Hypermutated Circulating Tumor DNA: Correlation with Response to Checkpoint Inhibitor-Based Immunotherapy
Tumor mutational burden detected by tissue next-generation sequencing (NGS) correlates with checkpoint inhibitor response. However, tissue biopsy may be costly and invasive. We sought to investigate the association between hypermutated blood-derived circulating tumor DNA (ctDNA) and checkpoint inhib...
Gespeichert in:
| Veröffentlicht in: | Clinical cancer research 2017-10, Vol.23 (19), p.5729-5736 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 5736 |
|---|---|
| container_issue | 19 |
| container_start_page | 5729 |
| container_title | Clinical cancer research |
| container_volume | 23 |
| creator | Khagi, Yulian Goodman, Aaron M Daniels, Gregory A Patel, Sandip P Sacco, Assuntina G Randall, James M Bazhenova, Lyudmila A Kurzrock, Razelle |
| description | Tumor mutational burden detected by tissue next-generation sequencing (NGS) correlates with checkpoint inhibitor response. However, tissue biopsy may be costly and invasive. We sought to investigate the association between hypermutated blood-derived circulating tumor DNA (ctDNA) and checkpoint inhibitor response.
We assessed 69 patients with diverse malignancies who received checkpoint inhibitor-based immunotherapy and blood-derived ctDNA NGS testing (54-70 genes). Rates of stable disease (SD) ≥6 months, partial and complete response (PR, CR), progression-free survival (PFS), and overall survival (OS) were assessed based on total and VUS alterations.
Statistically significant improvement in PFS was associated with high versus low alteration number in variants of unknown significance (VUS, >3 alterations versus VUS ≤3 alterations), SD ≥6 months/PR/CR 45% versus 15%, respectively;
= 0.014. Similar results were seen with high versus low total alteration number (characterized plus VUS, ≥6 vs. 3 had a median PFS of 23 versus 2.3 months (
= 0.0004).
Given the association of alteration number on liquid biopsy and checkpoint inhibitor-based immunotherapy outcomes, further investigation of hypermutated ctDNA as a predictive biomarker is warranted.
. |
| doi_str_mv | 10.1158/1078-0432.CCR-17-1439 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1946424585</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1983410675</sourcerecordid><originalsourceid>FETCH-LOGICAL-c384t-58693257a43d731dcb4c4ad747a2eec1c35f8f2c268d25341d3c874eb7e8578c3</originalsourceid><addsrcrecordid>eNpdkUtLxDAUhYMovn-CEnDjpmOeTcad1teAKIiuQya940SnTU1SZP69LT4Wru7l8p3D5RyEjiiZUCr1GSVKF0RwNqmqp4Kqggo-3UC7VEpVcFbKzWH_ZXbQXkpvhFBBidhGO0xPFSNa7CJ_t-4gNn22GWpc-ej6lc2-fcXPfRMivnq4OMdViBHGc2jxp89L_ASpC20CnAOuluDeu-DbjGft0s99DrG4tGmwmzVN34a8hGi79QHaWthVgsOfuY9ebq6fq7vi_vF2Vl3cF45rkQupyylnUlnBa8Vp7ebCCVsroSwDcNRxudAL5lipaya5oDV3WgmYK9BSacf30em3bxfDRw8pm8YnB6uVbSH0ydCpKAUTUssBPfmHvoU-tsN3A6UHb1KqkZLflIshpQgL00Xf2Lg2lJixCzPmbMaczdCFocqMXQy64x_3ft5A_af6DZ9_AdjphTk</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1983410675</pqid></control><display><type>article</type><title>Hypermutated Circulating Tumor DNA: Correlation with Response to Checkpoint Inhibitor-Based Immunotherapy</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Khagi, Yulian ; Goodman, Aaron M ; Daniels, Gregory A ; Patel, Sandip P ; Sacco, Assuntina G ; Randall, James M ; Bazhenova, Lyudmila A ; Kurzrock, Razelle</creator><creatorcontrib>Khagi, Yulian ; Goodman, Aaron M ; Daniels, Gregory A ; Patel, Sandip P ; Sacco, Assuntina G ; Randall, James M ; Bazhenova, Lyudmila A ; Kurzrock, Razelle</creatorcontrib><description>Tumor mutational burden detected by tissue next-generation sequencing (NGS) correlates with checkpoint inhibitor response. However, tissue biopsy may be costly and invasive. We sought to investigate the association between hypermutated blood-derived circulating tumor DNA (ctDNA) and checkpoint inhibitor response.
We assessed 69 patients with diverse malignancies who received checkpoint inhibitor-based immunotherapy and blood-derived ctDNA NGS testing (54-70 genes). Rates of stable disease (SD) ≥6 months, partial and complete response (PR, CR), progression-free survival (PFS), and overall survival (OS) were assessed based on total and VUS alterations.
Statistically significant improvement in PFS was associated with high versus low alteration number in variants of unknown significance (VUS, >3 alterations versus VUS ≤3 alterations), SD ≥6 months/PR/CR 45% versus 15%, respectively;
= 0.014. Similar results were seen with high versus low total alteration number (characterized plus VUS, ≥6 vs. <6). Statistically significant OS improvement was also associated with high VUS alteration status. Two-month landmark analysis showed that responders versus nonresponders with VUS >3 had a median PFS of 23 versus 2.3 months (
= 0.0004).
Given the association of alteration number on liquid biopsy and checkpoint inhibitor-based immunotherapy outcomes, further investigation of hypermutated ctDNA as a predictive biomarker is warranted.
.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-17-1439</identifier><identifier>PMID: 28972084</identifier><language>eng</language><publisher>United States: American Association for Cancer Research Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Biomarkers ; Biomarkers, Tumor - blood ; Biomarkers, Tumor - genetics ; Biopsy ; Blood ; Blood circulation ; Cancer ; Circulating Tumor DNA - blood ; Circulating Tumor DNA - genetics ; Deoxyribonucleic acid ; Disease-Free Survival ; DNA ; DNA, Neoplasm - blood ; Experimental design ; Female ; Gene Expression Regulation, Neoplastic - drug effects ; Genes, cdc - drug effects ; High-Throughput Nucleotide Sequencing ; Humans ; Immune checkpoint ; Immunotherapy ; Inhibitors ; Invasiveness ; Male ; Middle Aged ; Mutation ; Neoplasm Proteins ; Neoplasms - blood ; Neoplasms - drug therapy ; Neoplasms - genetics ; Neoplasms - pathology ; Statistical analysis ; Statistical significance ; Survival</subject><ispartof>Clinical cancer research, 2017-10, Vol.23 (19), p.5729-5736</ispartof><rights>2017 American Association for Cancer Research.</rights><rights>Copyright American Association for Cancer Research Inc Oct 1, 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-58693257a43d731dcb4c4ad747a2eec1c35f8f2c268d25341d3c874eb7e8578c3</citedby><cites>FETCH-LOGICAL-c384t-58693257a43d731dcb4c4ad747a2eec1c35f8f2c268d25341d3c874eb7e8578c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3356,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28972084$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Khagi, Yulian</creatorcontrib><creatorcontrib>Goodman, Aaron M</creatorcontrib><creatorcontrib>Daniels, Gregory A</creatorcontrib><creatorcontrib>Patel, Sandip P</creatorcontrib><creatorcontrib>Sacco, Assuntina G</creatorcontrib><creatorcontrib>Randall, James M</creatorcontrib><creatorcontrib>Bazhenova, Lyudmila A</creatorcontrib><creatorcontrib>Kurzrock, Razelle</creatorcontrib><title>Hypermutated Circulating Tumor DNA: Correlation with Response to Checkpoint Inhibitor-Based Immunotherapy</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Tumor mutational burden detected by tissue next-generation sequencing (NGS) correlates with checkpoint inhibitor response. However, tissue biopsy may be costly and invasive. We sought to investigate the association between hypermutated blood-derived circulating tumor DNA (ctDNA) and checkpoint inhibitor response.
We assessed 69 patients with diverse malignancies who received checkpoint inhibitor-based immunotherapy and blood-derived ctDNA NGS testing (54-70 genes). Rates of stable disease (SD) ≥6 months, partial and complete response (PR, CR), progression-free survival (PFS), and overall survival (OS) were assessed based on total and VUS alterations.
Statistically significant improvement in PFS was associated with high versus low alteration number in variants of unknown significance (VUS, >3 alterations versus VUS ≤3 alterations), SD ≥6 months/PR/CR 45% versus 15%, respectively;
= 0.014. Similar results were seen with high versus low total alteration number (characterized plus VUS, ≥6 vs. <6). Statistically significant OS improvement was also associated with high VUS alteration status. Two-month landmark analysis showed that responders versus nonresponders with VUS >3 had a median PFS of 23 versus 2.3 months (
= 0.0004).
Given the association of alteration number on liquid biopsy and checkpoint inhibitor-based immunotherapy outcomes, further investigation of hypermutated ctDNA as a predictive biomarker is warranted.
.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - blood</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biopsy</subject><subject>Blood</subject><subject>Blood circulation</subject><subject>Cancer</subject><subject>Circulating Tumor DNA - blood</subject><subject>Circulating Tumor DNA - genetics</subject><subject>Deoxyribonucleic acid</subject><subject>Disease-Free Survival</subject><subject>DNA</subject><subject>DNA, Neoplasm - blood</subject><subject>Experimental design</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Genes, cdc - drug effects</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Humans</subject><subject>Immune checkpoint</subject><subject>Immunotherapy</subject><subject>Inhibitors</subject><subject>Invasiveness</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Neoplasm Proteins</subject><subject>Neoplasms - blood</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - pathology</subject><subject>Statistical analysis</subject><subject>Statistical significance</subject><subject>Survival</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkUtLxDAUhYMovn-CEnDjpmOeTcad1teAKIiuQya940SnTU1SZP69LT4Wru7l8p3D5RyEjiiZUCr1GSVKF0RwNqmqp4Kqggo-3UC7VEpVcFbKzWH_ZXbQXkpvhFBBidhGO0xPFSNa7CJ_t-4gNn22GWpc-ej6lc2-fcXPfRMivnq4OMdViBHGc2jxp89L_ASpC20CnAOuluDeu-DbjGft0s99DrG4tGmwmzVN34a8hGi79QHaWthVgsOfuY9ebq6fq7vi_vF2Vl3cF45rkQupyylnUlnBa8Vp7ebCCVsroSwDcNRxudAL5lipaya5oDV3WgmYK9BSacf30em3bxfDRw8pm8YnB6uVbSH0ydCpKAUTUssBPfmHvoU-tsN3A6UHb1KqkZLflIshpQgL00Xf2Lg2lJixCzPmbMaczdCFocqMXQy64x_3ft5A_af6DZ9_AdjphTk</recordid><startdate>20171001</startdate><enddate>20171001</enddate><creator>Khagi, Yulian</creator><creator>Goodman, Aaron M</creator><creator>Daniels, Gregory A</creator><creator>Patel, Sandip P</creator><creator>Sacco, Assuntina G</creator><creator>Randall, James M</creator><creator>Bazhenova, Lyudmila A</creator><creator>Kurzrock, Razelle</creator><general>American Association for Cancer Research Inc</general><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>7QO</scope><scope>7T5</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20171001</creationdate><title>Hypermutated Circulating Tumor DNA: Correlation with Response to Checkpoint Inhibitor-Based Immunotherapy</title><author>Khagi, Yulian ; Goodman, Aaron M ; Daniels, Gregory A ; Patel, Sandip P ; Sacco, Assuntina G ; Randall, James M ; Bazhenova, Lyudmila A ; Kurzrock, Razelle</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-58693257a43d731dcb4c4ad747a2eec1c35f8f2c268d25341d3c874eb7e8578c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - blood</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biopsy</topic><topic>Blood</topic><topic>Blood circulation</topic><topic>Cancer</topic><topic>Circulating Tumor DNA - blood</topic><topic>Circulating Tumor DNA - genetics</topic><topic>Deoxyribonucleic acid</topic><topic>Disease-Free Survival</topic><topic>DNA</topic><topic>DNA, Neoplasm - blood</topic><topic>Experimental design</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Genes, cdc - drug effects</topic><topic>High-Throughput Nucleotide Sequencing</topic><topic>Humans</topic><topic>Immune checkpoint</topic><topic>Immunotherapy</topic><topic>Inhibitors</topic><topic>Invasiveness</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Neoplasm Proteins</topic><topic>Neoplasms - blood</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - genetics</topic><topic>Neoplasms - pathology</topic><topic>Statistical analysis</topic><topic>Statistical significance</topic><topic>Survival</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Khagi, Yulian</creatorcontrib><creatorcontrib>Goodman, Aaron M</creatorcontrib><creatorcontrib>Daniels, Gregory A</creatorcontrib><creatorcontrib>Patel, Sandip P</creatorcontrib><creatorcontrib>Sacco, Assuntina G</creatorcontrib><creatorcontrib>Randall, James M</creatorcontrib><creatorcontrib>Bazhenova, Lyudmila A</creatorcontrib><creatorcontrib>Kurzrock, Razelle</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Khagi, Yulian</au><au>Goodman, Aaron M</au><au>Daniels, Gregory A</au><au>Patel, Sandip P</au><au>Sacco, Assuntina G</au><au>Randall, James M</au><au>Bazhenova, Lyudmila A</au><au>Kurzrock, Razelle</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hypermutated Circulating Tumor DNA: Correlation with Response to Checkpoint Inhibitor-Based Immunotherapy</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2017-10-01</date><risdate>2017</risdate><volume>23</volume><issue>19</issue><spage>5729</spage><epage>5736</epage><pages>5729-5736</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Tumor mutational burden detected by tissue next-generation sequencing (NGS) correlates with checkpoint inhibitor response. However, tissue biopsy may be costly and invasive. We sought to investigate the association between hypermutated blood-derived circulating tumor DNA (ctDNA) and checkpoint inhibitor response.
We assessed 69 patients with diverse malignancies who received checkpoint inhibitor-based immunotherapy and blood-derived ctDNA NGS testing (54-70 genes). Rates of stable disease (SD) ≥6 months, partial and complete response (PR, CR), progression-free survival (PFS), and overall survival (OS) were assessed based on total and VUS alterations.
Statistically significant improvement in PFS was associated with high versus low alteration number in variants of unknown significance (VUS, >3 alterations versus VUS ≤3 alterations), SD ≥6 months/PR/CR 45% versus 15%, respectively;
= 0.014. Similar results were seen with high versus low total alteration number (characterized plus VUS, ≥6 vs. <6). Statistically significant OS improvement was also associated with high VUS alteration status. Two-month landmark analysis showed that responders versus nonresponders with VUS >3 had a median PFS of 23 versus 2.3 months (
= 0.0004).
Given the association of alteration number on liquid biopsy and checkpoint inhibitor-based immunotherapy outcomes, further investigation of hypermutated ctDNA as a predictive biomarker is warranted.
.</abstract><cop>United States</cop><pub>American Association for Cancer Research Inc</pub><pmid>28972084</pmid><doi>10.1158/1078-0432.CCR-17-1439</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1078-0432 |
| ispartof | Clinical cancer research, 2017-10, Vol.23 (19), p.5729-5736 |
| issn | 1078-0432 1557-3265 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1946424585 |
| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adult Aged Aged, 80 and over Biomarkers Biomarkers, Tumor - blood Biomarkers, Tumor - genetics Biopsy Blood Blood circulation Cancer Circulating Tumor DNA - blood Circulating Tumor DNA - genetics Deoxyribonucleic acid Disease-Free Survival DNA DNA, Neoplasm - blood Experimental design Female Gene Expression Regulation, Neoplastic - drug effects Genes, cdc - drug effects High-Throughput Nucleotide Sequencing Humans Immune checkpoint Immunotherapy Inhibitors Invasiveness Male Middle Aged Mutation Neoplasm Proteins Neoplasms - blood Neoplasms - drug therapy Neoplasms - genetics Neoplasms - pathology Statistical analysis Statistical significance Survival |
| title | Hypermutated Circulating Tumor DNA: Correlation with Response to Checkpoint Inhibitor-Based Immunotherapy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-03T05%3A22%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Hypermutated%20Circulating%20Tumor%20DNA:%20Correlation%20with%20Response%20to%20Checkpoint%20Inhibitor-Based%20Immunotherapy&rft.jtitle=Clinical%20cancer%20research&rft.au=Khagi,%20Yulian&rft.date=2017-10-01&rft.volume=23&rft.issue=19&rft.spage=5729&rft.epage=5736&rft.pages=5729-5736&rft.issn=1078-0432&rft.eissn=1557-3265&rft_id=info:doi/10.1158/1078-0432.CCR-17-1439&rft_dat=%3Cproquest_cross%3E1983410675%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1983410675&rft_id=info:pmid/28972084&rfr_iscdi=true |