RT Journal Article
T1 The dynamics of circulating tumour DNA (ctDNA) during treatment reflects tumour response in advanced melanoma patients
A1 Di Nardo, Lucia
A1 Del Regno, Laura
A1 Di Stefani, Alessandro
A1 Mannino, Maria
A1 Fossati, Barbara
A1 Catapano, Silvia
A1 Quattrini, Laura
A1 Alpay, Yeliney
A1 Pellegrini, Cristina
A1 Cortellini, Alessio
A1 Parisi, Alessandro
A1 Capoluongo, Ettore
A1 Autilio, Chiara
A1 Fargnoli, Maria Concetta
A1 Peris, Ketty
AB Despite the introduction of targeted (BRAFi/MEKi) and immune checkpoint inhibitors (ICIs) has significantly reduced the recurrence rate and improved the overall survival (OS) of patients with Stage III and IV melanoma, only a percentage will benefit of durable disease control. The aim of this study was to examine whether the levels of circulating tumour DNA (ctDNA) in plasma of advanced melanoma patients undergoing BRAFi/MEKi or ICIs vary according to the patients' survival outcomes (i.e. progression-free survival (PFS) and OS) and disease progression. Plasma samples of Stage III-IV melanoma patients were collected at baseline (treatment initiation) and thereafter every 3 months. Circulating BRAFV600E/K and NRASQ61R/K mutations were analysed through droplet digital PCR (ddPCR, Bio-Rad) in a total of 177 plasma samples from 48 melanoma patients (19 Stage III, 29 Stage IV). Baseline ctDNA concentration was significantly associated with OS (HR = 1.003, 95% CI = 1.000–1.006, p = 0.043) and PFS (HR = 1.004, 95% CI = 1.000–1.007, p = 0.029) independent of clinical-prognostic confounders. For each unit increase in the ∆ctDNA (concentration difference between the last follow-up and baseline) there was a 24% increased risk of disease progression, irrespective of treatment type and stage at diagnosis (OR = 1.24, 95% CI = 1.03–1.49, p = 0.020, AUC = 0.93). Patients with reduction of ctDNA level from baseline to the last follow-up had longer OS (HR = 0.14; 95% CI = 0.05–0.44, p = 0.001) and PFS (HR = 0.08; 95% CI = 0.03–0.27, p < 0.0001) compared to patients with increased ctDNA, including adjustment for confounding factors. Our findings suggest that variation of ctDNA over time during melanoma treatment reflects the clinical outcome and tumour response to therapy and might be helpful in clinical monitoring.
PB Wiley
SN 0906-6705
YR 2023
FD 2023-08
LK https://hdl.handle.net/20.500.14352/121240
UL https://hdl.handle.net/20.500.14352/121240
LA eng
NO Di Nardo L, Del Regno L, Di Stefani A, Mannino M, Fossati B, Catapano S, Quattrini L, Alpay Y, Pellegrini C, Cortellini A, Parisi A, Capoluongo E, Autilio C, Fargnoli MC, Peris K. The dynamics of circulating tumour DNA ( ctDNA ) during treatment reflects tumour response in advanced melanoma patients. Experimental Dermatology 2023;32:1785–93. https://doi.org/10.1111/exd.14901.
NO Correcciones al artículo en : https://onlinelibrary.wiley.com/doi/10.1111/exd.70091
NO National Institute for Health and Care Research (United Kingdom)
NO Imperial Biomedical Research Centre (United Kingdom)
DS Docta Complutense
RD 15 jun 2025