Single cell AI-based detection of DNA mismatch repair deficiency in 1,988 colorectal cancers reveals prognostic and predictive value in the SCOT trial
Nowak, M.; Jabbar, F.; Rodewald, A.-K.; Gneo, L.; Tomasevic, T.; Harkin, A.; Iveson, T.; Saunders, M.; Kerr, R.; Oein, K.; Maka, N.; Hay, J.; Edwards, J.; Tomlinson, I.; Sansom, O.; Kelly, C.; Easton, A.; Domingo, E.; TransSCOT consortium, ; Koelzer, V. H.; Church, D. N.
Show abstract
Testing for DNA mismatch repair deficiency (MMRd) is recommended for all colorectal cancers (CRC). Automation of this would facilitate precision medicine, particularly if it provided information on likely aetiology. We developed AIMMer, an AI-based method for determination of MMR protein expression at single cell level in routine pathology samples. We applied it to over 2,000 colorectal cancers (CRC) from the SCOT clinical trial, which compared 3 vs 6 months of oxaliplatin-based adjuvant chemotherapy (FOLFOX or CAPOX). Benchmarking of AIMMeR against pathologist ground truth MMR calls revealed AUROC of 0.98, and positive predictive value (PPV) greater than 95% for the commonest pa[ern of somatic MMRd, and for retained MMR expression. Analysis of CRC recurrence confirmed the prognostic value of MMRd in oxaliplatin-treated patients. While MMRd did not predict differential benefit from chemotherapy duration, it correlated with difference in clinical outcome by chemotherapy regimen (PInteraction=0.04). AIMMeR holds promise to reduce pathologist workflow and streamline clinical diagnostics in CRC.
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