The 31-Gene Expression Profile Test Outperforms AJCC in Stratifying Risk of Recurrence in Patients with Stage I Cutaneous Melanoma.

BACKGROUND: Patients with stage I cutaneous melanoma (CM) are considered at low risk for metastasis or melanoma specific death; however, because the majority of patients are diagnosed with stage I disease, they represent the largest number of melanoma deaths annually. The 31-gene expression profile (31-GEP) test has been prospectively validated to provide prognostic information independent of staging, classifying patients as low (Class 1A), intermediate (Class 1B/2A), or high (Class 2B) risk of poor outcomes. METHODS: Patients enrolled in previous studies of the 31-GEP were combined and evaluated for recurrence-free (RFS) and melanoma-specific survival (MSS) (n = 1261, "combined"). A second large, unselected real-world cohort (n = 5651) comprising clinically tested patients diagnosed 2013-2018 who were linked to outcomes data from the NCI Surveillance, Epidemiology, and End Results (SEER) Program registries was evaluated for MSS. RESULTS: Combined cohort Class 1A patients had significantly higher RFS than Class 1B/2A or Class 2B patients (97.3%, 88.6%, 77.3%, p < 0.001)-better risk stratification than AJCC8 stage IA (97.5%) versus IB (89.3%). The SEER cohort showed better MSS stratification by the 31-GEP (Class 1A = 98.0%, Class 1B/2A = 97.5%, Class 2B = 92.3%; p < 0.001) than by AJCC8 staging (stage IA = 97.6%, stage IB = 97.9%; p < 0.001). CONCLUSIONS: The 31-GEP test significantly improved patient risk stratification, independent of AJCC8 staging in patients with stage I CM. The 31-GEP provided greater separation between high- (Class 2B) and low-risk (Class 1A) groups than seen between AJCC stage IA and IB. These data support integrating the 31-GEP into clinical decision making for more risk-aligned management plans.

31-Gene Expression Profile Testing in Cutaneous Melanoma and Survival Outcomes in a Population-Based Analysis: A SEER Collaboration.

PURPOSE: The DecisionDx-Melanoma 31-gene expression profile (31-GEP) test is validated to classify cutaneous malignant melanoma (CM) patient risk of recurrence, metastasis, or death as low (class 1A), intermediate (class 1B/2A), or high (class 2B). This study aimed to examine the effect of 31-GEP testing on survival outcomes and confirm the prognostic ability of the 31-GEP at the population level. METHODS: Patients with stage I-III CM with a clinical 31-GEP result between 2016 and 2018 were linked to data from 17 SEER registries (n = 4,687) following registries' operation procedures for linkages. Melanoma-specific survival (MSS) and overall survival (OS) differences by 31-GEP risk category were examined using Kaplan-Meier analysis and the log-rank test. Crude and adjusted hazard ratios (HRs) were calculated using Cox regression model to evaluate variables associated with survival. 31-GEP tested patients were propensity score-matched to a cohort of non-31-GEP tested patients from the SEER database. Robustness of the effect of 31-GEP testing was assessed using resampling. RESULTS: Patients with a 31-GEP class 1A result had higher 3-year MSS and OS than patients with a class 1B/2A or class 2B result (MSS: 99.7% v 97.1% v 89.6%, P < .001; OS: 96.6% v 90.2% v 79.4%, P < .001). A class 2B result was an independent predictor of MSS (HR, 7.00; 95% CI, 2.70 to 18.00) and OS (HR, 2.39; 95% CI, 1.54 to 3.70). 31-GEP testing was associated with a 29% lower MSS mortality (HR, 0.71; 95% CI, 0.53 to 0.94) and 17% lower overall mortality (HR, 0.83; 95% CI, 0.70 to 0.99) relative to untested patients. CONCLUSION: In a population-based, clinically tested melanoma cohort, the 31-GEP stratified patients by their risk of dying from melanoma.

The 31-gene expression profile test informs sentinel lymph node biopsy decisions in patients with cutaneous melanoma: results of a prospective, multicenter study.

BACKGROUND: The 31-gene expression profile test (Class 1A: low-risk; 1B/2A: intermediate-risk; 2B: high-risk) is validated to identify patients with cutaneous melanoma who can safely forego sentinel lymph node biopsy (SLNB). The objective of the current study is to quantify SLNB reduction by clinicians using 31-GEP. METHODS: Patients with T1-T2 tumors eligible for SLNB were seen by surgical oncologists (89.1%), dermatologists (7.8%), and medical oncologists (3.1%). After receiving 31-GEP results but before SLNB, clinicians were asked which clinical and pathological features influenced SLNB decisions (n = 191). The Exact binomial test was used to compare SLNB procedure rates to a contemporary study (78% SLNB baseline rate). Logistic regression modeling (odds ratio [OR], 95% CI) was used to identify features associated with SLNB procedure rates. RESULTS: One hundred clinical decisions (52.4%) were influenced by the 31-GEP to forego SLNB and 70% (70/100) were not performed. Of the 30 performed, 0% (0/30) were positive. The 31-GEP influenced sixty-three clinical decisions (33.0%) to perform SLNB, and 92.1% (58/63) were performed. There was a clinically meaningful 29.4% reduction of SLNBs performed in patients with a Class 1A result relative to the baseline rate of 78.0% (p < .01). In patients ≥55 or ≥65-year-old, SLNB reduction was 32.3% (p < .01), 28.3% (p < .01), respectively. Overall, 85.3% of decisions relating to SLNB were influenced by 31-GEP results. CONCLUSION: In this prospective, multicenter study, clinicians demonstrated clinically meaningful use of the 31-GEP test to forego or pursue SLNB in patients with T1-T2 tumors resulting in a significant, risk appropriate decrease in SLNBs.

Optimizing treatment approaches for patients with cutaneous melanoma by integrating clinical and pathologic features with the 31-gene expression profile test.

BACKGROUND: Many patients with low-stage cutaneous melanoma will experience tumor recurrence, metastasis, or death, and many higher staged patients will not. OBJECTIVE: To develop an algorithm by integrating the 31-gene expression profile test with clinicopathologic data for an optimized, personalized risk of recurrence (integrated 31 risk of recurrence [i31-ROR]) or death and use i31-ROR in conjunction with a previously validated algorithm for precise sentinel lymph node positivity risk estimates (i31-SLNB) for optimized treatment plan decisions. METHODS: Cox regression models for ROR were developed (n = 1581) and independently validated (n = 523) on a cohort with stage I-III melanoma. Using National Comprehensive Cancer Network cut points, i31-ROR performance was evaluated using the midpoint survival rates between patients with stage IIA and stage IIB disease as a risk threshold. RESULTS: Patients with a low-risk i31-ROR result had significantly higher 5-year recurrence-free survival (91% vs 45%, P < .001), distant metastasis-free survival (95% vs 53%, P < .001), and melanoma-specific survival (98% vs 73%, P < .001) than patients with a high-risk i31-ROR result. A combined i31-SLNB/ROR analysis identified 44% of patients who could forego sentinel lymph node biopsy while maintaining high survival rates (>98%) or were restratified as being at a higher or lower risk of recurrence or death. LIMITATIONS: Multicenter, retrospective study. CONCLUSION: Integrating clinicopathologic features with the 31-GEP optimizes patient risk stratification compared to clinicopathologic features alone.

Using a 31-Gene Expression Profile Test to Stratify Patients with Stage I-II Cutaneous Melanoma According to Recurrence Risk: Update to a Prospective, Multicenter Study.

BACKGROUND: Fifteen to forty percent of patients with localized cutaneous melanoma (CM) (stages I-II) will experience disease relapse. The 31-gene expression profile (31-GEP) uses gene expression data from the primary tumor in conjunction with clinicopathologic features to refine patient prognosis. The study's objective was to evaluate 31-GEP risk stratification for disease-free survival (DFS) in a previously published cohort with longer follow-up. METHODS: Patients with stage IB-II CM (n = 86) were prospectively tested with the 31-GEP. Follow-up time increased from 2.2 to 3.9 years. Patient outcomes were compared using Kaplan-Meier and Cox regression analysis. RESULTS: A Class 2B result was a significant predictor of 3-year DFS (hazard ratio (HR) 8.4, p = 0.008) in univariate analysis. The 31-GEP significantly stratified patients by risk of relapse (p = 0.005). A Class 2B result was associated with a lower 3-year DFS (75.0%) than a Class 1A result (100%). The 31-GEP had a high sensitivity (77.8%) and negative predictive value (95.0%). CONCLUSIONS: The 31-GEP is a significant predictor of disease relapse in patients with stage IB-II melanoma and accurately stratified patients by risk of relapse.

Gene expression profiling for metastatic risk in head and neck cutaneous squamous cell carcinoma.

OBJECTIVE: Over 50% of newly diagnosed cutaneous squamous cell carcinoma (cSCC) lesions occur in the head and neck (cSCC-HN), and metastasis to nodal basins in this region further complicates surgical and adjuvant treatment. The current study addressed whether the 40-gene expression profile (40-GEP) test can predict metastatic risk in cSCC-HN with improved accuracy and provide independent prognostic value to complement current risk assessment methods. STUDY DESIGN: Multicenter, retrospective cohort study. METHODS: Formalin-fixed paraffin-embedded primary tumor tissue and associated clinical data from patients with cSCC-HN (n = 278) were collected from 33 independent centers. Samples were analyzed via the 40-GEP test. Cases were staged per American Joint Committee on Cancer, Eighth Edition (AJCC8) and Brigham and Women's Hospital (BWH) criteria after comprehensive medical record and pathology report review. Metastasis-free survival (MFS) rates were determined, and risk factors were analyzed via Cox regression. RESULTS: The 40-GEP test classified the cohort into low (Class 1, n = 126; 45.3%), moderate (Class 2A, n = 134; 48.2%), and high (Class 2B, n = 18; 6.5%) metastatic risk at 3 years postdiagnosis. Regional/distant metastasis occurred in 54 patients (19.4%). MFS rates were 92.1% (Class 1), 76.1% (Class 2A), and 44.4% (Class 2B; p < .0001). Multivariate analysis of 40-GEP results with AJCC8 or BWH tumor stage, or clinicopathologic risk factors, demonstrated independent prognostic value of the 40-GEP test (p < .03). Accuracy of predicting metastatic risk was also improved using 40-GEP classification (p < .02). CONCLUSIONS: Improved metastatic risk stratification through the 40-GEP test could complement cSCC-HN risk assessment for better-informed decision-making for treatment and surveillance and ultimately improve patient outcomes. LEVEL OF EVIDENCE: 3.