Evidence map›Paper›PMID 37363997›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023

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

Christopher J M Williams, Faye Elliott, Nancy Sapanara, Faranak Aghaei, Liping Zhang, Andrea Muranyi, Dongyao Yan, Isaac Bai, Zuo Zhao, Michael Shires and 44 more

Open access · hybridAbstract readEditorial
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
4.4field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 19 citations in OpenAlex.

  1. Amivantamab Monotherapy in ChemorefractoryJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026
    Trial
  2. Trial
  3. Systemic inflammation and prognosis in patients with RAS/BRAF wild-type metastatic colorectal cancer receiving anti-EGFR therapy: A real-world cohort study.Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland · 2026
    Article
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  15. Towards Multiomics-Based Dissection of Anti-EGFR Sensitivity in Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
    Article
  16. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

54 authors at 16 institutions in 4 countries.

Christopher J M WilliamsDivision of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom.ORCID 0000-0002-1574-653X
Faye ElliottLeeds Institute of Medical Research at St James's, University of Leeds, Leeds, United Kingdom.ORCID 0000-0002-3239-6914
Nancy SapanaraMedical & Scientific Affairs, Roche Molecular Systems Inc., Tucson, Arizona.ORCID 0009-0005-0994-837X
Faranak AghaeiMedical & Scientific Affairs, Roche Molecular Systems Inc., Tucson, Arizona.ORCID 0009-0000-6076-5978
Liping ZhangMedical & Scientific Affairs, Roche Molecular Systems Inc., Tucson, Arizona.ORCID 0009-0006-7739-4396
Andrea MuranyiMedical & Scientific Affairs, Roche Molecular Systems Inc., Tucson, Arizona.ORCID 0000-0002-7938-8225
Dongyao YanMedical & Scientific Affairs, Roche Molecular Systems Inc., Tucson, Arizona.ORCID 0009-0001-9482-3539
Isaac BaiMedical & Scientific Affairs, Roche Molecular Systems Inc., Tucson, Arizona.ORCID 0009-0009-9105-0997
Zuo ZhaoImaging and Algorithms, Digital Pathology, Roche Sequencing Solutions Inc., Santa Clara, California.ORCID 0009-0006-3340-082X
Michael ShiresDivision of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom.ORCID 0000-0003-0904-6200
Henry M WoodDivision of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom.ORCID 0000-0003-3009-5904
Susan D RichmanDivision of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom.ORCID 0000-0003-3993-5041
Gemma HemmingsDivision of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom.ORCID 0000-0003-2010-9735
Michael HaleDivision of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom.ORCID 0000-0001-8178-6882
Daniel BottomleyDivision of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom.ORCID 0009-0000-5749-2710
Leanne GalvinDivision of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom.ORCID 0009-0004-6316-5790
Caroline CartlidgeDivision of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom.ORCID 0000-0002-8366-4528
Sarah DanceMedical Affairs, Access and Innovation, Roche Diagnostics Limited, Burgess Hill, United Kingdom.ORCID 0009-0004-3529-7112
Chris M BaconTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.ORCID 0000-0002-8268-2812
Laura MansfieldNewcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.ORCID 0009-0009-2038-3081
Kathe Young-ZvandasaraNewcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.ORCID 0009-0005-2170-1396
Ajay SudanNewcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.ORCID 0009-0004-8624-8732
Katy LambertNewcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.ORCID 0009-0001-3461-310X
Irena BibbyNewcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.ORCID 0009-0007-3105-9864
Sarah E CouplandDepartment of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom.ORCID 0000-0002-1464-2069
Amir MontazeriThe Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, United Kingdom.ORCID 0000-0002-2942-3205
Natalie KiplingDepartment of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom.ORCID 0009-0008-5292-4981
Kathryn HughesThe Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, United Kingdom.ORCID 0009-0007-9004-4873
Simon S CrossAcademic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, United Kingdom.ORCID 0000-0003-2044-1754
Alice DewdneyWeston Park Cancer Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom.ORCID 0000-0001-5078-768X
Leanne PheaseyWeston Park Cancer Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom.ORCID 0009-0008-2981-1671
Cathryn LengWeston Park Cancer Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom.ORCID 0009-0005-8757-1555
Tatenda GocheraWeston Park Cancer Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom.ORCID 0009-0000-6797-0376
D Chas ManghamAdult Histopathology, Laboratory Medicine, Manchester University NHS Foundation Trust, Health Innovation Manchester, Manchester, United Kingdom.ORCID 0000-0001-5983-2598
Mark SaundersThe Christie NHS Foundation Trust, Manchester, United Kingdom.ORCID 0000-0002-7195-4712
Martin PritchardAdult Histopathology, Laboratory Medicine, Manchester University NHS Foundation Trust, Health Innovation Manchester, Manchester, United Kingdom.ORCID 0009-0005-2514-6932
Helen StottThe Christie NHS Foundation Trust, Manchester, United Kingdom.ORCID 0009-0004-1708-0665
Abhik MukherjeeTranslational Medical Sciences, Cancer and Stem Cells, School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham, United Kingdom.ORCID 0000-0003-1828-4155
Mohammad IlyasTranslational Medical Sciences, Cancer and Stem Cells, School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham, United Kingdom.ORCID 0000-0001-7949-7504
Rafael SilvermanNottingham University Hospitals NHS Trust, Nottingham, United Kingdom.ORCID 0000-0003-1186-4165
Georgina HylandTranslational Medical Sciences, Cancer and Stem Cells, School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham, United Kingdom.ORCID 0009-0008-6903-2074
Declan SculthorpeTranslational Medical Sciences, Cancer and Stem Cells, School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham, United Kingdom.ORCID 0000-0001-7557-8454
Kirsty ThorntonNottingham University Hospitals NHS Trust, Nottingham, United Kingdom.ORCID 0009-0005-6950-085X
Imogen GouldTranslational Medical Sciences, Cancer and Stem Cells, School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham, United Kingdom.ORCID 0000-0002-3308-4429
Ann O'CallaghanPortsmouth Hospitals NHS Trust, Portsmouth, United Kingdom.ORCID 0009-0005-7311-3764
Nicholas BrownCalderdale and Huddersfield NHS Foundation Trust, Huddersfield, United Kingdom.ORCID 0009-0006-3399-1308
Samantha TurnbullCalderdale and Huddersfield NHS Foundation Trust, Huddersfield, United Kingdom.ORCID 0000-0002-1664-3292
Lisa ShawCalderdale and Huddersfield NHS Foundation Trust, Huddersfield, United Kingdom.ORCID 0009-0005-6104-7739
Matthew T SeymourLeeds Institute of Medical Research at St James's, University of Leeds, Leeds, United Kingdom.ORCID 0000-0002-2441-9629
Nicholas P WestDivision of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom.ORCID 0000-0002-0346-6709
Jenny F SeligmannLeeds Institute of Medical Research at St James's, University of Leeds, Leeds, United Kingdom.ORCID 0000-0003-4379-6005
Shalini SinghMedical & Scientific Affairs, Roche Molecular Systems Inc., Tucson, Arizona.ORCID 0000-0002-1604-5292
Kandavel Shanmugam *Medical & Scientific Affairs, Roche Molecular Systems Inc., Tucson, Arizona.ORCID 0000-0002-9076-3444
Philip Quirke *Division of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom.ORCID 0000-0002-3597-5444
University of Leeds · GBArizona Optical Systems (United States) · USNewcastle upon Tyne Hospitals NHS Foundation Trust · GBUniversity of Nottingham · GBWeston Park Cancer Centre · GBCalderdale and Huddersfield NHS Foundation Trust · GBSt James's University Hospital · GBClatterbridge Cancer Centre NHS Foundation Trust · GBManchester University NHS Foundation Trust · GBNottingham University Hospitals NHS Trust · GBThe Christie NHS Foundation Trust · GBUniversity of Liverpool · GBComputer Algorithms for Medicine · ATPortsmouth Hospitals NHS Trust · GBRoche (Switzerland) · CHUniversity of Sheffield · GB

Funding

Medical Research Council MR/N005872/1
6 · The paper itself

Abstract

purposeHigh 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

designPatients 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).

resultsA 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.

conclusionsHigh 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.

Indexed as

Colonic NeoplasmsColorectal NeoplasmsRectal NeoplasmsAmphiregulinAntineoplastic Combined Chemotherapy ProtocolsArtificial IntelligenceCetuximabEpiregulinErbB ReceptorsHumansIntercellular Signaling Peptides and ProteinsPanitumumabProto-Oncogene Proteins p21(ras)Retrospective StudiesAmphiregulinCetuximabEGFR protein, humanEpiregulinErbB ReceptorsIntercellular Signaling Peptides and ProteinsPanitumumabProto-Oncogene Proteins p21(ras)

Identifiers

PMID37363997
PMCPMC10570673
OpenAlexW4382047835

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.