Melanoma in the skin biopsy with H&E staining – this case can represent a superficial melanoma. Photo credit: Wikipedia / CC BY-SA 3.0

A test that monitors blood levels of DNA fragments released by dying tumor cells may serve as an accurate early indicator of treatment success in people with late-stage cancer of one of the most aggressive forms of skin cancer, according to a new study.

Under the direction of researchers from NYU’s Grossman School of Medicine and the Perlmutter Cancer Center, adults with undetectable amounts of freely circulating tumor examined four weeks after starting drug treatment for metastatic melanoma tumors that could not be surgically removed (non-resectable) DNA (ctDNA). The study showed that these patients, who all had common genetic changes (BRAFV600 mutations) related to cancer, lived without cancer growth for almost twice as long as those who continued to have detectable levels.

Typically, according to the study’s authors, doctors would have to wait three months before an X-ray, CT scan, or other measure could reveal whether a tumor was growing or shrinking in response to treatment.

“Our results suggest that ctDNA levels can serve as a quick and reliable tool to assess whether a cancer drug is working,” says lead author of the study, David Polsky, MD, Ph.D. “The results of the blood test could help continue with current treatment strategy or encourage patients and doctors to consider other options,” added Polsky, Dr. med. Alfred W. Kopf, Professor of Dermatological Oncology at NYU Langone Health and the Perlmutter Cancer Center.

Polsky notes that a quick change in treatment could potentially help with a disease as aggressive as melanoma, which kills nearly 7,000 Americans annually and which is notoriously difficult to treat if it spreads to other parts of the body. Early feedback from a blood test could save lives, he says.

Researchers have long sought better ways to monitor certain types of cancer using blood tests, or so-called biomarkers, which are easier, more frequent, and cheaper than imaging or surgery, and which provide a clearer picture of tumor behavior over time. In melanoma, a commonly used option, a test for the presence of an enzyme called lactate dehydrogenase (LDH) in the blood, has had limited success as such an instrument, as non-cancerous conditions such as liver damage and bone damage can also spike levels. Although more specific biomarkers have been identified in cancers of the prostate, breast, and colon, the study’s researchers say that a reliable guide to melanoma has remained elusive.

Polsky, also a professor in NYU Langone’s Pathology Department, said early research by the same team pointed to ctDNA as a promising candidate. This method targets the most common mutations in the DNA code found in melanoma cells. This mutated DNA gets into the surrounding blood when the cancer cells break down. In previous small studies, the blood test has been shown to outperform the LDH in predicting melanoma recurrence as well as tracking the progression of other cancers.

The new research, published February 11 in The Lancet Oncology magazine, spanned two years and is the largest analysis of the potential benefits of this blood test in skin cancer to date, according to Polsky.

For the study, the research team analyzed blood samples from two key clinical trials involving 383 American, European and Australian men and women. All received targeted treatment with the drugs dabrafenib and trametinib for unresectable metastatic melanoma tumors with mutations in the BRAF gene, which researchers say is found in around half of all patients with this disease. The researchers measured the ctDNA levels in patients whose tumors had this mutation before treatment and one month after starting therapy. As part of the clinical study, the patients were regularly examined using CT until the end of treatment.

Other findings from the study included that patients with 64 or fewer copies of the ctDNA per milliliter of blood prior to treatment were likely to respond well to therapy and survived on average for almost three years. In contrast, values ​​above this threshold were associated with a significantly poorer chance of survival, with the patients living just over a year.

The researchers say the blood test is very reliable because they found ctDNA in 93 percent of the patients. These blood test results were also reproduced in a second group of patients at the same stage of the disease who were enrolled in another clinical study.

“Although this gene-based test focuses on tumors with BRAFV600 mutations, we believe it will be similarly useful for melanomas with other mutations, such as defects in the NRAS and TERT genes, which are also frequently mutated in this disease.” according to the study author Mahrukh Syeda, MS. “Ultimately, we want this test to be used routinely in the clinic to help make treatment decisions,” added Syeda, a researcher in the Department of Dermatology at NYU Langone Health.

She warns that the blood test has not yet been approved by the FDA, but notes that evidence of its accuracy and value supports future filings for approval to make it available for clinical use.

According to Syeda, the team plans to next evaluate the ctDNA approach in patients with earlier stages of melanoma.

Blood test that better monitors the DNA of dead cancer cells to help track the spread of melanoma. Provided by NYU Langone Health

Quote: The gene-based blood test for melanoma spread assesses treatment progress (2021, February 12), retrieved from https://medicalxpress.com/news/2021-02-gene-based-blood-melanoma-treatment.html on February 12, 2021 has been

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