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.

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, 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 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).

scholarly journals Gene Expression Profiling in Uveal Melanoma: Five-Year Prospective Outcomes and Meta-Analysis

2020 ◽  
Vol 6 (5) ◽  
pp. 360-367
Author(s):  
Thomas M. Aaberg ◽  
Kyle R. Covington ◽  
Tony Tsai ◽  
Yevgeniy Shildkrot ◽  
Kristen M. Plasseraud ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Outcomes ◽  
Uveal Melanoma ◽  
Meta Analysis ◽  
Tumor Biology ◽  
Survival Rates ◽  
Increased Risk ◽  
Class 1 ◽  
Risk Patients ◽  
Metastatic Risk

Introduction: The prognostic 15-gene expression profile (15-GEP) test for uveal melanoma (UM) predicts metastatic risk based on primary tumor biology. Here we report outcomes from a prospective registry of 15-GEP-tested patients, and a meta-analysis with published cohorts. Objectives: Management and 5-year clinical outcomes following 15-GEP testing were evaluated. Methods: Eighty-nine patients with 15-GEP results were prospectively enrolled at four centers. Physician-recommended management plans were collected, and clinical outcomes tracked every 6 months. Results: Eighty percent of Class 1 (low-risk) patients underwent low-intensity management; all Class 2 (high-risk) patients underwent high-intensity management (p < 0.0001). Median follow-up for event-free patients was 4.9 years. Five Class 1 (10%) and 23 Class 2 (58%) tumors metastasized (p < 0.0001). Five-year Class 1 and 2 metastasis-free survival rates were 90% (81–100%) and 41% (27–62%; p < 0.0001), and melanoma-specific survival rates were 94% (87–100%) and 63% (49–82%; p = 0.0007). Class 2 was the only independent predictor of metastasis and was associated with increased risk for metastasis and mortality by meta-analysis. Conclusions: UM patient management is guided by 15-GEP testing. Class 2 patients were managed more intensely, in accordance with an observed metastatic rate of >50%; Class 1 patients were safely spared intensive surveillance, resulting in appropriate utilization of healthcare resources.

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 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 Intratumor Heterogeneity in Uveal Melanoma BAP-1 Expression

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1143
Author(s):  
Gustav Stålhammar ◽  
Hans E. Grossniklaus
Keyword(s):  
Gene Expression ◽  
Uveal Melanoma ◽  
Tumor Size ◽  
Hot Spots ◽  
Malignant Tumors ◽  
Intratumor Heterogeneity ◽  
Prognostic Information ◽  
Size Category ◽  
Cold Spots ◽  
Metastatic Risk

Malignant tumors are rarely homogenous on the morphological, genome, transcriptome or proteome level. In this study, we investigate the intratumor heterogeneity of BAP-1 expression in uveal melanoma with digital image analysis of 40 tumors. The proportion of BAP-1 positive cells was measured in full tumor sections, hot spots, cold spots and in scleral margins. The mean difference between hot spots and cold spots was 41 percentage points (pp, SD 29). Tumors with gene expression class 1 (associated with low metastatic risk) and 2 (high metastatic risk) had similar intratumor heterogeneity. Similarly, the level of intratumor heterogeneity was comparable in tumors from patients that later developed metastases as in patients that did not. BAP-1 measured in any tumor region added significant prognostic information to both American Joint Committee on Cancer (AJCC) tumor size category (p ≤ 0.001) and gene expression class (p ≤ 0.04). We conclude that there is substantial intratumor heterogeneity in uveal melanoma BAP-1 expression. However, it is of limited prognostic importance. Regardless of region, analysis of BAP-1 expression adds significant prognostic information beyond tumor size and gene expression class.

High PTP4A3 Phosphatase Expression Correlates with Metastatic Risk in Uveal Melanoma Patients

2010 ◽  
Vol 71 (3) ◽  
pp. 666-674 ◽  
Author(s):  
Cécile Laurent ◽  
Fabien Valet ◽  
Nathalie Planque ◽  
Licia Silveri ◽  
Selma Maacha ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Melanoma Patients ◽  
Metastatic Risk

Development of a Streamlined, Non-invasive Robotic Radiosurgery Method for Treatment of Uveal Melanoma

2008 ◽  
Vol 7 (5) ◽  
pp. 369-373 ◽  
Author(s):  
Alexander Muacevic ◽  
Martin Nentwich ◽  
Berndt Wowra ◽  
Sibylle Staerk ◽  
Anselm Kampik ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Treatment Plan ◽  
Three Dimensional ◽  
Ct Scanning ◽  
Single Session ◽  
Image Guided ◽  
Robotic Radiosurgery ◽  
Retrobulbar Anaesthesia ◽  
Treat All

To analyze the feasibility and safety of frameless, image-guided robotic radiosurgery against uveal melanoma, we developed a streamlined procedure that is completed within 3 hours under retrobulbar anesthesia without immobilization. Twenty patients (10 men and 10 women) with medium (3–5-mm prominence) and large (>5-mm prominence) unilateral uveal melanomas were treated with a frameless robotic radiosurgery system. Median age was 61 years (range 32–78 years). All patients underwent a single-session procedure beginning with retrobulbar anaesthesia, followed by computerized tomography (CT) scanning that was used in the generation of a treatment plan, and then the delivery of a radiosurgical tumor dose between 18 and 22 Gy to the 70% isodose line. Three-dimensional treatment planning was aimed at securing the optical lens and the optic disc as much as possible. Follow-up occurred at 3, 6, 12, and 18 months after the radiosurgery with clinical, ultrasound, and CT studies. We were able to treat all patients in the frameless setup within 3 hours. In five patients with lateral and dorsal tumors, the dose to the optic lens could be kept below 2 Gy. The clinical response was evaluated for the first seven patients treated with a follow-up of at least 6 months. No local recurrences occurred with any of the clinically evaluated patients for a mean 13-month follow-up (range 6–22 months). Maximum median apical tumor height according to standardized A-scan ultrasound evaluations decreased from 7.7 to 5.6 mm (p < 0.1). The median reflectivity increased from 41% to 70% (p < 0.01). None of the patients developed a secondary glaucoma during the short-term follow-up period. Frameless, single-session, image-guided robotic radiosurgery is a feasible, safe and comfortable treatment option for patients with uveal melanoma. Longer follow-up and analysis of a larger patient series is required for definitive clinical recommendations.

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