Therapeutic Advances in Barrett’s Esophagus

Therapeutic Advances in Barrett’s Esophagus

2019 DDW Review

Christopher Hibbard, DODepartment of Digestive Diseases and Transplantation

Einstein Healthcare Network

Barrett’s Esophagus in 2019

• Background of Barrett’s esophagus and Endoscopic Eradication Therapy of neoplastic disease

• Success of achieving CE-IM and CE-D and risk factors associated with recurrence

• New Cryotherapy data and indications for use

• New, less invasive screening for Barrett’s esophagus

Esophageal Cancer

Rustgi AK, El-Serag HB. N Engl J Med 2014;371:2499-2509.

Esophageal Cancer

Kong, CY, et al. Cancer Epidemiol Biomarkers Prev; 23(6); 997–1006.

Evolution of Barrett’s and Esophageal Cancer

1. Kountourakis P, et al. BE, a review of biology and therapeutic approaches. Gastrointest Cancer Res 2012;5:49-57

2. Ong CJ, et al. Biomarkers in BE and EAC: predictors of progression and prognosis. World J Gastroenterol 2010;16(45):5669-5681

SQUAMOUS ESOPHAGUS CHRONIC INFLAMMATION BARRETT’S METAPLASIA LOW-GRADE DYSPLASIA HIGH-GRADE DYSPLASIA INVASIVE

ADENOCARCINOMA

v

v

ACCUMULATE GENETIC CHANGESv

CHRONIC INJURY: ACIDIC AND NON-ACIDIC REFLUX

Endoscopic Eradication Therapy

Rustgi AK, El-Serag HB. N Engl J Med 2014;371:2499-2509.

RFAABLATION: CIRCUMFERENTIAL FOCAL FOCAL FOCAL FOCAL

BARRXTM

FLEX GENERATORBARRXTM 360 BARRXTM

ULTRA LONGBARRXTM 60 BARRXTM 90 BARRXTM

CHANNEL

CIRCUMFERENTIAL ABLATION

FOCAL ABLATION

Cryotherapy

RFA AIM-D 5 Years

▪ AIM Dysplasia Trial Extension II▪ 127 patients with HGD or LGD▪ CE-IM (n=108), CE-D (n=110)▪ 61% (n=72) had follow-up at 5 years▪ Allowing interim RFA:

▪ CE-IM 90%, CE-D 99%▪ Without interim RFA:

▪ CE-IM 78%

Wani, et al. DDW 2019

WIDE AREA TRANSEPITHELIAL SAMPLING IMPROVES DETECTION OF INTESTINAL METAPLASIA AND DYSPLASIA FOLLOWING

ENDOSCOPIC ABLATION OF BARRETT'S ESOPHAGUS• AuthorBlock: Michael S. Smith, Vivek Kaul, Robert Odze

• Background: Despite recent technical advances in endoscopic ablation of Barrett’s esophagus (BE), a significant percentage of patients have residual/recurrent intestinal metaplasia (RRIM) on pathology, even with a negative endoscopy. The lack of distinctive endoscopic features, disease focality and sampling error make diagnosing residual or recurrent disease a challenge. Adjunctive use of Wide Area Transepithelial Sampling with computer-assisted analysis (WATS) has been shown to increase detection of BE and associated dysplasia in patients undergoing BE screening or surveillance. We evaluated how WATS impacts detection of RRIM and its associated dysplasia in the post-BE ablation setting.

• Methods: A retrospective review was performed on multi-site IRB-approved registries capturing data from patients who underwent BE ablation and subsequently were evaluated using both WATS and forceps biopsy (FB). FB were interpreted by each site’s pathologist and WATS specimens were assessed at a central laboratory (CDx Diagnostics, Suffern, NY). The presence or absence of IM (defined as columnar epithelium with goblet cells) and grade of dysplasia, if present, were catalogued for each case.

WIDE AREA TRANSEPITHELIAL SAMPLING IMPROVES DETECTION OF INTESTINAL METAPLASIA AND DYSPLASIA FOLLOWING

ENDOSCOPIC ABLATION OF BARRETT'S ESOPHAGUS• Results: A total of 802 patients with a history of BE ablation were included (mean age 67 years, range 20-93

years, 64% male). Short segment BE (<=3 cm) was documented in 89% of patients, and most were treated with radiofrequency ablation. A total of 913 post-ablation endoscopies were performed by 118 endoscopists at 76 sites. On FB alone, RRIM was detected in 245 cases (27%), including 17 cases having more advanced disease (9 low grade dysplasia (LGD), 6 high grade dysplasia (HGD), 2 adenocarcinoma). Another 10 cases were indefinite for dysplasia (IND). Adjunctive use of WATS identified an additional 194 RRIM cases missed on FB, including 38 cases with more advanced disease (27 crypt dysplasia, 5 LGD and 6 HGD). Another 2 cases were IND. Compared to FB alone, adding WATS increased detection of RRIM by 79% (65% - 95%, p<.05) and associated dysplasia by 224% (129.7% - 447%, p<.05), corresponding to absolute increases in detection of 21.2% and 4.2%, respectively. The number needed to test (NNT) with WATS to identify an additional case of RRIM was 4.7, and 24 for an additional case of dysplasia. Further analysis demonstrated no significant difference in demographics or pre-ablation dysplasia grade when cases with WATS-only detection were compared to those where the diagnosis did not change with WATS.

• Conclusion: WATS is a highly effective adjunct to FB in the detection of RRIM and associated dysplasia in post-BE ablation patients. Identifying these findings, especially when dysplasia is present, directly impacts patient management. Thus, post BE-ablation tissue sampling should include both FB and WATS to maximize detection of residual or recurrent disease.

Eluri, et al. DDW 2019

A MULTICENTER STUDY OF THE SAFETY AND ACCEPTABILITY OF CYTOSPONGE™: FIRST REPORT IN AN AMERICAN

POPULATION WITH BARRETT’S ESOPHAGUS AND GERD

• AuthorBlock: Nicholas J. Shaheen, John M. Haydek, Sri Komanduri, V. Raman Muthusamy, Sachin B. Wani, Rajinder Kaushal

• Introduction: Screening for Barrett’s esophagus (BE) uses endoscopy, an invasive and costly procedure. Non-endoscopic techniques to screen patients with BE have the potential to overcome these issues. The Cytosponge™ is a minimally invasive, sponge-based device used to sample esophageal mucosa. This study assessed the safety and acceptability of a new commercial prototype of Cytosponge™ in patients with BE undergoing surveillance and patients with gastroesophageal reflux disease (GERD) undergoing screening.

• Methods: This cross-sectional study was conducted at 6 U.S. sites between 2015 and 2018. Eligible patients were ≥18 yr, and had either confirmed BE or patient-reported heartburn or regurgitation at least monthly for ≥6 months. The Cytosponge™ (Medtronic) was administered with 150-250 cc water, and dwelled in the stomach for 7 minutes to allow the capsule surrounding the sponge to dissolve. It was then retracted via the attached suture through the esophagus and out of the mouth. Cytosponge™ administration was followed by sedated esophagogastroduodenoscopy (EGD). In cases where an inadequate sample was collected, patients were invited to repeat Cytosponge™ administration. A follow-up phone call was performed 7 days post-procedure. Acceptability was evaluated using the Impact of Event Scale (IES; a standardized measure of psychological impact), a visual analog scale for pain, and the patient’s willingness to undergo repeat Cytosponge™ administration. Adverse events were catalogued using MedDRA classification.

A MULTICENTER STUDY OF THE SAFETY AND ACCEPTABILITY OF CYTOSPONGE™: FIRST REPORT IN AN AMERICAN

POPULATION WITH BARRETT’S ESOPHAGUS AND GERD• Results: A total of 191 patients were enrolled, including 129 BE patients and 62 GERD patients; 181

patients completed the follow-up call. Average age was 61 ± 13 yr and 69% of patients were male. In the BE arm, 68% of patients had non-dysplastic BE; low-grade or high-grade dysplasia were reported in 10% and 5%, respectively (Table 1). Of 191 patients, 99.5% successfully swallowed the Cytosponge™. On a 1-10 scale, patient acceptability of Cytosponge™ and endoscopy procedures were not significantly different (7.2 ± 2.5 vs 8.5 ± 2.5). Patients indicated that if the physician indicated that it was medically necessary, 93% would be willing to repeat Cytosponge™, and 65% preferred Cytosponge™ over EGD. On a scale of 100, the average Visual Analog Scale for pain was 16.2 ± 18.3, and 88% of patients rated the Cytosponge™ as having no meaningful impact on IES (Table 2). The most common adverse events included oropharyngeal pain (N=4, 2%) and throat irritation (N=2, 1%)). Two cases of sponge detachment occurred, both retrieved during subsequent EGD, leading to an alteration in device design for the planned commercial product.

• Conclusions: The acceptability of the Cytosponge™ procedure was high, and the reported patient experience good in this U.S. population. This non-endoscopic method may provide an alternative to EGD for initial screening for BE.

Take Home Points• Endoscopic Eradication Therapy of neoplastic Barrett’s esophagus

is standard of care

• Risk factors for developing recurrence of neoplastic disease have been identified and WATS is becoming biopsy method of choice

• Cryotherapy data are encouraging, but randomized, placebo controlled trial lacking

• New technology for Barrett’s screening on the horizon

Thank You

Therapeutic Advances in Barrett’s Esophagus

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