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 ◽  
...  

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).

2018 ◽  
Vol 2 (2) ◽  
pp. 111-121 ◽  
Author(s):  
Larry D Dillon ◽  
Joseph E Gadzia ◽  
Robert S Davidson ◽  
Michael McPhee ◽  
Kyle R Covington ◽  
...  

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.


2020 ◽  
Vol 7 (1) ◽  
pp. 17-25 ◽  
Author(s):  
Amy C Schefler ◽  
Alison Skalet ◽  
Scott C N Oliver ◽  
John Mason ◽  
Anthony B Daniels ◽  
...  

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.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8543-8543 ◽  
Author(s):  
Navneet Dhillon ◽  
Anna R Rogers ◽  
Keith A. Delman ◽  
Derek Maetzold ◽  
Kristen M. Oelschlager ◽  
...  

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.


2020 ◽  
Vol 6 (5) ◽  
pp. 360-367
Author(s):  
Thomas M. Aaberg ◽  
Kyle R. Covington ◽  
Tony Tsai ◽  
Yevgeniy Shildkrot ◽  
Kristen M. Plasseraud ◽  
...  

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.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7106-7106
Author(s):  
Yesim Gokmen-Polar ◽  
Chirayu Pankaj Goswami ◽  
Robert W. Cook ◽  
Kristen M. Oelschlager ◽  
Derek Maetzold ◽  
...  

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.


2017 ◽  
Vol 5 (2) ◽  
pp. 163
Author(s):  
Mohammed Al Moaleem ◽  
Abdulrahman A Mobaraky ◽  
Hassan A Madkhali ◽  
Muneera R Gohal ◽  
Amna M Mobaraki ◽  
...  

Statement of the problem: restoring endodontically treated teeth (ETT) is one of the major treatments provided by a dentist. Glass fiber posts (GFP) showed good clinical performance during last few years.Aim of the study; to assess and compare the clinical as well as the radiographic performance of different types of ceramic crown systems used in restoration of maxillary anterior teeth over a cemented GFP and composite resin core.Materials and methods: 50 ETT with GFP were included in this study. These teeth were divided into four gropes (composite resin. Porcelain fused to metal (PFM), e. max and zirconia restorations). Both the clinical and radiographic assessments were done for the restoration at a period of one week, 3, 6, 9, and 12 months after composite build up and crown's cementations. All data were registered and analyzed by SPSS program using percentages and Kaplan-Meyer analysis. Fisher’s exact test was used for categorical values while log-rank test was used for descriptive statistical analysis.Results: the clinical assessment showed no changes in the one week, 3 and 6 months in the four groups. While during the 9 and 12 months, a movement of the crown margin under finger pressure was present in one case, loss or retention in 2 cases of zirconia, the periodontal status with violation of biological width was present in one case of PFM and finally the color changes were obvious in one case of PFM and 2 cases of composite restoration. All the restorations in the four groups had no radiographic changes in the one week and three-month assessments. While during six-month follow-up, a loosed of retention in one case of the zirconia crown was detected. At the 9 and 12 months, two cases showed recurrent caries at the cervical margin of the composite restoration, cases with periapical infection and other with loss of retention of the post were recorded in the PFM restoration.Conclusion: e. Max and zirconia all ceramic crowns showed better clinical and radiographic performance than the PFM and composite restorations over 12 months recall.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9003-9003 ◽  
Author(s):  
R. J. Sullivan ◽  
Y. Hoshida ◽  
J. Brunet ◽  
S. Tahan ◽  
J. Aldridge ◽  
...  

9003 Background: HD IL-2 remains one of two FDA-approved therapies for the treatment of patients (pts) with advanced melanoma. Initial studies conducted 15–20 years ago reported 16% response rate with 8% of pts achieving durable responses. The toxicity of HD IL-2 limits its application to pts treated in specialized centers. We present the clinical outcome of pts treated over a recent 2 year period with HD IL-2 at a single institution and an associated retrospective pilot study evaluating the predictive value of a novel tumor gene expression signature. Methods: Clinical and radiological data were collected and analyzed on 49 consecutive pts treated with HD IL-2 at Beth Israel Deaconess Medical Center from 10/05 - 10/07. Response was evaluated via RECIST. Formalin-fixed paraffin embedded tumor was obtained on consenting pts and classified as either Class 1, defined by melanocyte-specific genes including MITF, or Class 2, represented by immune genes, using the DNA-mediated Annealing, Selection, and Ligation (DASL) technique. Two-sided Fisher's Exact test was used to compare the proportion of responses for pts in the two classes. Results: Clinical response occurred in 16 of the 49 pts (32.6%), with 5 pts (10.2%) having a CR. Two other pts had stable disease > 12 mos; 3 pts who progressed after response had resection to NED. 10 pts remain disease/progression free at a minimum of 16 mos following treatment. 28 pts (including 13 of 16 responders) had sufficient tumor for DASL analysis. Among the 21 categorized as Class 1, 7 (33%) were responders. Of the 7 classified as Class 2, 6 (86%) were responders. This difference in response was statistically significant (p = 0.0286). Conclusions: The overall and CR rates in a contemporary series of pts with metastatic melanoma treated with HD IL-2 are twice that reported in initial studies suggesting some treatment selection on clinical grounds since the 1990s. Pts with tumors expressing an immune signature by DASL appeared more likely to respond. This finding requires prospective validation, but suggests immune-related gene expression might contribute to IL-2 responsiveness. [Table: see text]


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9576-9576
Author(s):  
John T. Vetto ◽  
Sancy Ann Leachman ◽  
Brooke Middlebrook ◽  
Kyle R. Covington ◽  
Jeffrey D. Wayne ◽  
...  

9576 Background: Accurate prognostication of distant metastatic risk using sentinel lymph node (SLN) biopsy for CM can be challenging in melanomas of the head and neck due to a higher false negative rate compared to other anatomical areas. A GEP signature that predicts metastatic risk based on primary tumor biology, providing a binary outcome of Class 1 (low risk of metastasis) or Class 2 (high risk), was previously described. The prognostic capabilities of the GEP independently and in combination with SLN status in a cohort of patients with primary head and neck CM are assessed here. Methods: All samples and clinical data were collected under an IRB-approved multicenter protocol. qPCR analysis was used to assess expression of the gene signature (Class 1 vs. Class 2). Distant metastasis-free survival (DMFS) and melanoma-specific survival (MSS) were assessed. Results: 157 subjects with primary CMs in the head and neck region were identified. 110 of 157 subjects had a SLN biopsy performed. Median age was 65 years (range 25-89) and median Breslow depth was 1.6 mm (range 0.2-15.0 mm). In 71 SLN-negative patients, 18 of 27 (67%) distant metastatic events were GEP Class 2. Overall, 73% (47 of 64) distant metastases, and 88% (22 of 25) deaths due to CM were called Class 2. By comparison, sensitivities for DMFS and MSS were 41% (26 of 64) and 52% (13 of 25), respectively, using SLN biopsy alone, and increased to 80% (51 of 64) and 88% (22 of 25), respectively, when combining the SLN status and GEP class. Kaplan-Meier 5-year DMFS and MSS rates based on SLN status alone or in combination with GEP are shown in the table. Conclusions: These data support the ability of the GEP test to accurately identify low- and high-risk cases of head and neck melanoma. The results strongly support the role of GEP testing to enhance current staging by better predicting the risk of distant metastasis and death for patients with melanoma in an anatomic region that is associated with a higher SLN biopsy false negative rate. [Table: see text]


2021 ◽  
Author(s):  
Sherri Borman ◽  
Jeff Wilkinson ◽  
Lauren Meldi-Sholl ◽  
Clare Johnson ◽  
Kelsey Carter ◽  
...  

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.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii225-ii225
Author(s):  
Anupam Rishi ◽  
Homan Mohammadi ◽  
Daniela Martir ◽  
Eric Welsh ◽  
Timothy Robinson ◽  
...  

Abstract OBJECTIVE Tumor-associated microglia and macrophages (TAMs) influence brain tumor biology and promote tumor-proliferating phenotype. Studies have shown these cell types predict outcomes in various tumor sites with limited evidence in high-grade gliomas (HGG). In this study, we assessed the presence of immune cell infiltrate (ICI) and overall survival (OS) in HGGs. METHODS A total of 97 consecutively treated patients with primary HGG with complete gene expression profiling were identified from our IRB-approved institutional tissue biorepository. Patients underwent primary surgical resection between 02/2004 and 03/2011. Gene expression levels were assessed by Affymetrix Hu-RSTA assays (Affymetrix; Santa Clara, CA). CIBERSORT estimated the presence of ICI via gene expression deconvolution. Tumor characteristics and the presence of 22 individual ICI subtypes were assessed with respect to OS. Time-to-event analyses were performed with Kaplan-Meier estimates and compared via log-rank test. Associations between the ICI and outcomes were explored using Cox-regression. P&lt; 0.05 (two-tailed) was considered statistically significant. RESULTS Median follow-up from primary surgical resection was 12.8 months (range: 0.1-162.8), and median age was 58 years (20-85). Most patients were male (n=63; 65%) and had grade 4 tumors (n=71; 73%). OS differed by grade with 24-month actuarial OS rates of 81% and 34% (P&lt; 0.0001) for grade 3 and 4 gliomas, respectively. The presence of M0 (HR 2.2; 95% CI 1.4-3.6; P=0.001), M1 (HR 1.8; 95%CI 1.1-2.9; P=0.01), and M2 macrophages (HR 1.9; 95%CI 1.2-3.2; P=0.007) predicted OS. No other ICI subtypes were predictive of OS. The presence of M0- and M2-polarized macrophages were more common in grade 4 compared to grade 3 gliomas 46% vs. 11% (P=0.002) and 69% vs. 31% (P=0.0007), respectively. CONCLUSION The increased presence of non-polarized or M2 TAMs within the glioma microenvironment was significantly associated with OS in HGG. Their presence may serve as unique stratification and a potential therapeutic target.


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