Introduction

Endoscopic eradication therapy (EET) is well-established for treatment of Barrett’s Esophagus (BE) related neoplasia. Despite very low risks of neoplasia recurrence, current protocols for endoscopic follow-up (FU) after successful EET are quite strict and do not take into account the significant risk of mortality due to other causes than esophageal cancer. An accurate prediction of the risk for unrelated mortality is key to patient-tailored and cost-effective care.

Aims & Methods

We evaluated the performance of the well-known Charlson Comorbidity Index (CCI) for prediction of unrelated mortality during follow-up in a cohort of patients successfully treated with EET for BE neoplasia. In the Netherlands, EET is centralized in 9 Barrett Expert Centers (BEC) who follow a joint treatment and FU protocol and have a joint registry. This registry is merged with National Statistics for accurate survival outcomes, including date and cause of death. This study included all patients who achieved complete eradication of BE after EET (from 2008-2018) and with at least one year FU. CCI was calculated at the start of EET based on existing medical records. The predictive value of the CCI on the primary outcome mortality during FU was evaluated using C-statistic and calibration plots (predicted vs observed rates).

Results

A total of 1,154 patients were followed for median 59 months (IQR 37-91) per patient after achieving complete eradication of EET. At start of FU, mean age was 64 years (±9). Most common comorbidities were: myocardial infarction (n=165, 14%), diabetes mellitus (n=158, 14%), and chronic obstructive pulmonary disease (n=155, 13%). Median CCI was 3 (IQR 2-4, range 0-10). During FU, 154 (13%) patients died due to unrelated causes. The time to death was median 58 months (IQR 36-90) after start of EET. Baseline CCI score was significantly higher among the patients who died from unrelated causes (4.0 ±1.7) as compared to patients alive (2.9 ±1.6, p<0.05). With increasing baseline CCI, mortality risk increased significantly. For each quartile of CCI (i.e. CCI <2; 2-3; 3-4; and >4), mortality during FU was 7%, 11%, 21% and 27% respectively. Discrimination of CCI was acceptable (C-statistic 0.78 [95% CI 0.72-0.84], with higher scores indicating better ability of the model to distinguish individuals with and without mortality). The calibration plot indicated reasonable calibration, based on comparable predicted and observed risks. Sensitivity analyses showed comparable results, indicating the model is robust.

Conclusion

CCI predicts unrelated mortality well in a population of BE patients after successful EET. This simple-to-calculate score could be used to guide decisions for patient-tailored management such as when to stop follow-up after successful EET.

Introduction

Current guidelines advise esophagectomy for submucosal esophageal adenocarcinoma (T1b EAC). However, data from retrospective studies suggest that endoscopic follow-up (FU) may be a valid alternative in patients without signs of lymph node metastases (LNM) at baseline. In this international multicenter, prospective cohort study (NCT03222635), we aim to evaluate the safety of a watchful waiting strategy with regular endoscopic FU in patients treated endoscopically for T1b EAC.

Aims & Methods

This ongoing prospective study is conducted in 19 hospitals in Europe and Australia, and aims to include 141 patients with 5-year FU. After radical endoscopic resection of T1b EAC, patients are re-staged with endoscopic ultrasound (EUS) and CT/PET. In the absence of LNM or distant metastases (N0M0), and upon consent for endoscopic FU, patients are included and undergo strict endoscopic FU with gastroscopy and EUS every 3 months during year 1 and 2, every 6 months during year 3 and 4, and at year 5. CT/PET is repeated after 1 year. We divided our cohort into two groups: ‘high-risk’ (submucosal invasion ≥500um, a/o poorly/undifferentiated tumor (G3-4), a/o lymphovascular invasion (LVI+)) and ‘low-risk’ if no high risk features are present. Primary outcome parameters are 5-year disease specific survival and overall survival; secondary outcome parameters are rate of LNM and local recurrence.

Results

Since July 2017, 134 patients (112 men, median age 69 ±10 years) were included with a median FU of 22 (IQR 11-35) months: 87 high-risk and 47 low-risk patients. 6 patients (4% [95%CI 0.2-8.8]) were diagnosed with LNM (table 1) after median FU of 8 (IQR 5-16) months. Of these 6 patients, 2/6 were referred for neoadjuvant chemo(radio)therapy with esophagectomy (ypT0N1M0, ypT0N0M0), 1/6 underwent esophagectomy only (pT0N2M0), 3/6 underwent a selective surgical resection of the tumor-positive LN.
7 patients (5% [95%CI 0.8-9.6] were diagnosed with an intra-luminal tumor recurrence not eligible for endoscopic re-treatment after median FU of 7 (IQR 6-15) months. 5 had initial ESD and 2 cap-based EMR. Of these 7 patients, 2/7 underwent esophagectomy (pT1bN0M0, pTisN0M0), 1/7 had neoadjuvant chemoradiotherapy and esophagectomy (ypT1aN0M0), 3/7 underwent (chemo)radiotherapy only, of which 1 patient eventually died as result of stenosing EAC, 1/7 refused additional treatment. No distant metastases were diagnosed during FU in both cohorts. Five patients died during FU of a cause unrelated to EAC. Five patients discontinued FU due to old age. Two patients were lost to FU.

Conclusion

The preliminary analysis from our ongoing prospective study suggest that in patients with radically removed high- or low-risk T1b EAC, without LNM at baseline, a strict endoscopic follow-up protocol is feasible and the window for curative therapy remains open for those patients who develop LNM (4%) or a local intra-luminal recurrence (5%) during FU. Most patients demonstrate uneventful FU.

Disclosure

No conflict of interests.

Introduction

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.

Aims & Methods

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, 5/107 patients are still under treatment and therefore excluded from further analysis. Of the remaining patients, 97 (97/102; 95%) patients have finished the treatment phase per protocol, while four (4/102; 4%) patients left the study prematurely. Only one (1/102; 1%) patient could not be treated with FCBA due to a device malfunction requiring a switch to radiofrequency ablation. Overall, 65/102 (64%) patients underwent endoscopic resection at entry followed by a median of 2 (IQR 2-2) FCBA treatments with a median of 7 (IQR 5-9) ablations per treatment session. During the treatment phase, 3/102 (3%) 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 38/102 (37%) patients, of whom the most were treated with APC for small remaining Barrett islands (37/38; 97%). CE-D was achieved in 95% (97/102) and CE-IM in 91% (93/102), per intention-to-treat analysis. Per-protocol analysis, CE-D and CE-IM were achieved in 100% (97/97) and 96% (93/97), respectively. Esophageal stricture was the most common adverse event in 13/102 (13%) patients, which resolved after a median of 2 (IQR 1-4) dilations. Only three (3/102; 3%) patients suffered a severe stricture requiring >3 dilations. No perforation or bleeding were observed, while buried BE glands were seen in 1/102 (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.

Disclosure

C.N. Frederiks have received speaker's fee and reimbursement of study-related travel costs from Pentax Medical. A. Overwater has received reimbursement of study-related travel costs from Pentax Medical. J.J.G.H.M. Bergman is a consultant for Medtronic, Cook Medical, and Boston Scientific, and has received research funding from Pentax Medical, C2 Therapeutics, Medtronic, Aqua Medical, Olympus Endoscopy, and Fuji-film. R.E. Pouw is a consultant for MicroTech, and has received speaker’s fee from Medtronic. R. Bisschops is a consultant for Pentax Medical, Medtronic, and Erbe Medical, and has received research funding and speaker’s fees from Pentax Medical, Medtronic, and Erbe Medical. T. Beyna is consultant for Medtronic, Erbe Medical, Microtech Endoscopy, Olympus Endoscopy, and Boston Scientific. B.L.A.M. Weusten has received research funding from Pentax Medical, C2 Therapeutics, and Aqua Medical. The remaining authors declare to have no disclosures relevant to this manuscript.