Expanded evidence that the 31-gene expression profile test provides clinical utility for melanoma management in a multicenter study

Dillon, Larry D; McPhee, Michael; Davidson, Robert S.; Quick, Ann P.; Martin, Brian J.; Covington, Kyle R.; Zolochevska, Olga; Cook, Robert W.; Vetto, John T.; Jarell, Abel; Fleming, Martin D.

doi:10.1080/03007995.2022.2033560

Cited by 12 publications

(15 citation statements)

References 28 publications

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“…The 31-GEP test was developed and validated through gene expression analysis using RT-PCR and radial basis machine learning to provide a risk score from 0-1.0 with reproducible test results during analytic validation, 16,31 has been validated in multiple retrospective and prospective studies, and has been shown to influence treatment decisions in 50% of cases. [6][7][8]10,17,32,33 The 31-GEP has been integrated with clinical and pathological factors using a neural network algorithm to provide an individualized, precise risk of SLN positivity (i31-GEP). 12 Of the variables included in the i31-GEP neural network, the 31-GEP risk score was the most significant contributor to the model.…”

Section: Discussionmentioning

confidence: 99%

The Integrated 31-Gene Expression Profile Test (i31-GEP) for Cutaneous Melanoma Outperforms the CP-GEP at Identifying Patients who can Forego Sentinel Lymph Node Biopsy when Applying NCCN Guidelines

et al. 2022

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Introduction: Eighty-eight percent of patients who receive a sentinel lymph node biopsy (SLNB) receive a negative result. Current guidelines suggest avoiding SLNB if the risk of positivity is <5%. A low threshold for performing SLNB indicates worry about missing positive nodes but results in many unnecessary biopsies. The integrated 31-gene expression profile (i31-GEP) test combines the 31-GEP with Breslow thickness, age, ulceration, and mitotic rate using a validated neural network algorithm to identify patients with <5% risk by reporting a precise, individualized likelihood score. Using logistic regression, a separate GEP (8 genes plus Breslow thickness and age; CP-GEP) also aims to identify patients who can forego SLNB by binning patients into low- and high-risk categories. This study compared the i31-GEP for SLNB with the CP-GEP to identify patients who can safely forego SLNB. Methods: This study evaluated the genes, gene pathways, and relative contribution of the two gene signatures relative to clinical and pathologic factors and further analyzed patients with T1b-T2 tumors from previously published studies in U.S. cohorts for the i31-GEP (n=763) and CP-GEP (n=153). A ratio of true-to-false-negative i31-GEP for SLNB and CP-GEP test results was compared to the guideline-established ratio of 19 negatives to one missed positive (19:1) if foregoing SLNB using a 5% risk threshold. Results: The i31-GEP had a 30:1 true-to-false-negative ratio, compared to 15:1 using CP-GEP. In T1b tumors, the i31-GEP ratio increased to 35:1 compared to 14:1 using CP-GEP. Limitations: Retrospective design, which could lead to bias. Patients included in both analyses were primarily from institutional surgical centers, and referral bias may not make the result generalizable. Conclusion: Only the i31-GEP provided benefit over guideline-established care for identifying patients with low risk of SLN positivity.

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Section: Discussionmentioning

confidence: 99%

The Integrated 31-Gene Expression Profile Test (i31-GEP) for Cutaneous Melanoma Outperforms the CP-GEP at Identifying Patients who can Forego Sentinel Lymph Node Biopsy when Applying NCCN Guidelines

et al. 2022

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“…After screening the articles, 32 met inclusion criteria and were distributed to the panelists for review prior to the roundtable discussion. Of these articles, the number of papers that specifically studied the validity, accuracy, or clinical utility of each test was: 22 for the 31-GEP test 4,[19][20][21][22][23][24][26][27][28][29][30][31][34][35][36][37][38][39][40][41][42] , 2 for the 11-GEP test 11,34 , and 7 for the 8-GEP + CP test. 5,13,23,[43][44][45][46]…”

Section: Comprehensive Literature Searchmentioning

confidence: 99%

“…For the 8-GEP + CEP test, a validation study analyzing the test's ability to predict SLNB positivity found that this model has a NPV of 90.5% (95% Confidence Interval [CI]: 77.9-96.2%) in T1-4 CMs. 44 In comparing the three GEP tests, the panel consensus was that there were significantly more studies supporting the validity, accuracy, and clinical utility of the 31-GEP test compared to the 11-GEP and 8-GEP + CP tests (22 studies validating the 31-GEP test 4,[19][20][21][22][23][24][26][27][28][29][30][31][34][35][36][37][38][39][40][41][42] , compared to just 2 studies validating the 11-GEP test 11,34 and 7 studies validating the 8-GEP + CP test 5,13,23,[43][44][45][46] ). Based on the limited studies for the 8-GEP + CP and the 11-GEP test, the panel concluded that there was insufficient data to assess their validity and utility or currently recommend usage in the clinical setting until further studies are performed.…”

Section: Consensus Recommendationsmentioning

confidence: 99%

Incorporating Prognostic Gene Expression Profile Assays into the Management of Cutaneous Melanoma: An Expert Consensus Panel

Zakria

Brownstone²,

Berman³

et al. 2023

J of Skin

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Background: Cutaneous melanoma (CM) guidelines put forth by the eighth edition of the American Joint Committee on Cancer (AJCC8) and the National Comprehensive Cancer Network (NCCN) do not currently account for lesion genomics when assessing prognosis. Gene Expression Profile (GEP) tests have become a widely adopted tool to help clinicians identify patients at higher risk for metastasis and recurrence. Objective: To review the available literature that has been published since a consensus panel in 2018 on three commercially available GEP tests used in the prognostic assessment of CM and create updated guidelines and consensus statements for their optimal use. Methods: A comprehensive literature search of PubMed and Google Scholar was conducted for relevant English-language original research articles, meta-analyses, and systematic reviews published from 2019 through 2022. A panel of 6 key opinion leaders in dermatology with specialized expertise in diagnosing and managing CM then convened to review the articles and create guidelines. A modified Delphi process was used to approve each statement. The panel assigned each article a level of evidence and each consensus statement a strength of recommendation using Strength of Recommendation Taxonomy (SORT) criteria. Results: The literature search identified 785 articles that met the search criteria. Of these, there were 22 articles that validated the 31-GEP test, 2 that validated the 11-GEP test, and 7 that validated the 8-GEP + CP test. The panel unanimously approved 6 usage guidelines and 5 consensus supporting statements for the appropriate use of these tests. Conclusion: Based on the currently available literature, GEP tests provide valuable information beyond AJCC8 and NCCN guidelines for the prognostic assessment of CM. There are significantly more validation studies supporting the use of the 31-GEP test compared to the 11-GEP test and the 8-GEP + CP test.

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“…Multiple studies have demonstrated that clinicians combine 31-GEP results with other factors to align management plans with patient risk. [26][27][28] No DISCUSSION Table 3. Reclassification of risk in patients with 5-10% SLN positivity risk ("consider" SLNB; T1aHR-T1b) for whom SLNB guidance is not definitive Limitations of this study include its retrospective nature and that this selected population from primarily surgical centers may not represent the general population.…”

Section: Skinmentioning

confidence: 99%

“…Despite these limitations, this study provides evidence that the i31-GEP for SLNB can guide risk-aligned SLNB decisions. 22,26,27 Decisions regarding patient care are made in multi-disciplinary settings, and tools such as the i31-GEP for SLNB supplement traditional clinical and pathologic factors and offer independent, objective risk prediction to aid clinicians in determining the best treatment plan for individual patients. However, clinicians need confidence that a tool will provide precise prognostic information.…”

Section: Skinmentioning

confidence: 99%

The Integrated 31-Gene Expression Profile (i31-GEP) Test for Cutaneous Melanoma Outperforms a Clinicopathologic-only Nomogram at Identifying Patients who can Forego Sentinel Lymph Node Biopsy

Zakria¹,

Brownstone²,

Rigel

2022

J of Skin

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Introduction: National guidelines for cutaneous melanoma suggest avoiding sentinel lymph node biopsy (SLNB) if the risk of SLN positivity is <5% (T1a with no high-risk features), considering SLNB if the risk is 5-10% (T1a with additional high-risk features (T1aHR) and T1b), and offering SLNB if the risk is >10% (T2-T4). Because most patients (88%) who undergo an SLNB have a negative result, novel tools to identify patients who can safely forgo SLNB are critical. The integrated 31-gene expression profile (i31-GEP for SLNB) test for cutaneous melanoma combines tumor molecular biology with clinicopathologic features to provide a precise risk of SLN positivity. The Melanoma Institute of Australia (MIA) developed a nomogram that uses only clinicopathologic features to predict SLN positivity. Methods: We compared the i31-GEP for SLNB to the MIA nomogram in patients with T1-T2 tumors with complete data (n=582). The precision of each tool to identify patients with <5% SLN positivity risk was analyzed using 95% confidence intervals. To be considered low risk, the predicted risk must be <5% and the upper 95% confidence interval must be ≤10%, and to be considered high-risk, the predicted risk must be >10% and the lower 95% CI ≥5%. Results: The i31-GEP for SLNB identified 28.5% (166/582) of patients as having a <5% risk of SLN positivity while also having an upper 95% CI ≤10% compared with 0.9% (5/582, p<0.001) using the MIA nomogram. In patients with a pre-test likelihood of SLN positivity of 5-10% (T1aHR-T1b), the i31-GEP reclassified risk in 60.2% (171/284) of patients as being <5% or >10% compared to 13.7% (39/284, p<0.001) using the MIA nomogram. In patients with a known SLN status (n=466), the i31-GEP for SLNB identified 22.1% (103/466) of patients as having <5% risk, with a 3.9% (4/103) SLN positivity rate compared to 0.6% (3/466, p<0.001) identified by the MIA as having a <5% risk with a 33.3% (1/3) SLN positivity rate. Conclusions: The i31-GEP test outperformed the MIA nomogram in identifying patients who could safely forego SLNB. Integrating the 31-GEP molecular risk stratification tool with clinicopathologic features provides precise SLN positivity risk to better guide patient management in patients with T1-T2 tumors, for whom SLNB guidance could be most impactful.

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Expanded evidence that the 31-gene expression profile test provides clinical utility for melanoma management in a multicenter study

Cited by 12 publications

References 28 publications

The Integrated 31-Gene Expression Profile Test (i31-GEP) for Cutaneous Melanoma Outperforms the CP-GEP at Identifying Patients who can Forego Sentinel Lymph Node Biopsy when Applying NCCN Guidelines

The Integrated 31-Gene Expression Profile Test (i31-GEP) for Cutaneous Melanoma Outperforms the CP-GEP at Identifying Patients who can Forego Sentinel Lymph Node Biopsy when Applying NCCN Guidelines

Incorporating Prognostic Gene Expression Profile Assays into the Management of Cutaneous Melanoma: An Expert Consensus Panel

The Integrated 31-Gene Expression Profile (i31-GEP) Test for Cutaneous Melanoma Outperforms a Clinicopathologic-only Nomogram at Identifying Patients who can Forego Sentinel Lymph Node Biopsy

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