Melanoma (Skin Cancer)
Conditions
Keywords
ctdna, melanoma, stratification, ddpcr, ngs, biomarker
Brief summary
This study examines circulating tumor DNA (ctDNA) as a biomarker in patients with primary melanoma, prior to surgical excision. The hypothesis is that ctDNA may be detectable in pre-operative blood samples from patients with high-risk primary melanoma, potentially providing a baseline measurement for future disease monitoring.
Detailed description
This prospective, single-institution study recruits patients presenting with suspected primary melanoma at the department of Plastic and Reconstructive Surgery, Herlev and Gentofte University Hospital, Copenhagen University. Patients with invasive melanoma of stage T3a or higher, or with sentinel node metastasis (N1a or higher), and no distant metastasis (M0) will be selected for final analysis. Pre-operative blood samples are collected prior to surgical excision. Plasma is harvested and stored. Tumor tissue from excised melanomas is analyzed using next-generation sequencing (NGS, Oncomine Tumor Mutational Load panel) to determine the mutational profile. For patients with targetable mutations, corresponding plasma samples are analyzed for ctDNA using either digital droplet PCR (ddPCR) or plasma NGS depending on the local availability of validated mutation-specific assays. Enrollment will take place from September 2021 to December 2022, with laboratory analyses expected to be completed in 2025 and final analysis completed by May 2026. This study shares the ethical approval (H-18008586) and biobank infrastructure with a parallel study investigating ctDNA for detection of melanoma recurrence (NCT06246227).
Interventions
None listed
Sponsors
Herlev and Gentofte Hospital
Danish Cancer Society
Danish Cancer Research Foundation
DCCC ctDNA Research Center
CAG in Cancer immunotherapy
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older * Clinical suspicion of primary cutaneous melanoma * Presenting at the Department of Plastic and Reconstructive Surgery, Herlev and Gentofte University Hospital * Able to provide written informed consent
Exclusion criteria
* Age less than 18 years * Pregnancy * Inability to provide written informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Detectable Circulating Tumor DNA (ctDNA) in Pre-operative Plasma as Assessed by ddPCR or Targeted NGS | At a single time point prior to surgical excision of the primary melanoma, at the patient's initial clinical presentation | A venous blood sample is drawn before surgical excision of the primary melanoma. Plasma is isolated and analyzed for the presence of the same cancer-specific DNA mutation previously identified in the patient's tumor tissue. Two methods are used depending on mutation type: digital droplet PCR (ddPCR, Bio-Rad QX200) for BRAF V600E mutations, or targeted next-generation sequencing (Oncomine Tumor Mutational Load panel, Ion Torrent S5) for other mutations. A sample is classified as "detected" if at least one confirmed mutant DNA copy is identified by ddPCR, or if the tumor-specific variant is present above the assay detection threshold by NGS. The outcome is reported as the number of participants with detected ctDNA out of the total number of participants analyzed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Detectable ctDNA by Tumor Stage as Assessed by ddPCR or Targeted NGS | At a single time point prior to surgical excision of the primary melanoma, at the patient's initial clinical presentation. | The number of participants with detectable ctDNA is reported separately for each AJCC 8th edition stage group (IIB, IIC, IIIA, IIIB, IIIC) represented in the study patient cohort. This exploratory outcome evaluates whether more advanced tumor stage is associated with a higher likelihood of ctDNA detection. Stage is determined from pathological T-classification (based on Breslow thickness and ulceration) and sentinel node status according to AJCC Cancer Staging Manual, 8th edition. |
Countries
Denmark
Contacts
STUDY_DIRECTORLisbet R Hölmich, MD, DMSc, Professor
Dept. of Plastic and Reconstructive Surgery, Herlev and Gentofte University Hospital
Outcome results
None listed