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Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer.
Hoeppner, Jens M.D.; Brunner, Thomas M.D.; Schmoor, Claudia Ph.D.; Bronsert, Peter M.D.; Kulemann, Birte M.D.; Claus, Rainer M.D.; Utzolino, Stefan M.D.; Izbicki, Jakob Robert M.D.; Gockel, Ines M.D.; Gerdes, Berthold M.D.; Ghadimi, Michael M.D.; Reichert, Benedikt M.D.; Lock, Johan F. M.D.; Bruns, Christiane M.D.; Reitsamer, Ernst M.D.; Schmeding, Maximillian M.D.; Benedix, Frank M.D.; Keck, Tobias M.D.; Folprecht, Gunnar M.D.; Thuss-Patience, Peter M.D.; Neumann, Ulf Peter M.D.; Pascher, Andreas M.D.; Imhof, Detlef M.D.; Daum, Severin M.D.; Strieder, Tanja M.D.; Krautz, Christian M.D.; Zimmermann, Simone; Werner, Jens M.D.; Mahlberg, Rolf M.D.; Illerhaus, Gerald M.D.; Grimminger, Peter M.D.; Lordick, Florian M.D.
[Article] New England Journal of Medicine. 16(1):323-335, January 2025.

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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. (Funded by the German Research Foundation; ESOPEC ClinicalTrials.gov number, NCT02509286.)

Perioperative Chemotherapy in Esophageal Cancer: A large randomized trial involving patients with resectable esophageal cancer showed that perioperative chemotherapy improved overall survival as compared with preoperative chemoradiotherapy.