4mm) primary melanomas. The research team faced a unique hurdle in acquiring enough samples to conduct a robust study. Unlike most tumors, which are removed by a surgeon at a hospital, skin lesions can be removed in private practices and ambulatory clinics, which means that specimens are not concentrated in hospital settings. In addition, specimens must be kept for several years after removal, delaying their availability for research studies. To collect enough samples, investigators from the Brigham collaborated with colleagues at the Melanoma Institute of Australia and the Zealand University Hospital in Denmark to share resources. The current analysis includes more than 300 samples from patients across these sites. The team compared samples from patients whose primary melanoma progressed to metastatic disease to patients whose primary melanoma did not. They used high-throughput DNA sequencing, performed by Adaptive Biotechnologies, to analyze the T cell repertoire of the tumors. The investigators found that of all variables identified, the T-cell fraction (TCFr; or proportion of cells in the lesion that were T cells) was a powerful, independent predictor of which patients would progress. Even for patients whose lesion thickness (T) was the same, TCFr was able to predict which patients were more likely to have metastatic disease. Patients with a TCFr of lower than 20 percent were more at risk of disease progression than patients with a TCFr of higher than 20 percent. For example, for patients with T3 melanoma (2-4mm thickness), five years after having their primary lesion removed, 51 percent of those with lower TCFr experienced recurrence, compared to 24 percent with higher TCFr. The test used in this work is commercially available for research use only and is not currently yet available in the clinic. The authors also note that the current study is retrospective, looking at samples from patients whose outcomes are already known. Prospective studies of patients whose outcomes are not yet known will be needed to further validate the test. If brought to the clinic, Kupper and colleagues envision that the test could strengthen current prediction models and improve patient care. "This is a simple, elegant test. It's quantitative rather than subjective, and it may be able to add value to predictions about disease progression," said Kupper. "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."" />
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New Technique Predicts Which Melanoma Patients Are at Risk for Cancer Recurrence, Spread

Medical Xpress



For most patients, melanoma begins with a small, pigmented spot on their skin that they notice starts to change. Many primary melanomas can be cured by having this lesion removed, but melanoma can also recur and spread; an analysis of the removed lesion can offer some information on the likelihood that the cancer will come back. Today, lesions are analyzed in much the same way that they were 100 years ago. Despite advances in molecular diagnostics for other forms of cancer, analysis of a skin cancer lesion is surprisingly simplistic. The lesion's thickness—patients ...