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Circulating Tumor DNA Correlates with Outcome in Metastatic Melanoma Treated by BRAF and MEK Inhibitors – Results of a Prospective Biomarker Study

PURPOSE: BRAF and MEK inhibitors significantly improved the prognosis of metastatic melanoma. Nevertheless, initial treatment response may be only temporary. Liquid biopsies (LB) offer a possibility to monitor patients by measuring circulating tumor DNA (ctDNA). We sought to find out whether ctDNA c...

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Autores principales: Forschner, Andrea, Weißgraeber, Stephanie, Hadaschik, Dirk, Schulze, Martin, Kopp, Maria, Kelkenberg, Sabine, Sinnberg, Tobias, Garbe, Claus, Biskup, Saskia, Battke, Florian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280255/
https://www.ncbi.nlm.nih.gov/pubmed/32581559
http://dx.doi.org/10.2147/OTT.S248237
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author Forschner, Andrea
Weißgraeber, Stephanie
Hadaschik, Dirk
Schulze, Martin
Kopp, Maria
Kelkenberg, Sabine
Sinnberg, Tobias
Garbe, Claus
Biskup, Saskia
Battke, Florian
author_facet Forschner, Andrea
Weißgraeber, Stephanie
Hadaschik, Dirk
Schulze, Martin
Kopp, Maria
Kelkenberg, Sabine
Sinnberg, Tobias
Garbe, Claus
Biskup, Saskia
Battke, Florian
author_sort Forschner, Andrea
collection PubMed
description PURPOSE: BRAF and MEK inhibitors significantly improved the prognosis of metastatic melanoma. Nevertheless, initial treatment response may be only temporary. Liquid biopsies (LB) offer a possibility to monitor patients by measuring circulating tumor DNA (ctDNA). We sought to find out whether ctDNA can be used to reliably determine progressive disease under targeted therapy. In addition, we wanted to check whether ctDNA may represent a possible prognostic marker for survival. PATIENTS AND METHODS: We included 19 melanoma patients with BRAF and MEK inhibitor therapy. For each patient, a 710 gene panel was analyzed on the latest available tumor tissue before the start of therapy. Repetitive LB were collected in which BRAF V600E/K mutations were monitored using digital droplet PCR (ddPCR). We correlated radiological staging results and overall survival with ctDNA results. RESULTS: In 13 patients, ctDNA was detectable when starting targeted therapy, whereas in six patients, ddPCR was always negative, which we confirmed with ultra-deep sequencing. All patients with initially detectable ctDNA had ctDNA values declining to zero during follow-up, increasing again at the time of extracerebral progression or even slightly before detection by imaging. Survival was significantly worse for patients with elevated LDH (p=0.034) or detectable ctDNA (p=0.008) at the start of targeted therapy. CONCLUSION: Therapy monitoring by ctDNA seems to be a reliable method for detecting extracranial progression, even more sensitive and specific than LDH or S100B. However, due to the small number of cases in our study, further studies are necessary.
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spelling pubmed-72802552020-06-23 Circulating Tumor DNA Correlates with Outcome in Metastatic Melanoma Treated by BRAF and MEK Inhibitors – Results of a Prospective Biomarker Study Forschner, Andrea Weißgraeber, Stephanie Hadaschik, Dirk Schulze, Martin Kopp, Maria Kelkenberg, Sabine Sinnberg, Tobias Garbe, Claus Biskup, Saskia Battke, Florian Onco Targets Ther Original Research PURPOSE: BRAF and MEK inhibitors significantly improved the prognosis of metastatic melanoma. Nevertheless, initial treatment response may be only temporary. Liquid biopsies (LB) offer a possibility to monitor patients by measuring circulating tumor DNA (ctDNA). We sought to find out whether ctDNA can be used to reliably determine progressive disease under targeted therapy. In addition, we wanted to check whether ctDNA may represent a possible prognostic marker for survival. PATIENTS AND METHODS: We included 19 melanoma patients with BRAF and MEK inhibitor therapy. For each patient, a 710 gene panel was analyzed on the latest available tumor tissue before the start of therapy. Repetitive LB were collected in which BRAF V600E/K mutations were monitored using digital droplet PCR (ddPCR). We correlated radiological staging results and overall survival with ctDNA results. RESULTS: In 13 patients, ctDNA was detectable when starting targeted therapy, whereas in six patients, ddPCR was always negative, which we confirmed with ultra-deep sequencing. All patients with initially detectable ctDNA had ctDNA values declining to zero during follow-up, increasing again at the time of extracerebral progression or even slightly before detection by imaging. Survival was significantly worse for patients with elevated LDH (p=0.034) or detectable ctDNA (p=0.008) at the start of targeted therapy. CONCLUSION: Therapy monitoring by ctDNA seems to be a reliable method for detecting extracranial progression, even more sensitive and specific than LDH or S100B. However, due to the small number of cases in our study, further studies are necessary. Dove 2020-06-04 /pmc/articles/PMC7280255/ /pubmed/32581559 http://dx.doi.org/10.2147/OTT.S248237 Text en © 2020 Forschner et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Forschner, Andrea
Weißgraeber, Stephanie
Hadaschik, Dirk
Schulze, Martin
Kopp, Maria
Kelkenberg, Sabine
Sinnberg, Tobias
Garbe, Claus
Biskup, Saskia
Battke, Florian
Circulating Tumor DNA Correlates with Outcome in Metastatic Melanoma Treated by BRAF and MEK Inhibitors – Results of a Prospective Biomarker Study
title Circulating Tumor DNA Correlates with Outcome in Metastatic Melanoma Treated by BRAF and MEK Inhibitors – Results of a Prospective Biomarker Study
title_full Circulating Tumor DNA Correlates with Outcome in Metastatic Melanoma Treated by BRAF and MEK Inhibitors – Results of a Prospective Biomarker Study
title_fullStr Circulating Tumor DNA Correlates with Outcome in Metastatic Melanoma Treated by BRAF and MEK Inhibitors – Results of a Prospective Biomarker Study
title_full_unstemmed Circulating Tumor DNA Correlates with Outcome in Metastatic Melanoma Treated by BRAF and MEK Inhibitors – Results of a Prospective Biomarker Study
title_short Circulating Tumor DNA Correlates with Outcome in Metastatic Melanoma Treated by BRAF and MEK Inhibitors – Results of a Prospective Biomarker Study
title_sort circulating tumor dna correlates with outcome in metastatic melanoma treated by braf and mek inhibitors – results of a prospective biomarker study
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280255/
https://www.ncbi.nlm.nih.gov/pubmed/32581559
http://dx.doi.org/10.2147/OTT.S248237
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