Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients.
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SUBMITTER: Zager JS
PROVIDER: S-EPMC5800282 | biostudies-literature | 2018 Feb
REPOSITORIES: biostudies-literature
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Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients.
Zager Jonathan S JS Gastman Brian R BR Leachman Sancy S Gonzalez Rene C RC Fleming Martin D MD Ferris Laura K LK Ho Jonhan J Miller Alexander R AR Cook Robert W RW Covington Kyle R KR Meldi-Plasseraud Kristen K Middlebrook Brooke B Kaminester Lewis H LH Greisinger Anthony A Estrada Sarah I SI Pariser David M DM Cranmer Lee D LD Messina Jane L JL Vetto John T JT Wayne Jeffrey D JD Delman Keith A KA Lawson David H DH Gerami Pedram P
BMC cancer 20180205 1
<h4>Background</h4>The heterogeneous behavior of patients with melanoma makes prognostication challenging. To address this, a gene expression profile (GEP) test to predict metastatic risk was previously developed. This study evaluates the GEP's prognostic accuracy in an independent cohort of cutaneous melanoma patients.<h4>Methods</h4>This multi-center study analyzed primary melanoma tumors from 523 patients, using the GEP to classify patients as Class 1 (low risk) and Class 2 (high risk). Molec ...[more]
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Project description:PurposeCurrent guidelines for postoperative management of patients with stage I-IIA cutaneous melanoma (CM) do not recommend routine cross-sectional imaging, yet many of these patients develop metastases. Methods that complement American Joint Committee on Cancer (AJCC) staging are needed to improve identification and treatment of these patients. A 31-gene expression profile (31-GEP) test predicts metastatic risk as low (class 1) or high (class 2). Prospective analysis of CM outcomes was performed to test the hypotheses that the 31-GEP provides prognostic value for patients with stage I-III CM, and that patients with stage I-IIA melanoma and class 2 31-GEP results have metastatic risk similar to patients for whom surveillance is recommended.Materials and methodsTwo multicenter registry studies, INTEGRATE (ClinicalTrials.gov identifier:NCT02355574) and EXPAND (ClinicalTrials.gov identifier:NCT02355587), were initiated under institutional review board approval, and 323 patients with stage I-III CM and median follow-up time of 3.2 years met inclusion criteria. Primary end points were 3-year recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS).ResultsThe 31-GEP was significant for RFS, DMFS, and OS in a univariate analysis and was a significant, independent predictor of RFS, DMFS, and OS in a multivariable analysis. GEP class 2 results were significantly associated with lower 3-year RFS, DMFS, and OS in all patients and those with stage I-IIA disease. Patients with stage I-IIA CM and a class 2 result had recurrence, distant metastasis, and death rates similar to patients with stage IIB-III CM. Combining 31-GEP results and AJCC staging enhanced sensitivity over each approach alone.ConclusionThese data provide a rationale for using the 31-GEP along with AJCC staging, and suggest that patients with stage I-IIA CM and a class 2 31-GEP signature may be candidates for more intense follow-up.
| S-EPMC8140806 | biostudies-literature
Project description:ObjectiveAlthough most patients diagnosed with early-stage cutaneous melanoma (CM) have excellent outcomes, because of the large number diagnosed each year, many will experience recurrence or death. Prognostic testing for CM using the 31-gene expression profile (31-GEP) test can benefit patients by helping guide risk-appropriate treatment and surveillance plans. We sought to evaluate patients' attitudes toward prognostic testing with the 31-GEP and assess whether patients experience decision regret about having 31-GEP testing.MethodsA 43-question survey was distributed by the Melanoma Research Foundation in June-August 2021 to CM patients enrolled in their database. Patients were asked questions regarding their decision to undergo 31-GEP testing and the extent to which they experienced decision regret using a validated set of Decision Regret Scale questions.ResultsWe analyzed responses from patients diagnosed in 2014 or later (n = 120). Of these, 28 had received 31-GEP testing. Most respondents (n = 108, 90%) desired prognostic information when diagnosed. Of those who received 31-GEP testing, most felt the results were useful (n = 22 out of 24) and had regret scores significantly less than neutral regret, regardless of their test results (Class 1: p < 0.001; Class 2: p = 0.036). Further, decision regret scores were not significantly different between patients who received a Class 1 31-GEP result and those who received a Class 2 result (mean Class 1 = 1.39 and mean Class 2 = 1.90, p = 0.058).ConclusionsMost newly diagnosed CM patients desired prognostic information about their tumors. Patients who received 31-GEP testing felt it was useful and did not regret their decision to undergo 31-GEP testing.
| S-EPMC9883557 | biostudies-literature
Project description:BackgroundA 31-gene expression profile (GEP) test that provides risk classification of cutaneous melanoma (CM) patients has been validated in several retrospective studies. The objective of the reported study was a prospective evaluation of the GEP performance in patients enrolled in two clinical registries.MethodsThree-hundred twenty two CM patients enrolled in the EXPAND (NCT02355587) and INTEGRATE (NCT02355574) registries met the criteria of age ≥ 16 years, successful GEP result and ≥1 follow-up visit for inclusion in this interim analysis. Primary endpoints were recurrence-free (RFS), distant metastasis-free (DMFS), and overall survival (OS).ResultsMedian follow-up was 1.5 years for event-free patients. Median age for subjects was 58 years (range 18-87) and median Breslow thickness was 1.2 mm (range 0.2-12.0). Eighty-eight percent (282/322) of cases had stage I/II disease and 74% (237/322) had a SLN biopsy. Seventy-seven percent (248/322) had class 1 molecular profiles. 1.5-year RFS, DMFS, and OS rates were 97 vs. 77%, 99 vs. 89%, and 99 vs. 92% for class 1 vs. class 2, respectively (p < 0.0001 for each). Multivariate Cox regression showed Breslow thickness, mitotic rate, and GEP class to significantly predict recurrence (p < 0.01), while tumor thickness was the only significant predictor of distant metastasis and overall survival in this interim analysis.ConclusionsInterim analysis of patient outcomes from a combined prospective cohort supports the 31-gene GEP's ability to stratify early-stage CM patients into two groups with significantly different metastatic risk. RFS outcomes in this real-world cohort are consistent with previously published analyses with retrospective specimens. GEP testing complements current clinicopathologic features and increases identification of high-risk patients.Trial registrationClinicalTrials.gov, NCT02355574 and NCT02355587.
| S-EPMC5576286 | biostudies-literature
Project description:BackgroundGene expression profiling (GEP) has been integrated into cancer treatment decision-making in multiple neoplasms. We prospectively evaluated the prognostic utility of the 31-GEP test (DecisionDx-Melanoma, Castle Biosciences, Inc) in cutaneous melanoma (CM) patients undergoing sentinel node biopsy (SNB).MethodsOne hundred fifty-nine patients (age 26-88) diagnosed with melanoma between 01/2013 and 8/2015 underwent SNB and concurrent GEP testing. GEP results were reported as low-risk Class 1 (subclasses 1A and 1B) or high-risk Class 2 (subclasses 2A and 2B). Statistical analyses were performed with chi-square analysis, t tests, log-rank tests, and Cox proportional hazard models. Recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) were estimated using Kaplan-Meier method.ResultsMedian follow-up was 44.9 months for event-free cases. Median Breslow thickness was 1.4 mm (0.2-15.0 mm). There were 117 Class 1 and 42 Class 2 patients. Gender, age, Breslow thickness, ulceration, SNB positivity, and AJCC stage were significantly associated with GEP classification (P < 0.05 for all). Recurrence and distant metastasis rates were 5% and 1% for Class 1 patients compared with 55% and 36% for Class 2 patients. Sensitivities of Class 2 and SNB for recurrence were 79% and 34%, respectively. Of 10 SNB-positive/Class 2 patients, 9 recurred. By multivariate analysis, only SNB result and GEP class were statistically associated with both RFS (P = 0.008 and 0.0001) and DMFS (P = 0.019 and 0.001).ConclusionsGene expression profiling Class 2 result and SNB positivity were independently associated with recurrence and distant metastasis in primary CM patients. GEP testing may have additive prognostic utility in initial staging work-up of these patients.
| S-EPMC6536922 | biostudies-literature
Project description:BackgroundThe like-Smith (LSM) family is a group of RNA-binding proteins involved in RNA metabolism. However, their involvement in tumors, particularly skin cutaneous melanoma (SKCM), is not fully understood. In this study, we focused on the expression profiles and prognostic values of the LSM family in SKCM.MethodsRaw data were downloaded from The Cancer Genome Atlas. The expression profile and prognostic value of LSM genes in SKCM were explored using the GEPIA, cBioPortal, and HPA databases. Protein-protein and gene-gene interaction analyses were performed using STRING and GeneMANIA. Enrichment and Cox regression analysis were conducted using R software. The TISIDB database was used to explore the relationship between LSMs and immunomodulators. Receiver operating characteristic curves and nomogram models were constructed to validate prognostic values.ResultsmRNA and protein expression levels of LSM2, LSM4, and LSM12 were significantly elevated in SKCM. The upregulated mRNA expression of LSM2 (p = 0.0013) and LSM4 (p = 0.0043) was significantly correlated with poor overall survival in patients with SKCM, whereas only LSM2 (p = 0.049) overexpression was markedly associated with worse disease-free survival. LSM2 overexpression was an independent risk factor (p = 0.013) and was confirmed to have a high prognostic value in SKCM using the receiver operating characteristic curve (AUC = 0.942) and nomogram models. All LSM genes were identified as genomic mutations, whereas alteration of LSM2 (p = 0.0153) significantly affected the overall survival in patients with SKCM. Significant correlations were observed between LSM family expression, immune cell infiltration, and immunomodulator. Furthermore, function and pathway enrichment analysis showed that the LSM family was mainly RNA binding proteins and involved in RNA splicing and degradation.ConclusionExpression profiles and prognostic values of LSM in SKCM were inconsistent. Among the LSM family, only LSM2 may serve as a potential poor prognosticator and immunotherapeutic target of SKCM.
| S-EPMC9656080 | biostudies-literature
Project description:IntroductionUp to 88% of sentinel lymph node biopsies (SLNBs) are negative. The 31-gene expression profile (31-GEP) test can help identify patients with a low risk of SLN metastasis who can safely forego SLNB. The 31-GEP classifies patients as low (Class 1 A), intermediate (Class 1B/2A), or high risk (Class 2B) for recurrence, metastasis, and SLN positivity. The integrated 31-GEP (i31-GEP) combines the 31-GEP risk score with clinicopathologic features using a neural network algorithm to personalize SLN risk prediction.MethodsPatients from a single surgical center with 31-GEP results were included (n = 156). An i31-GEP risk prediction < 5% was considered low risk of SLN positivity. Chi-square was used to compare SLN positivity rates between groups.ResultsPatients considered low risk by the i31-GEP had a 0% (0/30) SLN positivity rate compared to a 31.9% (30/94, p < 0.001) positivity rate in those with > 10% risk. Using the i31-GEP to guide SLNB decisions could have significantly reduced the number of unnecessary SLNBs by 19.2% (30/156, p < 0.001) for all patients and 33.0% (30/91, p < 0.001) for T1-T2 tumors. Patients with T1-T2 tumors and an i31-GEP-predicted SLN positivity risk > 10% had a similar SLN positivity rate (33.3%) as patients with T3-T4 tumors (31.3%).ConclusionThe i31-GEP identified patients with < 5% risk of SLN positivity who could safely forego SLNB. Combining the 31-GEP with clinicopathologic features for a precise risk estimate can help guide risk-aligned patient care decisions for SLNB to reduce the number of unnecessary SLNBs and increase the SLNB positivity yield if the procedure is performed.
| S-EPMC11363455 | biostudies-literature
Project description:ImportanceThe performance of prognostic gene expression profile (GEP) tests for cutaneous melanoma is poorly characterized.ObjectiveTo systematically assess the performance of commercially available GEP tests in patients with American Joint Committee on Cancer (AJCC) stage I or stage II disease.Data sourcesFor this systematic review and meta-analysis, comprehensive searches of PubMed/MEDLINE, Embase, and Web of Science were conducted on December 12, 2019, for English-language studies of humans without date restrictions.Study selectionTwo reviewers identified GEP external validation studies of patients with localized melanoma. After exclusion criteria were applied, 7 studies (8%; 5 assessing DecisionDx-Melanoma and 2 assessing MelaGenix) were included.Data extraction and synthesisData were extracted using an adaptation of the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies (CHARMS-PF). When feasible, meta-analysis using random-effects models was performed. Risk of bias and level of evidence were assessed with the Quality in Prognosis Studies tool and an adaptation of Grading of Recommendations Assessment, Development, and Evaluation.Main outcomes and measuresProportion of patients with or without melanoma recurrence correctly classified by the GEP test as being at high or low risk.ResultsIn the 7 included studies, a total of 1450 study participants contributed data (age and sex unknown). The performance of both GEP tests varied by AJCC stage. Of patients tested with DecisionDx-Melanoma, 623 had stage I disease (6 true-positive [TP], 15 false-negative, 61 false-positive, and 541 true-negative [TN] results) and 212 had stage II disease (59 TP, 13 FN, 78 FP, and 62 TN results). Among patients with recurrence, DecisionDx-Melanoma correctly classified 29% with stage I disease and 82% with stage II disease. Among patients without recurrence, the test correctly classified 90% with stage I disease and 44% with stage II disease. Of patients tested with MelaGenix, 88 had stage I disease (7 TP, 15 FN, 15 FP, and 51 TN results) and 245 had stage II disease (59 TP, 19 FN, 95 FP, and 72 TN results). Among patients with recurrence, MelaGenix correctly classified 32% with stage I disease and 76% with stage II disease. Among patients without recurrence, the test correctly classified 77% with stage I disease and 43% with stage II disease.Conclusions and relevanceThe prognostic ability of GEP tests among patients with localized melanoma varied by AJCC stage and appeared to be poor at correctly identifying recurrence in patients with stage I disease, suggesting limited potential for clinical utility in these patients.
| S-EPMC7391179 | biostudies-literature
Project description:BackgroundA high percentage of patients with thin melanoma (TM), defined as lesions with Breslow thickness ≤1 mm, presents excellent long-term survival, however, some patients develop metastases. Existing prognostic factors cannot reliably differentiate TM patients at risk for metastases.ObjectiveWe aimed at characterizing the clinical-pathologic and mutation profile of metastatic and not-metastatic TM in order to distinguish lesions at risk of metastases.MethodsClinical-pathologic characteristics were recorded for the TM cases analyzed. We used a Next Generation Sequencing (NGS) multi-gene panel to characterize TM for multiple somatic mutations.ResultsA statistically significant association emerged between the presence of metastases and Breslow thickness ≥0.6 mm (p=0.003). None of TM with lymph-node involvement had Breslow thickness <0.6 mm. Somatic mutations were identified in 19 of 21 TM analyzed (90.5%). No mutations were observed in two not-metastatic cases with the lowest Breslow thickness (≤0.4 mm), whereas mutations in more than one gene were detected in one metastatic case with the highest Breslow thickness (1.00 mm).ConclusionOur study indicates Breslow thickness ≥0.6 mm as a valid prognostic factor to distinguish TM at risk for metastases.
| S-EPMC6114949 | biostudies-literature
Project description: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. 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. 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%). 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.
| S-EPMC8870692 | biostudies-literature
Project description:National guidelines recommend sentinel lymph node biopsy (SLNB) be offered to patients with > 10% likelihood of sentinel lymph node (SLN) positivity. On the other hand, guidelines do not recommend SLNB for patients with T1a tumors without high-risk features who have < 5% likelihood of a positive SLN. However, the decision to perform SLNB is less certain for patients with higher-risk T1 melanomas in which a positive node is expected 5%-10% of the time. We hypothesized that integrating clinicopathologic features with the 31-gene expression profile (31-GEP) score using advanced artificial intelligence techniques would provide more precise SLN risk prediction. An integrated 31-GEP (i31-GEP) neural network algorithm incorporating clinicopathologic features with the continuous 31-GEP score was developed using a previously reported patient cohort (n = 1,398) and validated using an independent cohort (n = 1,674). Compared with other covariates in the i31-GEP, the continuous 31-GEP score had the largest likelihood ratio (G2 = 91.3, P < .001) for predicting SLN positivity. The i31-GEP demonstrated high concordance between predicted and observed SLN positivity rates (linear regression slope = 0.999). The i31-GEP increased the percentage of patients with T1-T4 tumors predicted to have < 5% SLN-positive likelihood from 8.5% to 27.7% with a negative predictive value of 98%. Importantly, for patients with T1 tumors originally classified with a likelihood of SLN positivity of 5%-10%, the i31-GEP reclassified 63% of cases as having < 5% or > 10% likelihood of positive SLN, for a more precise, personalized, and clinically actionable SLN-positive likelihood estimate. These data suggest the i31-GEP could reduce the number of SLNBs performed by identifying patients with likelihood under the 5% threshold for performance of SLNB and improve the yield of positive SLNBs by identifying patients more likely to have a positive SLNB.
| S-EPMC8457832 | biostudies-literature