Prediction of response to endoscopic therapy of Barrett's dysplasia by using genetic biomarkers

Endoscopic therapy for the treatment of high-grade dysplasia (HGD) and intramucosal cancer (IMC) in Barrett's esophagus (BE) may not always result in complete remission of dysplasia (CRD). To determine whether genetic alterations in the Barrett's mucosa can predict response to endoscopic therapy. Retrospective cohort study. Tertiary-care institution. Selected patients who underwent endoscopic therapy for BE containing HGD/IMC between 2003 and 2010. Endoscopic therapy combining mucosal resection and different ablation modalities was performed based on patient characteristics, endoscopic findings, and technique evolution. Fluorescence in situ hybridization was used to evaluate genetic alterations on baseline endoscopic cytology brushings by using probes directed to loci 8q24 (MYC), 9p21 (CDKN2A; alias P16), 17q12 (ERBB2; alias Her-2/neu), and 20q13.2 (ZNF217). Genetic biomarkers predicting achievement of CRD after endoscopic therapy. A total of 181 patients were included (145 men; 66 ± 10 years of age). There were 130 patients (72%) who responded to endoscopic therapy with CRD. Multiple gains detected by fluorescence in situ hybridization was found to be a negative predictor (hazard ratio 0.57; 95% confidence interval, 0.40-0.82) after adjusting for potential clinical confounders. Similar results were found when analyses were restricted to patients (n = 66) undergoing radiofrequency ablation (hazard ratio 0.58; 95% confidence interval, 0.31-1.09). Retrospective study, heterogeneity of treatment modalities. Patients with multiple gains detected by brush cytology specimens may have a lower response rate to endoscopic therapy. The presence of multiple gains can be an adjunct to standard histology in prognosticating BE patients with HGD/IMC undergoing endoscopic therap

Utility of biomarkers in prediction of response to ablative therapy in Barrett's esophagus

BACKGROUND & AIMS: Photodynamic therapy (PDT) has been shown to be effective in the treatment of high-grade dysplasia (HGD)/mucosal carcinoma in Barrett's esophagus (BE). Substantial proportions of patients do not respond to PDT or progress to carcinoma despite PDT. The role of biomarkers in predicting response to PDT is unknown. We aimed to determine if biomarkers known to be associated with neoplasia in BE can predict loss of dysplasia in patients treated with ablative therapy for HGD/intramucosal cancer. METHODS: Patients with BE and HGD/intramucosal cancer were studied prospectively from 2002 to 2006. Biomarkers were assessed using fluorescence in situ hybridization performed on cytology specimens, for region-specific and centromeric probes. Patients were treated with PDT using cylindric diffusing fibers (wavelength, 630 nm; energy, 200 J/cm fiber). Univariate and multiple variable logistic regression was performed to determine predictors of response to PDT. RESULTS: A total of 126 consecutive patients (71 who underwent PDT and 55 patients who did not undergo PDT and were under surveillance, to adjust for the natural history of HGD), were included in this study. Fifty (40%) patients were responders (no dysplasia or carcinoma) at 3 months after PDT. On multiple variable analysis, P16 allelic loss (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.10-0.96) predicted decreased response to PDT. BE segment length (OR, 0.71; 95% CI, 0.59-0.85), and performance of PDT (OR, 7.17; 95% CI, 2.50-20.53) were other independent predictors of loss of dysplasia. CONCLUSIONS: p16 loss detected by fluorescence in situ hybridization can help predict loss of dysplasia in patients with BE and HGD/mucosal cancer. Biomarkers may help in the selection of appropriate therapy for patients and improve treatment outcome