RSS-Feed abonnieren
![](/products/assets/desktop/img/oa-logo.png)
DOI: 10.1055/s-0042-103415
Endoscopic ablation is a cost-effective cancer preventative therapy in patients with Barrett’s esophagus who have elevated genomic instability
Publikationsverlauf
submitted: 28. Oktober 2015
accepted after revision: 08. Februar 2016
Publikationsdatum:
15. April 2016 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00025476/201605/lookinside/thumbnails/430_10-1055-s-0042-103415-1.jpg)
Background: The surveillance of patients with nondysplastic Barrett’s esophagus (NDBE) has a high cost and is of limited effectiveness in preventing esophageal adenocarcinoma (EAC). Ablation for NDBE remains expensive and controversial. Biomarkers of genomic instability have shown promise in identifying patients with NDBE at high risk for progression to EAC. Here, we evaluate the cost-effectiveness of using such biomarkers to stratify patients with NDBE by risk for EAC and, subsequently, the cost-effectiveness of ablative therapy.
Methods: A Markov decision tree was used to evaluate four strategies in a hypothetical cohort of 50-year old patients with NDBE over their lifetime: strategy I, natural history without surveillance; strategy II, surveillance per current guidelines; strategy III, ablation for all patients; strategy IV, risk stratification with use of a biomarker panel to assess genomic instability (i. e., mutational load [ML]). Patients with no ML underwent minimal surveillance, patients with low ML underwent standard surveillance, and patients with high ML underwent ablation. The incremental cost-effectiveness ratio (ICER) and incremental net health benefit (INHB) were assessed.
Results: Strategy IV provided the best values for quality-adjusted life years (QALYs), ICER, and INHB in comparison with strategies II and III. Results were robust in sensitivity analysis. In a Monte Carlo analysis, the relative risk for the development of cancer in the patients managed with strategy IV was decreased. Critical determinants of strategy IV cost-effectiveness were the complete response rate, cost of ablation, and surveillance interval in patients with no ML.
Conclusion: The use of ML to stratify patients with NDBE by risk was the most cost-effective strategy for preventive EAC treatment. Targeting ablation toward patients with high ML presents an opportunity for a paradigm shift in the management of NDBE.
-
References
- 1 Spechler SJ, Sharma P, Souza RF et al. American Gastroenterological Association medical position statement on the management of Barrett's esophagus. Gastroenterology 2011; 140: 1084-1091
- 2 Inadomi J, Madanick R, Somsouk M et al. Radiofrequency ablation is more cost-effective than endoscopic surveillance or esophagectomy among patients with Barrett’s esophagus and low-grade dysplasia. Gastroenterology 2007; 132: A53
- 3 Inadomi JM, Sampliner R, Lagergren J et al. Screening and surveillance for Barrett esophagus in high-risk groups: a cost-utility analysis. Ann Intern Med 2003; 138: 176-186
- 4 Das A, Wells C, Kim HJ et al. An economic analysis of endoscopic ablative therapy for management of nondysplastic Barrett's esophagus. Endoscopy 2009; 41: 400-408
- 5 Ellsworth E, Jackson SA, Thakkar SJ et al. Correlation of the presence and extent of loss of heterozygosity mutations with histological classifications of Barrett's esophagus. BMC Gastroenterol 2012; 12: 181
- 6 Galipeau PC, Li X, Blount PL et al. NSAIDs modulate CDKN2A, TP53, and DNA content risk for progression to esophageal adenocarcinoma. PLoS Med 2007; 4: e67
- 7 Khara HS, Jackson SA, Nair S et al. Assessment of mutational load in biopsy tissue provides additional information about genomic instability to histological classifications of Barrett's esophagus. J Gastrointest Cancer 2014; 45: 137-145
- 8 Eluri S, Brugge WR, Daglilar ES et al. The presence of genetic mutations at key loci predicts progression to esophageal adenocarcinoma in Barrett's esophagus. Am J Gastroenterol 2015; 110: 828-834
- 9 Spechler SJ, Sharma P, Souza RF et al. American Gastroenterological Association technical review on the management of Barrett's esophagus. Gastroenterology 2011; 140: e18-e52 ; quiz e13
- 10 Sampliner RE. Updated guidelines for the diagnosis, surveillance, and therapy of Barrett's esophagus. Am J Gastroenterol 2002; 97: 1888-1895
- 11 Sonnenberg FA, Beck JR. Markov models in medical decision making: a practical guide. Med Decis Making 1993; 13: 322-338
- 12 Weinstein MC, Siegel JE, Gold MR et al. Recommendations of the Panel on Cost-effectiveness in Health and Medicine. JAMA 1996; 276: 1253-1258
- 13 Doubilet P, Begg CB, Weinstein MC et al. Probabilistic sensitivity analysis using Monte Carlo simulation. A practical approach. Med Decis Making 1985; 5: 157-177
- 14 Heitjan DF. Fieller's method and net health benefits. Health Econ 2000; 9: 327-335
- 15 Stinnett A, Mullahy J. Net health benefits: a new framework for the analysis of uncertainty in cost-effectiveness analysis. Med Decis Making 1998; 18: 68-S80
- 16 Fitzgerald RC, di Pietro M, Ragunath K et al. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus. Gut 2014; 63: 7-42
- 17 Fleischer DE, Overholt BF, Sharma VK et al. Endoscopic radiofrequency ablation for Barrett's esophagus: 5-year outcomes from a prospective multicenter trial. Endoscopy 2010; 42: 781-789
- 18 Sharma VK, Wang KK, Overholt BF et al. Balloon-based, circumferential, endoscopic radiofrequency ablation of Barrett's esophagus: 1-year follow-up of 100 patients. Gastrointest Endosc 2007; 65: 185-195
- 19 Roorda AK, Marcus SN, Triadafilopoulos G. Early experience with radiofrequency energy ablation therapy for Barrett's esophagus with and without dysplasia. Dis Esophagus 2007; 20: 516-522
- 20 Phoa KN, van Vilsteren FG, Weusten BL et al. Radiofrequency ablation vs endoscopic surveillance for patients with Barrett esophagus and low-grade dysplasia: a randomized clinical trial. JAMA 2014; 311: 1209-1217
- 21 Bulsiewicz WJ, Kim HP, Dellon ES et al. Safety and efficacy of endoscopic mucosal therapy with radiofrequency ablation for patients with neoplastic Barrett's esophagus. Clin Gastroenterol Hepatol 2013; 11: 636-642
- 22 Maley CC. Multistage carcinogenesis in Barrett's esophagus. Cancer Lett 2007; 245: 22-32
- 23 Maley CC, Galipeau PC, Finley JC et al. Genetic clonal diversity predicts progression to esophageal adenocarcinoma. Nat Genet 2006; 38: 468-473
- 24 Maley CC, Galipeau PC, Li X et al. The combination of genetic instability and clonal expansion predicts progression to esophageal adenocarcinoma. Cancer Res 2004; 64: 7629-7633
- 25 Gordon LG, Mayne GC, Hirst NG et al. Cost-effectiveness of endoscopic surveillance of non-dysplastic Barrett's esophagus. Gastrointest Endosc 2014; 79: 242-256
- 26 Rubenstein JH, Vakil N, Inadomi JM. The cost-effectiveness of biomarkers for predicting the development of oesophageal adenocarcinoma. Aliment Pharmacol Ther 2005; 22: 135-146
-
Supplemental References
- 27 Khara HS, Jackson SA, Nair S et al. Assessment of mutational load in biopsy tissue provides additional information about genomic instability to histological classifications of Barrett's esophagus. J Gastrointest Cancer 2014; 45: 137-145
- 28 Ellsworth E, Jackson SA, Thakkar SJ et al. Correlation of the presence and extent of loss of heterozygosity mutations with histological classifications of Barrett's esophagus. BMC Gastroenterol 2012; 12: 181
- 29 Galipeau PC, Li X, Blount PL et al. NSAIDs modulate CDKN2A, TP53, and DNA content risk for progression to esophageal adenocarcinoma. PLoS Med 2007; 4: e67
- 30 Maley CC, Galipeau PC, Li X et al. The combination of genetic instability and clonal expansion predicts progression to esophageal adenocarcinoma. Cancer Res 2004; 64: 7629-7633
- 31 Eluri S, Brugge WR, Daglilar ES et al. The presence of genetic mutations at key loci predicts progression to esophageal adenocarcinoma in Barrett's esophagus. Am J Gastroenterol 2015; 110: 828-834
- 32 Gerson LB, Groeneveld PW, Triadafilopoulos G. Cost-effectiveness model of endoscopic screening and surveillance in patients with gastroesophageal reflux disease. Clin Gastroenterol Hepatol 2004; 2: 868-879
- 33 Hur C, Nishioka NS, Gazelle GS. Cost-effectiveness of aspirin chemoprevention for Barrett's esophagus. J Natl Cancer Inst 2004; 96: 316-325
- 34 Inadomi JM, Sampliner R, Lagergren J et al. Screening and surveillance for Barrett esophagus in high-risk groups: a cost-utility analysis. Ann Intern Med 2003; 138: 176-186
- 35 Shaheen NJ, Inadomi JM, Overholt BF et al. What is the best management strategy for high grade dysplasia in Barrett's oesophagus? A cost effectiveness analysis. Gut 2004; 53: 1736-1744
- 36 Sonnenberg A, Fennerty MB. Medical decision analysis of chemoprevention against esophageal adenocarcinoma. Gastroenterology 2003; 124: 1758-1766
- 37 Vij R, Triadafilopoulos G, Owens DK et al. Cost-effectiveness of photodynamic therapy for high-grade dysplasia in Barrett's esophagus. Gastrointest Endosc 2004; 60: 739-756
- 38 Sharma VK, Wang KK, Overholt BF et al. Balloon-based, circumferential, endoscopic radiofrequency ablation of Barrett's esophagus: 1-year follow-up of 100 patients. Gastrointest Endosc 2007; 65: 185-195
- 39 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
- 40 Ganz RA, Overholt BF, Sharma VK et al. Circumferential ablation of Barrett's esophagus that contains high-grade dysplasia: a U.S. Multicenter Registry. Gastrointest Endosc 2008; 68: 35-40
- 41 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
- 42 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
- 43 Shaheen N, Sharma P, Overholt B et al. A randomized, multicenter, sham-controlled trial of radiofrequency ablation (RFA) for subjects with Barrett’s esophagus (BE) containing dysplasia: interim results of the AIM Dysplasia Trial. Gastroenterology 2008; 134: A37
- 44 Sharma VK, Jae Kim H, Das A et al. Circumferential and focal ablation of Barrett's esophagus containing dysplasia. Am J Gastroenterol 2009; 104: 310-317
- 45 Sharma VK, Kim HJ, Das A et al. A prospective pilot trial of ablation of Barrett's esophagus with low-grade dysplasia using stepwise circumferential and focal ablation (HALO system). Endoscopy 2008; 40: 380-387
- 46 Schnell TG, Sontag SJ, Chejfec G et al. Long-term nonsurgical management of Barrett's esophagus with high-grade dysplasia. Gastroenterology 2001; 120: 1607-1619
- 47 Hameeteman W, Tytgat GN, Houthoff HJ et al. Barrett's esophagus: development of dysplasia and adenocarcinoma. Gastroenterology 1989; 96: 1249-1256
- 48 Weston AP, Sharma P, Topalovski M et al. Long-term follow-up of Barrett's high-grade dysplasia. Am J Gastroenterol 2000; 95: 1888-1893
- 49 Sharma P, Morales TG, Bhattacharyya A et al. Dysplasia in short-segment Barrett's esophagus: a prospective 3-year follow-up. Am J Gastroenterol 1997; 92: 2012-2016
- 50 Weston AP, Badr AS, Hassanein RS. Prospective multivariate analysis of clinical, endoscopic, and histological factors predictive of the development of Barrett's multifocal high-grade dysplasia or adenocarcinoma. Am J Gastroenterol 1999; 94: 3413-3419
- 51 Cameron AJ, Ott BJ, Payne WS. The incidence of adenocarcinoma in columnar-lined (Barrett's) esophagus. N Engl J Med 1985; 313: 857-859
- 52 Drewitz DJ, Sampliner RE, Garewal HS. The incidence of adenocarcinoma in Barrett's esophagus: a prospective study of 170 patients followed 4.8 years. Am J Gastroenterol 1997; 92: 212-215
- 53 O'Connor JB, Falk GW, Richter JE. The incidence of adenocarcinoma and dysplasia in Barrett's esophagus: report on the Cleveland Clinic Barrett's Esophagus Registry. Am J Gastroenterol 1999; 94: 2037-2042
- 54 Shaheen NJ, Crosby MA, Bozymski EM et al. Is there publication bias in the reporting of cancer risk in Barrett's esophagus?. Gastroenterology 2000; 119: 333-338
- 55 Spechler SJ, Lee E, Ahnen D et al. Long-term outcome of medical and surgical therapies for gastroesophageal reflux disease: follow-up of a randomized controlled trial. JAMA 2001; 285: 2331-2338
- 56 Katz D, Rothstein R, Schned A et al. The development of dysplasia and adenocarcinoma during endoscopic surveillance of Barrett's esophagus. Am J Gastroenterol 1998; 93: 536-541
- 57 Spechler SJ, Robbins AH, Rubins HB et al. Adenocarcinoma and Barrett's esophagus. An overrated risk?. Gastroenterology 1984; 87: 927-933
- 58 Weston AP, Badr AS, Hassanein RS. Prospective multivariate analysis of factors predictive of complete regression of Barrett's esophagus. Am J Gastroenterol 1999; 94: 3420-3426
- 59 Winters Jr C, Spurling TJ, Chobanian SJ et al. Barrett's esophagus. A prevalent, occult complication of gastroesophageal reflux disease. Gastroenterology 1987; 92: 118-124
- 60 Corley DA, Levin TR, Habel LA et al. Surveillance and survival in Barrett's adenocarcinomas: a population-based study. Gastroenterology 2002; 122: 633-640
- 61 Menke-Pluymers MB, Schoute NW, Mulder AH et al. Outcome of surgical treatment of adenocarcinoma in Barrett's oesophagus. Gut 1992; 33: 1454-1458
- 62 Pera M, Trastek VF, Carpenter HA et al. Barrett's esophagus with high-grade dysplasia: an indication for esophagectomy?. Ann Thorac Surg 1992; 54: 199-204
- 63 Peters JH, Clark GW, Ireland AP et al. Outcome of adenocarcinoma arising in Barrett's esophagus in endoscopically surveyed and nonsurveyed patients. J Thorac Cardiovasc Surg 1994; 108: 813-821 ; discussion 821 – 822
- 64 Streitz Jr JM, Andrews Jr CW, Ellis Jr FH. Endoscopic surveillance of Barrett's esophagus. Does it help?. J Thorac Cardiovasc Surg 1993; 105: 383-387 ; discussion 387 – 388
- 65 Overholt BF, Panjehpour M, Halberg DL. Photodynamic therapy for Barrett's esophagus with dysplasia and/or early stage carcinoma: long-term results. Gastrointest Endosc 2003; 58: 183-188
- 66 Sharma P, Wani S, Weston AP et al. A randomised controlled trial of ablation of Barrett's oesophagus with multipolar electrocoagulation versus argon plasma coagulation in combination with acid suppression: long term results. Gut 2006; 55: 1233-1239
- 67 Bousamra 2nd M, Haasler GB, Parviz M. A decade of experience with transthoracic and transhiatal esophagectomy. Am J Surg 2002; 183: 162-167
- 68 Lerut T, Coosemans W, Van Raemdonck D et al. Surgical treatment of Barrett's carcinoma. Correlations between morphologic findings and prognosis. J Thorac Cardiovasc Surg 1994; 107: 1059-1065 ; discussion 1065 – 1056
- 69 McLarty AJ, Deschamps C, Trastek VF et al. Esophageal resection for cancer of the esophagus: long-term function and quality of life. Ann Thorac Surg 1997; 63: 1568-1572
- 70 Patti MG, Corvera CU, Glasgow RE et al. A hospital's annual rate of esophagectomy influences the operative mortality rate. J Gastrointest Surg 1998; 2: 186-192
- 71 Zaninotto G, Parenti AR, Ruol A et al. Oesophageal resection for high-grade dysplasia in Barrett's oesophagus. Br J Surg 2000; 87: 1102-1105
- 72 Arrowsmith JB, Gerstman BB, Fleischer DE et al. Results from the American Society for Gastrointestinal Endoscopy/U.S. Food and Drug Administration collaborative study on complication rates and drug use during gastrointestinal endoscopy. Gastrointest Endosc 1991; 37: 421-427
- 73 Chan MF. Complications of upper gastrointestinal endoscopy. Gastrointest Endosc Clin N Am 1996; 6: 287-303
- 74 Hart R, Classen M. Complications of diagnostic gastrointestinal endoscopy. Endoscopy 1990; 22: 229-233
- 75 Hernandez LV, Jacobson JW, Harris MS. Comparison among the perforation rates of Maloney, balloon, and savary dilation of esophageal strictures. Gastrointest Endosc 2000; 51: 460-462
- 76 Kavic SM, Basson MD. Complications of endoscopy. Am J Surg 2001; 181: 319-332
- 77 Iannettoni MD, Vlessis AA, Whyte RI et al. Functional outcome after surgical treatment of esophageal perforation. Ann Thorac Surg 1997; 64: 1606-1609 ; discussion 1609 – 1610
- 78 Montgomery E, Bronner MP, Goldblum JR et al. Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation. Hum Pathol 2001; 32: 368-378
- 79 Ormsby AH, Petras RE, Henricks WH et al. Observer variation in the diagnosis of superficial oesophageal adenocarcinoma. Gut 2002; 51: 671-676
- 80 Provenzale D, Kemp JA, Arora S et al. A guide for surveillance of patients with Barrett's esophagus. Am J Gastroenterol 1994; 89: 670-680
- 81 Provenzale D, Schmitt C, Wong JB. Barrett's esophagus: a new look at surveillance based on emerging estimates of cancer risk. Am J Gastroenterol 1999; 94: 2043-2053
- 82 Alikhan M, Rex D, Khan A et al. Variable pathologic interpretation of columnar lined esophagus by general pathologists in community practice. Gastrointest Endosc 1999; 50: 23-26
- 83 Zaman A, Hapke R, Sahagun G et al. Unsedated peroral endoscopy with a video ultrathin endoscope: patient acceptance, tolerance, and diagnostic accuracy. Am J Gastroenterol 1998; 93: 1260-1263
- 84 de Boer AG, Stalmeier PF, Sprangers MA et al. Transhiatal vs extended transthoracic resection in oesophageal carcinoma: patients' utilities and treatment preferences. Br J Cancer 2002; 86: 851-857
- 85 Weinstein MC, Siegel JE, Gold MR et al. Recommendations of the Panel on Cost-effectiveness in Health and Medicine. JAMA 1996; 276: 1253-1258