The esophagus carries food and liquid from the mouth to the stomach. There are two main types of esophageal cancer: adenocarcinoma and squamous cell carcinoma. The most common form of the disease in the U.S. is adenocarcinoma and is most prevalent in Caucasian men between the ages of 50 and 70.

Adenocarcinoma, which is one of the fastest growing cancers in the country, has also been linked to obesity – perhaps related to chronic exposure to stomach acid. According to the National Cancer Institute, about 18,000 Americans were diagnosed with esophageal cancer in 2013.

Data from two clinical validation studies of its DecisionDx-EC multi-biomarker test were reviewed in an oral presentation by Castle Biosciences Inc. at the Digestive Disease Week (DDW) Annual Meeting. The data show that the test accurately predicts response to pre-surgical chemoradiation therapy (CTRT) in patients with esophageal adenocarcinoma. Also at the meeting, the Company presented initial data using the same biomarker panel to predict extreme resistance to chemoradiation in the treatment of rectal cancer.  

Castle Biosciences licensed the technology from The University of Texas MD Anderson Cancer Center, and validated the test under CLIA certified laboratory protocols. 

Clinical Validation Study Details

The DecisionDx-EC test analyzes the localization of three protein biomarkers, NFkB, Gli1 and SHH, to classify tumors as either responsive to, or resistant to, CTRT. Testing was performed on formalin-fixed paraffin embedded (FFPE) EC tissue. The first validation study was performed at a single center using 167 patient cases, all of whom underwent a chemoradiation regimen involving 5FU plus platinum/taxanes.

The study showed a specificity of 97% and positive (PPV) and negative (NPV) predictive values reaching 82% and 94%, respectively.

In a second, multi-center validation study, results were similar. Of 65 patient cases, 68% of whom had been treated with a 5FU regimen, the study reported 95% specificity with a PPV and NPV of 83% and 77%, respectively.

Both validation studies were subject to a blinded outcome review by two trained independent scientists. The inter-observer concordance rate in the second validation study was 95%, with a Kappa concordance equal to 0.88 (95% CI, 0.74 – 1.00).

"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, M.D., FRCPath, Professor of Pathology and Laboratory Medicine at the Indiana University School of Medicine, co-author of the study.

"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," said 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."

"For patients diagnosed with locoregional esophageal adenocarcinoma, the standard of care involves pre-operative chemotherapy and radiation followed by surgery," commented Dr. Weiwei Shan, Ph.D., Scientist at Castle Biosciences and study co-author. "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."

Castle Biosciences also presented initial data from a study of its new test for rectal adenocarcinoma (RC) that uses the same biomarkers as the EC test to predict resistance to pre-operative CTRT.

An estimated 40,000 new cases of rectal cancer were diagnosed in the U.S. in 2012. The disease affects men and women equally, but is more prevalent in African Americans. A major risk factor is a single-gene disorder, which can greatly increase one's odds of developing the disease. In the U.S., adenocarcinomas are the most common form of rectal tumors.

The study looked at FFPE samples from 10 patients with locoregional RC and showed an accuracy of 80%, with specificity and PPV values of 100%. These results suggest that the assay was able to identify 100% of those patients who would respond favorably to CTRT. Expanded validation of the biomarker panel for RC is currently underway.