Prognostic relevance of lactate dehydrogenase and serum S100 levels in stage IV melanoma with known BRAF mutation status
Summary Background Activating mutations of BRAF provide an important treatment target in patients with melanoma. The prognostic role of several biochemical markers in relation to mutation status is not clear. Objectives To analyse the prognostic significance of BRAF mutation in patients with melanom...
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| Veröffentlicht in: | British journal of dermatology (1951) 2016-04, Vol.174 (4), p.823-830 |
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| container_title | British journal of dermatology (1951) |
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| creator | Frauchiger, A.L. Mangana, J. Rechsteiner, M. Moch, H. Seifert, B. Braun, R.P. Dummer, R. Goldinger, S.M. |
| description | Summary
Background
Activating mutations of BRAF provide an important treatment target in patients with melanoma. The prognostic role of several biochemical markers in relation to mutation status is not clear.
Objectives
To analyse the prognostic significance of BRAF mutation in patients with melanoma and correlate it to different markers.
Methods
In total, 162 patients with stage IV melanoma and known BRAF mutation status were included. Clinical, histopathological and laboratory information was collected and compared between patients with BRAF mutant (BRAFm) and wild‐type (BRAFwt) melanoma at the time of first distant metastasis.
Results
In total, 88 patients (54%) had BRAFm melanoma (V600E/V600K). At the first distant metastasis, S100B levels in BRAFm patients were more frequently elevated (P = 0·01) and significantly higher (P = 0·02). Median overall survival (mOS) was significantly longer in BRAFwt patients with normal compared with patients with elevated S100B levels (P |
| doi_str_mv | 10.1111/bjd.14347 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1785216845</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1785216845</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4037-e5c2ef339c42fc85a6bee72c47d1918f1958fb42a03a33670842b1d998c09ffe3</originalsourceid><addsrcrecordid>eNp1kMFO3DAURa2qVRmgi_5A5WVZZLDj2I6XMGVgECoIpnRpOc4zBJKY2gnD_D2GAXZ9m7c59-jqIvSdkilNt1_d1VNasEJ-QhPKBM9yythnNCGEyIwowbbQdox3hFBGOPmKtnIhuKKKTtDTRfA3vY9DY3GAFh5NbwF7h1tjBzMAruF2XScGehMBm77GEcLY4StKCE48tBE3PY6DuQG8uMYdtKb3ncGrZrjF971f9fjw8mCOuzH5Gv-KDmPcRV-caSN8e_s76M_8aDk7yc7Ojxezg7PMFoTJDLjNwTGmbJE7W3IjKgCZ20LWqX_pqOKlq4rcEGYYE5KURV7RWqnSEuUcsB30c-N9CP7fCHHQXRMttKkl-DFqKkueU1EWPKF7G9QGH2MApx9C05mw1pTol6F1Glq_Dp3YH2_aseqg_iDfl03A_gZYNS2s_2_Sh6e_3pXZJtHEAZ4-EibcayGZ5Prv72N9eS3mM7Wc6SV7Bs3LltM</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1785216845</pqid></control><display><type>article</type><title>Prognostic relevance of lactate dehydrogenase and serum S100 levels in stage IV melanoma with known BRAF mutation status</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><source>Oxford University Press Journals All Titles (1996-Current)</source><creator>Frauchiger, A.L. ; Mangana, J. ; Rechsteiner, M. ; Moch, H. ; Seifert, B. ; Braun, R.P. ; Dummer, R. ; Goldinger, S.M.</creator><creatorcontrib>Frauchiger, A.L. ; Mangana, J. ; Rechsteiner, M. ; Moch, H. ; Seifert, B. ; Braun, R.P. ; Dummer, R. ; Goldinger, S.M.</creatorcontrib><description>Summary
Background
Activating mutations of BRAF provide an important treatment target in patients with melanoma. The prognostic role of several biochemical markers in relation to mutation status is not clear.
Objectives
To analyse the prognostic significance of BRAF mutation in patients with melanoma and correlate it to different markers.
Methods
In total, 162 patients with stage IV melanoma and known BRAF mutation status were included. Clinical, histopathological and laboratory information was collected and compared between patients with BRAF mutant (BRAFm) and wild‐type (BRAFwt) melanoma at the time of first distant metastasis.
Results
In total, 88 patients (54%) had BRAFm melanoma (V600E/V600K). At the first distant metastasis, S100B levels in BRAFm patients were more frequently elevated (P = 0·01) and significantly higher (P = 0·02). Median overall survival (mOS) was significantly longer in BRAFwt patients with normal compared with patients with elevated S100B levels (P < 0·01). In BRAFm melanoma, elevated S100B levels showed no prognostic influence (P = 0·18). Elevated lactate dehydrogenase (LDH) levels had a significantly negative impact on mOS in both groups. mOS was increased for BRAFm patients treated with a BRAF inhibitor (BRAFi) compared with BRAFm patients not receiving BRAFi (P = 0·01). No difference in mOS between BRAFm patients who did not receive BRAFi treatment and BRAFwt patients was observed.
Conclusions
Better mOS was observed in BRAFm patients treated with BRAFi. BRAFm patients not treated with BRAFi show similar survival curves to BRAFwt patients. Elevated LDH is a BRAF‐independent prognostic parameter; S100B has prognostic significance in BRAFwt melanoma only.
What's already known about this topic?
BRAF mutation is an important target in the treatment of metastatic melanoma.
BRAF inhibitors improve progression‐free and overall survival in patients with BRAF mutated melanoma.
Lactate dehydrogenase (LDH) and S100B are validated biomarkers in advanced melanoma.
What does this study add?
BRAF mutation does not seem to be a prognostic marker.
LDH is a good prognostic marker, whereas S100B seems to be prognostic only in patients with wild‐type BRAF melanoma.
We contribute to the ongoing discussion about treating BRAF mutant melanoma.
Linked Comment: Sullivan. Br J Dermatol 2016; 174:716–717.
Plain language summary available online</description><identifier>ISSN: 0007-0963</identifier><identifier>EISSN: 1365-2133</identifier><identifier>DOI: 10.1111/bjd.14347</identifier><identifier>PMID: 26659191</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; L-Lactate Dehydrogenase - metabolism ; Male ; Melanoma - genetics ; Melanoma - metabolism ; Melanoma - mortality ; Middle Aged ; Mutation - genetics ; Neoplasm Metastasis ; Prognosis ; Proto-Oncogene Proteins B-raf - genetics ; S100 Calcium Binding Protein beta Subunit - metabolism ; Skin Neoplasms - genetics ; Skin Neoplasms - metabolism ; Skin Neoplasms - mortality ; Survival Analysis ; Young Adult</subject><ispartof>British journal of dermatology (1951), 2016-04, Vol.174 (4), p.823-830</ispartof><rights>2015 British Association of Dermatologists</rights><rights>2015 British Association of Dermatologists.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4037-e5c2ef339c42fc85a6bee72c47d1918f1958fb42a03a33670842b1d998c09ffe3</citedby><cites>FETCH-LOGICAL-c4037-e5c2ef339c42fc85a6bee72c47d1918f1958fb42a03a33670842b1d998c09ffe3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fbjd.14347$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fbjd.14347$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26659191$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Frauchiger, A.L.</creatorcontrib><creatorcontrib>Mangana, J.</creatorcontrib><creatorcontrib>Rechsteiner, M.</creatorcontrib><creatorcontrib>Moch, H.</creatorcontrib><creatorcontrib>Seifert, B.</creatorcontrib><creatorcontrib>Braun, R.P.</creatorcontrib><creatorcontrib>Dummer, R.</creatorcontrib><creatorcontrib>Goldinger, S.M.</creatorcontrib><title>Prognostic relevance of lactate dehydrogenase and serum S100 levels in stage IV melanoma with known BRAF mutation status</title><title>British journal of dermatology (1951)</title><addtitle>Br J Dermatol</addtitle><description>Summary
Background
Activating mutations of BRAF provide an important treatment target in patients with melanoma. The prognostic role of several biochemical markers in relation to mutation status is not clear.
Objectives
To analyse the prognostic significance of BRAF mutation in patients with melanoma and correlate it to different markers.
Methods
In total, 162 patients with stage IV melanoma and known BRAF mutation status were included. Clinical, histopathological and laboratory information was collected and compared between patients with BRAF mutant (BRAFm) and wild‐type (BRAFwt) melanoma at the time of first distant metastasis.
Results
In total, 88 patients (54%) had BRAFm melanoma (V600E/V600K). At the first distant metastasis, S100B levels in BRAFm patients were more frequently elevated (P = 0·01) and significantly higher (P = 0·02). Median overall survival (mOS) was significantly longer in BRAFwt patients with normal compared with patients with elevated S100B levels (P < 0·01). In BRAFm melanoma, elevated S100B levels showed no prognostic influence (P = 0·18). Elevated lactate dehydrogenase (LDH) levels had a significantly negative impact on mOS in both groups. mOS was increased for BRAFm patients treated with a BRAF inhibitor (BRAFi) compared with BRAFm patients not receiving BRAFi (P = 0·01). No difference in mOS between BRAFm patients who did not receive BRAFi treatment and BRAFwt patients was observed.
Conclusions
Better mOS was observed in BRAFm patients treated with BRAFi. BRAFm patients not treated with BRAFi show similar survival curves to BRAFwt patients. Elevated LDH is a BRAF‐independent prognostic parameter; S100B has prognostic significance in BRAFwt melanoma only.
What's already known about this topic?
BRAF mutation is an important target in the treatment of metastatic melanoma.
BRAF inhibitors improve progression‐free and overall survival in patients with BRAF mutated melanoma.
Lactate dehydrogenase (LDH) and S100B are validated biomarkers in advanced melanoma.
What does this study add?
BRAF mutation does not seem to be a prognostic marker.
LDH is a good prognostic marker, whereas S100B seems to be prognostic only in patients with wild‐type BRAF melanoma.
We contribute to the ongoing discussion about treating BRAF mutant melanoma.
Linked Comment: Sullivan. Br J Dermatol 2016; 174:716–717.
Plain language summary available online</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Female</subject><subject>Humans</subject><subject>L-Lactate Dehydrogenase - metabolism</subject><subject>Male</subject><subject>Melanoma - genetics</subject><subject>Melanoma - metabolism</subject><subject>Melanoma - mortality</subject><subject>Middle Aged</subject><subject>Mutation - genetics</subject><subject>Neoplasm Metastasis</subject><subject>Prognosis</subject><subject>Proto-Oncogene Proteins B-raf - genetics</subject><subject>S100 Calcium Binding Protein beta Subunit - metabolism</subject><subject>Skin Neoplasms - genetics</subject><subject>Skin Neoplasms - metabolism</subject><subject>Skin Neoplasms - mortality</subject><subject>Survival Analysis</subject><subject>Young Adult</subject><issn>0007-0963</issn><issn>1365-2133</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMFO3DAURa2qVRmgi_5A5WVZZLDj2I6XMGVgECoIpnRpOc4zBJKY2gnD_D2GAXZ9m7c59-jqIvSdkilNt1_d1VNasEJ-QhPKBM9yythnNCGEyIwowbbQdox3hFBGOPmKtnIhuKKKTtDTRfA3vY9DY3GAFh5NbwF7h1tjBzMAruF2XScGehMBm77GEcLY4StKCE48tBE3PY6DuQG8uMYdtKb3ncGrZrjF971f9fjw8mCOuzH5Gv-KDmPcRV-caSN8e_s76M_8aDk7yc7Ojxezg7PMFoTJDLjNwTGmbJE7W3IjKgCZ20LWqX_pqOKlq4rcEGYYE5KURV7RWqnSEuUcsB30c-N9CP7fCHHQXRMttKkl-DFqKkueU1EWPKF7G9QGH2MApx9C05mw1pTol6F1Glq_Dp3YH2_aseqg_iDfl03A_gZYNS2s_2_Sh6e_3pXZJtHEAZ4-EibcayGZ5Prv72N9eS3mM7Wc6SV7Bs3LltM</recordid><startdate>201604</startdate><enddate>201604</enddate><creator>Frauchiger, A.L.</creator><creator>Mangana, J.</creator><creator>Rechsteiner, M.</creator><creator>Moch, H.</creator><creator>Seifert, B.</creator><creator>Braun, R.P.</creator><creator>Dummer, R.</creator><creator>Goldinger, S.M.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201604</creationdate><title>Prognostic relevance of lactate dehydrogenase and serum S100 levels in stage IV melanoma with known BRAF mutation status</title><author>Frauchiger, A.L. ; Mangana, J. ; Rechsteiner, M. ; Moch, H. ; Seifert, B. ; Braun, R.P. ; Dummer, R. ; Goldinger, S.M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4037-e5c2ef339c42fc85a6bee72c47d1918f1958fb42a03a33670842b1d998c09ffe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Female</topic><topic>Humans</topic><topic>L-Lactate Dehydrogenase - metabolism</topic><topic>Male</topic><topic>Melanoma - genetics</topic><topic>Melanoma - metabolism</topic><topic>Melanoma - mortality</topic><topic>Middle Aged</topic><topic>Mutation - genetics</topic><topic>Neoplasm Metastasis</topic><topic>Prognosis</topic><topic>Proto-Oncogene Proteins B-raf - genetics</topic><topic>S100 Calcium Binding Protein beta Subunit - metabolism</topic><topic>Skin Neoplasms - genetics</topic><topic>Skin Neoplasms - metabolism</topic><topic>Skin Neoplasms - mortality</topic><topic>Survival Analysis</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Frauchiger, A.L.</creatorcontrib><creatorcontrib>Mangana, J.</creatorcontrib><creatorcontrib>Rechsteiner, M.</creatorcontrib><creatorcontrib>Moch, H.</creatorcontrib><creatorcontrib>Seifert, B.</creatorcontrib><creatorcontrib>Braun, R.P.</creatorcontrib><creatorcontrib>Dummer, R.</creatorcontrib><creatorcontrib>Goldinger, S.M.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of dermatology (1951)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Frauchiger, A.L.</au><au>Mangana, J.</au><au>Rechsteiner, M.</au><au>Moch, H.</au><au>Seifert, B.</au><au>Braun, R.P.</au><au>Dummer, R.</au><au>Goldinger, S.M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prognostic relevance of lactate dehydrogenase and serum S100 levels in stage IV melanoma with known BRAF mutation status</atitle><jtitle>British journal of dermatology (1951)</jtitle><addtitle>Br J Dermatol</addtitle><date>2016-04</date><risdate>2016</risdate><volume>174</volume><issue>4</issue><spage>823</spage><epage>830</epage><pages>823-830</pages><issn>0007-0963</issn><eissn>1365-2133</eissn><abstract>Summary
Background
Activating mutations of BRAF provide an important treatment target in patients with melanoma. The prognostic role of several biochemical markers in relation to mutation status is not clear.
Objectives
To analyse the prognostic significance of BRAF mutation in patients with melanoma and correlate it to different markers.
Methods
In total, 162 patients with stage IV melanoma and known BRAF mutation status were included. Clinical, histopathological and laboratory information was collected and compared between patients with BRAF mutant (BRAFm) and wild‐type (BRAFwt) melanoma at the time of first distant metastasis.
Results
In total, 88 patients (54%) had BRAFm melanoma (V600E/V600K). At the first distant metastasis, S100B levels in BRAFm patients were more frequently elevated (P = 0·01) and significantly higher (P = 0·02). Median overall survival (mOS) was significantly longer in BRAFwt patients with normal compared with patients with elevated S100B levels (P < 0·01). In BRAFm melanoma, elevated S100B levels showed no prognostic influence (P = 0·18). Elevated lactate dehydrogenase (LDH) levels had a significantly negative impact on mOS in both groups. mOS was increased for BRAFm patients treated with a BRAF inhibitor (BRAFi) compared with BRAFm patients not receiving BRAFi (P = 0·01). No difference in mOS between BRAFm patients who did not receive BRAFi treatment and BRAFwt patients was observed.
Conclusions
Better mOS was observed in BRAFm patients treated with BRAFi. BRAFm patients not treated with BRAFi show similar survival curves to BRAFwt patients. Elevated LDH is a BRAF‐independent prognostic parameter; S100B has prognostic significance in BRAFwt melanoma only.
What's already known about this topic?
BRAF mutation is an important target in the treatment of metastatic melanoma.
BRAF inhibitors improve progression‐free and overall survival in patients with BRAF mutated melanoma.
Lactate dehydrogenase (LDH) and S100B are validated biomarkers in advanced melanoma.
What does this study add?
BRAF mutation does not seem to be a prognostic marker.
LDH is a good prognostic marker, whereas S100B seems to be prognostic only in patients with wild‐type BRAF melanoma.
We contribute to the ongoing discussion about treating BRAF mutant melanoma.
Linked Comment: Sullivan. Br J Dermatol 2016; 174:716–717.
Plain language summary available online</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>26659191</pmid><doi>10.1111/bjd.14347</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0007-0963 |
| ispartof | British journal of dermatology (1951), 2016-04, Vol.174 (4), p.823-830 |
| issn | 0007-0963 1365-2133 |
| language | eng |
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| source | MEDLINE; Access via Wiley Online Library; Oxford University Press Journals All Titles (1996-Current) |
| subjects | Adolescent Adult Aged Aged, 80 and over Female Humans L-Lactate Dehydrogenase - metabolism Male Melanoma - genetics Melanoma - metabolism Melanoma - mortality Middle Aged Mutation - genetics Neoplasm Metastasis Prognosis Proto-Oncogene Proteins B-raf - genetics S100 Calcium Binding Protein beta Subunit - metabolism Skin Neoplasms - genetics Skin Neoplasms - metabolism Skin Neoplasms - mortality Survival Analysis Young Adult |
| title | Prognostic relevance of lactate dehydrogenase and serum S100 levels in stage IV melanoma with known BRAF mutation status |
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