Longitudinal tracking of 97 esophageal adenocarcinomas using liquid biopsy sampling
The incidence of esophageal adenocarcinoma (EAC) is rapidly rising and has a 5-year survival rate of
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| Veröffentlicht in: | Annals of oncology 2021-04, Vol.32 (4), p.522-532 |
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| creator | Ococks, E. Frankell, A.M. Masque Soler, N. Grehan, N. Northrop, A. Coles, H. Redmond, A.M. Devonshire, G. Weaver, J.M.J. Hughes, C. Lehovsky, K. Blasko, A. Nutzinger, B. Fitzgerald, R.C. Smyth, E. |
| description | The incidence of esophageal adenocarcinoma (EAC) is rapidly rising and has a 5-year survival rate of |
| doi_str_mv | 10.1016/j.annonc.2020.12.010 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2473412846</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0923753420432168</els_id><sourcerecordid>2473412846</sourcerecordid><originalsourceid>FETCH-LOGICAL-c408t-c9f46e52987ecb34aa560649d1d4a3db246f63a3e45f9c0c317b78911fa76d723</originalsourceid><addsrcrecordid>eNp9kE1r3DAQhkVJ6W62_Qcl-JiLHX1Zsi6FEtImsJBD27OQpfFWG1vySnZg_3297DbHnAbeeWaGeRD6SnBFMBF3-8qEEIOtKKZLRCtM8Ae0JrVQZYM5uUJrrCgrZc34Cl3nvMcYC0XVJ7RijNWq5nKNfm1j2Plpdj6YvpiSsS8-7IrYFUoWkOP41-xg6RgHIVqTrA9xMLmY8wnr_WH2rmh9HPOxyGYY-yX-jD52ps_w5VI36M-Ph9_3j-X2-efT_fdtaTluptKqjguoqWok2JZxY2qBBVeOOG6YaykXnWCGAa87ZbFlRLayUYR0RgonKdug2_PeMcXDDHnSg88W-t4EiHPWlEvGCW24WFB-Rm2KOSfo9Jj8YNJRE6xPOvVen3Xqk05NqF50LmM3lwtzO4B7G_rvbwG-nQFY_nz1kHS2HoIF5xPYSbvo37_wD30-iIU</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2473412846</pqid></control><display><type>article</type><title>Longitudinal tracking of 97 esophageal adenocarcinomas using liquid biopsy sampling</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Ococks, E. ; Frankell, A.M. ; Masque Soler, N. ; Grehan, N. ; Northrop, A. ; Coles, H. ; Redmond, A.M. ; Devonshire, G. ; Weaver, J.M.J. ; Hughes, C. ; Lehovsky, K. ; Blasko, A. ; Nutzinger, B. ; Fitzgerald, R.C. ; Smyth, E.</creator><creatorcontrib>Ococks, E. ; Frankell, A.M. ; Masque Soler, N. ; Grehan, N. ; Northrop, A. ; Coles, H. ; Redmond, A.M. ; Devonshire, G. ; Weaver, J.M.J. ; Hughes, C. ; Lehovsky, K. ; Blasko, A. ; Nutzinger, B. ; Fitzgerald, R.C. ; Smyth, E. ; OCCAMS Consortium</creatorcontrib><description>The incidence of esophageal adenocarcinoma (EAC) is rapidly rising and has a 5-year survival rate of <20%. Beyond TNM (tumor–node–metastasis) staging, no reliable risk stratification tools exist and no large-scale studies have profiled circulating tumor DNA (ctDNA) at relapse in EAC. Here we analyze the prognostic potential of ctDNA dynamics in EAC, taking into account clonal hematopoiesis with indeterminate potential (CHIP).
A total of 245 samples from 97 patients treated with neoadjuvant chemotherapy and surgery were identified from the prospective national UK Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) consortium data set. A pan-cancer ctDNA panel comprising 77 genes was used. Plasma and peripheral blood cell samples were sequenced to a mean depth of 7082× (range 2196-28 524) and ctDNA results correlated with survival.
Characteristics of the 97 patients identified were as follows: 83/97 (86%) male, median age 68 years (SD 9.5 years), 100% cT3/T4, 75% cN+. EAC-specific drivers had higher variant allele fractions than passenger mutations. Using stringent quality criteria 16/79 (20%) were ctDNA positive following resection; recurrence was observed in 12/16 (75%) of these. As much as 78/97 (80%) had CHIP analyses that enabled filtering for CHIP variants, which were found in 18/78 (23%) of cases. When CHIP was excluded, 10/63 (16%) patients were ctDNA positive and 9/10 of these (90%) recurred. With correction for CHIP, median cancer-specific survival for ctDNA-positive patients was 10.0 months versus 29.9 months for ctDNA-negative patients (hazard ratio 5.55, 95% confidence interval 2.42-12.71; P = 0.0003). Similar outcomes were observed for disease-free survival.
We demonstrate in a large, national, prospectively collected data set that ctDNA in plasma following surgery for EAC is prognostic for relapse. Inclusion of peripheral blood cell samples can reduce or eliminate false positives from CHIP. In future, post-operative ctDNA could be used to risk stratify patients into high- and low-risk groups for intensification or de-escalation of adjuvant chemotherapy.
•Exclusion of clonal haematopoiesis variants increased the positive predictive value and specificity of MRD detection by 15% and 6% respectively.</description><identifier>ISSN: 0923-7534</identifier><identifier>EISSN: 1569-8041</identifier><identifier>DOI: 10.1016/j.annonc.2020.12.010</identifier><identifier>PMID: 33359547</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adenocarcinoma - drug therapy ; Adenocarcinoma - genetics ; Aged ; Biomarkers, Tumor ; CHIP ; ctDNA ; EAC ; esophageal adenocarcinoma ; Esophageal Neoplasms - genetics ; Humans ; Liquid Biopsy ; Male ; Neoplasm Recurrence, Local - genetics ; Prospective Studies</subject><ispartof>Annals of oncology, 2021-04, Vol.32 (4), p.522-532</ispartof><rights>2021 The Authors</rights><rights>Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-c9f46e52987ecb34aa560649d1d4a3db246f63a3e45f9c0c317b78911fa76d723</citedby><cites>FETCH-LOGICAL-c408t-c9f46e52987ecb34aa560649d1d4a3db246f63a3e45f9c0c317b78911fa76d723</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33359547$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ococks, E.</creatorcontrib><creatorcontrib>Frankell, A.M.</creatorcontrib><creatorcontrib>Masque Soler, N.</creatorcontrib><creatorcontrib>Grehan, N.</creatorcontrib><creatorcontrib>Northrop, A.</creatorcontrib><creatorcontrib>Coles, H.</creatorcontrib><creatorcontrib>Redmond, A.M.</creatorcontrib><creatorcontrib>Devonshire, G.</creatorcontrib><creatorcontrib>Weaver, J.M.J.</creatorcontrib><creatorcontrib>Hughes, C.</creatorcontrib><creatorcontrib>Lehovsky, K.</creatorcontrib><creatorcontrib>Blasko, A.</creatorcontrib><creatorcontrib>Nutzinger, B.</creatorcontrib><creatorcontrib>Fitzgerald, R.C.</creatorcontrib><creatorcontrib>Smyth, E.</creatorcontrib><creatorcontrib>OCCAMS Consortium</creatorcontrib><title>Longitudinal tracking of 97 esophageal adenocarcinomas using liquid biopsy sampling</title><title>Annals of oncology</title><addtitle>Ann Oncol</addtitle><description>The incidence of esophageal adenocarcinoma (EAC) is rapidly rising and has a 5-year survival rate of <20%. Beyond TNM (tumor–node–metastasis) staging, no reliable risk stratification tools exist and no large-scale studies have profiled circulating tumor DNA (ctDNA) at relapse in EAC. Here we analyze the prognostic potential of ctDNA dynamics in EAC, taking into account clonal hematopoiesis with indeterminate potential (CHIP).
A total of 245 samples from 97 patients treated with neoadjuvant chemotherapy and surgery were identified from the prospective national UK Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) consortium data set. A pan-cancer ctDNA panel comprising 77 genes was used. Plasma and peripheral blood cell samples were sequenced to a mean depth of 7082× (range 2196-28 524) and ctDNA results correlated with survival.
Characteristics of the 97 patients identified were as follows: 83/97 (86%) male, median age 68 years (SD 9.5 years), 100% cT3/T4, 75% cN+. EAC-specific drivers had higher variant allele fractions than passenger mutations. Using stringent quality criteria 16/79 (20%) were ctDNA positive following resection; recurrence was observed in 12/16 (75%) of these. As much as 78/97 (80%) had CHIP analyses that enabled filtering for CHIP variants, which were found in 18/78 (23%) of cases. When CHIP was excluded, 10/63 (16%) patients were ctDNA positive and 9/10 of these (90%) recurred. With correction for CHIP, median cancer-specific survival for ctDNA-positive patients was 10.0 months versus 29.9 months for ctDNA-negative patients (hazard ratio 5.55, 95% confidence interval 2.42-12.71; P = 0.0003). Similar outcomes were observed for disease-free survival.
We demonstrate in a large, national, prospectively collected data set that ctDNA in plasma following surgery for EAC is prognostic for relapse. Inclusion of peripheral blood cell samples can reduce or eliminate false positives from CHIP. In future, post-operative ctDNA could be used to risk stratify patients into high- and low-risk groups for intensification or de-escalation of adjuvant chemotherapy.
•Exclusion of clonal haematopoiesis variants increased the positive predictive value and specificity of MRD detection by 15% and 6% respectively.</description><subject>Adenocarcinoma - drug therapy</subject><subject>Adenocarcinoma - genetics</subject><subject>Aged</subject><subject>Biomarkers, Tumor</subject><subject>CHIP</subject><subject>ctDNA</subject><subject>EAC</subject><subject>esophageal adenocarcinoma</subject><subject>Esophageal Neoplasms - genetics</subject><subject>Humans</subject><subject>Liquid Biopsy</subject><subject>Male</subject><subject>Neoplasm Recurrence, Local - genetics</subject><subject>Prospective Studies</subject><issn>0923-7534</issn><issn>1569-8041</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1r3DAQhkVJ6W62_Qcl-JiLHX1Zsi6FEtImsJBD27OQpfFWG1vySnZg_3297DbHnAbeeWaGeRD6SnBFMBF3-8qEEIOtKKZLRCtM8Ae0JrVQZYM5uUJrrCgrZc34Cl3nvMcYC0XVJ7RijNWq5nKNfm1j2Plpdj6YvpiSsS8-7IrYFUoWkOP41-xg6RgHIVqTrA9xMLmY8wnr_WH2rmh9HPOxyGYY-yX-jD52ps_w5VI36M-Ph9_3j-X2-efT_fdtaTluptKqjguoqWok2JZxY2qBBVeOOG6YaykXnWCGAa87ZbFlRLayUYR0RgonKdug2_PeMcXDDHnSg88W-t4EiHPWlEvGCW24WFB-Rm2KOSfo9Jj8YNJRE6xPOvVen3Xqk05NqF50LmM3lwtzO4B7G_rvbwG-nQFY_nz1kHS2HoIF5xPYSbvo37_wD30-iIU</recordid><startdate>202104</startdate><enddate>202104</enddate><creator>Ococks, E.</creator><creator>Frankell, A.M.</creator><creator>Masque Soler, N.</creator><creator>Grehan, N.</creator><creator>Northrop, A.</creator><creator>Coles, H.</creator><creator>Redmond, A.M.</creator><creator>Devonshire, G.</creator><creator>Weaver, J.M.J.</creator><creator>Hughes, C.</creator><creator>Lehovsky, K.</creator><creator>Blasko, A.</creator><creator>Nutzinger, B.</creator><creator>Fitzgerald, R.C.</creator><creator>Smyth, E.</creator><general>Elsevier Ltd</general><scope>6I.</scope><scope>AAFTH</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>202104</creationdate><title>Longitudinal tracking of 97 esophageal adenocarcinomas using liquid biopsy sampling</title><author>Ococks, E. ; Frankell, A.M. ; Masque Soler, N. ; Grehan, N. ; Northrop, A. ; Coles, H. ; Redmond, A.M. ; Devonshire, G. ; Weaver, J.M.J. ; Hughes, C. ; Lehovsky, K. ; Blasko, A. ; Nutzinger, B. ; Fitzgerald, R.C. ; Smyth, E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-c9f46e52987ecb34aa560649d1d4a3db246f63a3e45f9c0c317b78911fa76d723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adenocarcinoma - drug therapy</topic><topic>Adenocarcinoma - genetics</topic><topic>Aged</topic><topic>Biomarkers, Tumor</topic><topic>CHIP</topic><topic>ctDNA</topic><topic>EAC</topic><topic>esophageal adenocarcinoma</topic><topic>Esophageal Neoplasms - genetics</topic><topic>Humans</topic><topic>Liquid Biopsy</topic><topic>Male</topic><topic>Neoplasm Recurrence, Local - genetics</topic><topic>Prospective Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ococks, E.</creatorcontrib><creatorcontrib>Frankell, A.M.</creatorcontrib><creatorcontrib>Masque Soler, N.</creatorcontrib><creatorcontrib>Grehan, N.</creatorcontrib><creatorcontrib>Northrop, A.</creatorcontrib><creatorcontrib>Coles, H.</creatorcontrib><creatorcontrib>Redmond, A.M.</creatorcontrib><creatorcontrib>Devonshire, G.</creatorcontrib><creatorcontrib>Weaver, J.M.J.</creatorcontrib><creatorcontrib>Hughes, C.</creatorcontrib><creatorcontrib>Lehovsky, K.</creatorcontrib><creatorcontrib>Blasko, A.</creatorcontrib><creatorcontrib>Nutzinger, B.</creatorcontrib><creatorcontrib>Fitzgerald, R.C.</creatorcontrib><creatorcontrib>Smyth, E.</creatorcontrib><creatorcontrib>OCCAMS Consortium</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</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>Annals of oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ococks, E.</au><au>Frankell, A.M.</au><au>Masque Soler, N.</au><au>Grehan, N.</au><au>Northrop, A.</au><au>Coles, H.</au><au>Redmond, A.M.</au><au>Devonshire, G.</au><au>Weaver, J.M.J.</au><au>Hughes, C.</au><au>Lehovsky, K.</au><au>Blasko, A.</au><au>Nutzinger, B.</au><au>Fitzgerald, R.C.</au><au>Smyth, E.</au><aucorp>OCCAMS Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Longitudinal tracking of 97 esophageal adenocarcinomas using liquid biopsy sampling</atitle><jtitle>Annals of oncology</jtitle><addtitle>Ann Oncol</addtitle><date>2021-04</date><risdate>2021</risdate><volume>32</volume><issue>4</issue><spage>522</spage><epage>532</epage><pages>522-532</pages><issn>0923-7534</issn><eissn>1569-8041</eissn><abstract>The incidence of esophageal adenocarcinoma (EAC) is rapidly rising and has a 5-year survival rate of <20%. Beyond TNM (tumor–node–metastasis) staging, no reliable risk stratification tools exist and no large-scale studies have profiled circulating tumor DNA (ctDNA) at relapse in EAC. Here we analyze the prognostic potential of ctDNA dynamics in EAC, taking into account clonal hematopoiesis with indeterminate potential (CHIP).
A total of 245 samples from 97 patients treated with neoadjuvant chemotherapy and surgery were identified from the prospective national UK Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) consortium data set. A pan-cancer ctDNA panel comprising 77 genes was used. Plasma and peripheral blood cell samples were sequenced to a mean depth of 7082× (range 2196-28 524) and ctDNA results correlated with survival.
Characteristics of the 97 patients identified were as follows: 83/97 (86%) male, median age 68 years (SD 9.5 years), 100% cT3/T4, 75% cN+. EAC-specific drivers had higher variant allele fractions than passenger mutations. Using stringent quality criteria 16/79 (20%) were ctDNA positive following resection; recurrence was observed in 12/16 (75%) of these. As much as 78/97 (80%) had CHIP analyses that enabled filtering for CHIP variants, which were found in 18/78 (23%) of cases. When CHIP was excluded, 10/63 (16%) patients were ctDNA positive and 9/10 of these (90%) recurred. With correction for CHIP, median cancer-specific survival for ctDNA-positive patients was 10.0 months versus 29.9 months for ctDNA-negative patients (hazard ratio 5.55, 95% confidence interval 2.42-12.71; P = 0.0003). Similar outcomes were observed for disease-free survival.
We demonstrate in a large, national, prospectively collected data set that ctDNA in plasma following surgery for EAC is prognostic for relapse. Inclusion of peripheral blood cell samples can reduce or eliminate false positives from CHIP. In future, post-operative ctDNA could be used to risk stratify patients into high- and low-risk groups for intensification or de-escalation of adjuvant chemotherapy.
•Exclusion of clonal haematopoiesis variants increased the positive predictive value and specificity of MRD detection by 15% and 6% respectively.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>33359547</pmid><doi>10.1016/j.annonc.2020.12.010</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adenocarcinoma - drug therapy Adenocarcinoma - genetics Aged Biomarkers, Tumor CHIP ctDNA EAC esophageal adenocarcinoma Esophageal Neoplasms - genetics Humans Liquid Biopsy Male Neoplasm Recurrence, Local - genetics Prospective Studies |
| title | Longitudinal tracking of 97 esophageal adenocarcinomas using liquid biopsy sampling |
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