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dc.contributor.authorAasebø, Kristineen_US
dc.contributor.authorDragomir, Ancaen_US
dc.contributor.authorSundström, Magnusen_US
dc.contributor.authorMezheyeuski, Arturen_US
dc.contributor.authorEdqvist, Per-Henriken_US
dc.contributor.authorEide, Geir Egilen_US
dc.contributor.authorPontén, Fredriken_US
dc.contributor.authorPfeiffer, Peren_US
dc.contributor.authorGlimelius, Bengten_US
dc.contributor.authorSorbye, Halfdanen_US
dc.PublishedAasebø KØ, Dragomir A, Sundström M, Mezheyeuski A, Edqvist, Eide GE, Pontén F, Pfeiffer P, Glimelius B, Sorbye H. Consequences of a high incidence of microsatellite instability and BRAF-mutated tumors: A population-based cohort of metastatic colorectal cancer patients. Cancer Medicine. 2019;8(7):3623-3635.eng
dc.description.abstractBackground: Immunotherapy for patients with microsatellite-instable (MSI-H) tumors or BRAF-inhibitors combination treatment for BRAF-mutated (mutBRAF) tumors in metastatic colorectal cancer (mCRC) is promising, but the frequency of these molecular changes in trial patients are low. Unselected population-based studies of these molecular changes are warranted. Methods: A population-based cohort of 798 mCRC patients in Scandinavia was studied. Patient and molecular tumor characteristics, overall survival (OS) and progression-free survival (PFS) were estimated. Results: Here, 40/583 (7%) tumor samples were MSI-H and 120/591 (20%) were mutBRAF; 87% of MSI-H tumors were mutBRAF (non-Lynch). Elderly (>75 years) had more often MSI-H (10% vs 6%) and MSI-H/mutBRAF (9% vs 4%) tumors. Response rate (5% vs 44%), PFS (4 vs 8 months), and OS (9 vs 18 months) after first-line chemotherapy was all significantly lower in patients with MSI-H compared to patients with microsatellite stable tumors. MSI-H and mutBRAF were both independent poor prognostic predictors for OS (P = 0.049, P < 0.001) and PFS (P = 0.045, P = 0.005) after first-line chemotherapy. Patients with MSI-H tumors received less second-line chemotherapy (15% vs 37%, P = 0.005). Conclusions: In unselected mCRC patients, MSI-H and mutBRAF cases were more common than previously reported. Patients with MSI-H tumors had worse survival, less benefit from chemotherapy, and they differed considerably from recent third-line immunotherapy trial patients as they were older and most had mutBRAF tumor (non-Lynch).
dc.rightsAttribution CC BY 4.0eng
dc.subjectcolorectal neoplasmeng
dc.subjectmicrosatellite instabilityeng
dc.subjectproto‐oncogene proteinseng
dc.subjectneoplasm metastasiseng
dc.subjectKRAS proteineng
dc.titleConsequences of a high incidence of microsatellite instability and BRAF-mutated tumors: A population-based cohort of metastatic colorectal cancer patientsen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2019 the authors
dc.source.journalCancer Medicine
dc.identifier.citationCancer Medicine. 2019, 8 (7), 3623-3635.

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