scholarly journals Prospective, Multicenter Clinical Impact Evaluation of a 31-Gene Expression Profile Test for Management of Melanoma Patients

2018 ◽  
Vol 2 (2) ◽  
pp. 111-121 ◽  
Author(s):  
Larry D Dillon ◽  
Joseph E Gadzia ◽  
Robert S Davidson ◽  
Michael McPhee ◽  
Kyle R Covington ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Tumor Biology ◽  
Primary Melanoma ◽  
Risk Class ◽  
Class 1 ◽  
Post Test ◽  
Melanoma Patients ◽  
And Performance

Objective: A 31-gene expression profile (GEP) test that has been clinically validated identifies melanoma patients with low (Class 1) or high (Class 2) risk of metastasis based on primary tumor biology.  This study aimed to prospectively evaluate the test impact on clinical management of melanoma patients.Methods:  Physicians at 16 dermatology, surgical or medical oncology centers examined patients to assess clinical features of the primary melanoma.  Recommendations for clinical follow-up and surveillance were collected.  Following consent of the patient and performance of the GEP test, recommendations for management were again collected, and pre- and post-test recommendations were assessed to determine changes in management resulting from the addition of GEP testing to traditional clinicopathologic risk factors.   Results:  Post-test management plans changed for 49% (122 of 247) of cases in the study when compared to pre-test plans. Thirty-six percent (66 of 181) of Class 1 cases had a management change, compared to 85% (56 of 66) of Class 2 cases.  GEP class was a significant factor for change in care during the study (p<0.001), with Class 1 accounting for 91% (39 of 43) of cases with decreased management intensity, and Class 2 accounting for 72% (49 of 68) of cases with increases.Conclusions: The reported study show that the 31-gene GEP test improves net health outcomes in the management of cutaneous melanoma.  Physicians used test results to guide risk-appropriate changes that match the biological risk of the tumor, including directing more frequent and intense surveillance to high-risk, Class 2 patients.

scholarly journals Analytical validity of DecisionDx-SCC, a gene expression profile test to identify risk of metastasis in cutaneous squamous cell carcinoma (SCC) patients

2021 ◽  
Author(s):  
Sherri Borman ◽  
Jeff Wilkinson ◽  
Lauren Meldi-Sholl ◽  
Clare Johnson ◽  
Kelsey Carter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Squamous Cell ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Risk Class ◽  
Class 1

Abstract Background To improve identification of patients with cutaneous squamous cell carcinoma (SCC) at high risk for metastatic disease, the DecisionDx-SCC assay, a prognostic 40-gene expression profile (40-GEP) test, was developed and validated. The 40-GEP assay utilizes RT-PCR gene expression analysis on primary tumor biopsy tissue to evaluate the expression of 34 signature gene targets and 6 normalization genes. The test provides classifications of low risk (Class 1), moderate risk (Class 2A), and high risk (Class 2B) of metastasis within 3 years of diagnosis. The primary objective of this study was to validate the analytical performance of the 40 gene expression signature. Methods The repeatability and reproducibility of the 40-GEP test was evaluated by performance of inter-assay, intra-assay, and inter-operator precision experiments along with monitoring the reliability of sample and reagent stability for class call concordance. The technical performance of clinical orders from September 2020 through July 2021 for the 40-GEP test was assessed. Results Patient hematoxylin and eosin (H&E) stained slides were reviewed by a board-certified pathologist to assess minimum acceptable tumor content. Class specific controls (Class 1 and Class 2B) were evaluated with Levey Jennings analysis and demonstrated consistent and reproducible results. Inter-assay, inter-operator and intra-assay concordance were all ≥90%, with short-term and long-term RNA stability also meeting minimum concordance requirements. Of the 2,446 orders received, 93.4% remained eligible for testing, with 96.8% of all tested samples that completed the assay demonstrating actionable class call results. Conclusion DecisionDx-SCC demonstrates a high degree of analytical precision, yielding high concordance rates across multiple performance experiments, along with exhibiting robust technical reliability on clinical samples.

scholarly journals Integrating the melanoma 31-gene expression profile test to surgical oncology practice within national guideline and staging recommendations

2020 ◽  
Author(s):  
David M Hyams ◽  
Kyle R Covington ◽  
Clare E Johnson ◽  
Kristen M Plasseraud ◽  
Robert W Cook
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Surgical Oncology ◽  
Stage I ◽  
Test Results ◽  
Risk Class ◽  
Class 1 ◽  
Oncology Practice

Aim: Define changes in clinical management resulting from use of the prognostic 31-gene expression profile (31-GEP) test for cutaneous melanoma in a surgical oncology practice. Patients & methods: Management plans for 112 consecutively tested patients with stage I–III melanoma were evaluated for duration and number of clinical visits, blood work and imaging. Results: 31-GEP high-risk (class 2; n = 46) patients received increased management compared with low-risk (class 1; n = 66) patients. Test results were most closely associated with follow-up and imaging. Of class 1 patients, 65% received surveillance intensity within guidelines for stage I–IIA patients; 98% of class 2 patients received surveillance intensity equal to stage IIB–IV patients. Conclusion: We suggest clinical follow-up and metastatic screening be adjusted according to 31-GEP test results.

scholarly journals The 31-gene expression profile stratifies recurrence and metastasis risk in patients with cutaneous melanoma

2021 ◽  
Author(s):  
Abel Jarell ◽  
Basil Skenderis ◽  
Larry D Dillon ◽  
Kelsey Dillon ◽  
Brian Martin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Primary Melanoma ◽  
Stage I ◽  
Molecular Signature ◽  
Significant Independent Predictor ◽  
Free Survival ◽  
Risk Class ◽  
Metastatic Recurrence

Aim: Sentinel node biopsy is a prognostic indicator of melanoma recurrence. We hypothesized that adding the primary melanoma molecular signature from the 31-gene expression profile (31-GEP) test could refine the risk of recurrence prognosis for patients with stage I–III melanoma. Materials & methods: Four hundred thirty-eight patients with stage I–III melanoma consecutively tested with the 31-GEP were retrospectively analyzed. The 31-GEP stratified patients as low-risk (Class 1A), intermediate-risk (Class 1B/2A) or high risk (Class 2B) of recurrence or metastasis. Results: The 31-GEP significantly stratified patient risk for recurrence-free survival (p < 0.001), distant metastasis-free survival (p < 0.001) and melanoma-specific survival (p < 0.001) and was a significant, independent predictor of metastatic recurrence (hazard ratio: 5.38; p = 0.014). Conclusion: The 31-GEP improves prognostic accuracy in stage I–III melanoma.

scholarly journals Prospective evaluation of risk-appropriate management of uveal melanoma patients informed by gene expression profiling

2020 ◽  
Vol 7 (1) ◽  
pp. 17-25 ◽  
Author(s):  
Amy C Schefler ◽  
Alison Skalet ◽  
Scott C N Oliver ◽  
John Mason ◽  
Anthony B Daniels ◽  
...  
Keyword(s):  
Gene Expression ◽  
Uveal Melanoma ◽  
Clinical Utility ◽  
Medical Oncology ◽  
Treatment Plan ◽  
Risk Class ◽  
Class 1 ◽  
Melanoma Patients ◽  
Metastatic Risk

Aim: The Clinical Application of DecisionDx-UM Gene Expression Assay Results study aimed to evaluate the clinical utility of the prognostic 15-gene expression profile (15-GEP) test for uveal melanoma (UM) patients in a large, prospective multicenter cohort. Patients & methods: Nine centers prospectively enrolled 138 UM patients clinically tested with the 15-GEP. Physician-recommended specialty referrals and metastatic surveillance regimens were collected. Results: A total of 93% of high-risk class 2 patients were referred to medical oncology for follow-up, compared with 51% of class 1 patients. A majority (62%) of class 2 patients were recommended overall high-intensity metastatic surveillance, while 85% of class 1 patients were recommended low-intensity metastatic surveillance. Conclusion: Treatment plan recommendations for UM patients are aligned with GEP-informed metastatic risk, consistent with prior studies.

scholarly journals Clinical Performance and Management Outcomes with the DecisionDx-UM Gene Expression Profile Test in a Prospective Multicenter Study

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Kristen Meldi Plasseraud ◽  
Robert W. Cook ◽  
Tony Tsai ◽  
Yevgeniy Shildkrot ◽  
Brooke Middlebrook ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Performance ◽  
Tumor Biology ◽  
Metastatic Potential ◽  
Rank Test ◽  
Risk Class ◽  
Exact Test ◽  
Oncology Clinical Trial ◽  
Class 1 ◽  
Metastatic Risk

Uveal melanoma management is challenging due to its metastatic propensity. DecisionDx-UM is a prospectively validated molecular test that interrogates primary tumor biology to provide objective information about metastatic potential that can be used in determining appropriate patient care. To evaluate the continued clinical validity and utility of DecisionDx-UM, beginning March 2010, 70 patients were enrolled in a prospective, multicenter, IRB-approved study to document patient management differences and clinical outcomes associated with low-risk Class 1 and high-risk Class 2 results indicated by DecisionDx-UM testing. Thirty-seven patients in the prospective study were Class 1 and 33 were Class 2. Class 1 patients had 100% 3-year metastasis-free survival compared to 63% for Class 2 (log rank testp=0.003) with 27.3 median follow-up months in this interim analysis. Class 2 patients received significantly higher-intensity monitoring and more oncology/clinical trial referrals compared to Class 1 patients (Fisher’s exact testp=2.1×10-13andp=0.04, resp.). The results of this study provide additional, prospective evidence in an independent cohort of patients that Class 1 and Class 2 patients are managed according to the differential metastatic risk indicated by DecisionDx-UM. The trial is registered with Clinical Application of DecisionDx-UM Gene Expression Assay Results (NCT02376920).

Clinical Impact of a 31-Gene Expression Profile Test on Physician Recommendations for Management of Melanoma Patients in a Prospectively Tested Cohort

2017 ◽  
Vol 1 ◽  
pp. s107
Author(s):  
Martin Fleming ◽  
Clare Johnson ◽  
Kyle Covington ◽  
Joseph Gadzia ◽  
Larry Dillon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Clinical Impact ◽  
Melanoma Patients ◽  
Physician Recommendations

Abstract Not AvailableStudy supported by Castle Biosciences.

scholarly journals Genes and biological functions governing intrinsic tumor biology utilized in cutaneous melanoma risk assessment through a clinically available 31-gene expression profile test

2019 ◽  
Vol 3 (2) ◽  
pp. 165
Author(s):  
Sarah J Kurley ◽  
Kyle R Covington ◽  
Kristen M Plasseraud ◽  
Et Al.
Keyword(s):  
Gene Expression ◽  
Risk Assessment ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Cutaneous Melanoma ◽  
Tumor Biology ◽  
Biological Functions ◽  
Melanoma Risk

Abstract not available. Disclosures: Study sponsored by Castle Biosciences.

Performance of a 31-gene expression profile in a previously unreported cohort of 334 cutaneous melanoma patients.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 9581-9581 ◽  
Author(s):  
Jonathan S. Zager ◽  
Jane Messina ◽  
Vernon K. Sondak ◽  
Laura Ferris ◽  
Robert W. Cook ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Cutaneous Melanoma ◽  
Melanoma Patients

Performance of a prognostic 31-gene expression profile test in stage III cutaneous melanoma subjects.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9578-9578
Author(s):  
Martin D. Fleming ◽  
Brooke Middlebrook ◽  
Kyle R. Covington ◽  
Pedram Gerami ◽  
Jeffrey D. Wayne ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Risk ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Distant Metastasis ◽  
Cutaneous Melanoma ◽  
Stage Iii ◽  
Melanoma Metastasis ◽  
Stage Iiia ◽  
Class 1

9578 Background: The management of stage III cutaneous melanoma (CM) patients has changed significantly with the introduction of contemporary therapies. A 31-gene expression profile (GEP) test that provides a prediction of low or high risk of melanoma metastasis has been validated as an independent prognosticator of distant metastasis-free (DMFS) and melanoma-specific survival (MSS). We examine the prognostic accuracy of the test in a cohort of stage III, and particularly stage IIIA, subjects from a multicenter validation study. Methods: 207 primary CM tumors from 16 centers were analyzed as part of an IRB-approved study. Quantitative RT-PCR and predictive modeling were performed to classify metastasis and survival risk as Class 1 (low risk) or Class 2 (high risk). Results for Kaplan-Meier and Cox regression survival analysis are reported. Results: Of the 207 subjects with stage III melanoma, 76 were stage IIIA. The table shows 5-year DMFS and MSS rates for all stage III and stage IIIA groups. Patients with Class 2 GEP had significantly worse outcomes compared to Class 1. In univariate analyses, GEP was a significant predictor of DMFS and MSS with a hazard ratio for DMFS of 2.8 (95%-CI; 1.7-4.6) and for MSS of 4.0 (95%-CI; 1.7-9.4) for all stage III, while HR of 2.2 for DMFS (95%-CI; 1.0-4.7) and 4.3 for MSS (95%-CI; 1.2-15.2) were observed for the stage IIIA group. For all stage III cases, Breslow thickness and GEP were significant predictors of DMFS and MSS in multivariate models including ulceration and mitotic rate (p < 0.05). Conclusions: The results support the capability of the GEP to accurately predict stage III distant metastasis and survival, and that the test complements existing prognostic factors. GEP testing may be useful in identifying stage IIIA patients who are appropriate for adjuvant therapies and/or enrollment in clinical trials. [Table: see text]

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