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Consequences of a h...
Consequences of a high incidence of microsatellite instability and BRAF-mutated tumors : A population-based cohort of metastatic colorectal cancer patients
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- Aasebö, Kristine Ö. (author)
- Univ Bergen, Dept Clin Sci, Bergen, Norway
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- Dragomir, Anca (author)
- Uppsala universitet,Klinisk och experimentell patologi,Fredrik Pontén
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- Sundström, Magnus (author)
- Uppsala universitet,Klinisk och experimentell patologi
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- Mezheyeuski, Artur (author)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Edqvist, Per-Henrik D (author)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Eide, Geir Egil (author)
- Univ Bergen, Dept Global Publ Hlth & Primary Care, Lifestyle Epidemiol Grp, Bergen, Norway;Haukeland Hosp, Ctr Clin Res, Bergen, Norway
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- Pontén, Fredrik (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Klinisk och experimentell patologi
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- Pfeiffer, Per (author)
- Odense Univ Hosp, Dept Oncol, Odense, Denmark
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- Glimelius, Bengt (author)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Sorbye, Halfdan (author)
- Univ Bergen, Dept Clin Sci, Bergen, Norway;Haukeland Hosp, Dept Oncol, Bergen, Norway
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(creator_code:org_t)
- 2019-05-09
- 2019
- English.
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In: Cancer Medicine. - : WILEY. - 2045-7634. ; 8:7, s. 3623-3635
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Abstract
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- 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).
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
Keyword
- colorectal neoplasm
- microsatellite instability
- proto-oncogene proteins
- B-raf
- prognosis
- neoplasm metastasis
- KRAS protein
- Pathology
- Patologi
Publication and Content Type
- ref (subject category)
- art (subject category)
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Aasebö, Kristine ...
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Dragomir, Anca
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Sundström, Magnu ...
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Mezheyeuski, Art ...
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Edqvist, Per-Hen ...
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Eide, Geir Egil
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Pontén, Fredrik
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Pfeiffer, Per
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Glimelius, Bengt
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Sorbye, Halfdan
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Cancer Medicine
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Uppsala University