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Circulating Tumor DNA is Unreliable to Detect Somatic Gene Alterations in Gastrointestinal Peritoneal Carcinomatosis
Introduction Tumor agnostic circulating tumor DNA (ctDNA) is routinely used to guide treatment decisions in gastrointestinal (GI) cancers, especially metastatic cancers. The amount of ctDNA detected in plasma is affected by stage, tumor burden, and tumor vascularization. We hypothesized that periton...
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| Published in: | Annals of surgical oncology 2023-01, Vol.30 (1), p.278-284 |
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| container_title | Annals of surgical oncology |
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| creator | Sullivan, Brittany G. Lo, Angelina Yu, Jingjing Gonda, Amber Dehkordi-Vakil, Farideh Dayyani, Farshid Senthil, Maheswari |
| description | Introduction
Tumor agnostic circulating tumor DNA (ctDNA) is routinely used to guide treatment decisions in gastrointestinal (GI) cancers, especially metastatic cancers. The amount of ctDNA detected in plasma is affected by stage, tumor burden, and tumor vascularization. We hypothesized that peritoneal carcinomatosis (PC) is associated with lower ctDNA levels than other metastatic sites in GI cancers due to the plasma–peritoneal barrier.
Methods
We conducted a retrospective analysis of patients with stage II–IV GI cancers treated at our institution between 2015 and 2020 with available panel-based ctDNA results (Guardant 360
TM
). ctDNA analysis was performed on early and pretreatment samples. We compared the reported maximum variant allele frequency (mVAF) of somatic mutations across metastatic sites.
Results
Of the 279 patients with GI cancers (colorectal, upper GI, pancreaticobiliary), 212 had stage IV disease (PC:
n
= 61; visceral metastases:
n
= 138; other metastases:
n
= 13). Mean mVAF increased with increasing stages of disease (stage II: 3.6 ± 7; stage III: 6.4 ± 10; stage IV: 28.0 ± 51;
p
|
| doi_str_mv | 10.1245/s10434-022-12399-y |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9726669</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2703985348</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-96b381212096114c85d03e06e9aa99eeead1fb3781a635bee4f14571ae3c6cf23</originalsourceid><addsrcrecordid>eNp9kU1vEzEQhi0EoqXwBzggS1y4LPh71xekKIWAVAES7dnyOrPBldcutrdS_j0OKeXjwMljzzPveOZF6DklrykT8k2hRHDREcY6yrjW3f4BOqWyPQk10IctJmroNFPyBD0p5ZoQ2nMiH6MTLvVApNCnqK59dkuw1ccdvlzmlPH5pxX2BV_FDMHbMQCuCZ9DBVfx1zQ31OENRMCrUCG3a4oF-4g3ttScfKxQmpoN-AtkX1OEFq5tdj4eilPx5Sl6NNlQ4NndeYau3r-7XH_oLj5vPq5XF50TvaidViMfKKOMaEWpcIPcEg5EgbZWawCwWzqNvB-oVVyOAGKiQvbUAnfKTYyfobdH3ZtlnGHrINZsg7nJfrZ5b5L15u9M9N_MLt0a3TOllG4Cr-4Ecvq-tLnM7IuDEGyEtBTDesL10DY-NPTlP-h1WnJbw4ES_WEMzRvFjpTLqZQM0_1nKDEHU83RVNNMNT9NNftW9OLPMe5LfrnYAH4ESkvFHeTfvf8j-wN1g6_h</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2747121293</pqid></control><display><type>article</type><title>Circulating Tumor DNA is Unreliable to Detect Somatic Gene Alterations in Gastrointestinal Peritoneal Carcinomatosis</title><source>Springer Nature</source><creator>Sullivan, Brittany G. ; Lo, Angelina ; Yu, Jingjing ; Gonda, Amber ; Dehkordi-Vakil, Farideh ; Dayyani, Farshid ; Senthil, Maheswari</creator><creatorcontrib>Sullivan, Brittany G. ; Lo, Angelina ; Yu, Jingjing ; Gonda, Amber ; Dehkordi-Vakil, Farideh ; Dayyani, Farshid ; Senthil, Maheswari</creatorcontrib><description>Introduction
Tumor agnostic circulating tumor DNA (ctDNA) is routinely used to guide treatment decisions in gastrointestinal (GI) cancers, especially metastatic cancers. The amount of ctDNA detected in plasma is affected by stage, tumor burden, and tumor vascularization. We hypothesized that peritoneal carcinomatosis (PC) is associated with lower ctDNA levels than other metastatic sites in GI cancers due to the plasma–peritoneal barrier.
Methods
We conducted a retrospective analysis of patients with stage II–IV GI cancers treated at our institution between 2015 and 2020 with available panel-based ctDNA results (Guardant 360
TM
). ctDNA analysis was performed on early and pretreatment samples. We compared the reported maximum variant allele frequency (mVAF) of somatic mutations across metastatic sites.
Results
Of the 279 patients with GI cancers (colorectal, upper GI, pancreaticobiliary), 212 had stage IV disease (PC:
n
= 61; visceral metastases:
n
= 138; other metastases:
n
= 13). Mean mVAF increased with increasing stages of disease (stage II: 3.6 ± 7; stage III: 6.4 ± 10; stage IV: 28.0 ± 51;
p
< 0.01). Among patients with stage IV disease, PC was associated with lower ctDNA levels independent of primary tumor site (PC only: 12.1%; PC+ visceral metastases: 26.8%; and visceral metastases only: 35.0%;
p
< 0.01). In a subset of patients (
n
= 27, matched pair analysis of genomic alterations (GAs) showed fewer GAs were detected in plasma compared with tissue.
Conclusions
PC of GI origin is associated with significantly lower ctDNA levels compared with visceral metastasis. Caution is warranted when interpreting ctDNA results from patients with PC due to lower sensitivity for detecting actionable mutations.</description><identifier>ISSN: 1068-9265</identifier><identifier>EISSN: 1534-4681</identifier><identifier>DOI: 10.1245/s10434-022-12399-y</identifier><identifier>PMID: 35980549</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Cancer ; Circulating Tumor DNA - genetics ; Gastric cancer ; Gastrointestinal Neoplasms - diagnosis ; Gastrointestinal Neoplasms - genetics ; Gastrointestinal Oncology ; Gene frequency ; Genomic analysis ; Genomics ; Humans ; Medicine ; Medicine & Public Health ; Metastases ; Metastasis ; Mutation ; Oncology ; Patients ; Peritoneum ; Retrospective Studies ; Surgery ; Surgical Oncology ; Tumors ; Vascularization</subject><ispartof>Annals of surgical oncology, 2023-01, Vol.30 (1), p.278-284</ispartof><rights>The Author(s) 2022</rights><rights>2022. The Author(s).</rights><rights>The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-96b381212096114c85d03e06e9aa99eeead1fb3781a635bee4f14571ae3c6cf23</citedby><cites>FETCH-LOGICAL-c474t-96b381212096114c85d03e06e9aa99eeead1fb3781a635bee4f14571ae3c6cf23</cites><orcidid>0000-0001-7295-2252</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35980549$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sullivan, Brittany G.</creatorcontrib><creatorcontrib>Lo, Angelina</creatorcontrib><creatorcontrib>Yu, Jingjing</creatorcontrib><creatorcontrib>Gonda, Amber</creatorcontrib><creatorcontrib>Dehkordi-Vakil, Farideh</creatorcontrib><creatorcontrib>Dayyani, Farshid</creatorcontrib><creatorcontrib>Senthil, Maheswari</creatorcontrib><title>Circulating Tumor DNA is Unreliable to Detect Somatic Gene Alterations in Gastrointestinal Peritoneal Carcinomatosis</title><title>Annals of surgical oncology</title><addtitle>Ann Surg Oncol</addtitle><addtitle>Ann Surg Oncol</addtitle><description>Introduction
Tumor agnostic circulating tumor DNA (ctDNA) is routinely used to guide treatment decisions in gastrointestinal (GI) cancers, especially metastatic cancers. The amount of ctDNA detected in plasma is affected by stage, tumor burden, and tumor vascularization. We hypothesized that peritoneal carcinomatosis (PC) is associated with lower ctDNA levels than other metastatic sites in GI cancers due to the plasma–peritoneal barrier.
Methods
We conducted a retrospective analysis of patients with stage II–IV GI cancers treated at our institution between 2015 and 2020 with available panel-based ctDNA results (Guardant 360
TM
). ctDNA analysis was performed on early and pretreatment samples. We compared the reported maximum variant allele frequency (mVAF) of somatic mutations across metastatic sites.
Results
Of the 279 patients with GI cancers (colorectal, upper GI, pancreaticobiliary), 212 had stage IV disease (PC:
n
= 61; visceral metastases:
n
= 138; other metastases:
n
= 13). Mean mVAF increased with increasing stages of disease (stage II: 3.6 ± 7; stage III: 6.4 ± 10; stage IV: 28.0 ± 51;
p
< 0.01). Among patients with stage IV disease, PC was associated with lower ctDNA levels independent of primary tumor site (PC only: 12.1%; PC+ visceral metastases: 26.8%; and visceral metastases only: 35.0%;
p
< 0.01). In a subset of patients (
n
= 27, matched pair analysis of genomic alterations (GAs) showed fewer GAs were detected in plasma compared with tissue.
Conclusions
PC of GI origin is associated with significantly lower ctDNA levels compared with visceral metastasis. Caution is warranted when interpreting ctDNA results from patients with PC due to lower sensitivity for detecting actionable mutations.</description><subject>Cancer</subject><subject>Circulating Tumor DNA - genetics</subject><subject>Gastric cancer</subject><subject>Gastrointestinal Neoplasms - diagnosis</subject><subject>Gastrointestinal Neoplasms - genetics</subject><subject>Gastrointestinal Oncology</subject><subject>Gene frequency</subject><subject>Genomic analysis</subject><subject>Genomics</subject><subject>Humans</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mutation</subject><subject>Oncology</subject><subject>Patients</subject><subject>Peritoneum</subject><subject>Retrospective Studies</subject><subject>Surgery</subject><subject>Surgical Oncology</subject><subject>Tumors</subject><subject>Vascularization</subject><issn>1068-9265</issn><issn>1534-4681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kU1vEzEQhi0EoqXwBzggS1y4LPh71xekKIWAVAES7dnyOrPBldcutrdS_j0OKeXjwMljzzPveOZF6DklrykT8k2hRHDREcY6yrjW3f4BOqWyPQk10IctJmroNFPyBD0p5ZoQ2nMiH6MTLvVApNCnqK59dkuw1ccdvlzmlPH5pxX2BV_FDMHbMQCuCZ9DBVfx1zQ31OENRMCrUCG3a4oF-4g3ttScfKxQmpoN-AtkX1OEFq5tdj4eilPx5Sl6NNlQ4NndeYau3r-7XH_oLj5vPq5XF50TvaidViMfKKOMaEWpcIPcEg5EgbZWawCwWzqNvB-oVVyOAGKiQvbUAnfKTYyfobdH3ZtlnGHrINZsg7nJfrZ5b5L15u9M9N_MLt0a3TOllG4Cr-4Ecvq-tLnM7IuDEGyEtBTDesL10DY-NPTlP-h1WnJbw4ES_WEMzRvFjpTLqZQM0_1nKDEHU83RVNNMNT9NNftW9OLPMe5LfrnYAH4ESkvFHeTfvf8j-wN1g6_h</recordid><startdate>20230101</startdate><enddate>20230101</enddate><creator>Sullivan, Brittany G.</creator><creator>Lo, Angelina</creator><creator>Yu, Jingjing</creator><creator>Gonda, Amber</creator><creator>Dehkordi-Vakil, Farideh</creator><creator>Dayyani, Farshid</creator><creator>Senthil, Maheswari</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>C6C</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>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7295-2252</orcidid></search><sort><creationdate>20230101</creationdate><title>Circulating Tumor DNA is Unreliable to Detect Somatic Gene Alterations in Gastrointestinal Peritoneal Carcinomatosis</title><author>Sullivan, Brittany G. ; Lo, Angelina ; Yu, Jingjing ; Gonda, Amber ; Dehkordi-Vakil, Farideh ; Dayyani, Farshid ; Senthil, Maheswari</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-96b381212096114c85d03e06e9aa99eeead1fb3781a635bee4f14571ae3c6cf23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Cancer</topic><topic>Circulating Tumor DNA - genetics</topic><topic>Gastric cancer</topic><topic>Gastrointestinal Neoplasms - diagnosis</topic><topic>Gastrointestinal Neoplasms - genetics</topic><topic>Gastrointestinal Oncology</topic><topic>Gene frequency</topic><topic>Genomic analysis</topic><topic>Genomics</topic><topic>Humans</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mutation</topic><topic>Oncology</topic><topic>Patients</topic><topic>Peritoneum</topic><topic>Retrospective Studies</topic><topic>Surgery</topic><topic>Surgical Oncology</topic><topic>Tumors</topic><topic>Vascularization</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sullivan, Brittany G.</creatorcontrib><creatorcontrib>Lo, Angelina</creatorcontrib><creatorcontrib>Yu, Jingjing</creatorcontrib><creatorcontrib>Gonda, Amber</creatorcontrib><creatorcontrib>Dehkordi-Vakil, Farideh</creatorcontrib><creatorcontrib>Dayyani, Farshid</creatorcontrib><creatorcontrib>Senthil, Maheswari</creatorcontrib><collection>Springer 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>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Annals of surgical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sullivan, Brittany G.</au><au>Lo, Angelina</au><au>Yu, Jingjing</au><au>Gonda, Amber</au><au>Dehkordi-Vakil, Farideh</au><au>Dayyani, Farshid</au><au>Senthil, Maheswari</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Circulating Tumor DNA is Unreliable to Detect Somatic Gene Alterations in Gastrointestinal Peritoneal Carcinomatosis</atitle><jtitle>Annals of surgical oncology</jtitle><stitle>Ann Surg Oncol</stitle><addtitle>Ann Surg Oncol</addtitle><date>2023-01-01</date><risdate>2023</risdate><volume>30</volume><issue>1</issue><spage>278</spage><epage>284</epage><pages>278-284</pages><issn>1068-9265</issn><eissn>1534-4681</eissn><abstract>Introduction
Tumor agnostic circulating tumor DNA (ctDNA) is routinely used to guide treatment decisions in gastrointestinal (GI) cancers, especially metastatic cancers. The amount of ctDNA detected in plasma is affected by stage, tumor burden, and tumor vascularization. We hypothesized that peritoneal carcinomatosis (PC) is associated with lower ctDNA levels than other metastatic sites in GI cancers due to the plasma–peritoneal barrier.
Methods
We conducted a retrospective analysis of patients with stage II–IV GI cancers treated at our institution between 2015 and 2020 with available panel-based ctDNA results (Guardant 360
TM
). ctDNA analysis was performed on early and pretreatment samples. We compared the reported maximum variant allele frequency (mVAF) of somatic mutations across metastatic sites.
Results
Of the 279 patients with GI cancers (colorectal, upper GI, pancreaticobiliary), 212 had stage IV disease (PC:
n
= 61; visceral metastases:
n
= 138; other metastases:
n
= 13). Mean mVAF increased with increasing stages of disease (stage II: 3.6 ± 7; stage III: 6.4 ± 10; stage IV: 28.0 ± 51;
p
< 0.01). Among patients with stage IV disease, PC was associated with lower ctDNA levels independent of primary tumor site (PC only: 12.1%; PC+ visceral metastases: 26.8%; and visceral metastases only: 35.0%;
p
< 0.01). In a subset of patients (
n
= 27, matched pair analysis of genomic alterations (GAs) showed fewer GAs were detected in plasma compared with tissue.
Conclusions
PC of GI origin is associated with significantly lower ctDNA levels compared with visceral metastasis. Caution is warranted when interpreting ctDNA results from patients with PC due to lower sensitivity for detecting actionable mutations.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>35980549</pmid><doi>10.1245/s10434-022-12399-y</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0001-7295-2252</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Annals of surgical oncology, 2023-01, Vol.30 (1), p.278-284 |
| issn | 1068-9265 1534-4681 |
| language | eng |
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| source | Springer Nature |
| subjects | Cancer Circulating Tumor DNA - genetics Gastric cancer Gastrointestinal Neoplasms - diagnosis Gastrointestinal Neoplasms - genetics Gastrointestinal Oncology Gene frequency Genomic analysis Genomics Humans Medicine Medicine & Public Health Metastases Metastasis Mutation Oncology Patients Peritoneum Retrospective Studies Surgery Surgical Oncology Tumors Vascularization |
| title | Circulating Tumor DNA is Unreliable to Detect Somatic Gene Alterations in Gastrointestinal Peritoneal Carcinomatosis |
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