Using 31-GEP and Clinicopatholic Data to Determine RFS in Skin Cancer

Integrating the combined ability of 2 independently validated algorithms using 31-gene expression profile (GEP) test (Castle Biosciences Inc) with clinicopathologic features may play a role in predicting the individual risk of sentinel lymph node (SLN) risk and recurrence-free survival (RFS) according to a poster presented at Maui Derm for Dermatologists 2022, being held Jan. 24-28, 2022, in Maui, Hawaii.^1,2

Using artificial intelligence (AI), an algorithm was created from 1,398 cases to determine the likelihood of SLN positivity. It was validated in a separate cohort of 1,674 cases (i31-GEP-SLNB). A different algorithm for personalized survival predictions for RFS, distant metastasis-free survival (DMFS), and melanoma-specific survival (MSS) was developed from 1,581 cases and were validated in an independent cohort of 523 cases (i31-GEP-outcomes). Based on the available data, 98% of patients in the validation cohort did not receive programmed cell death protein (PD)-1, cytotoxic T-lymphocyte-associated protein (CTLA)-4, or BRAF/MEK adjuvant therapy, according to the poster.

Risk cut-off point was created to align with the National Comprehensive Cancer Network (NCCN) guidelines. The decided cut-off were the midpoints between stage IIA and IIB (RFS: 69.8%; DMFS: 82.6%). All outcomes with i31-GEP-outcomes predicted RFS or DMFS higher than the cut-off were classified as low risk. Otherwise, they were classified as high risk.²

To determine the prognostic value of both algorithms, 433 patients that were not used in either algorithm development were then analyzed by i31-GEP- SLNB, followed by i31-GEP-outcomes.

The 5-year RFS for patients with SLN negative populations were:

• Low risk (n=172): 86.7% (81.2-92.7%) with a 95% CI. There were 10.5% (18/172) that experienced recurrences.
• SLN Negative (n=215): 79.2% (73.4-85.5%) with a 95% CI. There were 17.7% (38/215) that experienced recurrences.
• High Risk (n=43): 47.7% (33.6-67.7%) with a 95% CI. There were 46.5% (20/43) that experienced recurrences.

The 5-year RFS for patients with SLN positive populations were:

• Low risk (n=16): 85.9% (69.5-100%) with a 95% CI. There were 18.8% (3/16) that experienced recurrences.
• SLN positive (n=83): 48.7% (37.6-63.1%) with a 95% CI. There were 45.8% (38/83) that experienced recurrences.
• High risk (n=67): 37.9% (25.8-55.6%) with a 95% CI. There were 52.2% (35/67) that experienced recurrences.

Comparing this data for the 5-year RFS and DMFS for patients with stage IIB-IIC disease shows that the low-risk group for both RFS and DMFS had 0% recurrences or distant metastases. In the stage IIB/IIC group, 34.7% and 26.5%, respectively, experienced recurrences or distant metastases. In the high-risk group, 45.9% and 58.3%, respectively, experienced recurrences or distant metastases.

The data showed that the i31-GEP for SLNB algorithm identified 31.2% (135/433) of patients with a less than 5% likelihood of SLN positivity and these patients had high survival rates. This means that these patients could safely forego SLNB, according to researchers.² Also, in the SLN negative population, 20% of patients identified as high risk by the i31-GEP result and had 5- year RFS rates that were identical to patients with stage III disease (47.7% vs. 48.7%, respectively).²

“Overall, using NCCN treatment recommendations, the i31-GEP test identified 44.8% (194/433) of patients need to add how they were identified and what this meant.Take that from results or conclusions,” the authors concluded.

Reference:

1. Castle Biosciences to present data at Maui Derm for Dermatologists 2022. BioSpace. Published January 24, 2021. Accessed January 27, 2022. https://www.biospace.com/article/castle-biosciences-to-present-data-at-maui-derm-for-dermatologists-2022/
2. Martin, B. Taylor, N. Whitman, E. et al. Integrating the 31-gene expression profile and clinicopathologic data to determine the risk of sentinel lymph node positivity and recurrence-free survival in cutaneous melanoma. Presented at: Maui Derm 2022; January 24 to 28, 2022; Wailea, Hawaii.