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

Authors

  • Kalle E. Mattila Department of Oncology and Radiotherapy, Fican West Cancer Centre, University of Turku and Turku University Hospital, and InFLAMES Research Flagship Center, University of Turku, Turku, Finland
  • Siru Mäkelä Comprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
  • Soili Kytölä Department of Genetics, HUSLAB, HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland
  • Emma Andersson Department of Genetics, HUSLAB, HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland
  • Pia Vihinen Department of Oncology and Radiotherapy and Fican West Cancer Centre, University of Turku and Turku University Hospital, Turku, Finland
  • Susan Ramadan Department of Oncology and Radiotherapy and Fican West Cancer Centre, University of Turku and Turku University Hospital, Turku, Finland
  • Tanja Skyttä Department of Oncology and Radiotherapy, Tays Cancer Centre, Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
  • Leena Tiainen Department of Oncology and Radiotherapy, Tays Cancer Centre, Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
  • Meri-Sisko Vuoristo Department of Oncology and Radiotherapy, Fican West Cancer Centre, University of Turku and Turku University Hospital, and InFLAMES Research Flagship Center, University of Turku, Turku, Finland
  • Kristiina Tyynelä-Korhonen Center of Oncology, Kuopio University Hospital, Kuopio, Finland
  • Jussi Koivunen Department of Oncology and Radiotherapy, University of Oulu and Oulu University Hospital, MRC Oulu, Oulu, Finland
  • Laura Kohtamäki Comprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
  • Kristiina Aittomäki Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland
  • Micaela Hernberg Comprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland

DOI:

https://doi.org/10.1080/0284186X.2022.2137693

Keywords:

Biomarker, ctDNA, droplet digital PCR, melanoma, survival

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.

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Published

2022-10-03

How to Cite

Mattila, K. E. ., Mäkelä, S. ., Kytölä, S. ., Andersson, E. ., Vihinen, P. ., Ramadan, S. ., … 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

Issue

Vol. 61 No. 10 (2022): Acta Oncologica

Section

Articles