Publication date: Feb 06, 2019
The advent of effective adjuvant therapies for patients with resected melanoma has highlighted the need to stratify patients based on risk of relapse given the cost and toxicities associated with treatment. Here we assessed circulating tumor DNA (ctDNA) to predict and monitor relapse in resected stage III melanoma.
Somatic mutations were identified in 99/133 (74%) patients through tumor tissue sequencing. Personalized droplet digital PCR (ddPCR) assays were used to detect known mutations in 315 prospectively collected plasma samples from mutation-positive patients. External validation was performed in a prospective independent cohort (n = 29).
ctDNA was detected in 37 of 99 (37%) individuals. In 81 patients who did not receive adjuvant therapy, 90% of patients with ctDNA detected at baseline and 100% of patients with ctDNA detected at the postoperative timepoint relapsed at a median follow up of 20 months. ctDNA detection predicted patients at high risk of relapse at baseline [relapse-free survival (RFS) hazard ratio (HR) 2.9; 95% confidence interval (CI) 1.5-5.6; P = 0.002] and postoperatively (HR 10; 95% CI 4.3-24; P
Tan, L., Sandhu, S., Lee, R.J., Li, J., Callahan, J., Ftouni, S., Dhomen, N., Middlehurst, P., Wallace, A., Raleigh, J., Hatzimihalis, A., Henderson, M.A., Shackleton, M., Haydon, A., , Mar, Gyorki, D.E., Oudit, D., Dawson, M.A., Hicks, R.J., Lorigan, P., McArthur, G.A., Marais, R., Wong, S.Q., and Dawson, S.J. Prediction and monitoring of relapse in stage III melanoma using circulating tumor DNA. 21954. 2019 Ann Oncol.
- Accuracy of partial biopsies in the management of cutaneous melanoma.
- Pre-operative ctDNA predicts survival in high-risk stage III cutaneous melanoma patients.
- Molecular genomic profiling of melanocytic nevi.