Prognostic value of Lynch syndrome, BRAFV600E, and RAS mutational status in dMMR/MSI‐H metastatic colorectal cancer in a pooled analysis of Dutch and French cohorts

Abstract Background Current knowledge on prognostic biomarkers (especially BRAFV600E/RAS 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. Methods This observational cohort study combined a population‐based Dutch cohort (2014–2019) and a large French multicenter cohort (2007–2017). All mCRC patients with a histologically proven dMMR tumor were included. Results In our real‐world dat... Mehr ...

Verfasser: Koen Zwart
Frederieke H. van derBaan
Romain Cohen
Thomas Aparicio
Christelle de laFouchardiére
Thierry Lecomte
Cornelis J. A. Punt
David Sefrioui
Rik J. Verheijden
Geraldine R. Vink
G. Emerens Wensink
Aziz Zaanan
Miriam Koopman
David Tougeron
Jeanine M. L. Roodhart
Dokumenttyp: Artikel
Erscheinungsdatum: 2023
Reihe/Periodikum: Cancer Medicine, Vol 12, Iss 15, Pp 15841-15853 (2023)
Verlag/Hrsg.: Wiley
Schlagwörter: deficient mismatch repair / Lynch syndrome / metastatic colorectal cancer / microsatellite instability / molecular biology / Neoplasms. Tumors. Oncology. Including cancer and carcinogens / RC254-282
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-28987281
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : https://doi.org/10.1002/cam4.6223

Abstract Background Current knowledge on prognostic biomarkers (especially BRAFV600E/RAS 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. Methods This observational cohort study combined a population‐based Dutch cohort (2014–2019) and a large French multicenter cohort (2007–2017). All mCRC patients with a histologically proven dMMR tumor were included. Results In our real‐world data cohort of 707 dMMR mCRC patients, 438 patients were treated with first‐line palliative systemic chemotherapy. Mean age of first‐line treated patients was 61.9 years, 49% were male, and 40% had Lynch syndrome. BRAFV600E mutation was present in 47% of tumors and 30% harbored a RAS 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: 0.66–1.72), BRAFV600E mutational status (HR: 1.02, 95% CI: 0.67–1.54), and RAS mutational status (HR: 1.01, 95% CI: 0.64–1.59), with similar results for PFS. Conclusion BRAFV600E and RAS 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‐making in dMMR mCRC patients and underline the complex heterogeneity of mCRC.