A powerful multi-biomarker test produced by Castle Biosciences Inc. and developed by researchers at University of Texas MD Anderson Cancer Center was the subject of two clinical validation studies presented at the Digestive Disease Week Annual Meeting. The test, DecisionDx-EC, is designed to protect the 20-30% of esophageal cancer patients who unnecessarily receive preoperative chemoradiation without seeing a benefit. “For patients diagnosed with locoregional esophageal adenocarcinoma, the standard of care involves pre-operative chemotherapy and radiation (CTRT) followed by surgery,” said Dr. Weiwei Shan, PhD, from Castle Biosciences, in a news release. “Studies consistently show that 20-30% of these patients experience no benefit from CTRT, yet are still exposed to serious toxicities from these therapies while delaying more effective treatment options, including surgery.”
Esophageal cancer presents in two forms: squamous cell carcinoma and adenocarcinoma. Adenocarcinoma is more common, and its prevalence is on the rise, according to the National Cancer Institute. This makes DecisionDx-EC an important diagnostic for clinicians. “The ability to identify resistance to standard of care therapies could allow for selection of more appropriate treatment strategies and improved patient outcomes,” said Dr. Sunil Badve, MD, FRCPath, from Indiana University School of Medicine, who co-authored the study with Dr. Shan.
Data from the presentation show DecisionDx-EC accurately predicts adenocarcinoma patient response to CTRT and can even be used to predict extreme resistance to CTRT in rectal cancer patients. The test’s prediction power works by localizing three protein biomarkers in cancerous tissue. Nuclear factor kappa-B (NFkB), Gli1, and Sonic hedgehog (SHH) classify tumors as responsive to, or resistant to, CTRT.
The first study of 167 patient cases from a single center revealed a test specificity of 97%, a positive predictive value of 82%, and a negative predictive value of 94%. Similarly, the second study of 65 cases showed a specificity of 95%, a positive predictive value of 83%, and a negative predictive value of 77%. Patients received a chemoradiation regimen of 5-fluoruracil (5FU) with platinum/taxanes. The study was blinded and results were interpreted by two trained independent scientists.
Importantly, the results of DecisionDx-EC are taken to heart by clinicians. “To gain further insight into the clinical impact of our test, we conducted a survey with thoracic surgeons and found that 61% reported they would change their treatment recommendation if they knew the likelihood of a patient’s pre-operative chemoradiation response,” commented Derek Maetzold, President and CEO of Castle Biosciences. “Use of this test in the treatment planning process could help patients with esophageal adenocarcinoma avoid the toxicities of ineffective therapies, and move more quickly to therapies that are likely to be effective for them.”
In the case of rectal adenocarcinoma, the test was conducted on 10 patient samples and yielded an accuracy of 80% with 100% specificity and a positive predictive value of 100%. This will prompt further validation to expand the indication of DecisionDx-EC to be used in rectal adenocarcinoma.