Associations between AI-Assisted Tumor Amphiregulin and Epiregulin IHC and Outcomes from Anti-EGFR Therapy in the Routine Management of Metastatic Colorectal Cancer.

Autor:	Williams CJM; Division of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom.; Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, United Kingdom., Elliott F; Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, United Kingdom., Sapanara N; Medical & Scientific Affairs, Roche Molecular Systems Inc., Tucson, Arizona., Aghaei F; Medical & Scientific Affairs, Roche Molecular Systems Inc., Tucson, Arizona., Zhang L; Medical & Scientific Affairs, Roche Molecular Systems Inc., Tucson, Arizona., Muranyi A; Medical & Scientific Affairs, Roche Molecular Systems Inc., Tucson, Arizona., Yan D; Medical & Scientific Affairs, Roche Molecular Systems Inc., Tucson, Arizona., Bai I; Medical & Scientific Affairs, Roche Molecular Systems Inc., Tucson, Arizona., Zhao Z; Imaging and Algorithms, Digital Pathology, Roche Sequencing Solutions Inc., Santa Clara, California., Shires M; Division of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom., Wood HM; Division of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom., Richman SD; Division of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom., Hemmings G; Division of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom., Hale M; Division of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom., Bottomley D; Division of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom., Galvin L; Division of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom., Cartlidge C; Division of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom., Dance S; Medical Affairs, Access and Innovation, Roche Diagnostics Limited, Burgess Hill, United Kingdom., Bacon CM; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.; Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom., Mansfield L; Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom., Young-Zvandasara K; Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom., Sudan A; Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom., Lambert K; Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom., Bibby I; Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom., Coupland SE; Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom., Montazeri A; The Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, United Kingdom., Kipling N; Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom., Hughes K; The Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, United Kingdom., Cross SS; Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, United Kingdom., Dewdney A; Weston Park Cancer Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom., Pheasey L; Weston Park Cancer Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom., Leng C; Weston Park Cancer Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom., Gochera T; Weston Park Cancer Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom., Mangham DC; Adult Histopathology, Laboratory Medicine, Manchester University NHS Foundation Trust, Health Innovation Manchester, Manchester, United Kingdom., Saunders M; The Christie NHS Foundation Trust, Manchester, United Kingdom., Pritchard M; Adult Histopathology, Laboratory Medicine, Manchester University NHS Foundation Trust, Health Innovation Manchester, Manchester, United Kingdom., Stott H; The Christie NHS Foundation Trust, Manchester, United Kingdom., Mukherjee A; Translational Medical Sciences, Cancer and Stem Cells, School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham, United Kingdom., Ilyas M; Translational Medical Sciences, Cancer and Stem Cells, School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham, United Kingdom., Silverman R; Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom., Hyland G; Translational Medical Sciences, Cancer and Stem Cells, School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham, United Kingdom., Sculthorpe D; Translational Medical Sciences, Cancer and Stem Cells, School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham, United Kingdom., Thornton K; Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom., Gould I; Translational Medical Sciences, Cancer and Stem Cells, School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham, United Kingdom., O'Callaghan A; Portsmouth Hospitals NHS Trust, Portsmouth, United Kingdom., Brown N; Calderdale and Huddersfield NHS Foundation Trust, Huddersfield, United Kingdom., Turnbull S; Calderdale and Huddersfield NHS Foundation Trust, Huddersfield, United Kingdom., Shaw L; Calderdale and Huddersfield NHS Foundation Trust, Huddersfield, United Kingdom., Seymour MT; Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, United Kingdom., West NP; Division of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom., Seligmann JF; Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, United Kingdom., Singh S; Medical & Scientific Affairs, Roche Molecular Systems Inc., Tucson, Arizona., Shanmugam K; Medical & Scientific Affairs, Roche Molecular Systems Inc., Tucson, Arizona., Quirke P; Division of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2023 Oct 13; Vol. 29 (20), pp. 4153-4165.
DOI:	10.1158/1078-0432.CCR-23-0859
Abstrakt:	Purpose: High tumor production of the EGFR ligands, amphiregulin (AREG) and epiregulin (EREG), predicted benefit from anti-EGFR therapy for metastatic colorectal cancer (mCRC) in a retrospective analysis of clinical trial data. Here, AREG/EREG IHC was analyzed in a cohort of patients who received anti-EGFR therapy as part of routine care, including key clinical contexts not investigated in the previous analysis. Experimental Design: Patients who received panitumumab or cetuximab ± chemotherapy for treatment of RAS wild-type mCRC at eight UK cancer centers were eligible. Archival formalin-fixed paraffin-embedded tumor tissue was analyzed for AREG and EREG IHC in six regional laboratories using previously developed artificial intelligence technologies. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Results: A total of 494 of 541 patients (91.3%) had adequate tissue for analysis. A total of 45 were excluded after central extended RAS testing, leaving 449 patients in the primary analysis population. After adjustment for additional prognostic factors, high AREG/EREG expression (n = 360; 80.2%) was associated with significantly prolonged PFS [median: 8.5 vs. 4.4 months; HR, 0.73; 95% confidence interval (CI), 0.56-0.95; P = 0.02] and OS [median: 16.4 vs. 8.9 months; HR, 0.66 95% CI, 0.50-0.86; P = 0.002]. The significant OS benefit was maintained among patients with right primary tumor location (PTL), those receiving cetuximab or panitumumab, those with an oxaliplatin- or irinotecan-based chemotherapy backbone, and those with tumor tissue obtained by biopsy or surgical resection. Conclusions: High tumor AREG/EREG expression was associated with superior survival outcomes from anti-EGFR therapy in mCRC, including in right PTL disease. AREG/EREG IHC assessment could aid therapeutic decisions in routine practice. See related commentary by Randon and Pietrantonio, p. 4021. (©2023 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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