Atypical (non-V600E) BRAF mutations in metastatic colorectal cancer in population and real-world cohorts
Publiceringsår
2023
Upphovspersoner
Osterlund, Emerik; Ristimäki, Ari; Mäkinen, Markus J.; Kytölä, Soili; Kononen, Juha; Pfeiffer, Per; Soveri, Leena‐Maija; Keinänen, Mauri; Sorbye, Halfdan; Nunes, Luís; Salminen, Tapio; Nieminen, Lasse; Uutela, Aki; Halonen, Päivi; Ålgars, Annika; Sundström, Jari; Kallio, Raija; Ristamäki, Raija; Lamminmäki, Annamarja; Stedt, Hanna; Heervä, Eetu; Kuopio, Teijo; Sjöblom, Tobias; Isoniemi, Helena; Glimelius, Bengt; Osterlund, Pia
Visa merAbstrakt
BRAF-V600E mutation (mt) is a strong negative prognostic and predictive biomarker in metastatic colorectal cancer (mCRC). Non-V600Emt, designated atypical BRAFmt (aBRAFmt) are rare, and little is known about their frequency, co-mutations and prognostic and predictive role. These were compared between mutational groups of mCRC patients collected from three Nordic population-based or real-world cohorts. Pathology of aBRAFmt was studied. The study included 1449 mCRC patients with 51 (3%) aBRAFmt, 182 (13%) BRAF-V600Emt, 456 (31%) RAS&BRAF wild-type (wt) and 760 (52%) RASmt tumours. aBRAFmt were seen in 2% of real-world and 4% of population-based cohorts. Twenty-six different aBRAFmt were detected, 11 (22%) class 2 (serrated adenocarcinoma in 2/9 tested), 32 (64%) class 3 (serrated in 15/25) and 4 (8%) unclassified. aBRAFmt patients were predominantly male, had more rectal primaries, less peritoneal metastases, deficient mismatch repair in one (2%), and better survival after metastasectomy (89% 5-year overall survival [OS]-rate) compared with BRAF-V600Emt. aBRAFmt and BRAF-V600Emt had poorer performance status and received fewer treatment lines than RAS&BRAFwt and RASmt. OS among aBRAFmt (median 14.4 months) was longer than for BRAF-V600Emt (11.2 months), but shorter than for RAS&BRAFwt (30.5 months) and RASmt (23.4 months). Addition of bevacizumab trended for better OS for the aBRAFmt. Nine patients with aBRAFmt received cetuximab/panitumumab without response. aBRAFmt represents a distinct subgroup differing from other RAS/BRAF groups, with serrated adenocarcinoma in only half. OS for patients with aBRAFmt tumours was slightly better than for BRAF-V600Emt, but worse than for RASmt and RAS&BRAFwt. aBRAFmt should not be a contraindication for metastasectomy.
Visa merOrganisationer och upphovspersoner
Helsingfors universitet
Uutela Aki
Ristimäki Ari
Osterlund Emerik
Isoniemi Helena
Soveri Leena-Maija
Osterlund Pia
Halonen Päivi
Kytölä Soili
Tammerfors universitet
Salminen Tapio
Helsingforsregionens universitetscentralsjukhus specialupptagningsområde
Uutela Aki
Ristimäki Ari
Osterlund Emerik
Isoniemi Helena
Soveri Leena-Maija
Osterlund Pia
Halonen Päivi
Kytölä Soili
Tammerfors universitetssjukhus specialupptagningsområde
Keinänen Mauri
Publikationstyp
Publikationsform
Artikel
Moderpublikationens typ
Tidning
Artikelstyp
En originalartikel
Målgrupp
VetenskapligKollegialt utvärderad
Kollegialt utvärderadUKM:s publikationstyp
A1 Originalartikel i en vetenskaplig tidskriftPublikationskanalens uppgifter
Journal
Moderpublikationens namn
Volym
154
Nummer
3
Sidor
488-503
ISSN
Publikationsforum
Publikationsforumsnivå
2
Öppen tillgång
Öppen tillgänglighet i förläggarens tjänst
Ja
Öppen tillgång till publikationskanalen
Delvis öppen publikationskanal
Licens för förläggarens version
CC BY NC
Parallellsparad
Ja
Övriga uppgifter
Vetenskapsområden
Biomedicinska vetenskaper; Cancersjukdomar
Nyckelord
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Förlagets internationalitet
Internationell
Språk
engelska
Internationell sampublikation
Ja
Sampublikation med ett företag
Ja
DOI
10.1002/ijc.34733
Publikationen ingår i undervisnings- och kulturministeriets datainsamling
Ja