Esophageal cancer test identifies patients resistant to therapy
8 May 2014
Two validation studies show that a test can accurately predict response to chemoradiation therapy before surgery, in patients with esophageal adenocarcinoma.
The test is manufactured by Castle Biosciences Inc., which announced that data from two clinical validation studies of its DecisionDx-EC multi-biomarker test were reviewed in an oral presentation at the Digestive Disease Week Annual Meeting. Also at the meeting, the company presented initial data using the same biomarker panel to predict extreme resistance to chemoradiation (CTRT) in the treatment of rectal cancer.
"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."
Clinical Validation Study - statistical 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 esophageal cancer 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.
"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, and 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."
Rectal Adenocarcinoma Results
Castle Biosciences also presented initial data from a study of its new test for rectal adenocarcinoma that uses the same biomarkers as the test to predict resistance to pre-operative CTRT. The study looked at paraffin-embedded samples from 10 patients with locoregional rectal adenocarcinoma 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 rectal adenocarcinoma is currently underway.
Source: Medical News Today: http://www.medicalnewstoday.com/releases/276510.php