1 of 3 | Stage III melanoma patients who are cancer-free after surgery to remove tumors from their lymph nodes can have their chances for recurrence accurately measured with a new gene-based blood test under development at New York University. Photo by Ian Herbst/National Museum of Health and Medicine
New York University researchers say a simple, gene-based blood test has shown to be highly accurate in predicting whether some stage III melanoma patients are likely to suffer recurrences of cancerous tumors.
The new test looks for a specific type of DNA shed by tumors of stage III melanoma patients who, if found, indicates a strong likelihood their cancer will return in the aftermath of lymph node surgery, according to the authors of a study published Tuesday in The Lancet Oncology.
Stage III melanoma is an advanced form of skin cancer in which the malignancy has spread beyond the original site to nearby lymph nodes or surrounding tissue, requiring aggressive treatment such as surgery, immunotherapy or targeted therapy to restrict its progression.
Using the new test, an analysis of hundreds of blood plasma samples taken from stage III melanoma patients with mutated BRAF genes — who make up about half of all skin cancer sufferers — determined that approximately 80% of those who had evidence of circulating tumor DNA, or ctDNA, in their samples eventually went on to develop recurrences of their cancers.
The research was funded by the Swiss pharmaceutical giant Novartis, maker of the melanoma-inhibiting drugs Tafinlar and Mekinist.
The high level of prediction accuracy means oncologists and dermatologists may soon have a valuable new tool to quickly and easily tell which patients are most likely to respond well to follow-on “adjuvant” therapy after surgery, according to Dr. David Polsky, the Alfred W. Kopf Professor of Dermatologic Oncology in the Ronald O. Perelman Department of Dermatology at NYU, as well as an advisory board member for Novartis.
“We think [patients with resected stage III melanoma] would most likely benefit from ctDNA measurements shortly after their surgery — [for example} within 12 weeks or less as was done in this study — and periodically thereafter,” Polsky told UPI in emailed comments.
Those patients, he said, would for the first time have a “clear, direct measure of the disease itself” — a significant improvement over the current method of tissue-based analyses of tumor cells that can only suggest the likelihood of recurrence.
Potential benefits
Where the new test could have particularly strong benefits is among melanoma patients who have undergone successful lymph node resections and are currently cancer-free, but who choose to forego follow-up drug therapy due to financial burdens or other reasons. An accurate test for ctDNA could identify which of them are at higher risk and most in need of adjuvant therapy, Polsky said.
“Also, we did have samples from some patients who completed a year of treatment and then stopped their treatment according to the protocol rules,” he added. “In some of those patients we detected ctDNA beginning mostly three months after stopping treatment.
“So, another group of patients who might benefit from the test are those patients with resected stage III melanoma who stop their adjuvant therapy and would like to have a blood test to help identify melanoma recurrence should it happen.”
Although the test did not detect ctDNA in every patient who eventually recurred, when the test was positive, nearly everybody in that group developed a recurrence detectable on a radiographic scan, Polsky said, adding, “We’re hoping that with additional study this test can become part of the routine work-up for patients with melanoma that has escaped the skin and spread to other parts of the body.”
Doctors who see a positive ctDNA test result in patients carrying a mutation of the BRAF gene could then take proactive steps, such as ordering a computed tomography, or CT, scan ahead of schedule or requesting a more sensitive PET-CT scan, the authors suggest.
Latest evidence
The study “adds to the increasing evidence that circulating tumor DNA has a useful role in patients where the cancer has been surgically resected and patients are at high risk of recurrence,” said Dr. Alastair Greystoke, an oncologist at the Northern Center for Cancer Care in Newcastle-upon-Tyne, England, and an authority on genetic cancer biomarkers. He was not involved in the NYU study.
“[The authors] showed with a robust and relatively cheap blood test that you could predict patients who were likely to relapse following surgery for melanoma that had spread to the lymph nodes, where we hope patients are cured but there is a high chance it will come back,” Greystoke told UPI.
“At the moment, these patients are offered extra treatment with targeted drugs or immunotherapy, which reduce the chance of recurrence, but these drugs are expensive can be associated with significant and life changing side-effects and are not needed by all.”
Overall, the noted oncologist added, “this study adds to the utility of ctDNA, moving it strongly into the detection and measurement of minimal residual disease to inform decision-making in patients who have had surgery for BRAF-mutated melanoma. It is likely we will see increasing use in this and other tumor types.”
Meanwhile, the leader of the world’s largest private nonprofit funder of melanoma research told UPI the results of the NYU study are “exciting” and part of a “promising” front in the fight against the disease.
“CtDNA monitoring appears promising to help guide treatment escalation, switching, or de-escalation,” said Dr. Marc Hurlbert, CEO of the Melanoma Research Alliance.
Evidence is mounting that keeping an eye on levels of tumor-related genetic material can help in many areas of melanoma treatment, such as identifying patients at high risk of recurrence, monitoring response to treatments, helping to guide treatment selection, signaling “when a switch from an approved agent to a clinical trial might be necessary, and lastly to augment imaging tests for monitoring for disease recurrence,” he said.
Hurlbert noted his alliance has funded previous research on analyzing bloodstream biomarkers to detect cancer risk, including an study published this month in which scientists applied low-cost, whole-genome sequencing techniques to ctDNA to identify risks of mutations.
