<p>Early-stage cutaneous melanoma patients generally have a favorable prognosis, yet a significant proportion of metastatic melanoma cases arise from this group, highlighting the need for improved risk stratification using novel prognostic biomarkers. The Dutch Early-Stage Melanoma (D-ESMEL) study introduces a robust, population-based methodology to develop an absolute risk prediction model for stage I/II melanoma, incorporating clinical, imaging, and multi-omics data to identify patients at increased risk for distant metastases. Utilizing the Netherlands Cancer Registry and Dutch Nationwide Pathology Databank, we collected primary tumor samples from early-stage melanoma patients, with and without distant metastases during follow-up. Our study design includes a discovery set of metastatic cases and matched controls to identify novel prognostic factors, followed by a validation cohort using a nested case–control design to validate these factors and to build a risk prediction model. Tissue sections underwent Hematoxylin &amp; Eosin (H&amp;E) staining, RNA sequencing (RNAseq), DNA sequencing (DNAseq), immunohistochemistry (IHC), and multiplex immunofluorescence (MxIF).The discovery set included 442 primary melanoma samples (221 case–control sets), with 46% stage I and 54% stage II melanomas. The median time to distant metastasis was 3.4&#xa0;years, while controls had a median follow-up time of 9.8&#xa0;years. The validation cohort included 154 cases and 154 controls from a random population-based selection of 5,815 patients. Our approach enabled the collection of a large number of early-stage melanoma samples from population-based databases with extensive follow-up and a sufficient number of metastatic events. This methodology in prognostic cancer research holds the potential to impact clinical decision-making through absolute risk prediction.</p>

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The Dutch Early-Stage Melanoma (D-ESMEL) study: a discovery set and validation cohort to predict the absolute risk of distant metastases in stage I/II cutaneous melanoma

  • Catherine Zhou,
  • Antien L. Mooyaart,
  • Thamila Kerkour,
  • Marieke W. J. Louwman,
  • Marlies Wakkee,
  • Yunlei Li,
  • Quirinus J. M. Voorham,
  • Annette Bruggink,
  • Tamar E. C. Nijsten,
  • Loes M. Hollestein

摘要

Early-stage cutaneous melanoma patients generally have a favorable prognosis, yet a significant proportion of metastatic melanoma cases arise from this group, highlighting the need for improved risk stratification using novel prognostic biomarkers. The Dutch Early-Stage Melanoma (D-ESMEL) study introduces a robust, population-based methodology to develop an absolute risk prediction model for stage I/II melanoma, incorporating clinical, imaging, and multi-omics data to identify patients at increased risk for distant metastases. Utilizing the Netherlands Cancer Registry and Dutch Nationwide Pathology Databank, we collected primary tumor samples from early-stage melanoma patients, with and without distant metastases during follow-up. Our study design includes a discovery set of metastatic cases and matched controls to identify novel prognostic factors, followed by a validation cohort using a nested case–control design to validate these factors and to build a risk prediction model. Tissue sections underwent Hematoxylin & Eosin (H&E) staining, RNA sequencing (RNAseq), DNA sequencing (DNAseq), immunohistochemistry (IHC), and multiplex immunofluorescence (MxIF).The discovery set included 442 primary melanoma samples (221 case–control sets), with 46% stage I and 54% stage II melanomas. The median time to distant metastasis was 3.4 years, while controls had a median follow-up time of 9.8 years. The validation cohort included 154 cases and 154 controls from a random population-based selection of 5,815 patients. Our approach enabled the collection of a large number of early-stage melanoma samples from population-based databases with extensive follow-up and a sufficient number of metastatic events. This methodology in prognostic cancer research holds the potential to impact clinical decision-making through absolute risk prediction.