Predictive factors for initial treatment response after circumferential radiofrequency ablation for Barrett’s esophagus with early neoplasia: a prospective multicenter study

Background and study aims: Radiofrequency ablation (RFA) is safe and effective for the eradication of neoplastic Barrett’s esophagus; however, occasionally there is minimal regression after initial circumferential balloon-based RFA (c-RFA). This study aimed to identify predictive factors for a poor response 3 months after c-RFA, and to relate the percentage regression at 3 months to the final treatment outcome.

Methods: We included consecutive patients from 14 centers who underwent c-RFA for high grade dysplasia at worst. Patient and treatment characteristics were registered prospectively. “Poor initial response” was defined as < 50 % regression of the Barrett’s esophagus 3 months after c-RFA, graded by two expert endoscopists using endoscopic images. Predictors of initial response were identified through logistic regression analysis.

Results: There were 278 patients included (median Barrett’s segment C4M6). In poor initial responders (n = 36; 13 %), complete response for neoplasia (CR-neoplasia) was ultimately achieved in 86 % (vs. 98 % in good responders; P < 0.01) and complete response for intestinal metaplasia (CR-IM) in 66 % (vs. 95 %; P  < 0.01). Poor responders required 13 months treatment (vs. 7 months; P < 0.01) for a median of four RFA sessions (vs. three; P < 0.01). We identified four independent baseline predictors of poor response: active reflux esophagitis (odds ratio [OR] 37.4; 95 % confidence interval [CI] 3.2 – 433.2); endoscopic resection scar regeneration with Barrett’s epithelium (OR 4.7; 95 %CI 1.1 – 20.0); esophageal narrowing pre-RFA (OR 3.9; 95 %CI 1.0 – 15.1); and years of neoplasia pre-RFA (OR 1.2; 95 %CI 1.0 – 1.4).

Conclusions: Patients with a poor initial response to c-RFA have a lower ultimate success rate for CR-neoplasia/CR-IM, require more treatment sessions, and a longer treatment period. A poor initial response to c-RFA occurs more frequently in patients who regenerate their endoscopic resection scar with Barrett’s epithelium, and those with ongoing reflux esophagitis, neoplasia in Barrett’s esophagus for a longer time, or a narrow esophagus.

• References

• 1 Fleischer DE, Overholt BF, Sharma VK et al. Endoscopic ablation of Barrett's esophagus: a multicenter study with 2.5-year follow-up. Gastrointest Endosc 2008; 68: 867-876
• 2 Gondrie JJ, Pouw RE, Sondermeijer CM et al. Stepwise circumferential and focal ablation of Barrett's esophagus with high-grade dysplasia: results of the first prospective series of 11 patients. Endoscopy 2008; 40: 359-369
• 3 Gondrie JJ, Pouw RE, Sondermeijer CM et al. Effective treatment of early Barrett's neoplasia with stepwise circumferential and focal ablation using the HALO system. Endoscopy 2008; 40: 370-379
• 4 Pouw RE, Wirths K, Eisendrath P et al. Efficacy of radiofrequency ablation combined with endoscopic resection for Barrett's esophagus with early neoplasia. Clin Gastroenterol Hepatol 2010; 8: 23-29
• 5 Shaheen NJ, Sharma P, Overholt BF et al. Radiofrequency ablation in Barrett's esophagus with dysplasia. N Engl J Med 2009; 360: 2277-2288
• 6 Van Vilsteren FG, Pouw RE, Seewald S et al. Stepwise radical endoscopic resection vs. radiofrequency ablation for Barrett's oesophagus with high-grade dysplasia or early cancer: a multicentre randomised trial. Gut 2011; 60: 765-773
• 7 Pouw RE, Bisschops R, Pech O et al. Safety outcomes of balloon-based circumferential radiofrequency ablation after focal endoscopic resection of early Barrett's neoplasia in 118 patients: results of an ongoing European multicenter study. Gastrointest Endosc 2010; 71: AB126
• 8 Van Vilsteren FG, Bergman JJ. Endoscopic therapy using radiofrequency ablation for esophageal dysplasia and carcinoma in Barrett's esophagus. Gastrointest Endosc Clin N Am 2010; 20: 55-74, vi
• 9 Sharma P, Dent J, Armstrong D et al. The development and validation of an endoscopic grading system for Barrett's esophagus: the Prague C & M criteria. Gastroenterology 2006; 131: 1392-1399
• 10 Akiyama T, Inamori M, Iida H et al. Shape of Barrett's epithelium is associated with prevalence of erosive esophagitis. World J Gastroenterol 2010; 16: 484-489
• 11 Badreddine RJ, Prasad GA, Wang KK et al. Prevalence and predictors of recurrent neoplasia after ablation of Barrett's esophagus. Gastrointest Endosc 2010; 71: 697-703
• 12 Chak A, Falk G, Grady WM et al. Assessment of familiality, obesity, and other risk factors for early age of cancer diagnosis in adenocarcinomas of the esophagus and gastroesophageal junction. Am J Gastroenterol 2009; 104: 1913-1921
• 13 Herrero LA, Van Vilsteren FG, Pouw RE et al. Endoscopic radiofrequency ablation combined with endoscopic resection for early neoplasia in Barrett's esophagus longer than 10 cm. Gastrointest Endosc 2011; 73: 682-690
• 14 Korst RJ, Santana-Joseph S, Rutledge JR et al. Effect of hiatal hernia size and columnar segment length on the success of radiofrequency ablation for Barrett's esophagus: a single-center, phase II clinical trial. J Thorac Cardiovasc Surg 2011; 142: 1168-1173
• 15 Krishnan K, Pandolfino JE, Kahrilas PJ et al. Increased risk for persistent intestinal metaplasia in patients with Barrett's esophagus and uncontrolled reflux exposure before radiofrequency ablation. Gastroenterology 2012; 143: 576-581
• 16 Lyday WD, Corbett FS, Kuperman DA et al. Radiofrequency ablation of Barrett's esophagus: outcomes of 429 patients from a multicenter community practice registry. Endoscopy 2010; 42: 272-278
• 17 Pech O, Behrens A, May A et al. Long-term results and risk factor analysis for recurrence after curative endoscopic therapy in 349 patients with high-grade intraepithelial neoplasia and mucosal adenocarcinoma in Barrett's oesophagus. Gut 2008; 57: 1200-1206
• 18 Steevens J, Schouten LJ, Driessen AL et al. A prospective cohort study on overweight, smoking, alcohol consumption, and risk of Barrett's esophagus. Cancer Epidemiol Biomarkers Prev 2011; 20: 345-358
• 19 Weston AP, Sharma P, Mathur S et al. Risk stratification of Barrett's esophagus: updated prospective multivariate analysis. Am J Gastroenterol 2004; 99: 1657-1666
• 20 Yachimski P, Puricelli WP, Nishioka NS. Patient predictors of esophageal stricture development after photodynamic therapy. Clin Gastroenterol Hepatol 2008; 6: 302-308
• 21 Akiyama J, Marcus SN, Triadafilopoulos G. Effective intra-esophageal acid control is associated with improved radiofrequency ablation outcomes in Barrett's esophagus. Dig Dis Sci 2012; 57: 2625-2632
• 22 Bremner CG, Lynch VP, Ellis FH et al. Barrett's esophagus: congenital or acquired? An experimental study of esophageal mucosal regeneration in the dog. Surgery 1970; 68: 209-216
• 23 Dvorak K, Payne CM, Chavarria M et al. Bile acids in combination with low pH induce oxidative stress and oxidative DNA damage: relevance to the pathogenesis of Barrett's oesophagus. Gut 2007; 56: 763-771
• 24 Iascone C, DeMeester TR, Little AG et al. Barrett's esophagus. Functional assessment, proposed pathogenesis, and surgical therapy. Arch Surg 1983; 118: 543-549
• 25 Wakelin DE, Al-Mutawa T, Wendel C et al. A predictive model for length of Barrett's esophagus with hiatal hernia length and duration of esophageal acid exposure. Gastrointest Endosc 2003; 58: 350-355