DecisionDx-UM
DecisionDx-UM is a
The test classifies tumors as:
- Class 1A (low metastatic risk),
- Class 1B (long-term metastatic risk),
- Class 2 (immediate, high metastatic risk).[1]
Also referred to as the gene expression profile, the test has been directly compared to all other
Uveal Melanoma
While rare, uveal melanoma (ocular melanoma) is the most common form of eye cancer and the second most common form of
The lack of accurate prognostic tests to identify which patients are at risk of developing clinically overt metastatic disease has been a significant issue in the management of individual patients with uveal melanoma. Without accurate measures of individual metastatic risk, it is impossible to identify which patients are at high risk for clinical metastasis, which can then lead to either over or under-treatment of any given patient. The DecisionDx-UM test was developed to provide improved individual metastatic risk assessment which allows for more appropriate surveillance and treatment planning.
DecisionDx-UM GEP Assay
Discovery
The gene expression profile measured by DecisionDx-UM was discovered in the laboratory of J. William Harbour at Washington University in St. Louis.[8][9] The application of microarray analysis to primary untreated uveal melanomas revealed that the tumors clustered into two discreet groups based upon their expression profiles.[8] Filtering of the differentially expressed gene set led to the identification of a set of genes able to discriminate between Class 1 and Class 2 tumors.
In subsequent experiments, Dr. Harbour's group assembled microarray information from a larger subset of uveal melanoma tumor samples, and were able to identify candidate discriminatory genes for further analysis.
Prognostic Accuracy
The current DecisionDx-UM platform was clinically validated in the COOG study, which included 514 patients with UM treated at 12 ocular oncology centers in the United States between 1998 and 2010.[1] The report provides data showing that DecisionDx-UM has a high technical success rate (>95%).
Clinical Technical Success
Since the initial offering of DecisionDx-UM in December 2009, more than 800 clinical orders have been received for analysis by Castle Biosciences from over 55 ocular oncology centers across the U.S. Technical success and class determination was achieved for 96.2% of the samples.[11] Most of the failures were due to improper biopsy collection and/or handling. Tumor biopsy collection is critical for the successful reporting of metastatic risk Class assignment following DecisionDx-UM testing.
DecisionDx-UM Ordering and Reporting
Castle Biosciences, Incorporated only accepts service orders for DecisionDx-UM from licensed physicians (most commonly ocular oncologists, ophthalmologists, or retina specialists) who care for patients diagnosed with uveal melanoma. Physicians who are first time customers must contact Castle's for information and to establish an account. Sample submission requires submission of a DecisionDx-UM Requisition Form to be completed and faxed to Castle. FNAB specimens require use of a specimen collection kit, provided by Castle, to stabilize the sample and reduce the chance of technical failure. This kit must be received by the ordering physician prior to sample collection. Castle staff is available to assist with logistics concerning sample collection and shipping.
Castle provides a report to the ordering physician that will classify the tumor as Class 1A, Class 1B, or Class 2. The report will also describe the statistics associated with the classification, and provide a discriminant value that reflects the confidence regarding the classification. The information provided in the report from Castle identifies how likely a tumor is to metastasize (spread) with this risk being categorized as low (Class 1A), intermediate (Class 1B), or high (Class 2).
Other UM Metastasis Prognostic Factors
Histopathologic Factors and Imaging Techniques
Historically there are several clinical and pathologic features that have been statically associated with metastasis. While generalities regarding the UM patient population at large can be made based on these factors, none, alone or collectively, has demonstrated predictive accuracy with regard to metastatic activity.
Imaging techniques used to detect metastatic activity also have limitations. Systemic metastases are detected by
Genetic Factors
Genetic analysis techniques have led to the identification of chromosomal abnormalities associated with metastatic tumor progression in uveal melanoma. Loss of
While genetic aberrations in chromosomes 1, 6 and 8 have not independently been able to predict disease progression, cytogenetic profiling of chromosome 3 has uncovered an important genetic region highly associated with metastatic onset in uveal melanoma patients.
Despite a wealth of data that has identified the association of chromosome 3 mutation with UM metastasis, the clinical application of this data has yet to be realized.[29] Reasons for the uncertainty of chromosome 3 clinical use include:
- high false-positive rates (ranging from 5-22%)
- high false-negative rates (ranging from 4-50%)
- high technical failure rates (up to 50%) due to the large tissue requirement for current analysis techniques
- the adverse effects of cellular
Furthermore, unlike the DecisionDx-UM test, there are no published, peer-reviewed studies that demonstrate clinical validation in an independent set of patients.
Castle Biosciences, Incorporated
Nasdaq: CSTL |
Castle Biosciences, Incorporated is a molecular diagnostics company that develops diagnostic and prognostic assays for rare cancers. Castle's mission is to serve individuals afflicted with rare cancers by offering accurate prognostic tests which provide information for making critical decisions regarding an individual's surveillance and treatment regimens. In addition to DecisionDx-UM, Castle offers prognostic tests for
References
- ^ a b Harbour, J.W., Retina Times 2011;29: 36-7.
- ^ a b c Worley, L.A., et al., Clinical Cancer Research, 2007. 13(5): p. 1466-71.
- ^ Archives of Ophthalmology, 2006. 124(12): p. 1684-93.
- ^ Diener-West, M., et al., Archives of Ophthalmology, 2001. 119(7): p. 969-82.
- ^ Harbour, J.W., Clinical overview of uveal melanoma:introduction to tumors of the eye., ed. D.M. Albert, Polans, A.2003: Marcel Dekker. 1-18.
- ^ a b Finger, P.T., et al., The British Journal of Ophthalmology, 2005. 89(10): p. 1270-4.
- ^ Kurli, M., et al., American Journal of Ophthalmology, 2005. 140(2): p. 193-9.
- ^ a b Onken, M.D., et al., Cancer research, 2004. 64(20): p. 7205-9.
- ^ a b c d Onken, M.D., et al., The Journal of molecular diagnostics : JMD, 2010. 12(4): p. 461-8.
- ^ Onken, M.D., et al., The Journal of molecular diagnostics : JMD, 2006. 8(5): p. 567-73.
- ^ Bergstrom, C.S., Hovland, P. G., Stone, J. F., Oelschlager, K., and Cook, R. W., 2011.
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- ^ Servois, V., et al., European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology, 2010. 36(2): p. 189-94.
- ^ a b c Harbour, J.W., et al., Science, 2010. 330(6009): p. 1410-3.
- ^ a b Kilic, E., et al., Investigative ophthalmology & visual science, 2006. 47(9): p. 3703-7.
- ^ Onken, M.D., L.A. Worley, and J.W. Harbour, Clinical Cancer Research, 2008. 14(12): p. 3737-45.
- ^ a b Prescher, G., N. Bornfeld, and R. Becher, Journal of the National Cancer Institute, 1990. 82(22): p. 1765-9.
- ^ a b Sisley, K., et al., Genes, Chromosomes & Cancer, 1990. 2(3): p. 205-9.
- ^ a b Damato, B., J.A. Dopierala, and S.E. Coupland, Clinical Cancer Research, 2010. 16(24): p. 6083-92.
- ^ Sisley, K., et al., Genes, Chromosomes & Cancer, 1997. 19(1): p. 22-8.
- ^ a b Prescher, G., et al., Lancet, 1996. 347(9010): p. 1222-5.
- ^ Singh, A.D., et al., Archives of Pathology & Laboratory Medicine, 2009. 133(8): p. 1223-7.
- ^ Naus, N.C., et al., Clinical Cancer Research, 2002. 8(2): p. 534-9.
- ^ a b Onken, M.D., et al., Clinical Cancer Research, 2007. 13(10): p. 2923-7.
- ^ Sandinha, M.T., M.A. Farquharson, and F. Roberts, The British Journal of Ophthalmology, 2004. 88(12): p. 1527-32.
- ^ Tschentscher, F., et al., Cancer genetics and cytogenetics, 2000. 122(1): p. 13-7.
- ^ a b Damato, B. and S.E. Coupland, Archives of Ophthalmology, 2009. 127(4): p. 423-9.
- ^ Maat, W., et al., Archives of Pathology & Laboratory Medicine, 2007. 131(1): p. 91-6.
- ^ Mensink, H.W., et al., Investigative ophthalmology & visual science, 2009. 50(2): p. 500-4.
- ^ Midena, E., et al., European journal of ophthalmology, 2006. 16(3): p. 422-5.
- ^ Shields, C.L., et al., Transactions of the American Ophthalmological Society, 2007. 105: p. 43-52; discussion 52-3.
- ^ Young, T.A., et al., Ophthalmology, 2007. 114(1): p. 142-6.
External links
- The Tumori Foundation
- The Ocular Melanoma Foundation. A cancer nonprofit foundation.
- The Ocular Oncology Service at Washington University in St. Louis Archived 2011-09-30 at the Wayback Machine
- The Eye Cancer Network
- OCU-MEL - Ocular Melanoma e-mail list for patients, caregivers and healthcare professionals
- All NCI-approved clinical trials for uveal melanoma that has spread to the liver
- A phase III clinical trial for uveal melanoma that has spread to the liver
- EyeMelanoma.org