Cell-free Circulating Tumor DNA Variant Allele Frequency Associates with Survival in Metastatic Cancer
Physicians are expected to assess prognosis both for patient counseling and for determining suitability for clinical trials. Increasingly, cell-free circulating tumor DNA (cfDNA) sequencing is being performed for clinical decision making. We sought to determine whether variant allele frequency (VAF)...
Gespeichert in:
| Veröffentlicht in: | Clinical cancer research 2020-04, Vol.26 (8), p.1924-1931 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1931 |
|---|---|
| container_issue | 8 |
| container_start_page | 1924 |
| container_title | Clinical cancer research |
| container_volume | 26 |
| creator | Pairawan, Seyed Hess, Kenneth R Janku, Filip Sanchez, Nora S Mills Shaw, Kenna R Eng, Cathy Damodaran, Senthilkumar Javle, Milind Kaseb, Ahmed O Hong, David S Subbiah, Vivek Fu, Siqing Fogelman, David R Raymond, Victoria M Lanman, Richard B Meric-Bernstam, Funda |
| description | Physicians are expected to assess prognosis both for patient counseling and for determining suitability for clinical trials. Increasingly, cell-free circulating tumor DNA (cfDNA) sequencing is being performed for clinical decision making. We sought to determine whether variant allele frequency (VAF) in cfDNA is associated with prognosis.
We performed a retrospective analysis of 298 patients with metastatic disease who underwent clinical comprehensive cfDNA analysis and assessed association between VAF and overall survival.
cfDNA mutations were detected in 240 patients (80.5%). Median overall survival (OS) was 11.5 months. cfDNA mutation detection and number of nonsynonymous mutations (NSM) significantly differed between tumor types, being lowest in appendiceal cancer and highest in colon cancer. Having more than one NSM detected was associated with significantly worse OS (HR = 2.3;
< 0.0001). VAF was classified by quartiles, Q1 lowest, Q4 highest VAF. Higher VAF levels were associated with a significantly worse overall survival (VAF Q3 HR 2.3,
= 0.0069; VAF Q4 HR = 3.8,
< 0.0001) on univariate analysis. On multivariate analysis, VAF Q4, male sex, albumin level 0 and number of prior therapies >4 were independent predictors of worse OS.
Higher levels of cfDNA VAF and a higher number of NSMs were associated with worse OS in patients with metastatic disease. Further study is needed to determine optimal VAF thresholds for clinical decision making and the utility of cfDNA VAF as a prognostic marker in different tumor types. |
| doi_str_mv | 10.1158/1078-0432.CCR-19-0306 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7771658</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2328771368</sourcerecordid><originalsourceid>FETCH-LOGICAL-c411t-3a6cd583b437e1bfdd717fa66b463b6a2dee3febbec7c5e30e6cd5154b6299433</originalsourceid><addsrcrecordid>eNpVkUtv1TAQhS0E6uPSnwDykk1aTya2czdIV4E-pAIStN1ajjNpjXyTYjsX9d-TqA-V1Viab86Mz2HsA4hjAFmfgNB1ISosj5vmZwHrQqBQb9gBSKkLLJV8O7-fmX12mNJvIaACUe2xfYRaljXiAesbCqHoIxFvfHRTsNkPt_xq2o6Rf_m-4Tc2ejtkvgmBAvHTSH8mGtwD36Q0Om8zJf7X5zv-a4o7v7OB-4F_o2xTnqUcb-zgKL5n73obEh091RW7Pv161ZwXlz_OLprNZeEqgFygVa6TNbYVaoK27zoNurdKtZXCVtmyI8Ke2pacdpJQ0MKDrFpVrtcV4op9ftS9n9otdY6GHG0w99FvbXwwo_Xm_87g78ztuDNaa1Dz5hX79CQQx_mjKZutT272yA40TsmUWNYzimpB5SPq4phSpP5lDQizZGQW_83iv5kzMrA2S0bz3MfXN75MPYeC_wANXY-z</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2328771368</pqid></control><display><type>article</type><title>Cell-free Circulating Tumor DNA Variant Allele Frequency Associates with Survival in Metastatic Cancer</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>American Association for Cancer Research</source><source>Alma/SFX Local Collection</source><creator>Pairawan, Seyed ; Hess, Kenneth R ; Janku, Filip ; Sanchez, Nora S ; Mills Shaw, Kenna R ; Eng, Cathy ; Damodaran, Senthilkumar ; Javle, Milind ; Kaseb, Ahmed O ; Hong, David S ; Subbiah, Vivek ; Fu, Siqing ; Fogelman, David R ; Raymond, Victoria M ; Lanman, Richard B ; Meric-Bernstam, Funda</creator><creatorcontrib>Pairawan, Seyed ; Hess, Kenneth R ; Janku, Filip ; Sanchez, Nora S ; Mills Shaw, Kenna R ; Eng, Cathy ; Damodaran, Senthilkumar ; Javle, Milind ; Kaseb, Ahmed O ; Hong, David S ; Subbiah, Vivek ; Fu, Siqing ; Fogelman, David R ; Raymond, Victoria M ; Lanman, Richard B ; Meric-Bernstam, Funda</creatorcontrib><description>Physicians are expected to assess prognosis both for patient counseling and for determining suitability for clinical trials. Increasingly, cell-free circulating tumor DNA (cfDNA) sequencing is being performed for clinical decision making. We sought to determine whether variant allele frequency (VAF) in cfDNA is associated with prognosis.
We performed a retrospective analysis of 298 patients with metastatic disease who underwent clinical comprehensive cfDNA analysis and assessed association between VAF and overall survival.
cfDNA mutations were detected in 240 patients (80.5%). Median overall survival (OS) was 11.5 months. cfDNA mutation detection and number of nonsynonymous mutations (NSM) significantly differed between tumor types, being lowest in appendiceal cancer and highest in colon cancer. Having more than one NSM detected was associated with significantly worse OS (HR = 2.3;
< 0.0001). VAF was classified by quartiles, Q1 lowest, Q4 highest VAF. Higher VAF levels were associated with a significantly worse overall survival (VAF Q3 HR 2.3,
= 0.0069; VAF Q4 HR = 3.8,
< 0.0001) on univariate analysis. On multivariate analysis, VAF Q4, male sex, albumin level <3.5 g/dL, number of nonvisceral metastatic sites >0 and number of prior therapies >4 were independent predictors of worse OS.
Higher levels of cfDNA VAF and a higher number of NSMs were associated with worse OS in patients with metastatic disease. Further study is needed to determine optimal VAF thresholds for clinical decision making and the utility of cfDNA VAF as a prognostic marker in different tumor types.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-19-0306</identifier><identifier>PMID: 31852833</identifier><language>eng</language><publisher>United States</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor - blood ; Biomarkers, Tumor - genetics ; Cell-Free Nucleic Acids - blood ; Cell-Free Nucleic Acids - genetics ; Child ; Female ; Gene Frequency ; High-Throughput Nucleotide Sequencing - methods ; Humans ; Male ; Middle Aged ; Mutation ; Neoplasm Metastasis ; Neoplasms - blood ; Neoplasms - genetics ; Neoplasms - mortality ; Neoplasms - pathology ; Prognosis ; Retrospective Studies ; Survival Rate ; Young Adult</subject><ispartof>Clinical cancer research, 2020-04, Vol.26 (8), p.1924-1931</ispartof><rights>2020 American Association for Cancer Research.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c411t-3a6cd583b437e1bfdd717fa66b463b6a2dee3febbec7c5e30e6cd5154b6299433</citedby><cites>FETCH-LOGICAL-c411t-3a6cd583b437e1bfdd717fa66b463b6a2dee3febbec7c5e30e6cd5154b6299433</cites><orcidid>0000-0002-6064-6837 ; 0000-0001-8721-1609 ; 0000-0001-5223-0981 ; 0000-0002-8123-4065 ; 0000-0001-8122-4329</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,3347,27915,27916</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31852833$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pairawan, Seyed</creatorcontrib><creatorcontrib>Hess, Kenneth R</creatorcontrib><creatorcontrib>Janku, Filip</creatorcontrib><creatorcontrib>Sanchez, Nora S</creatorcontrib><creatorcontrib>Mills Shaw, Kenna R</creatorcontrib><creatorcontrib>Eng, Cathy</creatorcontrib><creatorcontrib>Damodaran, Senthilkumar</creatorcontrib><creatorcontrib>Javle, Milind</creatorcontrib><creatorcontrib>Kaseb, Ahmed O</creatorcontrib><creatorcontrib>Hong, David S</creatorcontrib><creatorcontrib>Subbiah, Vivek</creatorcontrib><creatorcontrib>Fu, Siqing</creatorcontrib><creatorcontrib>Fogelman, David R</creatorcontrib><creatorcontrib>Raymond, Victoria M</creatorcontrib><creatorcontrib>Lanman, Richard B</creatorcontrib><creatorcontrib>Meric-Bernstam, Funda</creatorcontrib><title>Cell-free Circulating Tumor DNA Variant Allele Frequency Associates with Survival in Metastatic Cancer</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Physicians are expected to assess prognosis both for patient counseling and for determining suitability for clinical trials. Increasingly, cell-free circulating tumor DNA (cfDNA) sequencing is being performed for clinical decision making. We sought to determine whether variant allele frequency (VAF) in cfDNA is associated with prognosis.
We performed a retrospective analysis of 298 patients with metastatic disease who underwent clinical comprehensive cfDNA analysis and assessed association between VAF and overall survival.
cfDNA mutations were detected in 240 patients (80.5%). Median overall survival (OS) was 11.5 months. cfDNA mutation detection and number of nonsynonymous mutations (NSM) significantly differed between tumor types, being lowest in appendiceal cancer and highest in colon cancer. Having more than one NSM detected was associated with significantly worse OS (HR = 2.3;
< 0.0001). VAF was classified by quartiles, Q1 lowest, Q4 highest VAF. Higher VAF levels were associated with a significantly worse overall survival (VAF Q3 HR 2.3,
= 0.0069; VAF Q4 HR = 3.8,
< 0.0001) on univariate analysis. On multivariate analysis, VAF Q4, male sex, albumin level <3.5 g/dL, number of nonvisceral metastatic sites >0 and number of prior therapies >4 were independent predictors of worse OS.
Higher levels of cfDNA VAF and a higher number of NSMs were associated with worse OS in patients with metastatic disease. Further study is needed to determine optimal VAF thresholds for clinical decision making and the utility of cfDNA VAF as a prognostic marker in different tumor types.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biomarkers, Tumor - blood</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Cell-Free Nucleic Acids - blood</subject><subject>Cell-Free Nucleic Acids - genetics</subject><subject>Child</subject><subject>Female</subject><subject>Gene Frequency</subject><subject>High-Throughput Nucleotide Sequencing - methods</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Neoplasm Metastasis</subject><subject>Neoplasms - blood</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - mortality</subject><subject>Neoplasms - pathology</subject><subject>Prognosis</subject><subject>Retrospective Studies</subject><subject>Survival Rate</subject><subject>Young Adult</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkUtv1TAQhS0E6uPSnwDykk1aTya2czdIV4E-pAIStN1ajjNpjXyTYjsX9d-TqA-V1Viab86Mz2HsA4hjAFmfgNB1ISosj5vmZwHrQqBQb9gBSKkLLJV8O7-fmX12mNJvIaACUe2xfYRaljXiAesbCqHoIxFvfHRTsNkPt_xq2o6Rf_m-4Tc2ejtkvgmBAvHTSH8mGtwD36Q0Om8zJf7X5zv-a4o7v7OB-4F_o2xTnqUcb-zgKL5n73obEh091RW7Pv161ZwXlz_OLprNZeEqgFygVa6TNbYVaoK27zoNurdKtZXCVtmyI8Ke2pacdpJQ0MKDrFpVrtcV4op9ftS9n9otdY6GHG0w99FvbXwwo_Xm_87g78ztuDNaa1Dz5hX79CQQx_mjKZutT272yA40TsmUWNYzimpB5SPq4phSpP5lDQizZGQW_83iv5kzMrA2S0bz3MfXN75MPYeC_wANXY-z</recordid><startdate>20200415</startdate><enddate>20200415</enddate><creator>Pairawan, Seyed</creator><creator>Hess, Kenneth R</creator><creator>Janku, Filip</creator><creator>Sanchez, Nora S</creator><creator>Mills Shaw, Kenna R</creator><creator>Eng, Cathy</creator><creator>Damodaran, Senthilkumar</creator><creator>Javle, Milind</creator><creator>Kaseb, Ahmed O</creator><creator>Hong, David S</creator><creator>Subbiah, Vivek</creator><creator>Fu, Siqing</creator><creator>Fogelman, David R</creator><creator>Raymond, Victoria M</creator><creator>Lanman, Richard B</creator><creator>Meric-Bernstam, Funda</creator><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><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6064-6837</orcidid><orcidid>https://orcid.org/0000-0001-8721-1609</orcidid><orcidid>https://orcid.org/0000-0001-5223-0981</orcidid><orcidid>https://orcid.org/0000-0002-8123-4065</orcidid><orcidid>https://orcid.org/0000-0001-8122-4329</orcidid></search><sort><creationdate>20200415</creationdate><title>Cell-free Circulating Tumor DNA Variant Allele Frequency Associates with Survival in Metastatic Cancer</title><author>Pairawan, Seyed ; Hess, Kenneth R ; Janku, Filip ; Sanchez, Nora S ; Mills Shaw, Kenna R ; Eng, Cathy ; Damodaran, Senthilkumar ; Javle, Milind ; Kaseb, Ahmed O ; Hong, David S ; Subbiah, Vivek ; Fu, Siqing ; Fogelman, David R ; Raymond, Victoria M ; Lanman, Richard B ; Meric-Bernstam, Funda</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c411t-3a6cd583b437e1bfdd717fa66b463b6a2dee3febbec7c5e30e6cd5154b6299433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biomarkers, Tumor - blood</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Cell-Free Nucleic Acids - blood</topic><topic>Cell-Free Nucleic Acids - genetics</topic><topic>Child</topic><topic>Female</topic><topic>Gene Frequency</topic><topic>High-Throughput Nucleotide Sequencing - methods</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Neoplasm Metastasis</topic><topic>Neoplasms - blood</topic><topic>Neoplasms - genetics</topic><topic>Neoplasms - mortality</topic><topic>Neoplasms - pathology</topic><topic>Prognosis</topic><topic>Retrospective Studies</topic><topic>Survival Rate</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pairawan, Seyed</creatorcontrib><creatorcontrib>Hess, Kenneth R</creatorcontrib><creatorcontrib>Janku, Filip</creatorcontrib><creatorcontrib>Sanchez, Nora S</creatorcontrib><creatorcontrib>Mills Shaw, Kenna R</creatorcontrib><creatorcontrib>Eng, Cathy</creatorcontrib><creatorcontrib>Damodaran, Senthilkumar</creatorcontrib><creatorcontrib>Javle, Milind</creatorcontrib><creatorcontrib>Kaseb, Ahmed O</creatorcontrib><creatorcontrib>Hong, David S</creatorcontrib><creatorcontrib>Subbiah, Vivek</creatorcontrib><creatorcontrib>Fu, Siqing</creatorcontrib><creatorcontrib>Fogelman, David R</creatorcontrib><creatorcontrib>Raymond, Victoria M</creatorcontrib><creatorcontrib>Lanman, Richard B</creatorcontrib><creatorcontrib>Meric-Bernstam, Funda</creatorcontrib><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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pairawan, Seyed</au><au>Hess, Kenneth R</au><au>Janku, Filip</au><au>Sanchez, Nora S</au><au>Mills Shaw, Kenna R</au><au>Eng, Cathy</au><au>Damodaran, Senthilkumar</au><au>Javle, Milind</au><au>Kaseb, Ahmed O</au><au>Hong, David S</au><au>Subbiah, Vivek</au><au>Fu, Siqing</au><au>Fogelman, David R</au><au>Raymond, Victoria M</au><au>Lanman, Richard B</au><au>Meric-Bernstam, Funda</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cell-free Circulating Tumor DNA Variant Allele Frequency Associates with Survival in Metastatic Cancer</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2020-04-15</date><risdate>2020</risdate><volume>26</volume><issue>8</issue><spage>1924</spage><epage>1931</epage><pages>1924-1931</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Physicians are expected to assess prognosis both for patient counseling and for determining suitability for clinical trials. Increasingly, cell-free circulating tumor DNA (cfDNA) sequencing is being performed for clinical decision making. We sought to determine whether variant allele frequency (VAF) in cfDNA is associated with prognosis.
We performed a retrospective analysis of 298 patients with metastatic disease who underwent clinical comprehensive cfDNA analysis and assessed association between VAF and overall survival.
cfDNA mutations were detected in 240 patients (80.5%). Median overall survival (OS) was 11.5 months. cfDNA mutation detection and number of nonsynonymous mutations (NSM) significantly differed between tumor types, being lowest in appendiceal cancer and highest in colon cancer. Having more than one NSM detected was associated with significantly worse OS (HR = 2.3;
< 0.0001). VAF was classified by quartiles, Q1 lowest, Q4 highest VAF. Higher VAF levels were associated with a significantly worse overall survival (VAF Q3 HR 2.3,
= 0.0069; VAF Q4 HR = 3.8,
< 0.0001) on univariate analysis. On multivariate analysis, VAF Q4, male sex, albumin level <3.5 g/dL, number of nonvisceral metastatic sites >0 and number of prior therapies >4 were independent predictors of worse OS.
Higher levels of cfDNA VAF and a higher number of NSMs were associated with worse OS in patients with metastatic disease. Further study is needed to determine optimal VAF thresholds for clinical decision making and the utility of cfDNA VAF as a prognostic marker in different tumor types.</abstract><cop>United States</cop><pmid>31852833</pmid><doi>10.1158/1078-0432.CCR-19-0306</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-6064-6837</orcidid><orcidid>https://orcid.org/0000-0001-8721-1609</orcidid><orcidid>https://orcid.org/0000-0001-5223-0981</orcidid><orcidid>https://orcid.org/0000-0002-8123-4065</orcidid><orcidid>https://orcid.org/0000-0001-8122-4329</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1078-0432 |
| ispartof | Clinical cancer research, 2020-04, Vol.26 (8), p.1924-1931 |
| issn | 1078-0432 1557-3265 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7771658 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research; Alma/SFX Local Collection |
| subjects | Adolescent Adult Aged Aged, 80 and over Biomarkers, Tumor - blood Biomarkers, Tumor - genetics Cell-Free Nucleic Acids - blood Cell-Free Nucleic Acids - genetics Child Female Gene Frequency High-Throughput Nucleotide Sequencing - methods Humans Male Middle Aged Mutation Neoplasm Metastasis Neoplasms - blood Neoplasms - genetics Neoplasms - mortality Neoplasms - pathology Prognosis Retrospective Studies Survival Rate Young Adult |
| title | Cell-free Circulating Tumor DNA Variant Allele Frequency Associates with Survival in Metastatic Cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T06%3A42%3A48IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cell-free%20Circulating%20Tumor%20DNA%20Variant%20Allele%20Frequency%20Associates%20with%20Survival%20in%20Metastatic%20Cancer&rft.jtitle=Clinical%20cancer%20research&rft.au=Pairawan,%20Seyed&rft.date=2020-04-15&rft.volume=26&rft.issue=8&rft.spage=1924&rft.epage=1931&rft.pages=1924-1931&rft.issn=1078-0432&rft.eissn=1557-3265&rft_id=info:doi/10.1158/1078-0432.CCR-19-0306&rft_dat=%3Cproquest_pubme%3E2328771368%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2328771368&rft_id=info:pmid/31852833&rfr_iscdi=true |