of Surgical Pathology, University Medical Center Freiburg, Germany (P.B.); the Department of Surgery, University Medical Center Schleswig-Holstein-Campus Lübeck, Lübeck, Germany (B.K., T.K.); Comprehensive Cancer Center Augsburg, Faculty of Medicine, University of Augsburg, Augsburg, Germany (R.C.); the Department of General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany (S.U.); the Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (J.R.I.); the Department of Gastrointestinal Surgery, IRCCS San Raffaele Scientific Institute and San Raffaele Vita-Salute University, Milan (I.G.); the Department of General, Visceral, Thoracic, and Endocrine Surgery, Johannes Wesling University Hospital Minden, Ruhr University Bochum, Minden, Germany (B.G.); the Department of General, Visceral, and Pediatric Surgery, University Medical Center Göttingen, Göttingen, Germany (M.G.); the Department of General, Visceral, Thoracic, Transplantation, and Pediatric Surgery, University Medical Center Schleswig-Holstein-Campus Kiel, Kiel, Germany (B.R.); the Department of General, Visceral, Transplantation, Vascular, and Pediatric Surgery, University Hospital, University of Würzburg, Würzburg, Germany (J.F.L.); the Department of General, Visceral, Cancer, and Transplantation Surgery, University Hospital of Cologne, Cologne, Germany (C.B.); the Department of Hematology and Oncology, Sana Klinikum Offenbach, Offenbach am Main, Germany (E.R.); the Department of Surgery, Klinikum Dortmund, Klinikum der Universität Witten-Herdecke, Dortmund, Germany (M.S.); the Department of Surgery, University Hospital Magdeburg, Magdeburg, Germany (F.B.); the Department of Medicine I, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany (G.F.); the Department of Hematology, Oncology, and Cancer Immunology, Charité-University Medicine Berlin, Campus Virchow-Klinikum, Berlin (P.T.-P.); the Department of General, Visceral, Cancer, and Transplantation Surgery, University Hospital Essen, Essen, Germany (U.P.N.); the Department of General, Visceral, and Transplantation Surgery, University Hospital Muenster, Muenster, Germany (A.P.); the Department of Radiotherapy and Oncology, Goethe University Frankfurt, University Hospital, Frankfurt, Germany (D.I.); the Division of Gastroenterology, Rheumatology, and Infectology, Department of Medicine, Charité-Universitätsmedizin Berlin, Berlin (S.D.); the Department of Surgery, Robert Bosch Hospital, Stuttgart, Germany (T.S.); the Department of Surgery, University Medical Center Erlangen, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany (C.K.); the Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany (S.Z.); the Department of General, Visceral, and Transplant Surgery, Ludwig Maximilian University Hospital, Munich, Germany (J.W.); the Department of Internal Medicine I, Klinikum Mutterhaus der Borromaerinnen, Trier, Germany (R.M.); the Departments of Hematology, Oncology, and Palliative Care, Klinikum Stuttgart, Stuttgart, Germany (G.I.); the Department of General, Visceral, and Transplant Surgery, University Medical Center Mainz, Mainz, Germany (P.G.); and the Department of Medicine II, University Cancer Center Leipzig, Cancer Center Central Germany, University Medical Center Leipzig, Leipzig, Germany (F.L.).
N Engl J Med. 2025 Jan 23;392(4):323-335. doi: 10.1056/NEJMoa2409408.
The best multimodal approach for resectable locally advanced esophageal adenocarcinoma is unclear. An important question is whether perioperative chemotherapy is preferable to preoperative chemoradiotherapy.
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.
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.
Perioperative chemotherapy with FLOT led to improved survival among patients with resectable esophageal adenocarcinoma as compared with preoperative chemoradiotherapy. (Funded by the German Research Foundation; ESOPEC ClinicalTrials.gov number, NCT02509286.).
对于可切除的局部晚期食管腺癌，最佳的多模式治疗方法尚不清楚。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3期、多中心、随机试验中，我们将可切除食管腺癌患者按1:1的比例分配，分别接受氟尿嘧啶、亚叶酸钙、奥沙利铂和多西他赛（FLOT）方案的围手术期化疗加手术，或术前放化疗（41.4 Gy放疗加卡铂和紫杉醇）加手术。入选标准包括临床分期为cT1 cN +、cT2 - 4a cN +或cT2 - 4a cN0的原发性肿瘤，其中T表示肿瘤的大小和范围（数字越大表示肿瘤越晚期），N表示癌症是否扩散至淋巴结（N +表示有扩散，N0表示无扩散），且无远处转移证据。主要终点为总生存期。
从2016年2月至2020年4月，我们将221例患者分配至FLOT组，217例患者分配至术前放化疗组。中位随访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，0.70；95% CI，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% CI，28.4%至41.7%）（疾病进展或死亡风险比，0.66；95% CI，0.51至0.85）。在开始指定治疗的患者中，FLOT组207例患者中有120例（58.0%）发生3级或更高等级不良事件，术前放化疗组196例患者中有98例（50.0%）发生。FLOT组207例患者中有98例（47.3%）发生严重不良事件，术前放化疗组196例患者中有82例（41.8%）发生。FLOT组术后90天死亡率为3.1%，术前放化疗组为5.6%。
与术前放化疗相比，FLOT方案的围手术期化疗可提高可切除食管腺癌患者的生存率。（由德国研究基金会资助；ESOPEC临床试验注册号，NCT02509286）
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