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Circulating tumor DNA predicts survival in patients with resected high-risk stage II/III melanoma

BACKGROUND: Patients with high-risk stage II/III resected melanoma commonly develop distant metastases. At present, we cannot differentiate between patients who will recur or those who are cured by surgery. We investigated if circulating tumor DNA (ctDNA) can predict relapse and survival in patients...

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Autores principales: Lee, R J, Gremel, G, Marshall, A, Myers, K A, Fisher, N, Dunn, J A, Dhomen, N, Corrie, P G, Middleton, M R, Lorigan, P, Marais, R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834029/
https://www.ncbi.nlm.nih.gov/pubmed/29112704
http://dx.doi.org/10.1093/annonc/mdx717
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author Lee, R J
Gremel, G
Marshall, A
Myers, K A
Fisher, N
Dunn, J A
Dhomen, N
Corrie, P G
Middleton, M R
Lorigan, P
Marais, R
author_facet Lee, R J
Gremel, G
Marshall, A
Myers, K A
Fisher, N
Dunn, J A
Dhomen, N
Corrie, P G
Middleton, M R
Lorigan, P
Marais, R
author_sort Lee, R J
collection PubMed
description BACKGROUND: Patients with high-risk stage II/III resected melanoma commonly develop distant metastases. At present, we cannot differentiate between patients who will recur or those who are cured by surgery. We investigated if circulating tumor DNA (ctDNA) can predict relapse and survival in patients with resected melanoma. PATIENTS AND METHODS: We carried out droplet digital polymerase chain reaction to detect BRAF and NRAS mutations in plasma taken after surgery from 161 stage II/III high-risk melanoma patients enrolled in the AVAST-M adjuvant trial. RESULTS: Mutant BRAF or NRAS ctDNA was detected (≥1 copy of mutant ctDNA) in 15/132 (11%) BRAF mutant patient samples and 4/29 (14%) NRAS mutant patient samples. Patients with detectable ctDNA had a decreased disease-free interval [DFI; hazard ratio (HR) 3.12; 95% confidence interval (CI) 1.79–5.47; P < 0.0001] and distant metastasis-free interval (DMFI; HR 3.22; 95% CI 1.80–5.79; P < 0.0001) versus those with undetectable ctDNA. Detectable ctDNA remained a significant predictor after adjustment for performance status and disease stage (DFI: HR 3.26, 95% CI 1.83–5.83, P < 0.0001; DMFI: HR 3.45, 95% CI 1.88–6.34, P < 0.0001). Five-year overall survival rate for patients with detectable ctDNA was 33% (95% CI 14%–55%) versus 65% (95% CI 56%–72%) for those with undetectable ctDNA. Overall survival was significantly worse for patients with detectable ctDNA (HR 2.63; 95% CI 1.40–4.96); P = 0.003) and remained significant after adjustment for performance status (HR 2.50, 95% CI 1.32–4.74, P = 0.005). CONCLUSION: ctDNA predicts for relapse and survival in high-risk resected melanoma and could aid selection of patients for adjuvant therapy. CLINICAL TRIAL NUMBER: ISRCTN 81261306
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spelling pubmed-58340292018-03-07 Circulating tumor DNA predicts survival in patients with resected high-risk stage II/III melanoma Lee, R J Gremel, G Marshall, A Myers, K A Fisher, N Dunn, J A Dhomen, N Corrie, P G Middleton, M R Lorigan, P Marais, R Ann Oncol Original Articles BACKGROUND: Patients with high-risk stage II/III resected melanoma commonly develop distant metastases. At present, we cannot differentiate between patients who will recur or those who are cured by surgery. We investigated if circulating tumor DNA (ctDNA) can predict relapse and survival in patients with resected melanoma. PATIENTS AND METHODS: We carried out droplet digital polymerase chain reaction to detect BRAF and NRAS mutations in plasma taken after surgery from 161 stage II/III high-risk melanoma patients enrolled in the AVAST-M adjuvant trial. RESULTS: Mutant BRAF or NRAS ctDNA was detected (≥1 copy of mutant ctDNA) in 15/132 (11%) BRAF mutant patient samples and 4/29 (14%) NRAS mutant patient samples. Patients with detectable ctDNA had a decreased disease-free interval [DFI; hazard ratio (HR) 3.12; 95% confidence interval (CI) 1.79–5.47; P < 0.0001] and distant metastasis-free interval (DMFI; HR 3.22; 95% CI 1.80–5.79; P < 0.0001) versus those with undetectable ctDNA. Detectable ctDNA remained a significant predictor after adjustment for performance status and disease stage (DFI: HR 3.26, 95% CI 1.83–5.83, P < 0.0001; DMFI: HR 3.45, 95% CI 1.88–6.34, P < 0.0001). Five-year overall survival rate for patients with detectable ctDNA was 33% (95% CI 14%–55%) versus 65% (95% CI 56%–72%) for those with undetectable ctDNA. Overall survival was significantly worse for patients with detectable ctDNA (HR 2.63; 95% CI 1.40–4.96); P = 0.003) and remained significant after adjustment for performance status (HR 2.50, 95% CI 1.32–4.74, P = 0.005). CONCLUSION: ctDNA predicts for relapse and survival in high-risk resected melanoma and could aid selection of patients for adjuvant therapy. CLINICAL TRIAL NUMBER: ISRCTN 81261306 Oxford University Press 2018-02 2017-11-03 /pmc/articles/PMC5834029/ /pubmed/29112704 http://dx.doi.org/10.1093/annonc/mdx717 Text en © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Lee, R J
Gremel, G
Marshall, A
Myers, K A
Fisher, N
Dunn, J A
Dhomen, N
Corrie, P G
Middleton, M R
Lorigan, P
Marais, R
Circulating tumor DNA predicts survival in patients with resected high-risk stage II/III melanoma
title Circulating tumor DNA predicts survival in patients with resected high-risk stage II/III melanoma
title_full Circulating tumor DNA predicts survival in patients with resected high-risk stage II/III melanoma
title_fullStr Circulating tumor DNA predicts survival in patients with resected high-risk stage II/III melanoma
title_full_unstemmed Circulating tumor DNA predicts survival in patients with resected high-risk stage II/III melanoma
title_short Circulating tumor DNA predicts survival in patients with resected high-risk stage II/III melanoma
title_sort circulating tumor dna predicts survival in patients with resected high-risk stage ii/iii melanoma
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834029/
https://www.ncbi.nlm.nih.gov/pubmed/29112704
http://dx.doi.org/10.1093/annonc/mdx717
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