Ultrasensitive detection of BRAF mutations in circulating tumor DNA of non-metastatic melanoma
Implementation of adjuvant therapies in non-metastatic melanoma improved treatment outcomes in some patients; however, adjuvant therapy can be associated with significant cost and risk of toxicity. Therefore, there is an unmet need to better identify patients at high risk of recurrence. We carried o...
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creator | Gouda, M.A. Polivka, J. Huang, H.J. Treskova, I. Pivovarcikova, K. Fikrle, T. Woznica, V. Dustin, D.J. Call, S.G. Meric-Bernstam, F. Pesta, M. Janku, F. |
description | Implementation of adjuvant therapies in non-metastatic melanoma improved treatment outcomes in some patients; however, adjuvant therapy can be associated with significant cost and risk of toxicity. Therefore, there is an unmet need to better identify patients at high risk of recurrence.
We carried out an ultrasensitive droplet digital PCR (ddPCR)-based detection of BRAFV600E-mutated circulating tumor DNA (ctDNA) from blood samples prospectively collected before surgery, 1 hour after surgery, and then serially during follow-up.
In 80 patients (stages ≤III), BRAFV600E mutations were detected in 47.2% of tissue, in 37.7% of ctDNA samples collected before surgery, and in 25.9% of ctDNA samples collected 1 hour after surgery. Patients with detected ctDNA in blood collected 1 hour after surgery compared to patients without detected ctDNA had higher likelihood of melanoma recurrence (P < 0.001) and shorter median disease-free survival (P = 0.001) and overall survival (P = 0.003).
Ultrasensitive ddPCR can detect ctDNA in pre- and post-surgical blood samples from patients with resectable melanoma. Detection of ctDNA in post-surgical samples is associated with inferior treatment outcomes.
•Ultrasensitive ddPCR can detect ctDNA in pre- and post-surgical samples.•Detection of ctDNA 1 hour after surgery is associated with inferior treatment outcomes.•There were no associations between ctDNA detection at other timepoints and clinical outcomes. |
doi_str_mv | 10.1016/j.esmoop.2021.100357 |
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We carried out an ultrasensitive droplet digital PCR (ddPCR)-based detection of BRAFV600E-mutated circulating tumor DNA (ctDNA) from blood samples prospectively collected before surgery, 1 hour after surgery, and then serially during follow-up.
In 80 patients (stages ≤III), BRAFV600E mutations were detected in 47.2% of tissue, in 37.7% of ctDNA samples collected before surgery, and in 25.9% of ctDNA samples collected 1 hour after surgery. Patients with detected ctDNA in blood collected 1 hour after surgery compared to patients without detected ctDNA had higher likelihood of melanoma recurrence (P < 0.001) and shorter median disease-free survival (P = 0.001) and overall survival (P = 0.003).
Ultrasensitive ddPCR can detect ctDNA in pre- and post-surgical blood samples from patients with resectable melanoma. Detection of ctDNA in post-surgical samples is associated with inferior treatment outcomes.
•Ultrasensitive ddPCR can detect ctDNA in pre- and post-surgical samples.•Detection of ctDNA 1 hour after surgery is associated with inferior treatment outcomes.•There were no associations between ctDNA detection at other timepoints and clinical outcomes.</description><identifier>ISSN: 2059-7029</identifier><identifier>EISSN: 2059-7029</identifier><identifier>DOI: 10.1016/j.esmoop.2021.100357</identifier><identifier>PMID: 34942440</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>circulating tumor DNA ; Circulating Tumor DNA - genetics ; Humans ; liquid biopsy ; melanoma ; Melanoma - genetics ; Mutation ; Original Research ; Polymerase Chain Reaction ; Proto-Oncogene Proteins B-raf - genetics</subject><ispartof>ESMO open, 2022-02, Vol.7 (1), p.100357-100357, Article 100357</ispartof><rights>2021 The Authors</rights><rights>Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.</rights><rights>2021 The Authors 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c463t-77889b5df9288d3876f1e06ea39fcaddcada289b7afc88fde5545d85a5ccfe8a3</citedby><cites>FETCH-LOGICAL-c463t-77889b5df9288d3876f1e06ea39fcaddcada289b7afc88fde5545d85a5ccfe8a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8695283/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8695283/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34942440$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gouda, M.A.</creatorcontrib><creatorcontrib>Polivka, J.</creatorcontrib><creatorcontrib>Huang, H.J.</creatorcontrib><creatorcontrib>Treskova, I.</creatorcontrib><creatorcontrib>Pivovarcikova, K.</creatorcontrib><creatorcontrib>Fikrle, T.</creatorcontrib><creatorcontrib>Woznica, V.</creatorcontrib><creatorcontrib>Dustin, D.J.</creatorcontrib><creatorcontrib>Call, S.G.</creatorcontrib><creatorcontrib>Meric-Bernstam, F.</creatorcontrib><creatorcontrib>Pesta, M.</creatorcontrib><creatorcontrib>Janku, F.</creatorcontrib><title>Ultrasensitive detection of BRAF mutations in circulating tumor DNA of non-metastatic melanoma</title><title>ESMO open</title><addtitle>ESMO Open</addtitle><description>Implementation of adjuvant therapies in non-metastatic melanoma improved treatment outcomes in some patients; however, adjuvant therapy can be associated with significant cost and risk of toxicity. Therefore, there is an unmet need to better identify patients at high risk of recurrence.
We carried out an ultrasensitive droplet digital PCR (ddPCR)-based detection of BRAFV600E-mutated circulating tumor DNA (ctDNA) from blood samples prospectively collected before surgery, 1 hour after surgery, and then serially during follow-up.
In 80 patients (stages ≤III), BRAFV600E mutations were detected in 47.2% of tissue, in 37.7% of ctDNA samples collected before surgery, and in 25.9% of ctDNA samples collected 1 hour after surgery. Patients with detected ctDNA in blood collected 1 hour after surgery compared to patients without detected ctDNA had higher likelihood of melanoma recurrence (P < 0.001) and shorter median disease-free survival (P = 0.001) and overall survival (P = 0.003).
Ultrasensitive ddPCR can detect ctDNA in pre- and post-surgical blood samples from patients with resectable melanoma. Detection of ctDNA in post-surgical samples is associated with inferior treatment outcomes.
•Ultrasensitive ddPCR can detect ctDNA in pre- and post-surgical samples.•Detection of ctDNA 1 hour after surgery is associated with inferior treatment outcomes.•There were no associations between ctDNA detection at other timepoints and clinical outcomes.</description><subject>circulating tumor DNA</subject><subject>Circulating Tumor DNA - genetics</subject><subject>Humans</subject><subject>liquid biopsy</subject><subject>melanoma</subject><subject>Melanoma - genetics</subject><subject>Mutation</subject><subject>Original Research</subject><subject>Polymerase Chain Reaction</subject><subject>Proto-Oncogene Proteins B-raf - genetics</subject><issn>2059-7029</issn><issn>2059-7029</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UU1v3CAURFWqJkrzD6qKYy7eYgw2vkTafLWVolaqmmsRgUfCysAG8Er598XaNE0vPSB4w7x5DIPQh5asWtL2nzYryD7G7YoS2laIdHx4g44o4WMzEDoevDofopOcN4SQdmAV7N-hw46NjDJGjtCv26kklSFkV9wOsIECurgYcLT4_Mf6Gvu5qAXI2AWsXdLzVOtwj8vsY8KX39YLNcTQeCgqL2SNPUwqRK_eo7dWTRlOnvdjdHt99fPiS3Pz_fPXi_VNo1nflWYYhBjvuLEjFcJ0YuhtC6QH1Y1WK2PqUrQyBmW1ENYA54wbwRXX2oJQ3TE62-tu5zsPRkOoria5Tc6r9CSjcvLfm-Ae5H3cSdGPnIquCpw-C6T4OEMu0rusYao2IM5Z0r5ltBIZrVS2p-oUc05gX8a0RC7pyI3cpyOXdOQ-ndr28fUTX5r-ZPHXA9SP2jlIMmsHQYNxqWYiTXT_n_Abwm2lpw</recordid><startdate>20220201</startdate><enddate>20220201</enddate><creator>Gouda, M.A.</creator><creator>Polivka, J.</creator><creator>Huang, H.J.</creator><creator>Treskova, I.</creator><creator>Pivovarcikova, K.</creator><creator>Fikrle, T.</creator><creator>Woznica, V.</creator><creator>Dustin, D.J.</creator><creator>Call, S.G.</creator><creator>Meric-Bernstam, F.</creator><creator>Pesta, M.</creator><creator>Janku, F.</creator><general>Elsevier Ltd</general><general>Elsevier</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><scope>5PM</scope></search><sort><creationdate>20220201</creationdate><title>Ultrasensitive detection of BRAF mutations in circulating tumor DNA of non-metastatic melanoma</title><author>Gouda, M.A. ; Polivka, J. ; Huang, H.J. ; Treskova, I. ; Pivovarcikova, K. ; Fikrle, T. ; Woznica, V. ; Dustin, D.J. ; Call, S.G. ; Meric-Bernstam, F. ; Pesta, M. ; Janku, F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c463t-77889b5df9288d3876f1e06ea39fcaddcada289b7afc88fde5545d85a5ccfe8a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>circulating tumor DNA</topic><topic>Circulating Tumor DNA - genetics</topic><topic>Humans</topic><topic>liquid biopsy</topic><topic>melanoma</topic><topic>Melanoma - genetics</topic><topic>Mutation</topic><topic>Original Research</topic><topic>Polymerase Chain Reaction</topic><topic>Proto-Oncogene Proteins B-raf - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gouda, M.A.</creatorcontrib><creatorcontrib>Polivka, J.</creatorcontrib><creatorcontrib>Huang, H.J.</creatorcontrib><creatorcontrib>Treskova, I.</creatorcontrib><creatorcontrib>Pivovarcikova, K.</creatorcontrib><creatorcontrib>Fikrle, T.</creatorcontrib><creatorcontrib>Woznica, V.</creatorcontrib><creatorcontrib>Dustin, D.J.</creatorcontrib><creatorcontrib>Call, S.G.</creatorcontrib><creatorcontrib>Meric-Bernstam, F.</creatorcontrib><creatorcontrib>Pesta, M.</creatorcontrib><creatorcontrib>Janku, F.</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>ESMO open</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gouda, M.A.</au><au>Polivka, J.</au><au>Huang, H.J.</au><au>Treskova, I.</au><au>Pivovarcikova, K.</au><au>Fikrle, T.</au><au>Woznica, V.</au><au>Dustin, D.J.</au><au>Call, S.G.</au><au>Meric-Bernstam, F.</au><au>Pesta, M.</au><au>Janku, F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ultrasensitive detection of BRAF mutations in circulating tumor DNA of non-metastatic melanoma</atitle><jtitle>ESMO open</jtitle><addtitle>ESMO Open</addtitle><date>2022-02-01</date><risdate>2022</risdate><volume>7</volume><issue>1</issue><spage>100357</spage><epage>100357</epage><pages>100357-100357</pages><artnum>100357</artnum><issn>2059-7029</issn><eissn>2059-7029</eissn><abstract>Implementation of adjuvant therapies in non-metastatic melanoma improved treatment outcomes in some patients; however, adjuvant therapy can be associated with significant cost and risk of toxicity. Therefore, there is an unmet need to better identify patients at high risk of recurrence.
We carried out an ultrasensitive droplet digital PCR (ddPCR)-based detection of BRAFV600E-mutated circulating tumor DNA (ctDNA) from blood samples prospectively collected before surgery, 1 hour after surgery, and then serially during follow-up.
In 80 patients (stages ≤III), BRAFV600E mutations were detected in 47.2% of tissue, in 37.7% of ctDNA samples collected before surgery, and in 25.9% of ctDNA samples collected 1 hour after surgery. Patients with detected ctDNA in blood collected 1 hour after surgery compared to patients without detected ctDNA had higher likelihood of melanoma recurrence (P < 0.001) and shorter median disease-free survival (P = 0.001) and overall survival (P = 0.003).
Ultrasensitive ddPCR can detect ctDNA in pre- and post-surgical blood samples from patients with resectable melanoma. Detection of ctDNA in post-surgical samples is associated with inferior treatment outcomes.
•Ultrasensitive ddPCR can detect ctDNA in pre- and post-surgical samples.•Detection of ctDNA 1 hour after surgery is associated with inferior treatment outcomes.•There were no associations between ctDNA detection at other timepoints and clinical outcomes.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>34942440</pmid><doi>10.1016/j.esmoop.2021.100357</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | circulating tumor DNA Circulating Tumor DNA - genetics Humans liquid biopsy melanoma Melanoma - genetics Mutation Original Research Polymerase Chain Reaction Proto-Oncogene Proteins B-raf - genetics |
title | Ultrasensitive detection of BRAF mutations in circulating tumor DNA of non-metastatic melanoma |
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