New melanoma test may better predict recurrence and improve patient care

By Sally Robertson, B.Sc.Jan 20 2020

Researchers at Brigham and Women's Hospital have developed a new technique that improves on the current method for assessing whether primary melanoma is likely to recur and spread, following surgical removal.

Image Credit: Evgeniy Kalinovskiy/Shutterstock.com

According to the study author Thomas Kupper, the “simple and elegant test,” which the team developed in collaboration with international colleagues, could improve current prediction models and patient care.

Generally, patients first suspect melanoma when noticing changes in the appearance of a pigmented spot such as a mole or freckle. A primary melanoma can often be cured through surgical removal, but, in some cases, the lesion can also recur and spread.

Lesion analysis has not changed significantly in the last hundred years

Analyzing the lesion post-removal provides a certain amount of information about whether it may recur. Currently, this analysis has not particularly moved on from a hundred years ago, despite the major advancements that have been made in the field of molecular cancer diagnostics.

The surprisingly simple procedure involves assessing the lesion’s thickness (thinner tends to be better) and microscopic features before assigning a cancer stage of T1 to T4, where increasing T number indicates larger tumor size, or more growth into nearby tissues.

As reported in Nature Cancer, Kupper and colleagues now present a novel, quantitative DNA sequencing technique that serves as a more sophisticated and accurate predictor of whether primary melanomas are likely to recur and spread.

New immunotherapies offer hope to patients

Kupper says that only a decade ago, the prognosis for metastatic melanoma was dismal, but that today, new immunotherapies can be offered to patients with metastatic disease and possibly to patients with primary melanoma that has not yet spread.

"Because of the advent of these new immunotherapy treatments, it's important to have a clear idea of which patients are likely to progress so that we can tailor treatment accordingly," adds Kupper.

The treatments discussed are called immune checkpoint inhibitors - agents that can reawaken T cells to launch an immune attack against cancer cells. The new therapies have radically changed patients’ options and outcomes in cases where melanoma has spread. In some patients, outcomes include long-term remission, which is essentially a cure.

An unmet need stands in the way

However, the ability to stratify patients by risk to identify who is most likely to experience disease progression remains an unmet need.

Kupper and colleagues, therefore, set out to determine whether certain features of T cells in tumors removed from patients could predict disease recurrence. Since T1 melanomas (<1mm) rarely spread, the team focused on T2 (1-2mm), T3 (2-4mm) and T4 (>4mm) primary melanomas.

A challenge that the team faced was obtaining enough samples to ensure the study was robust. Unlike most tumors, skin lesions are often not concentrated in a hospital setting because they have been removed in private and ambulatory clinics. They also must be stored for several years before they can be made available for research.

To ensure an adequate number of lesion samples, the Brigham investigators teamed up with colleagues at the Melanoma Institute of Australia and the Zealand University Hospital in Denmark to share resources.

What did the researchers find?

Using high-throughput DNA sequencing, the team assessed the T cell repertoire of 300 samples from patients across these sites and compared primary melanomas that had metastasized with those that had not.

The researchers found that of all the variable features identified, the T-cell fraction (TCFr) was a potent and independent predictor of which patients would experience disease progression.

Even among patients who had lesions of the same thickness, TCFr predicted which ones were at a greater risk of metastasis.

Patients were at a greater risk of progression if their TCFr was lower, rather than higher, than 2%.

For example, among patients with T3 melanoma (2-4mm thickness) five years after the primary lesion had been removed, a whole half of those with the lower TCFr experienced recurrence, compared with only a quarter of those with the higher TCFr.

Prospective studies are now needed to validate the test

The new test is currently only available for research purposes and cannot be accessed in the clinic. The authors also point out that the current study is retrospective, with the outcomes already known, and that prospective studies will be needed in the future to validate the test.  

However, if the test were implemented in the clinic, Kupper and the team think it could strengthen current prediction models and improve patient care.

Kupper says the simple and elegant test is quantitative rather than subjective and may be able to add value to predictions about disease progression.

"In the future, such a test could help us tailor treatment; patients with high TCFr may further benefit from checkpoint inhibitor therapy, while low TCFr patients may need additional intervention,” he concludes.