Test Identifies Resistance to Chemotherapy in Esophageal Cancer Patients

Approximately 25% of esophageal cancer patients exhibit extreme resistance to standard regimens of chemotherapy and radiation therapy, and therefore do not respond to the presurgical treatment, and can be considered for alternative neoadjuvant therapies or move directly to surgery to remove the tumor.

The test, a three-protein biomarker assay, was discovered by scientists at M.D. Anderson Cancer Center (Houston, TX, USA). Pretreatment tumor biopsies were used to evaluate treatment resistance with this predictive assay. The test reliably differentiates patients who are complete or partial responders to chemotherapy and radiation from those who are nonresponders. The initial, single center validation study of 167 patients demonstrated an accuracy of 92% and specificity of 97%.

In a second, independent, multicenter study, the accuracy was 79% and the specificity was 95% for classifying which patients are likely to be highly resistant to presurgical chemotherapy treatment for esophageal cancer. The predictive algorithm classifies patients as either extreme resistance to chemo-radiation (exCTRT; College of American Pathology Treatment Response Grade 3) or non-extreme resistance to chemo-radiation (non-exCTRT; College of American Pathology Treatment Response Grade 0, 1, or 2).

The test, DecisionDx-EC (Castle Biosciences, Friendswood, TX, USA), uses compartmental localization of the protein biomarkers: nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), Zinc finger protein, glioma-associated oncogene (Gli1) and sonic hedgehog (SHH) in pretreated tumor biopsies to determine a localization index score for each biomarker. This information is then analyzed using a proprietary algorithm to predict exCTRT or non-exCTRT.

Kenneth A. Kesler MD, Professor of Surgery, Thoracic Oncology Program, Indiana University (Indianapolis, IN, USA) said, “Induction chemotherapy and radiation therapy are recommended prior to surgery in most cases. However, induction therapy can result in significant toxicity and will achieve no clinical benefits in up to a quarter of patients. The ability to identify resistance to certain chemotherapy agents allows selection of alternative chemotherapy agents or treatment strategies.” The study was presented at the 2014 Gastrointestinal Cancers Symposium held January 16–18, 2014, in San Francisco, CA, USA).

Related Links:
M.D. Anderson Cancer Center
Castle Biosciences
Indiana University