January 21, 2019

Gene Profile Test Holds Predictive Potential for Early Stage Melanoma Patients

Test helpful for SLN-negative, stage I to IIA and thin tumors

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A 31-gene expression profile (31-GEP) test offers a predictive metric to overlay onto traditional melanoma staging for better stratification of metastatic risk. Brian Gastman, MD, medical and surgical director of Cleveland Clinic’s melanoma and high-risk skin cancer program, investigated the value of the test for predicting outcomes and guiding treatment for patients within three categories of early stage melanoma.

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The 31-GEP test uses biological information from tumor cells to predict risk of metastasis. “Until this test became available, staging and sentinel node biopsy [SLNB] have been the staples for informing treatment, but they are not sufficient,” Dr. Gastman says. Two out of three patients who develop metastatic disease had a negative SLNB upon diagnosis, and 3 percent of stage IA, 9 percent of stage IB and 19 percent of stage IIA tumors (all considered early stage) will likely prove fatal over a five-year period.

“We have needed enhanced tools to more specifically and accurately define risk. The 31-GEP is a leap forward in solving treatment conundrums for low-risk patients, by identifying those most likely to benefit from intensive surveillance and adjuvant therapy.”

Testing the test

Dr. Gastman led a study to determine 31-GEP’s predictive potential for metastasis in patients within low-risk subpopulations — those who have SLN-negative disease, stage I to IIA tumors and thin tumors. Results were published in the Journal of the American Academy of Dermatology.

He and his co-authors evaluated data from 690 pooled cases of patients with SLN-negative, stage I-IIA or thin tumors. They performed Kaplan-Meier and Cox regression analyses on 31-GEP class (1A-2B, low to high), tumor stage, Breslow thickness, ulceration, mitotic rate and survival outcomes.

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Endpoints were recurrence-free survival to either a regional or distant metastatic event; distant metastasis-free survival to any metastatic event beyond the regional nodal basin; and melanoma-specific survival from diagnosis to death from melanoma.

All non-recurrent cases had at least five years of follow-up.

Key findings include:

  • 31-GEP was able to identify a subset of stage I to IIA patients with a significant risk of recurrence and death. It was the strongest and only independent predictor of risk across all survival endpoints.
  • For SLN-negative patients, a GEP Class 2 result identified 71.3 percent, 70.4 percent and 78.6 percent of recurrences, metastases and melanoma-specific mortality events.
  • 31-GEP test was a significant, independent predictor of recurrence for patients with thin tumors, which account for 24-30 percent of deaths.
  • For patients with stage I to IIA and thin melanomas, a 31-GEP class 1A result had a negative predictive value of over 99 percent for melanoma-specific survival. This can offer reassurance to a large proportion of melanoma patients who are anxious about their risk of recurrence.

The highest-risk low-risk patients

Currently, national treatment guidelines do not include intensive surveillance and adjuvant therapy for patients considered at the lowest risk of metastasis. “With tumors < 1 mm, for example, the National Comprehensive Cancer Network (NCCN) recommends considering SLNB if there are adverse features. We wanted to know if GEP could add information regarding their risk, independent of SLNB recommendation or status, and this data strongly suggests it does,” Dr. Gastman says.

For example, with very thin tumors (Breslow thickness of 1 mm or less), long-term survival rates are so high and the number of these tumors so large that NCCN guidelines do not recommend intensive follow-up and imaging for these patients. But the 31-GEP identifies the small percentage among these low-risk patients whose tumors are more likely to metastasize.

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“The test also generates some false positives, but the net effect is that a small proportion of additional patients are earmarked for close scrutiny, and many in this subgroup will have been candidates for metastatic disease,” Gastman explains.

“Therapies are more effective when the tumor burden is low, and since the 31-GEP enables us to ferret out the higher-risk among ‘low-risk’ patients, we are primed for identifying these patients and implementing appropriate clinical follow-up and imaging to discover metastases as early as possible.”

Feature image: Superficial spreading melanoma arising from a dysplastic nevus. The 4-by-8-mm, pink-tan lesion with irregular borders at the upper left (arrow) is a dysplastic nevus. Arising from it is an invasive malignant melanoma, with its characteristic blue-black color, notched border and distorted surface. The gray area at the lower left represents tumor regression. Source: NCI Visuals Online.

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