{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T20:22:47Z","timestamp":1781295767319,"version":"3.54.1"},"reference-count":49,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T00:00:00Z","timestamp":1686873600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Current knowledge on prognostic biomarkers (especially <jats:italic>BRAF<\/jats:italic><jats:sup><jats:italic>V600E<\/jats:italic><\/jats:sup>\/<jats:italic>RAS<\/jats:italic> mutations) in metastatic colorectal cancer (mCRC) is mainly based on mCRC patients with proficient mismatch repair (pMMR) tumors. It is uncertain whether these biomarkers have the same prognostic value in mCRC patients with deficient mismatch repair (dMMR) tumors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This observational cohort study combined a population\u2010based Dutch cohort (2014\u20132019) and a large French multicenter cohort (2007\u20132017). All mCRC patients with a histologically proven dMMR tumor were included.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In our real\u2010world data cohort of 707 dMMR mCRC patients, 438 patients were treated with first\u2010line palliative systemic chemotherapy. Mean age of first\u2010line treated patients was 61.9\u2009years, 49% were male, and 40% had Lynch syndrome. <jats:italic>BRAF<\/jats:italic><jats:sup><jats:italic>V600E<\/jats:italic><\/jats:sup> mutation was present in 47% of tumors and 30% harbored a <jats:italic>RAS<\/jats:italic> mutation. Multivariable regression analysis on OS showed significant hazard rates (HR) for known prognostic factors as age and performance status, however showed no significance for Lynch syndrome (HR: 1.07, 95% CI: 0.66\u20131.72), <jats:italic>BRAF<\/jats:italic><jats:sup><jats:italic>V600E<\/jats:italic><\/jats:sup> mutational status (HR: 1.02, 95% CI: 0.67\u20131.54), and <jats:italic>RAS<\/jats:italic> mutational status (HR: 1.01, 95% CI: 0.64\u20131.59), with similar results for PFS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>BRAF<\/jats:italic><jats:sup><jats:italic>V600E<\/jats:italic><\/jats:sup> and <jats:italic>RAS<\/jats:italic> mutational status are not associated with prognosis in dMMR mCRC patients, in contrast to pMMR mCRC patients. Lynch syndrome is also not an independent prognostic factor for survival. These findings underline that prognostic factors of patients with dMMR mCRC are different of those with pMMR, which could be taken into consideration when prognosis is used for clinical decision\u2010making in dMMR mCRC patients and underline the complex heterogeneity of mCRC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.6223","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T10:27:16Z","timestamp":1686911236000},"page":"15841-15853","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Prognostic value of Lynch syndrome, <i>BRAF<sup>V600E<\/sup><\/i>, and <scp><i>RAS<\/i><\/scp> mutational status in <scp>dMMR<\/scp>\/<scp>MSI\u2010H<\/scp> metastatic colorectal cancer in a pooled analysis of Dutch and French cohorts"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0369-4509","authenticated-orcid":false,"given":"Koen","family":"Zwart","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, University Medical Center Utrecht Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederieke H.","family":"van der Baan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University Medical Center Utrecht Utrecht University  Utrecht The Netherlands"},{"name":"Department of Epidemiology, Julius Center for Health Sciences and Primary Care University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, \u00c9quipe Instabilit\u00e9 des Microsatellites et Cancer, \u00c9quipe Labellis\u00e9e par la Ligue Nationale Contre le Cancer et SIRIC CURAMUS Centre de recherche Saint Antoine, H\u00f4pital Saint\u2010Antoine, AP\u2010HP, and INSERM UMRS 938, Sorbonne Universit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Aparicio","sequence":"additional","affiliation":[{"name":"Gastroenterology Department, Saint Louis Hospital, AP\u2010HP University of Paris  Paris France"},{"name":"Gastroenterology Department Avicenne Hospital  Bobigny France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2291-5693","authenticated-orcid":false,"given":"Christelle","family":"de la Fouchardi\u00e9re","sequence":"additional","affiliation":[{"name":"Medical Oncology Department L\u00e9on B\u00e9rard Center  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Lecomte","sequence":"additional","affiliation":[{"name":"Department of Hepato\u2010Gastroenterology and Digestive Oncology, Tours University Hospital and INSERM UMR 1069 N2C University of Tours  Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelis J. A.","family":"Punt","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Julius Center for Health Sciences and Primary Care University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0821-5642","authenticated-orcid":false,"given":"David","family":"Sefrioui","sequence":"additional","affiliation":[{"name":"Digestive Oncology Unit, Department of Hepatogastroenterology, Rouen University Hospital, IRON Group and INSERM U1245 University of Normandy  Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rik J.","family":"Verheijden","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University Medical Center Utrecht Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geraldine R.","family":"Vink","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University Medical Center Utrecht Utrecht University  Utrecht The Netherlands"},{"name":"Department of Research and Development Netherlands Comprehensive Cancer Organisation (IKNL)  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4103-5811","authenticated-orcid":false,"given":"G. Emerens","family":"Wensink","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University Medical Center Utrecht Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aziz","family":"Zaanan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital Assistance publique\u2013H\u00f4pitaux de Paris, SIRIC CARPEM, University Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Koopman","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University Medical Center Utrecht Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8065-9635","authenticated-orcid":false,"given":"David","family":"Tougeron","sequence":"additional","affiliation":[{"name":"Hepato\u2010Gastroenterology Department Poitiers University Hospital, University of Poitiers  Poitiers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1398-8970","authenticated-orcid":false,"given":"Jeanine M. L.","family":"Roodhart","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University Medical Center Utrecht Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,16]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-011110-130235"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1145720"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0804588"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-0332"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2009.237"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604867"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2016.171"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13123063"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00122-9"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw261"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1305275"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1908075"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdu100"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-01076-0"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32879"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.26086"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2018-0914"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2017.09.022"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2017699"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30422-9"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14020406"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa022289"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.27.1825"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djv438"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2021.102174"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2022.07.020"},{"key":"e_1_2_12_28_1","first-page":"19","article-title":"Pathology databanking and biobanking in the Netherlands, a central role for PALGA, the nationwide histopathology and cytopathology data network and archive","volume":"29","author":"Casparie M","year":"2007","journal-title":"Cell Oncol"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.02.7227"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2011-100714"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2018.05.010"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0895-4356(96)00025-X"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280214521348"},{"key":"e_1_2_12_34_1","unstructured":"R: a language and environment for statistical computing.https:\/\/www.gbif.org\/tool\/81287\/r\u2010a\u2010language\u2010and\u2010environment\u2010for\u2010statistical\u2010computing"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajco.13130"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.2205"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2017-0289"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clcc.2016.11.001"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.05.113"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.7105"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70330-4"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.14.9930"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11530-0"},{"key":"e_1_2_12_44_1","article-title":"KRAS A146 mutations are associated with distinct clinical behavior in patients with colorectal liver metastases","volume":"5","author":"t Erve I","year":"2021","journal-title":"JCO Precis Oncologia"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2017.119"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2021.39.15_suppl.3500"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2021.39.3_suppl.58"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/oncolo\/oyad082"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2020-0014"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2022.05.044"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.6223","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T09:36:00Z","timestamp":1715765760000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.6223"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,16]]},"references-count":49,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1002\/cam4.6223"],"URL":"https:\/\/doi.org\/10.1002\/cam4.6223","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,16]]},"assertion":[{"value":"2023-03-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}