Abstract
BACKGROUND: The current standard of care for patients without sentinel node (SN) metastasis (i.e., stage I-II melanoma) is watchful waiting, while >40% of patients with stage IB-IIC will eventually present with disease recurrence or die as a result of melanoma. With the prospect of adjuvant therapeutic options for patients with a negative SN, we assessed the performance of a clinicopathologic and gene expression (CP-GEP) model, a model originally developed to predict SN metastasis, to identify patients with stage I-II melanoma at risk of disease relapse.
METHODS: This study included patients with cutaneous melanoma ≥18 years of age with a negative SN between October 2006 and December 2017 at the Sahlgrenska University Hospital (Sweden) and Erasmus MC Cancer Institute (the Netherlands). According to the CP-GEP model, which can be applied to the primary melanoma tissue, the patients were stratified into high or low risk of recurrence. The primary aim was to assess the 5-year recurrence-free survival (RFS) of low- and high-risk CP-GEP. A secondary aim was to compare the CP-GEP model with the EORTC nomogram, a model based on clinicopathological variables only.
RESULTS: In total, 535 patients (stage I-II) were included. CP-GEP stratification among these patients resulted in a 5-year RFS of 92.9% (95% confidence interval (CI): 86.4-96.4) in CP-GEP low-risk patients (n = 122) versus 80.7% (95%CI: 76.3-84.3) in CP-GEP high-risk patients (n = 413; hazard ratio 2.93 (95%CI: 1.41-6.09), p < 0.004). According to the EORTC nomogram, 25% of the patients were classified as having a 'low risk' of recurrence (96.8% 5-year RFS (95%CI 91.6-98.8), n = 130), 49% as 'intermediate risk' (88.4% 5-year RFS (95%CI 83.6-91.8), n = 261), and 26% as 'high risk' (61.1% 5-year RFS (95%CI 51.9-69.1), n = 137).
CONCLUSION: In these two independent European cohorts, the CP-GEP model was able to stratify patients with stage I-II melanoma into two groups differentiated by RFS.
| Original language | English |
|---|---|
| Article number | 2854 |
| Journal | Cancers |
| Volume | 14 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 9 Jun 2022 |
Bibliographical note
Funding Information:Conflicts of Interest: D.T., B.R.-P., and J.T.D. are employees and options holders of SkylineDx BV. A.V. is an advisory board member for Bristol-Myers Squibb (BMS), Eisai, Ipsen, Merck Sharp & Dohme (MSD), Novartis, Pierre Fabre, Pfizer, Roche, and Sanofi. M.W., T.E.C.N., and L.M.H. received two Health Holland research grants for consortium projects with SkylineDx. L.N. has received institutional research grants from MSD and Syndax Pharmaceuticals, speaker honorarium from BMS, Leo Pharma, Novartis, and Pfizer, and has served on advisory boards for BMS, MSD, Novartis, Pierre Fabre, and Sanofi Genzyme. R.O.B. has received institutional research grants from BMS and SkylineDx, speaker honorarium from Roche and Pfizer, and has served on advisory boards for Amgen, BD/BARD, BMS, MSD, Novartis, Roche, Eisa, Merck, and Sanofi Genzyme. E.E.A.P.M., I.J., D.J.G., D.V., A.L.M., C.V., and J.M. declare that they have no potential competing interests.
Funding Information:
Funding: This work was supported by the Netherlands Enterprise Agency (IK18007).
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
