Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients

Autores
Valpione, S.; Gremel, G.; Mundra, P.; Middlehurst, P.; Galvani, E.; Girotti, Maria Romina; Lee, R.J.; Garner, G.; Dhomen, N.; Lorigan, P.C.; Marais, R.
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Introduction Tumour burden is a prognostic biomarker in metastatic melanoma. However, tumour burden is difficult to measure and there are currently no reliable surrogate biomarkers to easily and reliably determine it. The aim of this study was to assess the potential of plasma total cell free DNA as biomarker of tumour burden and prognosis in metastatic melanoma patients. Materials and methods A prospective biomarker cohort study for total plasma circulating cell-free DNA (cfDNA) concentration was performed in 43 metastatic melanoma patients. For 38 patients, paired blood collections and scan assessments were available before treatment and at first response evaluation. Tumour burden was calculated as the sum of volumes from three-dimensional radiological measurements of all metastatic lesions in individual patients. Results Baseline cfDNA concentration correlated with pre-treatment tumour burden (ρ = 0.52, P < 0.001). Baseline cfDNA levels correlated significantly with hazard of death and overall survival, and a cut off value of 89 pg/μl identified two distinct prognostic groups (HR = 2.22 for high cfDNA, P = 0.004). Patients with cfDNA ≥89 pg/μl had shorter OS (10.0 versus 22.7 months, P = 0.009; HR = 2.22 for high cfDNA, P = 0.004) and the significance was maintained when compared with lactic dehydrogenase (LDH) in a multivariate analysis. We also found a correlation between the changes of cfDNA and treatment-related changes in tumour burden (ρ = 0.49, P = 0.002). In addition, the ratio between baseline cfDNA and tumour burden was prognostic (HR = 2.7 for cfDNA/tumour volume ≥8 pg/(μl*cm3), P = 0.024). Conclusions We have demonstrated that cfDNA is a surrogate marker of tumour burden in metastatic melanoma patients, and that it is prognostic for overall survival.
Fil: Valpione, S.. University of Manchester; Reino Unido. Christie NHS Foundation Trust; Reino Unido
Fil: Gremel, G.. University of Manchester; Reino Unido
Fil: Mundra, P.. University of Manchester; Reino Unido
Fil: Middlehurst, P.. University of Manchester; Reino Unido
Fil: Galvani, E.. Christie NHS Foundation Trust; Reino Unido. University of Manchester; Reino Unido
Fil: Girotti, Maria Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. University of Manchester; Reino Unido
Fil: Lee, R.J.. University of Manchester; Reino Unido
Fil: Garner, G.. University of Manchester; Reino Unido
Fil: Dhomen, N.. University of Manchester; Reino Unido
Fil: Lorigan, P.C.. Christie NHS Foundation Trust; Reino Unido
Fil: Marais, R.. University of Manchester; Reino Unido
Materia
MELANOMA
PROGNOSTIC BIOMARKER
TOTAL CIRCULATING CELL-FREE DNA
TUMOUR BURDEN
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/87378
Acceder
id CONICETDig_da39bc5136ff8eba2e02621b9b2313bf
oai_identifier_str oai:ri.conicet.gov.ar:11336/87378
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patientsValpione, S.Gremel, G.Mundra, P.Middlehurst, P.Galvani, E.Girotti, Maria RominaLee, R.J.Garner, G.Dhomen, N.Lorigan, P.C.Marais, R.MELANOMAPROGNOSTIC BIOMARKERTOTAL CIRCULATING CELL-FREE DNATUMOUR BURDENhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Introduction Tumour burden is a prognostic biomarker in metastatic melanoma. However, tumour burden is difficult to measure and there are currently no reliable surrogate biomarkers to easily and reliably determine it. The aim of this study was to assess the potential of plasma total cell free DNA as biomarker of tumour burden and prognosis in metastatic melanoma patients. Materials and methods A prospective biomarker cohort study for total plasma circulating cell-free DNA (cfDNA) concentration was performed in 43 metastatic melanoma patients. For 38 patients, paired blood collections and scan assessments were available before treatment and at first response evaluation. Tumour burden was calculated as the sum of volumes from three-dimensional radiological measurements of all metastatic lesions in individual patients. Results Baseline cfDNA concentration correlated with pre-treatment tumour burden (ρ = 0.52, P < 0.001). Baseline cfDNA levels correlated significantly with hazard of death and overall survival, and a cut off value of 89 pg/μl identified two distinct prognostic groups (HR = 2.22 for high cfDNA, P = 0.004). Patients with cfDNA ≥89 pg/μl had shorter OS (10.0 versus 22.7 months, P = 0.009; HR = 2.22 for high cfDNA, P = 0.004) and the significance was maintained when compared with lactic dehydrogenase (LDH) in a multivariate analysis. We also found a correlation between the changes of cfDNA and treatment-related changes in tumour burden (ρ = 0.49, P = 0.002). In addition, the ratio between baseline cfDNA and tumour burden was prognostic (HR = 2.7 for cfDNA/tumour volume ≥8 pg/(μl*cm3), P = 0.024). Conclusions We have demonstrated that cfDNA is a surrogate marker of tumour burden in metastatic melanoma patients, and that it is prognostic for overall survival.Fil: Valpione, S.. University of Manchester; Reino Unido. Christie NHS Foundation Trust; Reino UnidoFil: Gremel, G.. University of Manchester; Reino UnidoFil: Mundra, P.. University of Manchester; Reino UnidoFil: Middlehurst, P.. University of Manchester; Reino UnidoFil: Galvani, E.. Christie NHS Foundation Trust; Reino Unido. University of Manchester; Reino UnidoFil: Girotti, Maria Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. University of Manchester; Reino UnidoFil: Lee, R.J.. University of Manchester; Reino UnidoFil: Garner, G.. University of Manchester; Reino UnidoFil: Dhomen, N.. University of Manchester; Reino UnidoFil: Lorigan, P.C.. Christie NHS Foundation Trust; Reino UnidoFil: Marais, R.. University of Manchester; Reino UnidoElsevier2018-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/87378Valpione, S.; Gremel, G.; Mundra, P.; Middlehurst, P.; Galvani, E.; et al.; Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients; Elsevier; European Journal of Cancer; 88; 1-2018; 1-90959-8049CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejca.2017.10.029info:eu-repo/semantics/altIdentifier/url/https://www.ejcancer.com/article/S0959-8049(17)31369-2/fulltextinfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769519/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:05:32Zoai:ri.conicet.gov.ar:11336/87378instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:05:32.864CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients
title Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients
spellingShingle Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients
Valpione, S.
MELANOMA
PROGNOSTIC BIOMARKER
TOTAL CIRCULATING CELL-FREE DNA
TUMOUR BURDEN
title_short Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients
title_full Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients
title_fullStr Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients
title_full_unstemmed Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients
title_sort Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients
dc.creator.none.fl_str_mv Valpione, S.
Gremel, G.
Mundra, P.
Middlehurst, P.
Galvani, E.
Girotti, Maria Romina
Lee, R.J.
Garner, G.
Dhomen, N.
Lorigan, P.C.
Marais, R.
author Valpione, S.
author_facet Valpione, S.
Gremel, G.
Mundra, P.
Middlehurst, P.
Galvani, E.
Girotti, Maria Romina
Lee, R.J.
Garner, G.
Dhomen, N.
Lorigan, P.C.
Marais, R.
author_role author
author2 Gremel, G.
Mundra, P.
Middlehurst, P.
Galvani, E.
Girotti, Maria Romina
Lee, R.J.
Garner, G.
Dhomen, N.
Lorigan, P.C.
Marais, R.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv MELANOMA
PROGNOSTIC BIOMARKER
TOTAL CIRCULATING CELL-FREE DNA
TUMOUR BURDEN
topic MELANOMA
PROGNOSTIC BIOMARKER
TOTAL CIRCULATING CELL-FREE DNA
TUMOUR BURDEN
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Introduction Tumour burden is a prognostic biomarker in metastatic melanoma. However, tumour burden is difficult to measure and there are currently no reliable surrogate biomarkers to easily and reliably determine it. The aim of this study was to assess the potential of plasma total cell free DNA as biomarker of tumour burden and prognosis in metastatic melanoma patients. Materials and methods A prospective biomarker cohort study for total plasma circulating cell-free DNA (cfDNA) concentration was performed in 43 metastatic melanoma patients. For 38 patients, paired blood collections and scan assessments were available before treatment and at first response evaluation. Tumour burden was calculated as the sum of volumes from three-dimensional radiological measurements of all metastatic lesions in individual patients. Results Baseline cfDNA concentration correlated with pre-treatment tumour burden (ρ = 0.52, P < 0.001). Baseline cfDNA levels correlated significantly with hazard of death and overall survival, and a cut off value of 89 pg/μl identified two distinct prognostic groups (HR = 2.22 for high cfDNA, P = 0.004). Patients with cfDNA ≥89 pg/μl had shorter OS (10.0 versus 22.7 months, P = 0.009; HR = 2.22 for high cfDNA, P = 0.004) and the significance was maintained when compared with lactic dehydrogenase (LDH) in a multivariate analysis. We also found a correlation between the changes of cfDNA and treatment-related changes in tumour burden (ρ = 0.49, P = 0.002). In addition, the ratio between baseline cfDNA and tumour burden was prognostic (HR = 2.7 for cfDNA/tumour volume ≥8 pg/(μl*cm3), P = 0.024). Conclusions We have demonstrated that cfDNA is a surrogate marker of tumour burden in metastatic melanoma patients, and that it is prognostic for overall survival.
Fil: Valpione, S.. University of Manchester; Reino Unido. Christie NHS Foundation Trust; Reino Unido
Fil: Gremel, G.. University of Manchester; Reino Unido
Fil: Mundra, P.. University of Manchester; Reino Unido
Fil: Middlehurst, P.. University of Manchester; Reino Unido
Fil: Galvani, E.. Christie NHS Foundation Trust; Reino Unido. University of Manchester; Reino Unido
Fil: Girotti, Maria Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. University of Manchester; Reino Unido
Fil: Lee, R.J.. University of Manchester; Reino Unido
Fil: Garner, G.. University of Manchester; Reino Unido
Fil: Dhomen, N.. University of Manchester; Reino Unido
Fil: Lorigan, P.C.. Christie NHS Foundation Trust; Reino Unido
Fil: Marais, R.. University of Manchester; Reino Unido
description Introduction Tumour burden is a prognostic biomarker in metastatic melanoma. However, tumour burden is difficult to measure and there are currently no reliable surrogate biomarkers to easily and reliably determine it. The aim of this study was to assess the potential of plasma total cell free DNA as biomarker of tumour burden and prognosis in metastatic melanoma patients. Materials and methods A prospective biomarker cohort study for total plasma circulating cell-free DNA (cfDNA) concentration was performed in 43 metastatic melanoma patients. For 38 patients, paired blood collections and scan assessments were available before treatment and at first response evaluation. Tumour burden was calculated as the sum of volumes from three-dimensional radiological measurements of all metastatic lesions in individual patients. Results Baseline cfDNA concentration correlated with pre-treatment tumour burden (ρ = 0.52, P < 0.001). Baseline cfDNA levels correlated significantly with hazard of death and overall survival, and a cut off value of 89 pg/μl identified two distinct prognostic groups (HR = 2.22 for high cfDNA, P = 0.004). Patients with cfDNA ≥89 pg/μl had shorter OS (10.0 versus 22.7 months, P = 0.009; HR = 2.22 for high cfDNA, P = 0.004) and the significance was maintained when compared with lactic dehydrogenase (LDH) in a multivariate analysis. We also found a correlation between the changes of cfDNA and treatment-related changes in tumour burden (ρ = 0.49, P = 0.002). In addition, the ratio between baseline cfDNA and tumour burden was prognostic (HR = 2.7 for cfDNA/tumour volume ≥8 pg/(μl*cm3), P = 0.024). Conclusions We have demonstrated that cfDNA is a surrogate marker of tumour burden in metastatic melanoma patients, and that it is prognostic for overall survival.
publishDate 2018
dc.date.none.fl_str_mv 2018-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/87378
Valpione, S.; Gremel, G.; Mundra, P.; Middlehurst, P.; Galvani, E.; et al.; Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients; Elsevier; European Journal of Cancer; 88; 1-2018; 1-9
0959-8049
CONICET Digital
CONICET
url http://hdl.handle.net/11336/87378
identifier_str_mv Valpione, S.; Gremel, G.; Mundra, P.; Middlehurst, P.; Galvani, E.; et al.; Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients; Elsevier; European Journal of Cancer; 88; 1-2018; 1-9
0959-8049
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejca.2017.10.029
info:eu-repo/semantics/altIdentifier/url/https://www.ejcancer.com/article/S0959-8049(17)31369-2/fulltext
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769519/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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