Circulating tumor DNA: a promising biomarker in stage III BRAF+ melanoma Article Swipe
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· 2024
· Open Access
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· DOI: https://doi.org/10.1016/j.ejcskn.2024.100120
· OA: W4399123215
Background: In recent years, various melanoma biomarkers have undergone investigation in both preclinical and clinical settings. Among these, circulating tumor DNA (ctDNA) has emerged as a promising candidate. However, in the adjuvant setting, only a limited number of exploratory analyses have been conducted, and uncertainties persist regarding the link between ctDNA detection and patients' relapse. Methods: A cohort of 32 patients with resected stage III BRAF+ melanoma, who were diagnosed and underwent adjuvant therapy with either anti-PD1 or dabrafenib/trametinib, was collected from 2019 to 2021 and followed up until December 2023. A sensitive multiplexed digital droplet (dd)-PCR was used to detect and quantify the three most common hotspot mutations in codon 600 (V600E, V600R, V600K) of the BRAF oncogene in circulating free DNA isolated from plasma. Blood samples were retrieved monthly post-surgery, starting from the initial administration of adjuvant therapy. Samples were classified as mutated when the number of copies/reaction exceeded the limit of blank (LOB = meanblank + 1.645*SDblank). Results: At 36 months, the overall recurrence-free survival (RFS) for the cohort was 61.6%. Stratifying by basal circulating tumor DNA (ctDNA) status, those with negative ctDNA exhibited significantly higher 36-month RFS (75.0%) compared to the positive group (36.4%) (p=0.014). Cox univariate analysis identified in-transit metastasis (HR 4.20, 95% CI 1.11-15.87, p=0.034) and positive basal ctDNA (HR 3.79, 95% CI 1.20-12.00, p=0.023) as significant risk factors for relapse. The 36-month overall survival (OS) rate was 80.8%, with a significant difference between negative basal ctDNA (95.0%) and positive groups (54.6%) (p=0.004). Cox univariate analysis for OS revealed in-transit metastasis (HR 9.44, 95% CI 1.89-47.16, p=0.006), relapse during adjuvant therapy (HR 24.58, 95% CI 2.65-228.08, p=0.005), and positive basal ctDNA (HR 7.92, 95% CI 1.56-40.36, p=0.013) as significant predictors of death. Notably, basal ctDNA showed no correlation with clinical stage or basal LDH levels (p=0.324, Spearman test, logit p=0.1621). Conclusions: Basal ctDNA status may outperform clinical stage and LDH values in predicting relapse and survival in stage-III melanoma. It shows significant potential for forecasting treatment response and outcomes, advocating for broader evaluation in patients undergoing adjuvant therapy.
