Circulating tumor DNA is a prognostic biomarker in metastatic melanoma patients treated with chemoimmunotherapy and BRAF inhibitor
: Mattila Kalle E., Mäkelä Siru, Kytölä Soili, Andersson Emma, Vihinen Pia, Ramadan Susan, Skyttä Tanja, Tiainen Leena, Vuoristo Meri-Sisko, Tyynelä-Korhonen Kristiina, Koivunen Jussi, Kohtamäki Laura, Aittomäki Kristiina, Hernberg Micaela
Publisher: TAYLOR & FRANCIS LTD
: 2022
: Acta Oncologica
: ACTA ONCOLOGICA
: ACTA ONCOL
: 61
: 10
: 1263
: 1267
: 5
: 0284-186X
: 1651-226X
DOI: https://doi.org/10.1080/0284186X.2022.2137693
: https://doi.org/10.1080/0284186X.2022.2137693
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.
