Gene expression profile signature (DecisionDx-Melanoma) to predict visceral metastatic risk in patients with stage I and stage II cutaneous melanoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8543-8543 ◽  
Author(s):  
Navneet Dhillon ◽  
Anna R Rogers ◽  
Keith A. Delman ◽  
Derek Maetzold ◽  
Kristen M. Oelschlager ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cutaneous Melanoma ◽  
Stage I ◽  
Partition Tree ◽  
Tree Analysis ◽  
Risk Class ◽  
Class 1 ◽  
Visceral Metastases ◽  
Metastatic Risk

8543 Background: The current AJCC TNM staging system has poor specificity for predicting visceral metastatic risk in patients diagnosed with stage I or stage II cutaneous melanoma. We, therefore, developed a gene expression profile signature (GEP) following in silico investigation of previously published microarray analyses. Methods: 60 formalin fixed paraffin embedded primary cutaneous melanoma samples from patients with stage I or II cutaneous melanoma with at least a follow up period of at least 6 years were macrodissected and analyzed blindly. RNA was isolated, converted to cDNA and RT-PCR was performed to assess the expression of the gene set. Expression data and biostatistical analysis was performed using GeNorm and JMP Genomics (SAS) Predictive modeling included Radial Basis Machine (RBM) and Partition Tree Analysis (PTA) Metastasis-free survival (MFS) was assessed using Kaplan-Meier analysis. The following clinical data was retrieved from medical records: survival, metastases, types of metastases. 20 out of 60 patients had developed visceral metastases in the follow up period. Results: GEP was developed following multiple analytical approaches.Two types of signatures emerged: Low risk (Class 1) and High risk (Class 2). Without optimizing for sensitivity, the analyses of the 60 sample cohort by radial basis machine (RBM) resulted in 92% ROC (met. accuracy = 90%, non-met. accuracy = 85%), while partition tree analysis (PTA) yielded 99% ROC (met. accuracy = 100%, non-met. accuracy = 95%). RBM classification showed 6-year MFS rates of 97% for Class 1 and 19% for predicted Class 2 of metastasis (median MFS = NR and 5.6 yrs, resp., P<0.0001 Log-Rank respectively). PTA showed 6-year MFS rates of 100% for predicted Class 1 and 14% for Class 2 of metastasis (median MFS = NR and 5.4 yrs, resp., P<0.0001 Log-Rank respectively). Conclusions: This study shows that DecisionDx-Melanoma GEP signature can provide excellent accuracy in predicting metastatic risk in stage I and II cutaneous melanoma.To our knowledge, the GEP provides the most accurate predictor to date for development of visceral metastases in patients with Stage I and II cutaneous 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 Long-Term Outcomes in a Multicenter, Prospective Cohort Evaluating the Prognostic 31-Gene Expression Profile for Cutaneous Melanoma

2021 ◽  
pp. 589-601
Author(s):  
Eddy C. Hsueh ◽  
James R. DeBloom ◽  
Jonathan H. Lee ◽  
Jeffrey J. Sussman ◽  
Kyle R. Covington ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Distant Metastasis ◽  
Cutaneous Melanoma ◽  
Stage I ◽  
Free Survival ◽  
Metastatic Risk ◽  
Ajcc Staging

PURPOSE Current 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 METHODS Two 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). RESULTS The 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. CONCLUSION These 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.

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.

Molecular profiling and clinical characteristic of malignant melanoma in younger patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22087-e22087
Author(s):  
Jomjit Chantharasamee ◽  
Karlton Wong ◽  
Bartosz Chmielowski
Keyword(s):  
Gene Expression ◽  
General Population ◽  
Uveal Melanoma ◽  
Cutaneous Melanoma ◽  
Stage I ◽  
Stage Iii ◽  
Younger Patients ◽  
Adjuvant Immunotherapy ◽  
Better Than

e22087 Background: Combination of clinical and molecular data has not yet been well established in adolescent and younger adult patients with melanoma Methods: We performed a retrospective analysis of the molecular profiles and clinical outcome of patients diagnosed at the age younger than 40 treated at UCLA during 2010 to 2019. Patient’s molecular profile, characteristics, and treatment outcome were described using descriptive statistic. Kaplan-Meier curve was used for disease-free survival (DFS) and overall survival (OS). Results: 150 patients with a median age of 29 year (12-39) were analyzed. 101 (67.3%) patients had cutaneous melanoma, 49 (32.7%) had localized uveal melanoma. Of those 101, 23.8% had pre-existing benign or congenital nevus. 70/101 (69.3%) was stage I-II, 26/101 (25.7%) stage III and 5/101 (4.9%) stage IV. Of those 37 patients with molecularly characterized tissue, 23 (62%) had BRAF mutation including 17 V600E, 4 V600 unknown codon, 2 G469A, 2 NRAS and 1 NF-1 mutation. 11/37 were BRAF negative. 79.6% of patients who were not tested were stage I. For patients with stage III, 16/26 (61%) received adjuvant immunotherapy, none of adjuvant targeted therapy. At 35.1 months follow-up time, 27/96 (28%) localized cutaneous melanoma experienced relapse. 1-year DFS was 73% in adjuvant vs. 90% in no adjuvant immunotherapy group. Among 49 uveal melanoma patients, the median age was 27 years old. 23/49 (49%) had a T1 tumor, 18/49 (36.7%) T2, 6/49(12.2%) T3, 1/49(2%) T4. At 45 months follow-up time, three (6.1%) patients developed metastasis. 5-year DFS and OS was 90% and 100%, respectively. 45 patients had tissue for gene expression profiling and/or FISH testing. 15/45 (33%) had class IA, 13/45 (28%) had class IB, and 8/45 (17.7%) had class 2. 24 samples were analyzed by FISH: 14 with disomy 3, 5 with complex disomy 3 with gain of chromosome 6 or 8, and 5 with monosomy 3. Conclusions: Similarly to general population, most of younger patients with melanoma are diagnosed with stage I disease. Among patients with stage III melanoma treated with adjuvant immunotherapy 1-year DFS was comparable to the general population. Patients with stage III who did not receive adjuvant therapy had an excellent DFS which confirms that the decision on selecting patients for treatment was appropriate. The prognosis of younger patients with uveal melanoma was much better than predicted by molecular testing, and much better than expected regardless of gene expression profile or cytogenetic testing.

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).

A 19-gene prognostic GEP signature (DecisionDx-Thymoma) to determine metastatic risk associated with thymomas.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7106-7106
Author(s):  
Yesim Gokmen-Polar ◽  
Chirayu Pankaj Goswami ◽  
Robert W. Cook ◽  
Kristen M. Oelschlager ◽  
Derek Maetzold ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Risk ◽  
Gene Signature ◽  
Pcr Analysis ◽  
Rt Pcr ◽  
Risk Class ◽  
Metastatic Behavior ◽  
Class 1 ◽  
Rare Malignancy ◽  
Metastatic Risk

7106 Background: The treatment of thymomas is predominantly based on the stage of disease. Histologic classification is of limited value as all types of thymomas can give rise to metastases. In order to better predict the metastatic behavior of these tumors, we performed genome-wide gene expression analysis and identified a set of genes associated with presence or absence of metastases. In the current study, we sought to further develop and validate the gene signature using quantitative RT-PCR analysis. Methods: Thymomas with archived blocks and long-term follow-up data were reviewed. This training set study consisted of 50 cases, including 34 cases on which the discovery microarray analysis had been performed. RNA was extracted from 5 x 10-micron thick sections in a CAP-accredited CLIA certified laboratory and analyzed by RT-PCR using custom TLDA cards on an ABI7900HT instrument. Expression data and biostatistical analysis were performed using GeNorm and JMP Genomics (SAS). Predictive modeling using Partition Tree Analysis (PTA) and Logistic Regression Analysis (LRA) was performed. Metastasis-free survival (MFS) was assessed using Kaplan-Meier analysis. Results: A 19-gene expression profile (GEP) signature was developed using a cohort of 50 thymomas for predicting metastasis. PTA yielded ROC of 0.97 (met. accuracy = 96%, non-met. accuracy = 81%), while LRA yielded ROC of 0.895 (met. accuracy = 87%, non-met. accuracy = 85%). PTA classification showed 5-year MFS rates of 100% and 31% for predicted low risk (Class 1) and high risk (Class 2) of metastasis (median MFS = NR and 4.1 yrs, resp., P<0.0001 Log-Rank), respectively. LRA showed 5-year MFS rates of 100% and 17% for predicted Class 1 and high risk Class 2 of metastasis (median MFS = NR and 2.9 yrs, resp., P<0.0001 Log-Rank), respectively. Analysis of additional cohorts is ongoing. Conclusions: We have successfully completed development of a 19-gene signature (DecisionDx-Thymoma) that appears to predict metastatic behavior of thymomas more accurately than traditional staging. If validated in larger cohort, this signature will provide insight for the future management of patients with this rare malignancy.

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.

The impact of ultrasound scanning in the staging and follow-up of patients with clinical stage i cutaneous melanoma

1997 ◽  
Vol 33 (2) ◽  
pp. 200-203 ◽  
Author(s):  
C.R. Rossi ◽  
A Seno ◽  
A. Vecchiato ◽  
M. Foletto ◽  
A. Tregnaghi ◽  
...  
Keyword(s):  
Cutaneous Melanoma ◽  
Clinical Stage ◽  
Stage I ◽  
Ultrasound Scanning ◽  
The Impact

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.

First Recurrence Analysis of 840 Cutaneous Melanomas: A Proposal for a Follow-Up Schedule

1994 ◽  
Vol 80 (3) ◽  
pp. 188-197 ◽  
Author(s):  
Laura Martini ◽  
Paola Brandani ◽  
Cristina Chiarugi ◽  
Umberto M. Reali
Keyword(s):  
Cutaneous Melanoma ◽  
Primary Melanoma ◽  
Neck Region ◽  
Stage I ◽  
Lower Limbs ◽  
Depth Of Invasion ◽  
Number Of Patients ◽  
Melanoma Patients ◽  
First Recurrence

Aims and background A correct follow-up schedule for patients who underwent an excision for stage I cutaneous melanoma might allow the early detection of local and distant metastases. At present, there is no general agreement on follow-up protocols. In order to work out a follow-up guide, we have retrospectively evaluated the records of 840 stage I cutaneous melanoma patients surgically treated and followed during the postoperative period in the Division of Plastic Surgery of the University of Florence from 1975 to 1992. Methods We evaluated the patients’ records by analyzing time, pathway and site of any first recurrence in relation to the main prognostic factors such as patient sex, site, histological type and depth of invasion of each primary melanoma. A statistical analysis was performed. Results To summarize, the salient results were the following: 80% of relapses occurred in the first 3 years and they occurred significantly earlier when the primary melanoma was localized in the trunk and significantly later when the melanoma was localized in the lower limbs and for < 1.5 mm lesions. The first recurrence occurred earlier by the lymphatic than by the hematic pathway regarding the overall number of patients. The hematic pathway was the most frequent (with respect to the overall percentage of hematic metastases) for the melanomas localized in the head and neck region and for lentigo malignant melanomas, whereas the lymphatic pathway was most frequent for melanomas of the lower limbs and > 3 mm in thickness. Conclusions We suggest a follow-up schedule taking into consideration the postoperative behavior of stage I cutaneous melanoma patients (in terms of time and pathway of the first recurrence) in relation to the site and depth of invasion of the tumor.

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