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Updated: May 10, 2025
Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
Circulating tumor DNA monitoring in advanced mutated melanoma (LIQUID-MEL)
Martines Gianmarco1, Palazzi Carolina1, Monica Gregorio2
1Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
Introduction:
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic melanoma, but a percentage of patients did not show benefit. Circulating tumor DNA (ctDNA) has emerged as a potential non-invasive tool for monitoring disease evolution and treatment response. The present study aimed to evaluate the clinical utility of ctDNA dynamics in patients with metastatic melanoma receiving ICIs, while exploring its role in the oncological course.
Materials And Methods:
The LIQUID-MEL study is a prospective, single-centre pilot study including patients with BRAF/NRAS-mutant metastatic melanoma. ctDNA was quantified using digital droplet PCR (ddPCR) at four different time points. Uni- and multivariable Cox regression models were used to assess the correlation between shedding and progression-free survival (PFS), and overall survival (OS).
Results:
Overall, 23 patients were included. At baseline, ctDNA was detectable in 5/23 (21.7 %) cases. Baseline ctDNA shedding was associated with shorter PFS (3.88 months vs. 0.69 months, p=0.012). A strong numerical trend was observed also in OS (12.66 months vs. 2.53 months, p=0.287). Shedding at baseline did not demonstrate independent prognostic or predictive value in the uni- and multivariable analysis. The longitudinal analysis revealed intriguing patterns of ctDNA shedding in individual patients.
Conclusion:
ctDNA detectability and its dynamic changes during treatment may have potential clinical utility in patients with metastatic melanoma, offering a valuable non-invasive tool for monitoring disease and treatment response. The small sample size limited the statistical power of the analysis. Further studies with larger cohorts are needed to validate its role in routine clinical practice.
Insights
Circulating tumor DNA (ctDNA) shows potential for monitoring metastatic melanoma patients on immune checkpoint inhibitors (ICIs). Early ctDNA shedding is linked to shorter progression-free survival, but larger studies are needed for clinical validation.
Area of Science:
- Oncology
- Molecular Diagnostics
- Immunotherapy
Background:
- Immune checkpoint inhibitors (ICIs) have transformed metastatic melanoma treatment.
- Not all patients benefit from ICIs, necessitating better monitoring tools.
- Circulating tumor DNA (ctDNA) offers a non-invasive method to track disease and treatment response.
Purpose of the Study:
- To assess the clinical utility of ctDNA dynamics in metastatic melanoma patients receiving ICIs.
- To explore the relationship between ctDNA shedding and oncological outcomes.
- To investigate ctDNA's role in monitoring treatment response.
Main Methods:
- Prospective, single-centre pilot study (LIQUID-MEL) of BRAF/NRAS-mutant metastatic melanoma patients.
- ctDNA quantification via digital droplet PCR (ddPCR) at four time points.
- Uni- and multivariable Cox regression to correlate ctDNA shedding with progression-free survival (PFS) and overall survival (OS).
Main Results:
- 23 patients included; 21.7% had detectable baseline ctDNA.
- Baseline ctDNA shedding correlated with significantly shorter PFS (3.88 vs. 0.69 months, p=0.012).
- A trend towards shorter OS was observed (12.66 vs. 2.53 months, p=0.287), but baseline shedding lacked independent prognostic value.
Conclusions:
- ctDNA detectability and dynamics may offer clinical utility for monitoring metastatic melanoma.
- ctDNA serves as a potential non-invasive tool for disease and treatment response monitoring.
- Larger cohort studies are required to validate ctDNA's role in routine clinical practice due to the small sample size.
