Risk of Bowel Obstruction in Patients Undergoing Neoadjuvant Chemotherapy for High-risk Colon Cancer: A Nested Case-control Matched Analysis of an International, Multi-centre, Randomised Controlled Trial (FOxTROT)

FOxTROT Collaborating Group, James Glasbey*

*Corresponding author for this work

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Abstract

OBJECTIVE: This study aimed to identify risk-criteria available before the point of treatment initiation that can be used to stratify risk of obstruction in patients undergoing neoadjuvant chemotherapy (NAC) for high-risk colon cancer.

SUMMARY BACKGROUND DATA: Global implementation of neoadjuvant chemotherapy (NAC) for colon cancer, informed by the FOxTROT trial, may increase risk of bowel obstruction.

METHODS: A case-control study, nested within an international randomised controlled trial (FOxTROT. ClinicalTrials.gov: NCT00647530). Patients with high-risk operable colon cancer (radiologically-staged T3-4 N0-2 M0) that were randomised to NAC and developed large bowel obstruction were identified. Firstly, clinical outcomes were compared between patients receiving NAC in FOxTROT that did and did not develop obstruction. Secondly, obstructed patients (cases) were age- and sex-matched with patients that did not develop obstruction (controls) in a 1:3 ratio using random sampling. Bayesian conditional mixed-effects logistic regression modelling was used to explore clinical, radiological, and pathological features associated with obstruction. Absolute risk of obstruction based on the presence or absence of risk criteria was estimated for all patients receiving NAC.

RESULTS: Of 1053 patients randomised in FOxTROT, 699 received NAC, of whom 30 (4.3%) developed obstruction. Patients underwent care in European hospitals including 88 UK, 7 Danish and 3 Swedish centres. There was more open surgery (65.4% vs. 38.0%, P =0.01) and a higher pR1 rate in obstructed patients (12.0% vs. 3.8%, P =0.004), but otherwise comparable postoperative outcomes. In the case-control matched Bayesian model, two independent risk criteria were identified: (1) obstructing disease on endoscopy and/or being unable to pass through the tumour (adjusted odds ratio: 9.09, 95% credible interval: 2.34-39.66) and stricturing disease on radiology or endoscopy (OR: 7.18, 95% C.I.: 1.84-32.34). Three risk groups were defined according to the presence or absence of these criteria: 63.4% (443/698) of patients were at very low risk (<1%), 30.7% (214/698) at low risk (<10%), and 5.9% (41/698) at high risk (>10%).

CONCLUSIONS: Safe selection for NAC for colon cancer can be informed by using two features that are available before treatment initiation and identify a small number of patients with high risk of preoperative obstruction.

Original languageEnglish
Pages (from-to)283-293
JournalAnnals of surgery
Volume280
Issue number2
Early online date10 Nov 2023
DOIs
Publication statusPublished - 1 Aug 2024

Bibliographical note

Acknowledgements:
FOxTROT is funded by Cancer Research UK. Additional support was provided by the Birmingham and Leeds Experimental Cancer Medicine Centres (ECMC) network, Royal College of Surgeons of England and Rosetrees Trust, and the Swedish Cancer Society. Panitumumab was provided free of charge by Amgen, who also supported RAS testing and additional CT scans. Phil Quirke and Nick West are supported by Yorkshire Cancer Research, Richard Gray by the Medical Research Council. Dion Morton and Phil Quirke are NIHR Senior Investigators. Keigo Murakami, Alice Westwood and Nick West reported the mismatch repair protein immunohistochemistry. RAS testing was coordinated by Susan Richman (Leeds) and Philippe Taniere (Birmingham). James Glasbey is supported by a NIHR Doctoral Research Fellowship award. Most importantly, we wish to thank the patients and all staff who have supported the trial.

Copyright:
© 2023 The Author(s). Published by Wolters Kluwer Health, Inc.

Keywords

  • Colon cancer
  • Colorectal cancer
  • Gastrointestinal cancer
  • Obstruction
  • Neoadjuvant therapy
  • Chemotherapy
  • Surgical oncology
  • Multidisciplinary team
  • Casecontrol study
  • Randomised trial
  • FOxTROT trial

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