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.

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).

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.

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.

Sarcomas of Soft Tissue and Bone

2011 ◽  
Author(s):  
Adam Lerner ◽  
Huihong Xu ◽  
Karen H Antman
Keyword(s):  
Soft Tissue ◽  
Meta Analysis ◽  
Survival Rates ◽  
Fibrous Tissue ◽  
Soft Tissue Sarcomas ◽  
Kaposi Sarcoma ◽  
Uterine Leiomyosarcoma ◽  
Increased Risk ◽  
Bone Sarcomas ◽  
Epidemiologic Features

Sarcomas originate from bone or soft tissue. The most common bone sarcomas are osteosarcomas, Ewing sarcomas, and chondrosarcomas. Soft tissue sarcomas develop in fibrous tissue, fat, muscle, blood vessels, and nerves. Historically, soft tissue sarcomas of the trunk and extremities were reported separately from those of visceral organs (e.g., gastrointestinal and gynecologic sarcomas). This chapter discusses the classification, epidemiology, diagnosis, staging, and treatment of sarcomas of bone and cartilage, and classic soft tissue sarcomas. Management of Kaposi sarcoma, gastrointestinal stromal tumors (GISTs), mesothelioma, and rhabdomyosarcoma is also described. Figures include images of patients with osteosarcoma, liposarcoma, uterine leiomyosarcoma, GIST, and osteosarcoma in a patient with Paget disease of bone. Tables list epidemiologic features of sarcomas, a summary of sarcomas by histology, familial syndromes associated with increased risk of sarcoma, survival rates in sarcoma patients, staging of soft tissue sarcomas, and results of a meta-analysis of doxorubicin-based adjuvant chemotherapy for localized resectable soft tissue sarcoma. This chapter contains 126 references.

P960Association of peri-procedural intravenous morphine use on clinical outcomes in ST-elevation myocardial infarction treated by percutaneous coronary intervention: systematic review and meta-analysis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R Batchelor ◽  
D Liu ◽  
J Bloom ◽  
S Noaman ◽  
W Chan
Keyword(s):  
Myocardial Infarction ◽  
Systematic Review ◽  
Percutaneous Coronary Intervention ◽  
Clinical Outcomes ◽  
Odds Ratio ◽  
Meta Analysis ◽  
Coronary Intervention ◽  
Increased Risk ◽  
Percutaneous Coronary ◽  
St Elevation

Abstract Background Morphine analgesia may affect absorption of co-prescribed P2Y12 antagonists attenuating platelet inhibition. The impact of peri-procedural intravenous (IV) morphine administration on clinical outcomes in patients undergoing primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI) is not well defined. Purpose To conduct a systematic review and meta-analysis exploring clinical outcomes with peri-procedural IV morphine in patients undergoing PPCI for STEMI. Methods Analysis of the electronic databases MEDLINE, EMBASE, CENTRAL, Scopus, Web of Science and ClinicalTrials.gov for association of peri-PCI IV morphine use with myocardial infarction (MI) and mortality. Primary and secondary outcomes were in-hospital or 30-day MI and all-cause mortality respectively. Results Eleven studies (1 randomised controlled trial; 10 cohort studies) were included for systematic review. Five studies, including 3,748 patients were included in meta-analysis of the primary outcome. Of 3,748 patients, 2,239 were treated concurrently with ticagrelor, 1,256 treated with clopidogrel and 253 with prasugrel. As shown in the Figure, there was a trend towards increased risk of myocardial infarction with IV morphine (odds ratio 1.88; 95% CI 0.87–4.09, I2 0%). Across seven studies and 6585 patients, no increased risk of mortality at the same composite time endpoint was evident (odds ratio 0.70, 95% CI 0.40–1.23, I2 19%). Figure 1. MI in hospital or at 30 days Conclusion Based on current literature, evidence of an association between IV morphine and myocardial infarction in patients undergoing PPCI for STEMI is limited by observational methodology and conflicting results. There is no evidence of an association between intravenous peri-procedural morphine and mortality. Clinical trial evidence with strong documentation of adverse events data is required to demonstrate association or causality. Acknowledgement/Funding None

scholarly journals Prospective validation in epithelial tumors of a gene expression predictor of liver metastasis derived from uveal melanoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Petros Tsantoulis ◽  
Mauro Delorenzi ◽  
Ivan Bièche ◽  
Sophie Vacher ◽  
Pascale Mariani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Uveal Melanoma ◽  
Meta Analysis ◽  
Prognostic Score ◽  
Penalized Regression ◽  
Breast Cancer Patients ◽  
Public Data

AbstractPredicting the risk of liver metastasis can have important prognostic and therapeutic implications, given the availability of liver-directed therapy. Uveal melanoma has a striking predisposition for liver metastasis despite the absence of anatomical proximity. Understanding its biology may uncover factors promoting liver metastasis in other malignancies. We quantified gene expression by RNAseq in 76 uveal melanomas and combined with public data in a meta-analysis of 196 patients. The meta-analysis of uveal melanoma gene expression identified 63 genes which remained prognostic after adjustment for chromosome 3 status. Two genes, PTP4A3 and JPH1, were selected by L1-penalized regression and combined in a prognostic score. The score predicted liver-specific relapse in a public pan-cancer dataset and in two public colorectal cancer datasets. The score varied between colorectal consensus molecular subtypes (CMS), as did the risk of liver relapse, which was lowest in CMS1. Additional prospective validation was done by real-time PCR in 463 breast cancer patients. The score was significantly correlated with liver relapse in hormone receptor positive tumors. In conclusion, the expression of PTP4A3 and JPH1 correlates with risk of liver metastasis in colorectal cancer and breast cancer. The underlying biological mechanism is an interesting area for further research.

Performance of a 31-gene expression profile (GEP) test for metastatic risk prediction in cutaneous melanomas (CM) of the head and neck.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9576-9576
Author(s):  
John T. Vetto ◽  
Sancy Ann Leachman ◽  
Brooke Middlebrook ◽  
Kyle R. Covington ◽  
Jeffrey D. Wayne ◽  
...  
Keyword(s):  
High Risk ◽  
Head And Neck ◽  
Distant Metastasis ◽  
False Negative ◽  
Tumor Biology ◽  
False Negative Rate ◽  
Neck Region ◽  
Negative Rate ◽  
Class 1 ◽  
Metastatic Risk

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]

Midterm and Long-term Results of Medial Versus Lateral Meniscal Allograft Transplantation: A Meta-analysis

2017 ◽  
Vol 46 (5) ◽  
pp. 1243-1250 ◽  
Author(s):  
Seong-Il Bin ◽  
Kyung-Wook Nha ◽  
Ji-Young Cheong ◽  
Young-Soo Shin
Keyword(s):  
Clinical Outcomes ◽  
Meta Analysis ◽  
Survival Rates ◽  
Long Term Results ◽  
Functional Improvement ◽  
Meniscal Allograft Transplantation ◽  
Allograft Transplantation ◽  
Meniscal Allograft

Background: It is unclear whether lateral meniscal allograft transplantation (MAT) procedures lead to better clinical outcomes than medial MAT. Hypothesis: The survival rates are similar between medial and lateral MAT, but the clinical outcomes of lateral MAT are better than those of medial MAT at final follow-up. Study Design: Meta-analysis. Methods: In this meta-analysis, we reviewed studies that assessed survival rates in patients who underwent medial or lateral MAT with more than 5 years of follow-up and that used assessments such as pain and Lysholm scores to compare postoperative scores on knee outcome scales. The survival time was considered as the time to conversion to knee arthroplasty and/or subtotal resection of the allograft. Results: A total of 9 studies (including 287 knees undergoing surgery using medial MAT and 407 with lateral MAT) met the inclusion criteria and were analyzed in detail. The proportion of knees in which midterm (5-10 years) survival rates (medial, 97/113; lateral, 108/121; odds ratio [OR] 0.71; 95% CI, 0.31-1.64; P = .42) and long-term (>10 years) survival rates (medial, 303/576; lateral, 456/805; OR 0.78; 95% CI, 0.52-1.17; P = .22) were evaluated did not differ significantly between medial and lateral MAT. In addition, both groups had substantial proportions of knees exhibiting midterm survivorship (85.8% for medial MAT and 89.2% for lateral MAT) but much lower proportions of knees exhibiting long-term survivorship (52.6% for medial MAT and 56.6% for lateral MAT). In contrast, overall pain score (medial, 65.6 points; lateral, 71.3 points; 95% CI, −3.95 to −0.87; P = .002) and Lysholm score (medial, 67.5 points; lateral, 72.0 points; 95% CI, −10.17 to −3.94; P < .00001) were significantly higher for lateral MAT compared with medial MAT. Conclusion: Meta-analysis indicated that 85.8% of medial and 89.2% of lateral meniscal allograft transplants survive at midterm (5-10 years) while 52.6% of medial and 56.6% of lateral meniscal allograft transplants survive long term (>10 years). Patients undergoing lateral meniscal allograft transplantation demonstrated greater pain relief and functional improvement than patients undergoing medial meniscal allograft transplantations.

scholarly journals Meta-analysis of Clear Cell Renal Cell Carcinoma Gene Expression Defines a Variant Subgroup and Identifies Gender Influences on Tumor Biology

2012 ◽  
Vol 61 (2) ◽  
pp. 258-268 ◽  
Author(s):  
A. Rose Brannon ◽  
Scott M. Haake ◽  
Kathryn E. Hacker ◽  
Raj S. Pruthi ◽  
Eric M. Wallen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Meta Analysis ◽  
Tumor Biology ◽  
Cell Renal Cell Carcinoma ◽  
Gender Influences
Sign in / Sign up

Export Citation Format

Share Document