Evidence map›Paper›PMID 42642646›Full record

ArticleBritish journal of cancer2026

The role of DNA mismatch repair status in oesophagogastric cancer treated with perioperative chemotherapy: evidence from the MRC ST03 and OE05 trials.

Panagiotis Ntellas, Tom Lund, Georgina A Keogh, Manuel Salto-Tellez, Katharina von Loga, Tatiany Silveira, Susanna Riisnaes, Jon Laye, Ruth E Langley, Matthew G Nankivell and 4 more

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Article in British journal of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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14 authors.

Panagiotis NtellasDepartment of Gastrointestinal Medical Oncology, Royal Marsden Hospital, London and Surrey, UK.ORCID http://orcid.org/0000-0003-1708-3861
Tom LundThe Integrated Pathology Unit, The Institute of Cancer Research & The Royal Marsden Hospital, Sutton, UK.
Georgina A KeoghDepartment of Gastrointestinal Medical Oncology, Royal Marsden Hospital, London and Surrey, UK.
Manuel Salto-TellezThe Integrated Pathology Unit, The Institute of Cancer Research & The Royal Marsden Hospital, Sutton, UK.ORCID http://orcid.org/0000-0001-8586-282X
Katharina von LogaWaiv, Paris, France.
Tatiany SilveiraThe Integrated Pathology Unit, The Institute of Cancer Research & The Royal Marsden Hospital, Sutton, UK.
Susanna RiisnaesThe Integrated Pathology Unit, The Institute of Cancer Research & The Royal Marsden Hospital, Sutton, UK.
Jon LayePathology and Data Analytics, Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK.
Ruth E LangleyUCL Innovative Clinical Trials Unit, University College London, London, UK.ORCID http://orcid.org/0000-0002-9706-016X
Matthew G NankivellUCL Innovative Clinical Trials Unit, University College London, London, UK.
William H AllumDepartment of Oncology and Department of Surgery, Royal Marsden NHS Foundation Trust, London, UK.
Avani AthaudaDepartment of Gastrointestinal Medical Oncology, Royal Marsden Hospital, London and Surrey, UK.
David CunninghamDepartment of Gastrointestinal Medical Oncology, Royal Marsden Hospital, London and Surrey, UK. david.cunningham@rmh.nhs.uk.ORCID http://orcid.org/0000-0001-5158-1069
Heike I GrabschPathology and Data Analytics, Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK. h.i.grabsch@leeds.ac.uk.ORCID http://orcid.org/0000-0001-9520-6228

Funding

Cancer Research UK (CRUK) C26441/A8944 and A16251
6 · The paper itself

Abstract

backgroundMismatch repair deficiency (MMRd) is a key determinant of tumour biology, however, its prognostic significance in patients with resectable oesophagogastric adenocarcinoma treated with perioperative cytotoxic chemotherapy remains uncertain.

methodsMMR status was assessed in 1424 patients with oesophagogastric adenocarcinoma enroled in the MRC OE05 and ST03 trials, which investigated perioperative chemotherapy regimens. Associations between MMR status, clinicopathological variables, overall survival (OS), progression-free survival (PFS) and post-progression survival (PPS) were investigated.

resultsIn total, 78 (5.5%) tumours were MMRd, 80.8% due to MLH1 loss. Patients with MMRd tumours had improved OS compared with patients with MMR proficient (MMRp) tumours (median unreached vs 28.0 months; p = 0.0009; 5-year rates 50.1% vs. 34.3%), and PFS (median 56.7 vs 21.4 months; p = 0.0032). On multivariable analysis, MMRd remained associated with improved OS (HR 0.60, 95% CI 0.42-0.87; p = 0.007) and PFS (HR 0.64, 95% CI 0.45-0.90; p = 0.011). PPS did not differ by MMR status. DISCUSSION: This is the first study to suggest that perioperative cytotoxic chemotherapy does not abrogate the favourable prognostic impact of MMRd prior to disease progression. However, MMR status did not influence survival after progression. Our results challenge clinical concerns that cytotoxic chemotherapy may be detrimental in patients with resectable MMRd oesophagogastric adenocarcinoma.

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PMID42642646

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