Prospective study of endoscopic focal cryoballoon ablation for esophageal squamous cell neoplasia in China

Abstract

Background and aims: Esophageal squamous cell neoplasia (ESCN) has a significant risk for progression to cancer. Current treatment options, endoscopic mucosal resection (EMR) or submucosal dissection (ESD), have their limitations. The cryoballoon focal ablation system (CbFAS) is a novel endoscopic ablation therapy device. We aimed to assess the safety, tolerability, and efficacy of CbFAS for eradication of ESCN.

Methods: In this single-center prospective trial in China, patients with 1 flat unstained lesion (USL) on Lugol chromoendoscopy that contained moderate- or high-grade intraepithelial neoplasia (MGIN or HGIN, respectively) were enrolled. CbFAS was performed using side-by-side applications of 10 seconds, treatment was repeated at 3-month intervals until a complete response (CR) was established. The response at 12 months was the primary trial endpoint. Safety phone calls were performed at 2, 7, and 30 days after the initial CbFAS.

Results: We enrolled 80 patients (59 MGIN, 21 HGIN) with a median USL length of 3 cm (interquartile range [IQR], 3-4). Seventy-nine received treatment, with a median of 5 side-by-side applications (IQR, 4-7) per patient over a median of 8 minutes (IQR, 5-10). After a single treatment, 70 of 78 patients (90%) exhibited CR, and 1 was lost to follow-up. The other 8 with persisting USLs were retreated, and all achieved CR after this second treatment. At 12 months after the initial CbFAS, 76 of 78 patients (97%) exhibited CR and 2 (3%) had recurrent MGIN. No strictures or serious adverse events occurred. Four patients developed self-limiting mucosal lacerations on balloon inflation. The postprocedure median pain score was 1 of 10 (IQR, 0-2) at day 2 and 0 (0-0) at days 7 and 30.

Conclusions: The results suggest that the CbFAS is safe, well tolerated, and effective in inducing endoscopic and histologic remission in patients with ESCN of limited size. (Clinical trial registration number: NCT02605759.).

Copyright © 2019. Published by Elsevier Inc.

Figures

Figure 1. The focal Cryoballoon Ablation system

A + b. A 3.6mm diameter catheter is advanced through the working channel of a therapeutic endoscope c. The balloon can be inflated and it automatically adjusts to the size of the esophagus d. A 10-second flow of nitrous oxide results in focal ice patches of approximately 2cm2, and the entire lesion can be ablated with side-by-side applications.

Figure 2

Study Flowchart Abbreviations: CbFAS – cryoballoon focal ablation system; CR – complete remission of neoplasia; FU – follow-up; MGIN – moderate grade intraepithelial neoplasia; USL – unstained lesion *A single patient developed mucosal lacerations after inflation of the balloon and withdrew informed consent afterwards.

Figure 3

Images of a typical case in our study. At baseline, an unstained lesion was found after Lugol’s at 6 o’clock, which was not suspicious for invasive cancer (a, b, c). The balloon was advanced through the endoscope (d) and the entire lesion was ablated with 5 side-by-side ablations of 10 seconds duration each (e). A clear ice patch is visible directly after retraction of the balloon (f). At the 3-months follow-up endoscopy (g, h, i) a scar was found at the treated area and there was no endoscopic evidence of residual neoplasia, this was confirmed histologically with biopsies showing normal squamous epithelium. Patient was thus in complete remission of neoplasia, and this was persistent at the 12-months endoscopy.

Figure 4

Pain and dysphagia Postprocedural retrosternal pain was assessed by telephone at 2, 7 and 30 days after the procedure using a 11-point visual analogue scale for pain. Dysphagia was assessed using the validated 5-item scale for dysphagia.