Implementation of a Pilot Study to Analyze Circulating Tumor DNA in Early-Stage Lung Cancer
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | por eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/19487 |
Resumo: | Introduction: Liquid biopsies based on plasma circulating tumour deoxyribonucleic acid (ctDNA) have shown promise in monitoring lung cancer evolution. The expression of ctDNA across time, its relationship with clinicopathological parameters and its association with lung cancer progression through imaging allow us to weigh how useful ctDNA could be in monitoring surgically resectable lung cancer. The aim of this study was to assess the impact of ctDNA analysis implementation in early-stage lung cancer.Methods: A cohort of 47 patients was sequentially recruited. Only 34 patients with early-stage lung cancer were included. All patients had a tissue specimen and five blood samples drawn: at the preoperative stage, from the pulmonary vein, at surgical discharge, at the first follow-up and at the last follow-up. All blood samples were evaluated for ctDNA expression. Results: On average, the maximum yield of ctDNA was obtained in liquid biopsies at the surgical discharge of patients when compared with PO, PV, and F1 (p < 0.0001, p < 0.0001, p < 0.0001 respectively). No statistically significant differences were found when comparing the last follow-up to surgical discharge ctDNA expression (p = 0.851). The correlation between ctDNA concentration according to five-time points and the four clinicopathological characteristics showed that patients younger than 70 years had a statistically significant reduction of the concentration of ctDNA at the preoperative and surgical discharge time point [β = -16 734 (-27 707; - 5760); p = 0.003; β = -21 785 (-38 447; -5123); p = 0.010], as opposed to an increase of the concentration of ctDNA at the pulmonary vein and last follow-up time points [β = 8369 (0.359; 16 378); p = 0.041; β = 34 402 (12 549; 56 254); p = 0.002] all with a confidence level of 95%. In the cases where actionable mutations were identified in tissue biopsies, the expected mutation was found in five out of six patients plasma samples at the pre-operatory time point and in two out of six patients plasma samples at the pulmonary vein time point. Two out of six patients with actionable mutations had disease progression.Conclusion: The results of this pilot study suggest that the maximum yield of ctDNA is obtained at the surgical discharge of the patients and that the pre-operatory timepoint is the one offering the highest sensitivity for the detection of actionable mutations in ctDNA in early-stage lung cancer. |
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Implementation of a Pilot Study to Analyze Circulating Tumor DNA in Early-Stage Lung CancerImplementação de um Estudo Piloto para Análise de ADN Tumoral Circulante no Cancro do Pulmão em Estádio InicialCirculating Tumor DNAEarly Detection of Cancer/methodsHigh-Throughput Nucleotide SequencingLung NeoplasmsMutationNeoplasm StagingDetecção Precoce de Cancro/métodosDNA Tumoral CirculanteEstadiamento de NeoplasiasMutaçãoNeoplasias do PulmãoSequenciamento de Nucleotídeos em Larga EscalaIntroduction: Liquid biopsies based on plasma circulating tumour deoxyribonucleic acid (ctDNA) have shown promise in monitoring lung cancer evolution. The expression of ctDNA across time, its relationship with clinicopathological parameters and its association with lung cancer progression through imaging allow us to weigh how useful ctDNA could be in monitoring surgically resectable lung cancer. The aim of this study was to assess the impact of ctDNA analysis implementation in early-stage lung cancer.Methods: A cohort of 47 patients was sequentially recruited. Only 34 patients with early-stage lung cancer were included. All patients had a tissue specimen and five blood samples drawn: at the preoperative stage, from the pulmonary vein, at surgical discharge, at the first follow-up and at the last follow-up. All blood samples were evaluated for ctDNA expression. Results: On average, the maximum yield of ctDNA was obtained in liquid biopsies at the surgical discharge of patients when compared with PO, PV, and F1 (p < 0.0001, p < 0.0001, p < 0.0001 respectively). No statistically significant differences were found when comparing the last follow-up to surgical discharge ctDNA expression (p = 0.851). The correlation between ctDNA concentration according to five-time points and the four clinicopathological characteristics showed that patients younger than 70 years had a statistically significant reduction of the concentration of ctDNA at the preoperative and surgical discharge time point [β = -16 734 (-27 707; - 5760); p = 0.003; β = -21 785 (-38 447; -5123); p = 0.010], as opposed to an increase of the concentration of ctDNA at the pulmonary vein and last follow-up time points [β = 8369 (0.359; 16 378); p = 0.041; β = 34 402 (12 549; 56 254); p = 0.002] all with a confidence level of 95%. In the cases where actionable mutations were identified in tissue biopsies, the expected mutation was found in five out of six patients plasma samples at the pre-operatory time point and in two out of six patients plasma samples at the pulmonary vein time point. Two out of six patients with actionable mutations had disease progression.Conclusion: The results of this pilot study suggest that the maximum yield of ctDNA is obtained at the surgical discharge of the patients and that the pre-operatory timepoint is the one offering the highest sensitivity for the detection of actionable mutations in ctDNA in early-stage lung cancer.Introdução: As biópsias líquidas baseadas no ácido desoxirribonucleico tumoral circulante (ctADN) no plasma têm-se mostrado promissoras na monitorização da evolução do cancro do pulmão. A expressão do ctADN ao longo do tempo, sua relação com parâmetros clínico-patológicos e sua associação com a progressão do cancro de pulmão através da imagem, permitem-nos avaliar o quanto útil o ctADN pode ser na monitorização do cancro do pulmão ressecável cirurgicamente. O objetivo deste estudo foi avaliar o impacto da implementação da análise de ctADN no cancro do pulmão em estádio inicial.Métodos: Uma coorte de 47 pacientes com cancro de pulmão em estádio inicial foi recrutada sequencialmente. Apenas 34 pacientes foram incluídos. Todos os pacientes colheram uma amostra de tecido e cinco amostras de sangue: no pré-operatório, da veia pulmonar, na alta cirúrgica, no primeiro seguimento e no último seguimento. Todas as amostras de sangue foram avaliadas quanto à expressão de ctADN.Resultados: Em média, o rendimento máximo de ctADN foi obtido em biópsias líquidas obtidas na alta cirúrgica dos pacientes quando comparado com as colheitas nos momento pré-operatório, da veia pulmonar, e no primeiro seguimento (p < 0,0001, p < 0,0001, p < 0,0001, respetivamente). Não houve significado estatístico ao comparar as biópsias líquidas obtidas no último seguimento com a expressão do ctADN na alta cirúrgica (p = 0,851). A correlação entre a concentração de ctADN nos cinco momentos de colheita e as quatro características clínico-patológicas mostrou que pacientes com menos de 70 anos tiveram redução significativa da concentração de ctADN no momento pré-operatório e na alta cirúrgica [β = -16 734 (-27 707; -5760); p = 0,003; β = -21 785 (-38 447; -5123); p = 0,010] em oposição a um aumento da concentração de ctDNA na veia pulmonar e no último seguimento [β = 8369 (0,359; 16 378); p = 0,041; β = 34 402 (12 549; 56 254); p = 0,002] todos com nível de confiança de 95%. Nos casos em que foram identificadas mutações acionáveis em biópsias de tecido, a mutação esperada foi encontrada em cinco de seis amostras de plasma de pacientes no momento pré-operatório e em duas de seis amostras de plasma de pacientes no momento da veia pulmonar. Dois dos seis pacientes com mutações acionáveis apresentaram progressão da doença.Conclusão: Os resultados deste estudo piloto sugerem que o rendimento máximo do ctDNA é obtido na alta cirúrgica dos pacientes e que o momento pré-operatório é o que oferece a maior sensibilidade para a deteção de mutações acionáveis no ctDNA no cancro do pulmão em estádio inicial.Ordem dos Médicos2023-07-25info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/19487Acta Médica Portuguesa; Vol. 37 No. 1 (2024): January; 10-19Acta Médica Portuguesa; Vol. 37 N.º 1 (2024): Janeiro; 10-191646-07580870-399Xreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAPporenghttps://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/19487https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/19487/15289https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/19487/15190Direitos de Autor (c) 2023 Acta Médica Portuguesainfo:eu-repo/semantics/openAccessMacedo, Joana Espiga de MacedoTaveira-Gomes, TiagoMachado, José CarlosHespanhol, Venceslau2024-01-07T03:00:32Zoai:ojs.www.actamedicaportuguesa.com:article/19487Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:10:13.157316Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Implementation of a Pilot Study to Analyze Circulating Tumor DNA in Early-Stage Lung Cancer Implementação de um Estudo Piloto para Análise de ADN Tumoral Circulante no Cancro do Pulmão em Estádio Inicial |
title |
Implementation of a Pilot Study to Analyze Circulating Tumor DNA in Early-Stage Lung Cancer |
spellingShingle |
Implementation of a Pilot Study to Analyze Circulating Tumor DNA in Early-Stage Lung Cancer Macedo, Joana Espiga de Macedo Circulating Tumor DNA Early Detection of Cancer/methods High-Throughput Nucleotide Sequencing Lung Neoplasms Mutation Neoplasm Staging Detecção Precoce de Cancro/métodos DNA Tumoral Circulante Estadiamento de Neoplasias Mutação Neoplasias do Pulmão Sequenciamento de Nucleotídeos em Larga Escala |
title_short |
Implementation of a Pilot Study to Analyze Circulating Tumor DNA in Early-Stage Lung Cancer |
title_full |
Implementation of a Pilot Study to Analyze Circulating Tumor DNA in Early-Stage Lung Cancer |
title_fullStr |
Implementation of a Pilot Study to Analyze Circulating Tumor DNA in Early-Stage Lung Cancer |
title_full_unstemmed |
Implementation of a Pilot Study to Analyze Circulating Tumor DNA in Early-Stage Lung Cancer |
title_sort |
Implementation of a Pilot Study to Analyze Circulating Tumor DNA in Early-Stage Lung Cancer |
author |
Macedo, Joana Espiga de Macedo |
author_facet |
Macedo, Joana Espiga de Macedo Taveira-Gomes, Tiago Machado, José Carlos Hespanhol, Venceslau |
author_role |
author |
author2 |
Taveira-Gomes, Tiago Machado, José Carlos Hespanhol, Venceslau |
author2_role |
author author author |
dc.contributor.author.fl_str_mv |
Macedo, Joana Espiga de Macedo Taveira-Gomes, Tiago Machado, José Carlos Hespanhol, Venceslau |
dc.subject.por.fl_str_mv |
Circulating Tumor DNA Early Detection of Cancer/methods High-Throughput Nucleotide Sequencing Lung Neoplasms Mutation Neoplasm Staging Detecção Precoce de Cancro/métodos DNA Tumoral Circulante Estadiamento de Neoplasias Mutação Neoplasias do Pulmão Sequenciamento de Nucleotídeos em Larga Escala |
topic |
Circulating Tumor DNA Early Detection of Cancer/methods High-Throughput Nucleotide Sequencing Lung Neoplasms Mutation Neoplasm Staging Detecção Precoce de Cancro/métodos DNA Tumoral Circulante Estadiamento de Neoplasias Mutação Neoplasias do Pulmão Sequenciamento de Nucleotídeos em Larga Escala |
description |
Introduction: Liquid biopsies based on plasma circulating tumour deoxyribonucleic acid (ctDNA) have shown promise in monitoring lung cancer evolution. The expression of ctDNA across time, its relationship with clinicopathological parameters and its association with lung cancer progression through imaging allow us to weigh how useful ctDNA could be in monitoring surgically resectable lung cancer. The aim of this study was to assess the impact of ctDNA analysis implementation in early-stage lung cancer.Methods: A cohort of 47 patients was sequentially recruited. Only 34 patients with early-stage lung cancer were included. All patients had a tissue specimen and five blood samples drawn: at the preoperative stage, from the pulmonary vein, at surgical discharge, at the first follow-up and at the last follow-up. All blood samples were evaluated for ctDNA expression. Results: On average, the maximum yield of ctDNA was obtained in liquid biopsies at the surgical discharge of patients when compared with PO, PV, and F1 (p < 0.0001, p < 0.0001, p < 0.0001 respectively). No statistically significant differences were found when comparing the last follow-up to surgical discharge ctDNA expression (p = 0.851). The correlation between ctDNA concentration according to five-time points and the four clinicopathological characteristics showed that patients younger than 70 years had a statistically significant reduction of the concentration of ctDNA at the preoperative and surgical discharge time point [β = -16 734 (-27 707; - 5760); p = 0.003; β = -21 785 (-38 447; -5123); p = 0.010], as opposed to an increase of the concentration of ctDNA at the pulmonary vein and last follow-up time points [β = 8369 (0.359; 16 378); p = 0.041; β = 34 402 (12 549; 56 254); p = 0.002] all with a confidence level of 95%. In the cases where actionable mutations were identified in tissue biopsies, the expected mutation was found in five out of six patients plasma samples at the pre-operatory time point and in two out of six patients plasma samples at the pulmonary vein time point. Two out of six patients with actionable mutations had disease progression.Conclusion: The results of this pilot study suggest that the maximum yield of ctDNA is obtained at the surgical discharge of the patients and that the pre-operatory timepoint is the one offering the highest sensitivity for the detection of actionable mutations in ctDNA in early-stage lung cancer. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-07-25 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/19487 |
url |
https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/19487 |
dc.language.iso.fl_str_mv |
por eng |
language |
por eng |
dc.relation.none.fl_str_mv |
https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/19487 https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/19487/15289 https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/19487/15190 |
dc.rights.driver.fl_str_mv |
Direitos de Autor (c) 2023 Acta Médica Portuguesa info:eu-repo/semantics/openAccess |
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Direitos de Autor (c) 2023 Acta Médica Portuguesa |
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openAccess |
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application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Ordem dos Médicos |
publisher.none.fl_str_mv |
Ordem dos Médicos |
dc.source.none.fl_str_mv |
Acta Médica Portuguesa; Vol. 37 No. 1 (2024): January; 10-19 Acta Médica Portuguesa; Vol. 37 N.º 1 (2024): Janeiro; 10-19 1646-0758 0870-399X reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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