Castle has five proprietary molecular diagnostic assays that are available for clinical use today:
Test for cutaneous melanoma (DecisionDx-Melanoma)
This year 35,000 people will be diagnosed with node-negative Stage I and II cutaneous melanoma (American Joint Committee on Cancer staging system, version 7; 2010; AJCC). Though they will have a 20% chance of metastasis within 5 years, few Stage I and II patients are aggressively treated or closely monitored after wide local excision and sentinel lymph node biopsy (AJCC, 2010; Kalady, 2003).
The new DecisionDx-Melanoma molecular test was developed to identify these at-risk node-negative patients. The test goes beyond traditional pathologic factors, analyzing the expression of 31 genes within a patient’s tumor to predict individual metastatic risk independent of stage. Clinical validation of a new molecular test, DecisionDx-Melanoma, was recently completed in the largest melanoma biomarker study of its kind. The study found that Stage I & II patients identified as having high-risk tumor biology had greater actual risk than AJCC Stage III patients.
The DecisionDx-Melanoma test is now available for clinical use.
To learn more, please visit
SkinMelanoma.com, a Castle site
dedicated to cutaneous melanoma
and the DecisionDx-Melanoma test.
Test for uveal melanoma (DecisionDx-UM)
Ocular melanoma, commonly known as uveal melanoma or choroidal melanoma, is a rare cancer of the eye. While the primary eye tumor is highly treatable, about half of patients are at high risk for metastasis (tumor spreading). Unfortunately, traditional staging methods used to assess the risk of metastasis are unreliable (have poor accuracy) and have not been routinely used to make clinical decisions regarding surveillance plans and treatment decisions.
The DecisionDx-UM test measures the gene expression profile, also called GEP, molecular signature, or gene expression patterns, of an ocular melanoma tumor and identifies with high accuracy the likelihood of metastasis. The DecisionDx-UM test has been formally compared in a prospective, multi-center 5-year study to both the traditional staging methods and to chromosome 3 testing. The DecisionDx-UM test was found to be clinically and statistically superior to both of these methods (Onken, 2012).
Today, the DecisionDx-UM test is standard of care in the management of ocular melanoma in the majority of ocular oncology practices. As of October, 2012, over 100 of the estimated 110 U.S. ocular oncology centers have adopted the DecisionDx-UM test for their patients with ocular melanoma. The test has achieved National Comprehensive Cancer Network (NCCN) Level of Evidence 1A – the highest level of evidence. This level of evidence is rarely achieved with tumor biomarkers for common cancers and represents one of the first tests to achieve this level of evidence for rare cancers (Febbo, 2011). Additionally the American Joint Committee on Cancer recommends the DecisionDx-UM GEP test for use as the results are "clinically significant" for patient care. The American Joint Committee on Cancer (AJCC, version 7, 2010) is the only national organization that reviews uveal melanoma.
To learn more, please visit
MyUvealMelanoma.com, a Castle site
dedicated to uveal melanoma
and the DecisionDx-UM test.
Test for thymoma (DecisionDx-Thymoma)
Thymomas are rare tumors of the thymus gland.
Surgery is the primary treatment for patients diagnosed with thymoma. Chemotherapy and radiation therapy may be used to reduce the likelihood of metastasis or recurrence. These treatment decisions are primarily based upon (i) Masoaka stage, (ii) extent of resection (surgically clean margins), and (iii) WHO schema classification.. Unfortunately these criteria are subjective and suffer from poor accuracy. This means that many patients thought to be at low risk of metastasis may actually be at high risk and could possibly be undertreated. Conversely, patients thought to be at high risk may actually be at low risk and could be overtreated.
The DecisionDx-Thymoma test is an objective test that measures the gene expression profile, also called GEP or molecular signature, of an individual's thymoma tumor and identifies the likelihood of metastasis. The DecisionDx-Thymoma test was validated in a prospectively-planned, multi-institutional validation study. The test was shown to have a higher accuracy than Masoaka stage, extent of resection, and WHO schema classification in predicting the likelihood of metastasis.
The DecisionDx-Thymoma test should be used in conjunction with the other clinical and pathologic factors in determining the appropriate treatment plan for an individual patient.
Test for methylation profile of gliomas (DecisionDx-G-CIMP)
Gliomas are graded as either WHO grade 2, 3 or 4. These WHO grades are primarily used to determine the appropriate treatment plan for an individual patient. Interventions such as surgical approach and dosing with radiation and/or chemotherapy are based largely on subjective WHO grading, imaging, and other clinical and pathologic factors.
The WHO grades are achieved through traditional, subjective histopathological techniques and are meant to predict likelihood of survival (prognosis). Multiple studies have shown clinically significant inter-observer and intra-observer variances – some showing error rates of 40% or more. While the WHO grading system does distinguish differences in overall survival between grades (with grade 2 having the longest overall survival and grade 4 the shortest), there is a wide range in overall survival between grade 2 and 3 and significant overlap. What this means is some patients with a grade 2 diagnosis may have a tumor-specific (functional) prognosis that is closer to an average grade 3. Receiving a grade 2 treatment plan may represent under-treatment relative to the tumor-specific prognosis. Likewise, the tumor-specific prognosis of some grade 3 tumors may be closer to the median grade 2 survival and these patients may be relatively over-treated.
The DecisionDx-G-CIMP test is an objective test that identifies the methylation profile (so called CIMP+ or CIMP-) of a glioma and predicts survival for patients treated with standard of care. The DecisionDx-G-CIMP test has been prospectively validated as a secondary endpoint in the multi-center Radiation Therapy Oncology Group 0525 study (RTOG-0525). Thus, the DecisionDx-G-CIMP test has achieved the National Comprehensive Cancer Network (NCCN) Level of Evidence 2B. The DecisionDx-G-CIMP test is intended to be used in conjunction with WHO grade, imaging and other clinical factors in determining the appropriate treatment plan for an individual patient.
Test for glioblastoma (DecisionDx-GBM)
Glioblastoma, also known as glioblastoma multiforme or GBM, is the most common and aggressive form of brain cancer.
GBM is graded using traditional histopathology techniques, but these fail to identify an individual's prognosis or likelihood of response to today’s standard of care treatment which consists of radiation with temozolomide. The DecisionDx-GBM test was developed to enable doctors to identify those patients with a high likelihood of long-term response to this treatment compared to those who may be refractory to the same treatment. The results are reported as a Class 1 pro-neural phenotype or a Class 2 mesenchymal / angiogenic phenotype. The DecisionDx-GBM test has been compared to MGMT methylation status and clinical factors and found to be an independent predictor of survival for patients receiving temozolomide. The DecisionDx-GBM test was also evaluated as a secondary endpoint in the prospective multi-center Radiation Therapy Oncology Group 0525 study (RTOG-0525). Similar to the earlier studies, this study found that the DecisionDx-GBM test demonstrated greater differentiation between long-term (Class 1) and average (Class 2) overall survival than methylation status using MGMT testing (Aldape, 2011). The DecisionDx-GBM test has achieved the National Comprehensive Cancer Network (NCCN) Level of Evidence 2B.
The DecisionDx-GBM test is intended to be used in conjunction with WHO grade and other clinical factors in determining the appropriate treatment plan for an individual patient.