Integrating the melanoma 31-gene expression profile test with surgical oncology practice within national guideline and staging recommendations.

Aim: Define changes in clinical management resulting from the 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 risk prediction in cutaneous melanoma: A meta-analysis of the 31-gene expression profile prognostic test in 1,479 patients.

BACKGROUND: Multiple studies have reported on the accuracy of the prognostic 31-gene expression profile test for cutaneous melanoma. Consistency of the test results across studies has not been systematically evaluated. OBJECTIVE: To assess the robustness of the prognostic value of the 31-gene expression profile. METHODS: Raw data were obtained from studies identified from systematic review. A meta-analysis was performed to determine overall effect of the 31-gene expression profile. Clinical outcome metrics for the 31-gene expression profile were compared with American Joint Committee on Cancer staging. RESULTS: Three studies met inclusion criteria; data from a novel cohort of 211 patients were included (n = 1,479). Five-year recurrence-free and distant metastasis-free survival rates were 91.4% and 94.1% for Class 1A patients and 43.6% and 55.5% for Class 2B patients (P < .0001). Meta-analysis results showed that Class 2 was significantly associated with recurrence (hazard ratio 2.90; P < .0001) and distant metastasis (hazard ratio 2.75; P < .0001). The 31-gene expression profile identified American Joint Committee on Cancer stage I to III patient subsets with high likelihood for recurrence and distant metastasis. Sensitivity was 76% (95% confidence interval 71%-80%) and 76% (95% confidence interval 70%-82%) for each end point, respectively. When 31-gene expression profile and sentinel lymph node biopsy results were considered together, sensitivity and negative predictive value for distant metastasis-free survival were both improved. CONCLUSION: The 31-gene expression profile test consistently and accurately identifies melanoma patients at increased risk of metastasis, is independent of other clinicopathologic covariates, and augments current risk stratification by reclassifying patients for heightened surveillance who were previously designated as being at low risk.

Hybrid Convergent ablation for atrial fibrillation: A systematic review and meta-analysis.

Background: Hybrid Convergent ablation for atrial fibrillation (AF) combines minimally invasive surgical (epicardial) and catheter (endocardial) ablation. The procedural goal is to achieve more extensive, enduring ablation of AF substrate around the pulmonary veins, posterior wall, and vestibule of the posterior wall left atrium. Objective: To perform a systematic review and meta-analysis on safety and effectiveness of contemporary Hybrid Convergent procedures. Methods: PubMed, Embase, and manual searches identified primary research articles on Hybrid Convergent. Inclusion criteria focused on contemporary practices (epicardial ablation device and lesions). Clinical outcomes at 1 year or later follow-up, patient population, procedural details, and major adverse events (MAE) were recorded. Results: Of 249 records, 6 studies (5 observational, 1 randomized controlled trial) including 551 patients were included. Endocardial energy sources included radiofrequency and cryoballoon. Hybrid Convergent ablation was mostly performed in patients with drug-refractory persistent and longstanding persistent AF. Mean preprocedural AF duration ranged between 2 and 5.1 years. Most patients (∼92%) underwent Hybrid Convergent in a single hospitalization. At 1 year follow-up or later, 69% (95% confidence interval [CI]: 61%-78%, n = 523) were free from atrial arrhythmias and 50% (95% CI: 42%-58%, n = 343) were free from atrial arrhythmias off antiarrhythmic drugs. Thirty-day MAE rate was 6% (95% CI: 3%-8%, n = 551). Conclusion: Hybrid Convergent ablation is an effective ablation strategy for persistent and longstanding persistent AF. Contemporary procedural approaches and published strategies aim to mitigate complications reported in early experience and address delayed inflammatory effusions.

Hybrid Convergent Procedure for the Treatment of Persistent and Long-standing Persistent Atrial Fibrillation.

Recent advances have been made in AF treatment, including the role of early rhythm control and landmark clinical trials using ablation therapy. However, some treatment gaps remain, including the creation of durable lesions outside the pulmonary veins and effective treatment of longstanding persistent AF. A novel epicardial-endocardial ablation approach - the hybrid convergent procedure - was developed to combine surgical and catheter ablation techniques into a collaborative, multidisciplinary approach to managing AF. In this review, the authors discuss recently published data on hybrid convergent ablation, including results of the CONVERGE clinical trial, in the context of current challenges to treatment of persistent and long-standing persistent AF. The review also aims to provide perspective on outstanding questions and future directions in this area.

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

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.

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

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 profiling in uveal melanoma: technical reliability and correlation of molecular class with pathologic characteristics.

BACKGROUND: A 15-gene expression profile test has been clinically validated and is widely utilized in newly diagnosed uveal melanoma (UM) patients to assess metastatic potential of the tumor. As most patients are treated with eye-sparing radiotherapy, there is limited tumor tissue available for testing, and technical reliability and success of prognostic testing are critical. This study assessed the analytical performance of the 15-gene expression test for UM and the correlation of molecular class with pathologic characteristics. METHODS: Inter-assay, intra-assay, inter-instrument/operator, and inter-site experiments were conducted, and concordance of the 15-gene expression profile test results and associated discriminant scores for matched tumor samples were evaluated. Technical success was determined from de-identified clinical reports from January 2010 - May 2016. Pathologic characteristics of enucleated tumors were correlated with molecular class results. RESULTS: Inter-assay concordance on 16 samples run on 3 consecutive days was 100%, and matched discriminant scores were strongly correlated (R2 = 0.9944). Inter-assay concordance of 46 samples assayed within a one year period was 100%, with an R2 value of 0.9747 for the discriminant scores. Intra-assay concordance of 12 samples run concurrently in duplicates was 100%; discriminant score correlation yielded an R2 of 0.9934. Concordance between two sites assessing the same tumors was 100% with an R2 of 0.9818 between discriminant scores. Inter-operator/instrument concordance was 96% for Class 1/2 calls and 90% for Class 1A/1B calls, and the discriminant scores had a correlation R2 of 0.9636. Technical success was 96.3% on 5516 samples tested since 2010. Increased largest basal diameter and thickness were significantly associated with Class 1B and Class 2 vs. Class 1A signatures. CONCLUSIONS: These results show that the 15-gene expression profile test for UM has robust, reproducible performance characteristics. The technical success rate during clinical testing remains as high as first reported during validation. As molecular testing becomes more prevalent for supporting precision medicine efforts, high technical success and reliability are key characteristics when testing such limited and precious samples. The performance of the 15-gene expression profile test in this study should provide confidence to physicians who use the test's molecular classification to inform patient management decisions.