Circulating tumor DNA is a prognostic biomarker in metastatic melanoma patients treated with chemoimmunotherapy and BRAF inhibitor

Kalle E. Mattila; Siru Mäkelä; Soili Kytölä; Emma Andersson; Pia Vihinen; Susan Ramadan; Tanja Skyttä; Leena Tiainen; Meri Sisko Vuoristo; Kristiina Tyynelä-Korhonen; Jussi Koivunen; Laura Kohtamäki; Kristiina Aittomäki; Micaela Hernberg

doi:10.1080/0284186X.2022.2137693

Circulating tumor DNA is a prognostic biomarker in metastatic melanoma patients treated with chemoimmunotherapy and BRAF inhibitor

Kalle E. Mattila, Siru Mäkelä, Soili Kytölä, Emma Andersson, Pia Vihinen, Susan Ramadan, Tanja Skyttä, Leena Tiainen, Meri Sisko Vuoristo, Kristiina Tyynelä-Korhonen, Jussi Koivunen, Laura Kohtamäki, Kristiina Aittomäki, Micaela Hernberg

Research output: Contribution to journal › Article › Scientific › peer-review

4 Citations (Scopus)

Abstract

Background: Detectable circulating tumor DNA (ctDNA) has been associated with worse prognosis in melanoma patients. Material and methods: We studied plasma ctDNA as a prognostic biomarker in 19 patients with metastatic melanoma and a detectable tumor mutation (13 BRAF, 5 NRAS, and 1 KRAS). Patients had received chemotherapy, interferon-alpha, and vemurafenib in a prospective clinical trial. Mutant allele frequency (MAF %) was determined with droplet digital PCR from pretreatment and sequential plasma samples. Results: Higher pretreatment plasma ctDNA levels (MAF ≥3%) and detectable plasma ctDNA levels (MAF >0%) at the time of radiologically confirmed best objective response were associated with poor prognosis even when accounting for other relevant prognostic factors including performance status, tumor mutation, metastasis stage, and lactate dehydrogenase levels in multivariable analysis. Conclusion: Higher pretreatment plasma ctDNA levels and sustained detectable plasma ctDNA levels during treatment indicated poor prognosis in metastatic melanoma patients.

Original language	English
Pages (from-to)	1263-1267
Number of pages	5
Journal	Acta Oncologica
Volume	61
Issue number	10
DOIs	https://doi.org/10.1080/0284186X.2022.2137693
Publication status	Published - 2022
Publication type	A1 Journal article-refereed

Keywords

Biomarker
ctDNA
droplet digital PCR
melanoma
survival

Publication forum classification

Publication forum level 1

ASJC Scopus subject areas

Hematology
Oncology
Radiology Nuclear Medicine and imaging

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10.1080/0284186X.2022.2137693

Circulating tumor DNA is a prognostic biomarker in metastatic melanoma patients treated with chemoimmunotherapy and BRAF inhibitor
Mattila, K. E. (Creator), Mäkelä, S. (Creator), Kytölä, S. (Creator), Andersson, E. (Creator), Vihinen, P. (Creator), Ramadan, S. (Creator), Skyttä, T. (Creator), Tiainen, L. (Creator), Vuoristo, M.-S. (Creator), Tyynelä-Korhonen, K. (Creator), Koivunen, J. (Creator), Kohtamäki, L. (Creator), Aittomäki, K. (Creator) & Hernberg, M. (Creator), figshare, 2022
DOI: 10.6084/m9.figshare.21431091.v1
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Mattila, K. E., Mäkelä, S., Kytölä, S., Andersson, E., Vihinen, P., Ramadan, S., Skyttä, T., Tiainen, L., Vuoristo, M. S., Tyynelä-Korhonen, K., Koivunen, J., Kohtamäki, L., Aittomäki, K., & Hernberg, M. (2022). Circulating tumor DNA is a prognostic biomarker in metastatic melanoma patients treated with chemoimmunotherapy and BRAF inhibitor. Acta Oncologica, 61(10), 1263-1267. https://doi.org/10.1080/0284186X.2022.2137693

@article{961b46d957a0468a9699fd2448799bd5,

title = "Circulating tumor DNA is a prognostic biomarker in metastatic melanoma patients treated with chemoimmunotherapy and BRAF inhibitor",

abstract = "Background: Detectable circulating tumor DNA (ctDNA) has been associated with worse prognosis in melanoma patients. Material and methods: We studied plasma ctDNA as a prognostic biomarker in 19 patients with metastatic melanoma and a detectable tumor mutation (13 BRAF, 5 NRAS, and 1 KRAS). Patients had received chemotherapy, interferon-alpha, and vemurafenib in a prospective clinical trial. Mutant allele frequency (MAF %) was determined with droplet digital PCR from pretreatment and sequential plasma samples. Results: Higher pretreatment plasma ctDNA levels (MAF ≥3%) and detectable plasma ctDNA levels (MAF >0%) at the time of radiologically confirmed best objective response were associated with poor prognosis even when accounting for other relevant prognostic factors including performance status, tumor mutation, metastasis stage, and lactate dehydrogenase levels in multivariable analysis. Conclusion: Higher pretreatment plasma ctDNA levels and sustained detectable plasma ctDNA levels during treatment indicated poor prognosis in metastatic melanoma patients.",

keywords = "Biomarker, ctDNA, droplet digital PCR, melanoma, survival",

author = "Mattila, {Kalle E.} and Siru M{\"a}kel{\"a} and Soili Kyt{\"o}l{\"a} and Emma Andersson and Pia Vihinen and Susan Ramadan and Tanja Skytt{\"a} and Leena Tiainen and Vuoristo, {Meri Sisko} and Kristiina Tyynel{\"a}-Korhonen and Jussi Koivunen and Laura Kohtam{\"a}ki and Kristiina Aittom{\"a}ki and Micaela Hernberg",

note = "Publisher Copyright: {\textcopyright} 2022 Acta Oncologica Foundation.",

year = "2022",

doi = "10.1080/0284186X.2022.2137693",

language = "English",

volume = "61",

pages = "1263--1267",

journal = "Acta Oncologica",

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publisher = "Taylor & Francis",

number = "10",

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Mattila, KE, Mäkelä, S, Kytölä, S, Andersson, E, Vihinen, P, Ramadan, S, Skyttä, T , Tiainen, L, Vuoristo, MS, Tyynelä-Korhonen, K, Koivunen, J, Kohtamäki, L, Aittomäki, K & Hernberg, M 2022, 'Circulating tumor DNA is a prognostic biomarker in metastatic melanoma patients treated with chemoimmunotherapy and BRAF inhibitor', Acta Oncologica, vol. 61, no. 10, pp. 1263-1267. https://doi.org/10.1080/0284186X.2022.2137693

TY - JOUR

T1 - Circulating tumor DNA is a prognostic biomarker in metastatic melanoma patients treated with chemoimmunotherapy and BRAF inhibitor

AU - Mattila, Kalle E.

AU - Mäkelä, Siru

AU - Kytölä, Soili

AU - Andersson, Emma

AU - Vihinen, Pia

AU - Ramadan, Susan

AU - Skyttä, Tanja

AU - Tiainen, Leena

AU - Vuoristo, Meri Sisko

AU - Tyynelä-Korhonen, Kristiina

AU - Koivunen, Jussi

AU - Kohtamäki, Laura

AU - Aittomäki, Kristiina

AU - Hernberg, Micaela

PY - 2022

Y1 - 2022

N2 - Background: Detectable circulating tumor DNA (ctDNA) has been associated with worse prognosis in melanoma patients. Material and methods: We studied plasma ctDNA as a prognostic biomarker in 19 patients with metastatic melanoma and a detectable tumor mutation (13 BRAF, 5 NRAS, and 1 KRAS). Patients had received chemotherapy, interferon-alpha, and vemurafenib in a prospective clinical trial. Mutant allele frequency (MAF %) was determined with droplet digital PCR from pretreatment and sequential plasma samples. Results: Higher pretreatment plasma ctDNA levels (MAF ≥3%) and detectable plasma ctDNA levels (MAF >0%) at the time of radiologically confirmed best objective response were associated with poor prognosis even when accounting for other relevant prognostic factors including performance status, tumor mutation, metastasis stage, and lactate dehydrogenase levels in multivariable analysis. Conclusion: Higher pretreatment plasma ctDNA levels and sustained detectable plasma ctDNA levels during treatment indicated poor prognosis in metastatic melanoma patients.

AB - Background: Detectable circulating tumor DNA (ctDNA) has been associated with worse prognosis in melanoma patients. Material and methods: We studied plasma ctDNA as a prognostic biomarker in 19 patients with metastatic melanoma and a detectable tumor mutation (13 BRAF, 5 NRAS, and 1 KRAS). Patients had received chemotherapy, interferon-alpha, and vemurafenib in a prospective clinical trial. Mutant allele frequency (MAF %) was determined with droplet digital PCR from pretreatment and sequential plasma samples. Results: Higher pretreatment plasma ctDNA levels (MAF ≥3%) and detectable plasma ctDNA levels (MAF >0%) at the time of radiologically confirmed best objective response were associated with poor prognosis even when accounting for other relevant prognostic factors including performance status, tumor mutation, metastasis stage, and lactate dehydrogenase levels in multivariable analysis. Conclusion: Higher pretreatment plasma ctDNA levels and sustained detectable plasma ctDNA levels during treatment indicated poor prognosis in metastatic melanoma patients.

KW - Biomarker

KW - ctDNA

KW - droplet digital PCR

KW - melanoma

KW - survival

U2 - 10.1080/0284186X.2022.2137693

DO - 10.1080/0284186X.2022.2137693

M3 - Article

C2 - 36307938

AN - SCOPUS:85141145172

SN - 0284-186X

VL - 61

SP - 1263

EP - 1267

JO - Acta Oncologica

JF - Acta Oncologica

IS - 10

ER -

Circulating tumor DNA is a prognostic biomarker in metastatic melanoma patients treated with chemoimmunotherapy and BRAF inhibitor

Abstract

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Circulating tumor DNA is a prognostic biomarker in metastatic melanoma patients treated with chemoimmunotherapy and BRAF inhibitor

Cite this