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
AU - Maccormick, Andrew D.
AU - Wilkins, James
AU - Pattison, Sharon
AU - Evennett, Nicholas
AU - Robertson, Jason
AU - Pang, Mark
AU - Gordon, Alexandra
AU - Bann, Simon
AU - Lim, Yu Kai
AU - Samarasam, Inian
AU - Gurunathan, Ramesh
AU - Yeung, Jonathan
AU - Allison, Frances
AU - Siblini, Aya
AU - Griffiths, Ewen A.
AU - Phillips, Alexander W.
AU - Prasad, Pooja
AU - Markar, Sheraz
AU - Chidambaram, Swathikan
AU - Chan, David
AU - Murphy, Thomas
AU - Reynolds, John
AU - Nilsson, Magnus
AU - Klevebro, Fredrik
AU - Piessen, Guillaume
AU - Lerooy, Justine
AU - Wijnhoven, Bas
AU - Van Der Zijden, Charlène
AU - Van Hillegersberg, Richard
AU - Triemstra, Lianne
AU - Ruurda, Jelle
AU - Van Berge Henegouwen, Mark Ivo
AU - Gisbertz, Suzanne Sarah
AU - Lombardi, Pietro Maria
AU - Edmondson, Aleksandra
AU - Wei, Joe Q.
AU - Lorenzo, Aldenb
AU - Alhayo, Sam
AU - Narendra, Aaditya
AU - Rahim, Aadil
AU - Ho, Rocita
AU - Granger, Jeremy
AU - Tran, Steven
AU - Koullouros, Michalis
AU - Nguyen, Alain
AU - Mcveay, Christina
AU - Gan, Siang Wei
AU - Hopping, Eve
AU - Thomson, Iain
AU - Barbour, Andrew
AU - Gotley, David
AU - Frankel, Adam
AU - Patel, Riteshkumar
AU - Chew, Shaun Jin Hui
AU - Lah, Kevin
AU - Barnett, Stephen A.
AU - Muralidharan, Vijayaragavan
AU - Phillips, Samantha
AU - Jamel, Wael
AU - Ko, Bung Kook
AU - Joglekar, Shantanu
AU - Rajagopalan, Ashray
AU - Jaya, Joseph
AU - Chung, Yat Cheung
AU - Peeroo, Saania
AU - Bak, Marek
AU - Tiong, Jonathan
AU - Zhou, Zhei
AU - Crowe, Amy
AU - Newbold, Ryan
AU - Trainor, Bethanie
AU - Pac Soo, Mei Lynn
AU - Khandelwal, Vaibhavee
AU - Eikelboom, Nicholas
AU - Kim, Kyungchul
AU - Moran, Emily
AU - Hammerschlag, Joshua
AU - Desmond, Brendan
AU - D'souza, Joel
AU - Lu, Jacky
AU - Mclay-Barnes, Rachel
AU - Gower, Alexandra
AU - Choi, Jenny
AU - Wood, Douglas
AU - Whytock, Kate
AU - Surendran, Suraj
AU - Paul, Negine
AU - Khan H, Feroz
AU - Chia, Daryl K.A.
AU - Leong, Eugene K.F.
AU - Ijner, Tvisha
AU - Lin, Yi Tzu Linda
AU - Liew, Mei Sien
AU - Jaretzke, Helen
AU - Dempster, Niall
AU - Bhanot, Kunal
AU - Mian, Areeb
AU - Mastoridis, Sotiris
AU - Gibbons, Ben
AU - Owen-Smith, Sam
AU - Walmsley, James
AU - Al Azzawi, Mohammed
AU - Doyle, Evin
AU - Okamura, Yasuhiro
AU - Keywani, Kammy
AU - Ferrari, Giovanni
AU - Gualtierotti, Monica
AU - De Martini, Paolo
AU - Bushati, Frida
PY - 2025/4
Y1 - 2025/4
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.
KW - fluorouracil
KW - cancer
KW - chemotherapy regimen
KW - immunologic adjuvants
KW - pharmaceutical adjuvants
KW - disease-free survival
KW - lleucovorin
KW - neoadjuvant therapy
KW - perioperative care
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 -
