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. 2020 Nov:140:11-18.
doi: 10.1016/j.ejca.2020.08.029. Epub 2020 Oct 5.

Identification of stage I/IIA melanoma patients at high risk for disease relapse using a clinicopathologic and gene expression model

Alexander M M Eggermont  1 , Domenico Bellomo  2 , Suzette M Arias-Mejias  3 , Enrica Quattrocchi  3 , Sindhuja Sominidi-Damodaran  3 , Alina G Bridges  3 , Julia S Lehman  3 , Tina J Hieken  3 , James W Jakub  3 , Dennis H Murphree  3 , Mark R Pittelkow  4 , Jason C Sluzevich  5 , Mark A Cappel  6 , Sanjay P Bagaria  5 , Charles Perniciaro  7 , Félicia J Tjien-Fooh  2 , Barbara Rentroia-Pacheco  2 , Renske Wever  2 , Martin H van Vliet  2 , Jvalini Dwarkasing  2 , Alexander Meves  8
Affiliations

Identification of stage I/IIA melanoma patients at high risk for disease relapse using a clinicopathologic and gene expression model

Alexander M M Eggermont et al. Eur J Cancer. 2020 Nov.

Abstract

Purpose: Patients with stage I/IIA cutaneous melanoma (CM) are currently not eligible for adjuvant therapies despite uncertainty in relapse risk. Here, we studied the ability of a recently developed model which combines clinicopathologic and gene expression variables (CP-GEP) to identify stage I/IIA melanoma patients who have a high risk for disease relapse.

Patients and methods: Archival specimens from a cohort of 837 consecutive primary CMs were used for assessing the prognostic performance of CP-GEP. The CP-GEP model combines Breslow thickness and patient age, with the expression of eight genes in the primary tumour. Our specific patient group, represented by 580 stage I/IIA patients, was stratified based on their risk of relapse: CP-GEP High Risk and CP-GEP Low Risk. The main clinical end-point of this study was five-year relapse-free survival (RFS).

Results: Within the stage I/IIA melanoma group, CP-GEP identified a high-risk patient group (47% of total stage I/IIA patients) which had a considerably worse five-year RFS than the low-risk patient group; 74% (95% confidence interval [CI]: 67%-80%) versus 89% (95% CI: 84%-93%); hazard ratio [HR] = 2.98 (95% CI: 1.78-4.98); P < 0.0001. Of patients in the high-risk group, those who relapsed were most likely to do so within the first 3 years.

Conclusion: The CP-GEP model can be used to identify stage I/IIA patients who have a high risk for disease relapse. These patients may benefit from adjuvant therapy.

Keywords: CP-GEP; Clinicopathologic; Gene expression variables; Metastasis; Primary cutaneous melanoma; Prognostic biomarkers; Relapse-free survival.

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Conflict of interest statement

Conflict of interest statement Dr. Eggermont reports receiving honoraria from Actelion, Agenus, Bayer, BIOCAD, Biovent, BMS, CatalYm, Celldex, Ellipses, Forbion, Gilead, GSK, HalioDx, Incyte, IO Biotech, ISA Pharmaceuticals, MedImmune, Merck GmbH, MSD, Novartis, Pfizer, Polynoma, Regeneron, Sanofi, SkylineDx and Stellas over the past five years; having equity stakes in SkylineDx and THERANOVIR and speaker engagements with BIOCAD, MSD and Novartis. Dr. Bellomo reports equity stakes in SkylineDx and Synlogic. Dr. Hieken reports receiving research funding from Genentech and Roche through Mayo Clinic. Dr. Sluzevich reports receiving research funding from Merck through Mayo Clinic. Dr. Pernaciaro reports receiving honoraria from Myriad Genetics and travel, accommodations and expenses paid for by Myriad Genetics. Ms. Tjien-Fooh, Ms. Rentroia-Pacheco, Ms. Wever, Dr. van Vliet, and Dr. Dwarkasing reports equity stakes in SkylineDx. Dr. Bellomo, Ms. Tjien-Fooh, Ms. Rentroia-Pacheco, Ms. Wever, Dr. van Vliet, and Dr. Dwarkasing reports being employees of SkylineDx. Dr. Bellomo and Dr. Meves report patents pending for gene signatures for predicting melanoma metastasis. All remaining authors have no conflict of interest to declare.

Figures

Figure 1.
Figure 1.. Kaplan-Meier analysis of the entire 837 cohort, stratification by SLNb status and CP-GEP classification.
Survival endpoints were relapse free survival (RFS), distant metastasis free survival (DMFS) and melanoma-specific survival (MSS) at five-years of follow-up. SLNb negative, CP-GEP Low Risk (light blue curve); SLNb negative, CP-GEP High Risk (dark blue curve); SLNb positive, CP-GEP Low Risk (orange curve); SLNb positive, CP-GEP High Risk (magenta curve).
Figure 2.
Figure 2.. Kaplan-Meier analysis of the 580 stage I/IIA patients, stratification by CP-GEP classification.
Survival endpoints were relapse free survival (RFS), distant metastasis free survival (DMFS) and melanoma-specific survival (MSS) at five-years of follow-up. CP-GEP Low Risk (light blue curve); CP-GEP High Risk (dark blue curve).
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References

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