CYTOFLOC: Evaluation of a non-endoscopic immunocytological device (Cytosponge (TM)) for post-chemoradiotherapy surveillance in patients with oesophageal cancer - a feasibility study

Abstract

Background: Accurate response assessment in patients with oesophageal cancer undergoing neo-adjuvant chemoradiotherapy would pave the way for more tailored management. Cytosponge TM consists of an expandable, spherical mesh attached to a string and contained within a soluble capsule. The capsule dissolves in the stomach, releasing the sponge which is retrieved by pulling the string. Oesophageal cells collected can be evaluated for molecular markers. CYTOFLOC evaluated feasibility, safety, acceptability and indicative accuracy of Cytosponge TM to assess response in patients with oesophageal cancer treated with definitive or neoadjuvant chemo radiotherapy (dCRT/nCRT). Methods: Inclusion: patients 16 years who have undergone dCRT/nCRT, 4-16 weeks post treatment, dysphagia score 0-2, able to swallow tablets and fit for endoscopy. Exclusion: varices, strictures, stent. Nurses were trained to administer the Cytosponge TM. Cytosponge TM was administered after 6 hours fast. Only 2 attempts at swallowing were provided. Acceptance was evaluated through patient questionnaires. Blood for ctDNA, and corresponding endoscopic/surgical histology assessment was optional. Primary Objective: Completion rate (The proportion of consented, evaluable, patients successfully undergoing Cytosponge TM). Secondary Objectives: Safety (all serious adverse events); Suitability of sample for biomarker analysis (Presence of cytological atypia and/or p53 mutation was considered +ve test); Acceptance rate (Proportion of eligible patients approached who consented; proportion of patients who would accept the procedure repeatedly). Tertiary Objectives: detection of ctDNA; Comparative efficacy of Cytosponge TM to resected/endoscopic histology. Results: 41 patients were recruited between April 2018 and January 2020 from 11 hospitals. Participant/tumour characteristics: Mean (SD) age 68.32 (10.3) years, median (IQR) baseline tumour length 5cm (2,7). Male:Female (33:8), Dysphagia grade 0:1:2(27:12:2), dCRT:nCRT (28:13), SCC:Adeno (25:16); Site upper:mid:lower:GO Junction (7:8:22:4). Overall completion rate was 39/41(95.1%, 95% CI 83.5-99.4). 41/ 96 (42.7%, 95% CI 32.7,53.2) eligible patients consented, and 37/39 (94.9%, 95% CI 82.7,99.4) were willing to accept repeated procedures. Three grade 1 AE were recorded (sore throat dysphagia, dyspepsia). 38/39 (97.4%, 95% CI 86.5,99.9) were considered suitable for biomarker analysis. 9/38 (24%) were considered positive by cytological criteria. Corresponding histology was available in 33 patients (3 positive on histology, 30 negative on histology). There was high-level agreement between negative samples. Of patients with negative histology, 4 patients were atypia positive/ uncertain on Cytosponge TM and 3 were p53 aberrant on Cytosponge TM.