Clinical Performance and Management Outcomes with the DecisionDx-UM Gene Expression Profile Test in a Prospective Multicenter Study

Abstract

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 test p = 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 test p = 2.1 × 10−13 and p = 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).

Genetic prognostication in uveal melanoma

“…Because of the lack of validation in post‐radiotherapy tumours and the potential radiobiological effects of irradiation on the genomics of the tumour, irradiated samples have been considered ineligible for genetic testing using the DecisionDx‐UM test (Plasseraud et al. ).…”

“…Further studies evaluating genetic testing pre-radiotherapy and postradiotherapy in larger cohorts with longer follow-up are necessary to determine the reliability of genetic tests after radiotherapy. Because of the lack of validation in post-radiotherapy tumours and the potential radiobiological effects of irradiation on the genomics of the tumour, irradiated samples have been considered ineligible for genetic testing using the DecisionDx-UM test (Plasseraud et al 2016).…”

Genetic and epigenetic insights into uveal melanoma

“…This prognostic classification had led to the commercially available DecisionDx‐UM gene expression profile (GEP) test (available through Castle Biosciences, Inc., Friendswood, Texas, 77546, USA) based on the simultaneous measurement of the expression of 12 genes that are differentially expressed in Class 2 tumors (upregulated: CDH1, ECM1, HTR2B, RAB31 ; downregulated: E1F1B, FXR1, ID2, LMCD1, LTA4H, MTUS1, ROBO1, SATB1 ) and 3 control genes ( MRPS21, RBM23, SAP130 ). The GEP test is applicable for fresh and paraffin‐embedded formalin‐fixed tissue from UM that has not been previously irradiated and allows for a relatively precise prognosis of patient outcome . However, given the still fatal outcome once metastases have occurred, there is an ongoing and controversial debate on how and if at all to implicate prognostic testing in the clinical monitoring of patients.…”

“…77 E1F1B, FXR1, ID2, LMCD1, LTA4H, MTUS1, ROBO1, SATB1) and 3 control genes (MRPS21, RBM23, SAP130). The GEP test is applicable for fresh and paraffin-embedded formalin-fixed tissue from UM that has not been previously irradiated 80,81 and allows for a relatively precise prognosis of patient outcome. 82 However, given the still fatal outcome once metastases have occurred, there is an ongoing and controversial debate on how and if at all to implicate prognostic testing in the clinical monitoring of patients.…”

Response to “Comparison of Gene Expression Profiling and Chromosome 3 Analysis by Fluorescent in situ Hybridization and Multiplex Ligation Probe Amplification in Fine-Needle Aspiration Biopsy Specimens of Uveal Melanoma”

“…In summary, it is inappropriate for the authors to claim superiority of chromosomal testing and to suggest that GEP is incorrect in predicting a good prognosis for Class 1/monosomy 3 tumors given the lack of metastasis and additional long-term outcomes in their study and the consistent evidence of the accuracy of the GEP test in the literature [7,8,9,10]. …”