Circulating tumor DNA in melanoma - Yep. AGAIN!!!

If you've hung around this space for half a minute, you know that I've long been yelling about "liquid assays" (including ctDNA) that can diagnose, predict, and evaluate progression or response in melanoma patients.  Perhaps more importantly, despite the clear benefit of these tests, they remain pretty much unavailable to most melanoma patients.  Here are only a zillion reports: Melanoma and circulating tumor DNA

Now there are these:

Prediction and monitoring of relapse in stage III melanoma using circulating tumor DNA.  Tan, Sandhu, Lee, et al.  Ann Oncol.  2019 May 30.

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 time point relapsed at a median follow up of 20 months. ctDNA detection predicted patients at high risk of relapse at baseline and postoperatively. ctDNA detection at baseline and postoperatively was also associated with inferior distant metastasis-free survival (DMFS). These findings were validated in the independent cohort. ctDNA detection remained an independent predictor of RFS and DMFS in multivariate analyses after adjustment for disease stage and BRAF mutation status.  Baseline and postoperative ctDNA detection in two independent prospective cohorts identified stage III melanoma patients at highest risk of relapse and has potential to inform adjuvant therapy decisions.

Circulating tumor cells and early relapse in node-positive melanoma.  Lucci, Hall, Patel, et al.  Clin Cancer Res. 2020 Feb 3. There is a need for sensitive, reproducible biomarkers for stage III melanoma patients to guide clinical decision making. Circulating tumor cells (CTCs) can be detected in melanoma patients; however, there is limited data regarding their significance in stage III disease. The aim of this study was to determine if CTCs are associated with early relapse in stage III melanoma. We prospectively assessed CTCs at first presentation in clinic (baseline) for 243 stage III melanoma patients. CTCs were measured using the CellSearch System. Relapse-free survival (RFS) was compared between patients with one or more baseline CTC versus those with no CTCs. Log-rank test and Cox regression analysis were applied to establish associations of CTCs with RFS. At least one baseline CTC was identified in 90/243 (37%) patients. Forty-five (19%), 67 (28%), 118 (49%), and 13 (5%) patients were stage IIIA, IIIB, IIIC, or IIID, respectively. CTC detection was not associated with sub stage, or primary tumor characteristics. Multivariable analysis demonstrated that the detection of greater than/= to 1 baseline CTC was significantly associated with decreased 6 month RFS and 54 month RFS. Greater than/= to 1 CTC was independently associated with melanoma relapse, suggesting that CTC assessment may be useful to identify patients at risk for relapse who could derive benefit from adjuvant therapy.

Circulating tumour cells as tumour biomarkers in melanoma: detection methods and clinical relevance.  Khola, Lorigan, Dive, et al.  Ann Oncol.  2019 Dec 4.

Circulating tumour cells (CTCs) are cells of solid tumour origin detectable in the peripheral blood. Their occurrence is considered a prerequisite step for establishing distant metastases. Metastatic melanoma was the first malignancy in which CTCs were detected and numerous studies have been published on CTC detection in melanoma at various stages of disease. In spite of this, there is no general consensus as to the clinical utility of CTCs in melanoma, largely due to conflicting results from heterogeneous studies and discrepancies in methods of detection between studies. In this review, we examine the possible clinical significance of CTCs in cutaneous, mucosal and ocular melanoma, focusing on detection methods and prognostic value of CTC detection.

Despite very convincing data and a desperate need in the patient population these tests remain unavailable to the average patient.  Will the desire of firms to make a buck, make a difference?

This report from CNBC tech, 2/2020 :  These start-ups are racing to help doctors detect cancer early with a simple blood test

Which states, in part:  "Getting a blood test to screen for cancer in the earliest stages might seem like a pipe dream. But a group of biotech entrepreneurs say they’re close to making it a reality. If Gabriel Otte’s start-up, Freenome, is successful, millions of people could get a blood test to screen for early-stage colorectal cancer. Freenome looks for two major biomarkers in the blood. It’s simultaneously hunting for tiny fragments of DNA that are shed into the bloodstream from a tumor, as well as early signals that the patient’s immune system is starting to respond.  The medical industry has known for years that that blood-based “liquid biopsies” can find signatures of cancer. But the tests on the market today focus on monitoring the progression of the disease once a patient has been diagnosed with cancer, including how it’s responding to treatment.  The next generation of companies want to detect cancer while it’s early and often easier to treat."

We know these tests work.  We know they could provide a great deal of helpful information for melanoma patients facing hard choices.  It is past time that they be made available.  For what it's worth. ~ c