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Cancer Med. 2019 Jul;8(7):3623-3635. doi: 10.1002/cam4.2205. Epub 2019 May 9.

Consequences of a high incidence of microsatellite instability and BRAF-mutated tumors: A population-based cohort of metastatic colorectal cancer patients.

Author information

1
Department of Clinical Science, University of Bergen, Bergen, Norway.
2
Department of Pathology, Uppsala University Hospital, Uppsala, Sweden.
3
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
4
Department of Global Public Health and Primary Care, Lifestyle Epidemiology Group, University of Bergen, Bergen, Norway.
5
Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway.
6
Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
7
Department of Oncology, Odense University Hospital, Odense, Denmark.
8
Department of Oncology, Haukeland University Hospital, Bergen, Norway.

Abstract

BACKGROUND:

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).

KEYWORDS:

B-raf; KRAS protein; colorectal neoplasm; microsatellite instability; neoplasm metastasis; prognosis; proto-oncogene proteins

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