A test that looks for the DNA of melanoma cells in the blood could tell us, in the not too distant future, if the treatment is working, or if instead the tumor has regained strength and it is therefore necessary to change the strategy as soon as possible. This is the meaning, and above all the potential clinical application, of a validation study conducted by researchers from the University of New York and the Perlmutter Cancer Center, the results of which are published in Lancet Oncology.
Today, for melanoma we do not have validated biomarkers available that with a simple blood test allow us to monitor the effectiveness of a drug over time, or to make us predict that the cure will work. In fact, oncologists wait a few months before understanding how the patient responds to treatments using usually Tac and or Rx. Now, however, according to this new research in the Lancet, there could be a good candidate and it is ctDNA (which stands for circulating tumor Dna) or the DNA released into the blood by cancer cells.
The authors analyzed blood samples from 383 US, European and Australian adults (approximately 85% of annual melanoma cases affect populations in North America, Europe and Oceania), all of whom had unresectable, i.e., untreatable, metastatic melanoma. surgically, treated with dabrafenib and trametinib, and all with V600 mutations in the BRAF gene, a type of alteration found in 40-50% of melanomas. The ctDNA was measured before treatment and one month after the start of therapy.
Threshold 64
One of the findings of the study was that patients who had 64 or fewer ctDNAs per milliliter of blood prior to treatment were more likely to respond well to therapy, surviving an average of nearly three years. In contrast to those with ctDNA levels above this threshold, whose survival was significantly lower: for some of just over a year.
Not only BRAF
Although this test focuses on melanomas with BRAF mutations, according to the authors it may also be useful for melanomas with other mutations, such as the NRAS gene (present in 10-15% of skin melanomas) and the TERT gene.
Feedback precoci
“Early feedback such as a blood test could actually save lives, and we would like the test to be used routinely in the NYU Department of Dermatology and senior author of the paper,” said Mahrukh Syeda. clinical practice, to help guide treatment decisions. “At this point, it should be emphasized that we are talking about a blood test not approved by the FDA, but that given its” accuracy and value “as the authors of the study say, it may be submitted for approval in the future so that it becomes available for clinical use.
Less invasive, less expensive and faster
Systems for the diagnosis and monitoring of cancer based on blood tests have been sought for years. And you understand why: blood tests have several benefits, for the patient for the oncologists and also for the health systems. Compared to CT, Rx or histological analyzes on biopsies, blood tests make it easier to get a picture of the behavior of the tumor over time, they are less invasive and also less expensive.
An aggressive tumor
Having the ability to quickly change a treatment strategy is always useful, especially in oncology. And this is evident. But it is particularly so for those particularly aggressive types of cancer, such as melanoma. In Italy cutaneous melanoma represents the third most frequent cancer under the age of 50 with 14,900 new diagnoses per year and 2,065 deaths. The risk factors of melanoma are genetic and environmental: the most important is exposure to UV rays and several published studies indicate that this risk increases significantly in people who use lamps or tanning beds, especially if they start to use them when young.
The treatment has radically changed
With the advent of new immunotherapeutic agents (ipilimumab, pembrolizumab, nivolumab) and target drugs (vemurafenib, dabrafenib, trametinib, cobimetinib, encorafenib and binimetinib) the treatment of advanced melanoma has changed dramatically. The first step in the treatment of a patient with metastatic disease is to assess the mutational status of his tumor. 40-50% of cutaneous melanomas have a V600 mutation of the BRAF gene. A tumor DNA abnormality that identifies who can benefit from treatment with the combination of dabrafenib / trametinib, vemurafenib / cobimetinib or encorafenib / binimetinib, which are capable of prolonging disease-free survival and overall survival. Other mutations important from a therapeutic point of view are those of the NRAS gene (present in 10-15% of cutaneous melanomas) and of the cKIT gene (typical in acro-lentiginous and mucosal melanomas with a frequency of about 1-2% ). Today, thanks to immunotherapy and target therapy, about 50% of patients with metastatic disease can obtain a long-term benefit.
.