Cargando…

Feasibility of personalized circulating tumor DNA detection in stage II and III melanoma

The objective of this study was to evaluate the feasibility of developing personalized, tumor-informed assays for patients with high-risk resectable melanoma and examine circulating tumor DNA (ctDNA) levels in relation to clinical status. Pilot prospective study of clinical stage IIB/C and resectabl...

Descripción completa

Detalles Bibliográficos
Autores principales: Brunsgaard, Elise K., Bowles, Tawnya L., Asare, Elliot A., Grossmann, Kenneth, Boucher, Kenneth M., Grossmann, Allie, Jackson, Julie A., Wada, David A., Rathore, Richa, Budde, Griffin, Grandemange, Andrew, Hyngstrom, John R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10144272/
https://www.ncbi.nlm.nih.gov/pubmed/37040662
http://dx.doi.org/10.1097/CMR.0000000000000892
_version_ 1785034061553598464
author Brunsgaard, Elise K.
Bowles, Tawnya L.
Asare, Elliot A.
Grossmann, Kenneth
Boucher, Kenneth M.
Grossmann, Allie
Jackson, Julie A.
Wada, David A.
Rathore, Richa
Budde, Griffin
Grandemange, Andrew
Hyngstrom, John R.
author_facet Brunsgaard, Elise K.
Bowles, Tawnya L.
Asare, Elliot A.
Grossmann, Kenneth
Boucher, Kenneth M.
Grossmann, Allie
Jackson, Julie A.
Wada, David A.
Rathore, Richa
Budde, Griffin
Grandemange, Andrew
Hyngstrom, John R.
author_sort Brunsgaard, Elise K.
collection PubMed
description The objective of this study was to evaluate the feasibility of developing personalized, tumor-informed assays for patients with high-risk resectable melanoma and examine circulating tumor DNA (ctDNA) levels in relation to clinical status. Pilot prospective study of clinical stage IIB/C and resectable stage III melanoma patients. Tumor tissue was used to design bespoke somatic assays for interrogating ctDNA in patients’ plasma using a multiplex PCR (mPCR) next-generation sequencing (NGS)-based approach. Plasma samples for ctDNA analysis were collected pre-/post-surgery and during surveillance. Out of 28 patients (mean 65 years, 50% male), 13 (46%) had detectable ctDNA prior to definitive surgery and 96% (27/28) tested ctDNA-negative within 4 weeks post-surgery. Pre-surgical detection of ctDNA was significantly associated with the later-stage (P = 0.02) and clinically evident stage III disease (P = 0.007). Twenty patients continue in surveillance with serial ctDNA testing every 3–6 months. With a median follow-up of 443 days, six out of 20 (30%) patients developed detectable ctDNA levels during surveillance. All six of these patients recurred with a mean time to recurrence of 280 days. Detection of ctDNA in surveillance preceded the diagnosis of clinical recurrence in three patients, was detected concurrent with clinical recurrence in two patients and followed clinical recurrence in one patient. One additional patient developed brain metastases without detection of ctDNA during surveillance but had positive pre-surgical ctDNA. Our results demonstrate the feasibility of obtaining a personalized, tumor-informed mPCR NGS-based ctDNA assay for patients with melanoma, particularly in resectable stage III disease.
format Online
Article
Text
id pubmed-10144272
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Lippincott Williams & Wilkins
record_format MEDLINE/PubMed
spelling pubmed-101442722023-04-29 Feasibility of personalized circulating tumor DNA detection in stage II and III melanoma Brunsgaard, Elise K. Bowles, Tawnya L. Asare, Elliot A. Grossmann, Kenneth Boucher, Kenneth M. Grossmann, Allie Jackson, Julie A. Wada, David A. Rathore, Richa Budde, Griffin Grandemange, Andrew Hyngstrom, John R. Melanoma Res Original Articles: Translational Research The objective of this study was to evaluate the feasibility of developing personalized, tumor-informed assays for patients with high-risk resectable melanoma and examine circulating tumor DNA (ctDNA) levels in relation to clinical status. Pilot prospective study of clinical stage IIB/C and resectable stage III melanoma patients. Tumor tissue was used to design bespoke somatic assays for interrogating ctDNA in patients’ plasma using a multiplex PCR (mPCR) next-generation sequencing (NGS)-based approach. Plasma samples for ctDNA analysis were collected pre-/post-surgery and during surveillance. Out of 28 patients (mean 65 years, 50% male), 13 (46%) had detectable ctDNA prior to definitive surgery and 96% (27/28) tested ctDNA-negative within 4 weeks post-surgery. Pre-surgical detection of ctDNA was significantly associated with the later-stage (P = 0.02) and clinically evident stage III disease (P = 0.007). Twenty patients continue in surveillance with serial ctDNA testing every 3–6 months. With a median follow-up of 443 days, six out of 20 (30%) patients developed detectable ctDNA levels during surveillance. All six of these patients recurred with a mean time to recurrence of 280 days. Detection of ctDNA in surveillance preceded the diagnosis of clinical recurrence in three patients, was detected concurrent with clinical recurrence in two patients and followed clinical recurrence in one patient. One additional patient developed brain metastases without detection of ctDNA during surveillance but had positive pre-surgical ctDNA. Our results demonstrate the feasibility of obtaining a personalized, tumor-informed mPCR NGS-based ctDNA assay for patients with melanoma, particularly in resectable stage III disease. Lippincott Williams & Wilkins 2023-06 2023-04-05 /pmc/articles/PMC10144272/ /pubmed/37040662 http://dx.doi.org/10.1097/CMR.0000000000000892 Text en Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Original Articles: Translational Research
Brunsgaard, Elise K.
Bowles, Tawnya L.
Asare, Elliot A.
Grossmann, Kenneth
Boucher, Kenneth M.
Grossmann, Allie
Jackson, Julie A.
Wada, David A.
Rathore, Richa
Budde, Griffin
Grandemange, Andrew
Hyngstrom, John R.
Feasibility of personalized circulating tumor DNA detection in stage II and III melanoma
title Feasibility of personalized circulating tumor DNA detection in stage II and III melanoma
title_full Feasibility of personalized circulating tumor DNA detection in stage II and III melanoma
title_fullStr Feasibility of personalized circulating tumor DNA detection in stage II and III melanoma
title_full_unstemmed Feasibility of personalized circulating tumor DNA detection in stage II and III melanoma
title_short Feasibility of personalized circulating tumor DNA detection in stage II and III melanoma
title_sort feasibility of personalized circulating tumor dna detection in stage ii and iii melanoma
topic Original Articles: Translational Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10144272/
https://www.ncbi.nlm.nih.gov/pubmed/37040662
http://dx.doi.org/10.1097/CMR.0000000000000892
work_keys_str_mv AT brunsgaardelisek feasibilityofpersonalizedcirculatingtumordnadetectioninstageiiandiiimelanoma
AT bowlestawnyal feasibilityofpersonalizedcirculatingtumordnadetectioninstageiiandiiimelanoma
AT asareelliota feasibilityofpersonalizedcirculatingtumordnadetectioninstageiiandiiimelanoma
AT grossmannkenneth feasibilityofpersonalizedcirculatingtumordnadetectioninstageiiandiiimelanoma
AT boucherkennethm feasibilityofpersonalizedcirculatingtumordnadetectioninstageiiandiiimelanoma
AT grossmannallie feasibilityofpersonalizedcirculatingtumordnadetectioninstageiiandiiimelanoma
AT jacksonjuliea feasibilityofpersonalizedcirculatingtumordnadetectioninstageiiandiiimelanoma
AT wadadavida feasibilityofpersonalizedcirculatingtumordnadetectioninstageiiandiiimelanoma
AT rathorericha feasibilityofpersonalizedcirculatingtumordnadetectioninstageiiandiiimelanoma
AT buddegriffin feasibilityofpersonalizedcirculatingtumordnadetectioninstageiiandiiimelanoma
AT grandemangeandrew feasibilityofpersonalizedcirculatingtumordnadetectioninstageiiandiiimelanoma
AT hyngstromjohnr feasibilityofpersonalizedcirculatingtumordnadetectioninstageiiandiiimelanoma