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Article

Using a Clinicopathologic and Gene Expression (CP-GEP) Model to Identify Stage I–II Melanoma Patients at Risk of Disease Relapse

by
Evalyn E. A. P. Mulder
1,2,†,
Iva Johansson
3,4,†,
Dirk J. Grünhagen
1,
Dennie Tempel
5,
Barbara Rentroia-Pacheco
5,
Jvalini T. Dwarkasing
5,
Daniëlle Verver
1,
Antien L. Mooyaart
6,
Astrid A. M. van der Veldt
2,7,
Marlies Wakkee
8,
Tamar E. C. Nijsten
8,
Cornelis Verhoef
1,
Jan Mattsson
9,
Lars Ny
4,10,
Loes M. Hollestein
8,11,*,‡ and
Roger Olofsson Bagge
9,12,13,‡
1
Departments of Surgical Oncology, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands
2
Departments of Medical Oncology, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands
3
Departments of Pathology, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden
4
Departments of Oncology, Institute of Clinical Sciences at Sahlgrenska Academy, Gothenburg University, 405 30 Gothenburg, Sweden
5
SkylineDx B.V., 3062 ME Rotterdam, The Netherlands
6
Department of Pathology, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands
7
Departments of Radiology & Nuclear Medicine, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands
8
Departments of Dermatology, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands
9
Departments of Surgery, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden
10
Departments of Oncology, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden
11
Department of Research, Netherlands Comprehensive Cancer Organization (IKNL), 3511 DT Utrecht, The Netherlands
12
Departments of Surgery, Institute of Clinical Sciences at Sahlgrenska Academy, Gothenburg University, 405 30 Gothenburg, Sweden
13
Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, 405 30 Gothenburg, Sweden
 
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*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
‡
These authors contributed equally to this work.
Academic Editor: Gerardo Ferrara
Cancers 2022, 14(12), 2854; https://doi.org/10.3390/cancers14122854
Received: 6 May 2022 / Revised: 1 June 2022 / Accepted: 5 June 2022 / Published: 9 June 2022
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Simple Summary

More than 40% of patients initially diagnosed with ‘low risk’ (stage I–II) melanoma eventually develop melanoma recurrence or die as a result of melanoma. While the current standard of care at diagnosis for these patients is watchful waiting, they may benefit from adjuvant systemic treatment. The primary aim of this retrospective study was to assess the performance of a clinicopathologic and gene expression (CP-GEP) model, a model originally developed to predict sentinel node metastasis, to identify patients with stage I–II melanoma at risk of disease relapse. This study included Swedish and Dutch patients (18 years of age or older) with a melanoma of the skin without sentinel node metastasis. Using the non-invasive CP-GEP model, the patients could be divided into two groups: high (413 patients) or low risk (122 patients) of recurrence. While these results are promising, optimization of the CP-GEP model is recommended before implementing the model in clinical practice.

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. View Full-Text
Keywords: primary cutaneous melanoma; clinicopathologic and gene expression model; risk stratification recurrence primary cutaneous melanoma; clinicopathologic and gene expression model; risk stratification recurrence
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MDPI and ACS Style

Mulder, E.E.A.P.; Johansson, I.; Grünhagen, D.J.; Tempel, D.; Rentroia-Pacheco, B.; Dwarkasing, J.T.; Verver, D.; Mooyaart, A.L.; van der Veldt, A.A.M.; Wakkee, M.; Nijsten, T.E.C.; Verhoef, C.; Mattsson, J.; Ny, L.; Hollestein, L.M.; Olofsson Bagge, R. Using a Clinicopathologic and Gene Expression (CP-GEP) Model to Identify Stage I–II Melanoma Patients at Risk of Disease Relapse. Cancers 2022, 14, 2854. https://doi.org/10.3390/cancers14122854

AMA Style

Mulder EEAP, Johansson I, Grünhagen DJ, Tempel D, Rentroia-Pacheco B, Dwarkasing JT, Verver D, Mooyaart AL, van der Veldt AAM, Wakkee M, Nijsten TEC, Verhoef C, Mattsson J, Ny L, Hollestein LM, Olofsson Bagge R. Using a Clinicopathologic and Gene Expression (CP-GEP) Model to Identify Stage I–II Melanoma Patients at Risk of Disease Relapse. Cancers. 2022; 14(12):2854. https://doi.org/10.3390/cancers14122854

Chicago/Turabian Style

Mulder, Evalyn E.A.P., Iva Johansson, Dirk J. Grünhagen, Dennie Tempel, Barbara Rentroia-Pacheco, Jvalini T. Dwarkasing, Daniëlle Verver, Antien L. Mooyaart, Astrid A.M. van der Veldt, Marlies Wakkee, Tamar E.C. Nijsten, Cornelis Verhoef, Jan Mattsson, Lars Ny, Loes M. Hollestein, and Roger Olofsson Bagge. 2022. "Using a Clinicopathologic and Gene Expression (CP-GEP) Model to Identify Stage I–II Melanoma Patients at Risk of Disease Relapse" Cancers 14, no. 12: 2854. https://doi.org/10.3390/cancers14122854

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