Overview of DecisionDx®-UM

Prognostic test is standard of care in eye cancer

Screen Shot 2013-01-09 at 5.47.07 PMOne of the primary challenges for doctors in managing uveal melanoma, as well as all cancers, is predicting the potential for the disease to spread. Fortunately, patients today have access to the DecisionDx-UM gene expression profile (GEP) test, which predicts a patient’s risk based upon their tumor’s own unique biology.

Developed by ocular oncologist Dr. J. William Harbour while at Washington University (now at Bascom Palmer Eye Institute) and exclusively licensed to Castle Biosciences Inc., DecisionDx-UM is the most widely used prognostic test in uveal melanoma. It is used to predict statistical rates of survival over five years, the period for which we currently have scientific data. According to a recent study published in Clinical Ophthalmology, molecular testing such as our GEP test has a significant impact on the management of uveal melanoma, ophthalmologists reporting that they are more likely to increase frequency of disease monitoring or recommend clinical trials for those patients whose test results showed they were at high risk of metastasis.

The GEP test is extremely valuable in guiding a patient’s care following treatment of the original eye tumor.  It measures the activity or “expression” of certain genes within the tumor to determine its risk profile, or Class:

  • Class 1A:  Very low risk, with a 2% chance of the eye cancer spreading over five years;
  • Class 1B: Low risk, with a 21% chance of metastasis over five years; and
  • Class 2: High risk, with 72% odds of metastasis over five years.

pullquote_decisionDXHistorically, doctors relied on physical characteristics like tumor size, location, and color patterns to determine metastatic risk. These factors still play a role, but alone, are not accurate predictors. In the 1990s, this method was improved upon by  tests that analyze a chromosome mutation. Called Monosomy 3, these tests identify tumors with a loss of one copy of chromosome 3, which is associated with a higher risk of metastasis than those with both copies intact. In a head-to-head study however, Monosomy 3 testing proved to be far less accurate than DecisionDx-UM.

For these reasons as well as the scientific rigor that went into its development, the GEP test has been adopted by the majority of the country’s leading ocular oncologists (100 of the estimated 110 specialists) as standard of care in the management of eye cancer.

DecisionDx-UM: Rigorously Validated for Accuracy, Reliability

The DecisionDx-UM test is the only test that has undergone extensive validation in multiple studies, including an independent, prospective study conducted by the Collaborative Ocular Oncology Group (COOG). In 494 patients at 12 centers in the United States and Canada, the researchers found the test could successfully classify tumors more than 97 percent of the time. The GEP test was found to be superior in predictive accuracy and reliability to all other prognostic methods. The COOG study results were published in Ophthalmology in August 2012.

Formal comparisons (using a method called net reclassification improvement) at the three-year mark of the study showed the DecisionDx-UM test to have a 43% improvement over physical characteristics like tumor size and shape, and a 38% improvement over Monosomy 3 testing.

In other studies, Monosomy 3 testing has been documented to technically fail to return a result in up to 50% of specimens tested (Young, 2007; Desjardins, 2010). Getting a result the first time is extremely important in uveal melanoma, since timing of the biopsy is critical.

DecisionDx-PRAME testing for additional prognostic information

PRAME, or preferentially expressed antigen in melanoma, is a gene that has been the focus of two recent studies in uveal melanoma that were published in Clinical Cancer Research and Oncotarget. PRAME is usually not found in normal adult tissues, but in some cancers, PRAME expression is elevated. Studies have suggested that elevated PRAME expression (“PRAME positive”) in a Class 1 uveal melanoma tumor may be associated with an increased risk of metastasis compared to a Class 1 tumor that does not express PRAME (“PRAME negative”). Class 2 tumors already have a higher risk of metastasis, and in these tumors, PRAME positivity may be associated with a shorter time to metastasis than PRAME-negative Class 2 tumors.

PRAME is a major focus of ongoing uveal melanoma clinical research, including an upcoming prospective, multi-center study. Additionally, therapies targeting PRAME are in clinical trials for other types of cancers and may be relevant to uveal melanoma in the future. Because most patients receive radiation as their primary eye treatment, there is usually not leftover tissue for future testing except for the biopsy tissue used for gene expression profiling. Due to the precious nature of each biopsy, Castle Biosciences is providing PRAME status testing at the request of physicians who order DecisionDx-UM. If you are having DecisionDx-UM testing performed on your tumor and are interested in knowing your PRAME status, please discuss this additional test for PRAME with your physician.

If you and your physician choose to have DecisionDx-PRAME testing in conjunction with your DecisionDx-UM test, your physician will evaluate your PRAME status in conjunction with your DecisionDx-UM test results.

The exact impact of PRAME status on your risk for metastasis has not yet been determined and is under further investigation. DecisionDx-PRAME results are reported only at the request of the ordering physician.

If you have questions about the DecisionDx-PRAME test, please contact us at 866-788-9007 or contact@castlebiosciences.com.

Know your TYPE, Know your RISK
You’ve just been diagnosed with uveal melanoma, and it’s important to know that there is a test that can identify your tumor type—and the risk of your cancer spreading.

GETTING TESTED       Timing is Critical
To know your tumor type and risk, a biopsy must be taken BEFORE radiation treatment.

Talk to                 Your Doctor
Use this discussion guide to talk to your doctor about the genomic test to learn your tumor type, or CLASS.


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