Prognostic Gene Expression Profiling in Cutaneous Melanoma

Abstract

gene expression profile (GEP) testing in cutaneous melanoma (CM) is rising despite a lack of endorsement as standard of care.OBJECTIVE To develop guidelines within the national Melanoma Prevention Working Group (MPWG) on integration of GEP testing into the management of patients with CM, including (1) review of published data using GEP tests, (2) definition of acceptable performance criteria, (3) current recommendations for use of GEP testing in clinical practice, and (4) considerations for future studies. EVIDENCE REVIEWThe MPWG members and other international melanoma specialists participated in 2 online surveys and then convened a summit meeting. Published data and meeting abstracts from 2015 to 2019 were reviewed.FINDINGS The MPWG members are optimistic about the future use of prognostic GEP testing to improve risk stratification and enhance clinical decision-making but acknowledge that current utility is limited by test performance in patients with stage I disease. Published studies of GEP testing have not evaluated results in the context of all relevant clinicopathologic factors or as predictors of regional nodal metastasis to replace sentinel lymph node biopsy (SLNB). The performance of GEP tests has generally been reported for small groups of patients representing particular tumor stages or in aggregate form, such that stage-specific performance cannot be ascertained, and without survival outcomes compared with data from the American Joint Committee on Cancer 8th edition melanoma staging system international database. There are significant challenges to performing clinical trials incorporating GEP testing with SLNB and adjuvant therapy. The MPWG members favor conducting retrospective studies that evaluate multiple GEP testing platforms on fully annotated archived samples before embarking on costly prospective studies and recommend avoiding routine use of GEP testing to direct patient management until prospective studies support their clinical utility.CONCLUSIONS AND RELEVANCE More evidence is needed to support using GEP testing to inform recommendations regarding SLNB, intensity of follow-up or imaging surveillance, and postoperative adjuvant therapy. The MPWG recommends further research to assess the validity and clinical applicability of existing and emerging GEP tests. Decisions on performing GEP testing and patient management based on these results should only be made in the context of discussion of testing limitations with the patient or within a multidisciplinary group.

Cross-Platform Omics Prediction procedure: a game changer for implementing precision medicine in patients with stage-III melanoma

“…Then, fit an unweighted ridge regression model (i.e. a WEN model with no weights and ↵ = 0) onto (Z 1,S (1) , y 1 ) and (Z 2,S (1) , y 2 ) to obtain b (2) 1 and b (2) 2 . Define another feature set S (2) = {j| sign( b (2) 1,j ) = sign( b (2) 2,j )}.…”

“…a WEN model with no weights and ↵ = 0) onto (Z 1,S (1) , y 1 ) and (Z 2,S (1) , y 2 ) to obtain b (2) 1 and b (2) 2 . Define another feature set S (2) = {j| sign( b (2) 1,j ) = sign( b (2) 2,j )}. We also include an additional step by iteratively fitting ridge regression to both Z 1,S (2) and Z 2,S (2) and in each iteration, we update the feature set S (2) by removing all features that do not satisfy sign( b (2) 1,j ) = sign( b (2) 2,j ).…”

“…Define another feature set S (2) = {j| sign( b (2) 1,j ) = sign( b (2) 2,j )}. We also include an additional step by iteratively fitting ridge regression to both Z 1,S (2) and Z 2,S (2) and in each iteration, we update the feature set S (2) by removing all features that do not satisfy sign( b (2) 1,j ) = sign( b (2) 2,j ). This removal of features using the ridge models means that the size of S (2) is non-increasing with each iteration.…”

“…This removal of features using the ridge models means that the size of S (2) is non-increasing with each iteration. This iterative step terminates when there is no further reduction in the size of S (2) .…”

“…In melanoma cancer, patients who have been diagnosed with American Joint Committee on Cancer (AJCC) 1 stage III melanoma have diverse prognostic outcomes after resection of the lymph node metastases, with ten-year survival rates ranging from 24% to 88% in the era prior to effective systemic therapies. However, no validated molecular signatures of prognosis are currently endorsed by clinical guidelines for melanoma care, and the few that are commercially available for early stage melanoma require testing at a single location by the supplier 2 . These limitations to implementation would be greatly reduced if such signatures could be measured reproducibly on different platforms, at any suitably equipped site, and be subject to widespread external validation.…”