A PROSPECTIVE MULTICENTER TRIAL OF THE CRYOBALLOON ABLATION SYSTEM FOR SUPERFICIAL ESOPHAGEAL SQUAMOUS CELL CARCINOMA ON THE POST-ENDOSCOPIC RESECTION SCAR. (CRYO-SCAR STUDY, EPOC1902)

Background
Focal cryoballoon ablation (FCBA) is a relatively new ablation modality for the treatment of Barrett’s esophagus (BE) related neoplasia. This prospective, European multicenter study (Euro-Coldplay, NTR NL7253) aimed to evaluate the efficacy and safety of FCBA for the treatment of limited BE.

Method
In eight European Barrett referral centers, patients with C≤2M≤5 BE with an indication for ablation therapy were eligible for inclusion. Before entry, any visible lesion had to be removed by endoscopic resection (max. 2cm in length and 50% of circumference). FCBA was performed by experienced and trained endoscopists at 3 month intervals until complete endoscopic eradication of BE (max. 5 sessions). During every session, the esophagogastric junction was treated circumferentially followed by all visible BE using side-by-side ablations with a dose of 8 seconds per ablation. After at least two FCBA sessions, add-on treatment was allowed with either argon plasma coagulation (APC) for BE lesions of <5mm (max. 2 sessions) or a single endoscopic mucosal resection for lesions of >5mm. Outcomes included complete eradication of intestinal metaplasia (CE-IM) and dysplasia (CE-D), and adverse event rate.

Results
107 patients (91 males; mean age 65) with a median BE length of C0M2 were included, containing low-grade dysplasia (32%), high-grade dysplasia (32%) or early cancer (39%) as worst baseline histology. Currently, 84/107 (79%) patients have finished the treatment phase of which the results are reported hereafter. 57/84 (68%) patients underwent endoscopic resection at entry followed by a median of 2 (IQR 2-2) FCBA treatments with a median of 7 (IQR 6-9) ablations per treatment session. Only one patient (1/84; 1%) could not be treated with FCBA owing to a device malfunction requiring a switch to radiofrequency ablation. During the treatment phase, 3/84 (4%) patients developed a new visible, neoplastic lesion amenable for endoscopic resection (high-grade dysplasia n=2, low-risk T1 cancer n=1). Add-on treatment after at least two FCBA sessions was performed in 32/84 (38%) patients, of whom the most were treated with APC (31/32; 97%). CE-D was achieved in 95% (80/84) and CE-IM in 93% (78/84), per intention-to-treat analysis. Per-protocol analysis, CE-D and CE-IM were achieved in 100% (80/80) and 98% (78/80), respectively. Esophageal stricture was the most common adverse event in 13/84 (15%) patients, which resolved after a median of 2 (IQR 1-4) dilations. No perforation or bleeding were observed, while buried BE glands were seen in 1/84 (1%).

Conclusion
In expert hands, endoscopic eradication therapy with FCBA seems to be highly effective with an acceptable safety profile for patients with limited BE. Long-term follow-up is warranted to evaluate the durability of the treatment response.

Introduction
Endoscopic resection (ER) including endoscopic submucosal dissection (ESD) is widely accepted as a minimally invasive treatment for superficial esophageal squamous cell carcinoma (SESCC). However, there is a risk for developing metachronous SESCC in the preserved esophagus after ER. ER for SESCC on the post-ER scar is generally difficult to achieve en bloc resection even with ESD. Recently, the efficacy of the cryoballoon ablation system (CBAS) has been demonstrated in the management of dysplastic and neoplastic Barrett’s esophagus. On the other hand, there is little evidence for CBAS treatment of SESCC. We aimed to evaluate the efficacy and safety of CBAS for SESCC on the post-ER scar.
Methods
This prospective single-arm study included patients with clinically T1a SESCC on the post-ER scar from two tertiary referral centers in Japan (JapicCTI-205427). The key exclusion criteria were lesions at cervical esophagus, lesions of >5 cm in size and/or involving whole circumferential, and 4 lesions or more. Cryoablation was performed using the focal CBAS (Pentax Medical, HOYA) with 8 or 10-second cryogen dose. No upper limit was set for number of ablation cycles. One repeat-cryoablation was allowed if there was residual disease within 4 months after the initial treatment. The primary endpoint was local complete response (L-CR) rate of the primary lesion (A largest lesion of all lesions) at 48 weeks after first cryoablation as judged by an independent committee. L-CR was defined as no histological and endoscopic recurrence findings. Secondary endpoints were L-CR rate judged by the investigators, L-CR rate for all lesions, technical success rate, procedure time, pain score (scored 0 to 10 within 7 days), recurrence free survival (RFS), overall survival (OS), and incidence of adverse event (AE). Planned sample size was set at 15, with threshold L-CR rate of 55%, expected one of 90%, one-sided alpha of 5% and power of 85%.
Results
From October 2020 to October 2021, 15 patients with 17 lesions were enrolled all of whom completed protocol treatment. Two patients underwent repeat-cryoablation. L-CR rate of the primary lesion judged by the independent committee was 100% (90%CI 81.9-100%). L-CR rate for all lesions was also 100% (17/17). The endoscopic assessment of L-CR by the principal and sub-investigators was consistent in all cases. Median treatment time was 15 min (8-28). For the pain score, 8 patients did not report any pain, and the maximum score was 3 in one patient. The technical success rate was 94.7% (18/19). No recurrence and death were occurred with a median follow-up of 14.3 months. There was no grade 3 or higher treatment-related AEs, one of grade 2 esophageal pain, two of grade 1 esophageal stricture, and one case of grade 1 vomiting.
Conclusion
CBAS is safe and effective for the treatment of patients with SESCC on the scar after ER.