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Low BRAF and NRAS expression levels are associated with clinical benefit from DTIC therapy and prognosis in metastatic melanoma

Birkeland, Einar ; Busch, Christian ; Berge, Elisabet Ognedal ; Geisler, Jurgen ; Jönsson, Göran B LU ; Lillehaug, Johan Richard ; Knappskog, Stian and Lonning, Per Eystein (2013) In Clinical and Experimental Metastasis 30(7). p.867-876
Abstract
Metastatic melanoma is characterized by a poor response to chemotherapy. Furthermore, there is a lack of established predictive and prognostic markers. In this single institution study, we correlated mutation status and expression levels of BRAF and NRAS to dacarbazine (DTIC) treatment response as well as progression-free and overall survival in a cohort of 85 patients diagnosed with advanced melanoma. Neither BRAF nor NRAS mutation status correlated to treatment response. However, patients with tumors harboring NRAS mutations had a shorter overall survival (p < 0.001) compared to patients with tumors wild-type for NRAS. Patients having a clinical benefit (objective response or stable disease at 3 months) on DTIC therapy had lower BRAF... (More)
Metastatic melanoma is characterized by a poor response to chemotherapy. Furthermore, there is a lack of established predictive and prognostic markers. In this single institution study, we correlated mutation status and expression levels of BRAF and NRAS to dacarbazine (DTIC) treatment response as well as progression-free and overall survival in a cohort of 85 patients diagnosed with advanced melanoma. Neither BRAF nor NRAS mutation status correlated to treatment response. However, patients with tumors harboring NRAS mutations had a shorter overall survival (p < 0.001) compared to patients with tumors wild-type for NRAS. Patients having a clinical benefit (objective response or stable disease at 3 months) on DTIC therapy had lower BRAF and NRAS expression levels compared to patients progressing on therapy (p = 0.037 and 0.003, respectively). For BRAF expression, this association was stronger among patients with tumors wild-type for BRAF (p = 0.005). Further, low BRAF as well as NRAS expression levels were associated with a longer progression-free survival in the total population (p = 0.004 and < 0.001, respectively). Contrasting low NRAS expression levels, which were associated with improved overall survival in the total population (p = 0.01), low BRAF levels were associated with improved overall survival only among patients with tumors wild-type for BRAF (p = 0.013). These findings indicate that BRAF and NRAS expression levels may influence responses to DTIC as well as prognosis in patients with advanced melanoma. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Melanoma, BRAF, NRAS, Chemoresistance, Dacarbazine
in
Clinical and Experimental Metastasis
volume
30
issue
7
pages
867 - 876
publisher
Springer
external identifiers
  • wos:000327433900004
  • scopus:84890429134
  • pmid:23673558
ISSN
1573-7276
DOI
10.1007/s10585-013-9587-4
language
English
LU publication?
yes
id
3426efc1-7bee-4d30-9ea9-64fa4efdfdc6 (old id 4274284)
date added to LUP
2016-04-01 09:57:14
date last changed
2020-06-10 01:08:59
@article{3426efc1-7bee-4d30-9ea9-64fa4efdfdc6,
  abstract     = {Metastatic melanoma is characterized by a poor response to chemotherapy. Furthermore, there is a lack of established predictive and prognostic markers. In this single institution study, we correlated mutation status and expression levels of BRAF and NRAS to dacarbazine (DTIC) treatment response as well as progression-free and overall survival in a cohort of 85 patients diagnosed with advanced melanoma. Neither BRAF nor NRAS mutation status correlated to treatment response. However, patients with tumors harboring NRAS mutations had a shorter overall survival (p &lt; 0.001) compared to patients with tumors wild-type for NRAS. Patients having a clinical benefit (objective response or stable disease at 3 months) on DTIC therapy had lower BRAF and NRAS expression levels compared to patients progressing on therapy (p = 0.037 and 0.003, respectively). For BRAF expression, this association was stronger among patients with tumors wild-type for BRAF (p = 0.005). Further, low BRAF as well as NRAS expression levels were associated with a longer progression-free survival in the total population (p = 0.004 and &lt; 0.001, respectively). Contrasting low NRAS expression levels, which were associated with improved overall survival in the total population (p = 0.01), low BRAF levels were associated with improved overall survival only among patients with tumors wild-type for BRAF (p = 0.013). These findings indicate that BRAF and NRAS expression levels may influence responses to DTIC as well as prognosis in patients with advanced melanoma.},
  author       = {Birkeland, Einar and Busch, Christian and Berge, Elisabet Ognedal and Geisler, Jurgen and Jönsson, Göran B and Lillehaug, Johan Richard and Knappskog, Stian and Lonning, Per Eystein},
  issn         = {1573-7276},
  language     = {eng},
  number       = {7},
  pages        = {867--876},
  publisher    = {Springer},
  series       = {Clinical and Experimental Metastasis},
  title        = {Low BRAF and NRAS expression levels are associated with clinical benefit from DTIC therapy and prognosis in metastatic melanoma},
  url          = {http://dx.doi.org/10.1007/s10585-013-9587-4},
  doi          = {10.1007/s10585-013-9587-4},
  volume       = {30},
  year         = {2013},
}