TY - JOUR
T1 - Pathological response guides adjuvant 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy in surgically resected gastro-oesophageal cancer (SPACE-FLOT)
T2 - international cohort study
AU - SPACE-FLOT Investigators
AU - Liu, David S.
AU - Lee, Margaret M.
AU - Hall, Katheryn
AU - Watson, David I.
AU - Ferri, Lorenzo
AU - So, Jimmy
AU - Donohoe, Claire L.
AU - Michael, Michael
AU - Tebbutt, Niall C.
AU - Wong, Darren J.
AU - Duong, Cuong P.
AU - Bright, Tim
AU - Aly, Ahmad
AU - Gill, Sonia
AU - Cheng, Chao
AU - Goh, Su Kah
AU - Read, Matthew
AU - Tan, James
AU - Stevens, Sean
AU - Wong, Enoch
AU - Ooi, Geraldine
AU - Lam, Yick Ho
AU - Lee, Eunice
AU - Williams, David
AU - Jackett, Louise
AU - Chan, Kevin
AU - Smith, Garett
AU - Chan, David L.
AU - Merrett, Neil
AU - Gananadha, Sivakumar
AU - Kanhere, Harsh
AU - Kennedy, Lauren
AU - Smithers, Mark
AU - Thomas, Janine
AU - Bozin, Michael
AU - Chong, Lynn
AU - Mori, Krinal
AU - Johnson, Mary Ann
AU - Martin, Sarah A.
AU - Usatoff, Val
AU - Jacobs, Rod
AU - Al-Habbal, Yahya
AU - Liew, Chon Hann
AU - Huynh, Fredrick
AU - Bohmer, Robert
AU - Pande, Girish
AU - Daruwalla, Jurstine
AU - Ballal, Mo
AU - Lee, Deanna
AU - Ranjan, Rukshan
N1 - Publisher Copyright:
© 2025 The Author(s). Published by Oxford University Press on behalf of BJS Foundation Ltd. All rights reserved.
PY - 2025/4/1
Y1 - 2025/4/1
N2 - Background: Many patients with locally advanced gastro-oesophageal cancers are unable to complete adjuvant 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy, raising questions about its therapeutic utility. The aim of this study was to examine whether pathological response to neoadjuvant FLOT can guide its adjuvant use. Methods: Patients with non-metastatic gastro-oesophageal adenocarcinoma who received neoadjuvant FLOT and underwent surgery from 1 January 2017 to 1 January 2022 from 43 hospitals across 12 countries were analysed. Pathological response was assessed using tumour regression grading systems, trichotomized into minimal responders (MR; worst category), complete responders (CR; pCR), and partial responders (PR; between MR and CR). Survival outcomes of patients who did and did not receive adjuvant FLOT were compared using Kaplan-Meier, Cox regression, propensity score matched, and sensitivity analysis. Results: A total of 1887 patients (459 MR, 221 CR, and 1207 PR) were evaluated. The median follow-up was 25.5 (interquartile range 15.0-39.1) months. In the MR group, there was no difference in disease-free survival (DFS; HR 1.03 (95% c.i. 0.78 to 1.36), P = 0.836) between those who did and did not receive adjuvant FLOT. Whilst there was a difference in non-adjusted OS, this became statistically non-significant after adjusting for baseline characteristics (HR 0.96 (95% c.i. 0.70 to 1.30), P = 0.801). In the CR group, there was no difference in DFS (HR 0.88 (95% c.i. 0.41 to 1.85), P = 0.724) or OS (HR 0.69 (95% c.i. 0.31 to 1.54), P = 0.343) between those who did and did not receive adjuvant FLOT. In the PR group, adjuvant FLOT conferred a significant DFS (HR 0.68 (95% c.i. 0.55 to 0.86), P < 0.001) and OS (HR 0.55 (95% c.i. 0.44 to 0.69), P < 0.001) benefit. Conclusion: Pathological response to neoadjuvant FLOT may guide the use of adjuvant FLOT, enabling personalized approaches to treatment.
AB - Background: Many patients with locally advanced gastro-oesophageal cancers are unable to complete adjuvant 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy, raising questions about its therapeutic utility. The aim of this study was to examine whether pathological response to neoadjuvant FLOT can guide its adjuvant use. Methods: Patients with non-metastatic gastro-oesophageal adenocarcinoma who received neoadjuvant FLOT and underwent surgery from 1 January 2017 to 1 January 2022 from 43 hospitals across 12 countries were analysed. Pathological response was assessed using tumour regression grading systems, trichotomized into minimal responders (MR; worst category), complete responders (CR; pCR), and partial responders (PR; between MR and CR). Survival outcomes of patients who did and did not receive adjuvant FLOT were compared using Kaplan-Meier, Cox regression, propensity score matched, and sensitivity analysis. Results: A total of 1887 patients (459 MR, 221 CR, and 1207 PR) were evaluated. The median follow-up was 25.5 (interquartile range 15.0-39.1) months. In the MR group, there was no difference in disease-free survival (DFS; HR 1.03 (95% c.i. 0.78 to 1.36), P = 0.836) between those who did and did not receive adjuvant FLOT. Whilst there was a difference in non-adjusted OS, this became statistically non-significant after adjusting for baseline characteristics (HR 0.96 (95% c.i. 0.70 to 1.30), P = 0.801). In the CR group, there was no difference in DFS (HR 0.88 (95% c.i. 0.41 to 1.85), P = 0.724) or OS (HR 0.69 (95% c.i. 0.31 to 1.54), P = 0.343) between those who did and did not receive adjuvant FLOT. In the PR group, adjuvant FLOT conferred a significant DFS (HR 0.68 (95% c.i. 0.55 to 0.86), P < 0.001) and OS (HR 0.55 (95% c.i. 0.44 to 0.69), P < 0.001) benefit. Conclusion: Pathological response to neoadjuvant FLOT may guide the use of adjuvant FLOT, enabling personalized approaches to treatment.
UR - http://www.scopus.com/inward/record.url?scp=105002054610&partnerID=8YFLogxK
U2 - 10.1093/bjs/znaf056
DO - 10.1093/bjs/znaf056
M3 - Article
AN - SCOPUS:105002054610
SN - 0007-1323
VL - 112
JO - British Journal of Surgery
JF - British Journal of Surgery
IS - 4
M1 - znaf056
ER -
