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In this retrospective real\u2010world analysis, we assessed the prognostic effect of markers of systemic inflammation in a cohort of patients with\n                      <jats:italic>RAS\/BRAF<\/jats:italic>\n                      wild\u2010type metastatic colorectal cancer (mCRC) who received anti\u2010EGFR therapy during routine care. We further examined the association between these markers and the known predictive biomarkers of anti\u2010EGFR efficacy, amphiregulin (AREG) and epiregulin (EREG).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>The prognostic effects of the neutrophil\u2010to\u2010lymphocyte ratio (NLR), platelet\u2010to\u2010lymphocyte ratio (PLR) and systemic immune\u2010inflammation index (SII) were tested. The cohort was randomly partitioned into training and validation sets (1:1). Cutoff values were defined in the training set, with analyses repeated in the validation set. The primary endpoint was overall survival (OS). Secondary endpoints were progression\u2010free survival (PFS), objective response rate and disease control rate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      374 patients with\n                      <jats:italic>RAS<\/jats:italic>\n                      and\n                      <jats:italic>BRAF<\/jats:italic>\n                      wild\u2010type mCRC who received treatment with cetuximab or panitumumab across eight UK centres were included. NLR (\u2264\u20094 vs. &gt;\u20094) and PLR (\u2264\u2009200 vs. &gt;\u2009200) were independently prognostic for both OS and PFS. SII (\u2264\u2009900 vs. &gt;\u2009900) gave the strongest prognostic signal (OS: adjusted HR 1.63 [1.26\u20132.11],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0002 and PFS: adjusted HR 1.62 [1.26\u20132.08],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0001). There were no associations between NLR or PLR with AREG or EREG, suggesting anti\u2010EGFR benefit in AREG\/EREG\u2010high tumours is not related to systemic inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Routinely assessed markers of systemic inflammation are independently prognostic in patients with mCRC receiving anti\u2010EGFR therapy and may serve as useful adjuncts in informing discussions with patients about prognosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/codi.70639","type":"journal-article","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:22:25Z","timestamp":1790400145000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Systemic inflammation and prognosis in patients with\n                    <scp>\n                      <i>RAS<\/i>\n                    <\/scp>\n                    \/\n                    <scp>\n                      <i>BRAF<\/i>\n                    <\/scp>\n                    wild\u2010type metastatic colorectal cancer receiving anti\u2010\n                    <scp>EGFR<\/scp>\n                    therapy: A real\u2010world cohort study"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0127-1219","authenticated-orcid":false,"given":"Jordan W.","family":"Appleyard","sequence":"first","affiliation":[{"name":"Division of Oncology, Leeds Institute of Medical Research University of Leeds  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faye","family":"Elliott","sequence":"additional","affiliation":[{"name":"Division of Haematology and Immunology, Leeds Institute of Medical Research University of Leeds  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy L.","family":"Sapanara","sequence":"additional","affiliation":[{"name":"Clinical Development &amp; Medical Affairs Roche Diagnostics Solutions  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Clinical Development &amp; Medical Affairs Roche Diagnostics Solutions  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uday","family":"Kurkure","sequence":"additional","affiliation":[{"name":"Computational Science and Informatics Roche Diagnostics Solutions  Santa Clara California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny F.","family":"Seligmann","sequence":"additional","affiliation":[{"name":"Division of Oncology, Leeds Institute of Medical Research University of Leeds  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0346-6709","authenticated-orcid":false,"given":"Nicholas P.","family":"West","sequence":"additional","affiliation":[{"name":"Division of Pathology and Data Analytics, Leeds Institute of Medical Research University of Leeds  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kandavel","family":"Shanmugam","sequence":"additional","affiliation":[{"name":"Clinical Development &amp; Medical Affairs Roche Diagnostics Solutions  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Quirke","sequence":"additional","affiliation":[{"name":"Division of Pathology and Data Analytics, Leeds Institute of Medical Research University of Leeds  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1574-653X","authenticated-orcid":false,"given":"Christopher J. 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