191. CIRCULATING TUMOR DNA (CTDNA) ANALYSIS FOR DETECTION OF RESIDUAL DISEASE AFTER NEOADJUVANT CHEMORADIOTHERAPY (NCRT) FOR ESOPHAGEAL SQUAMOUS CELL CARCINOMA (ESCC)

Abstract

Abstract Background High pathological complete response (pCR) rates were observed in ESCC patients after nCRT. A ‘Watch and Wait’ strategy has been proposed for patients with clinical complete response (cCR) after nCRT. However, clinical assessments (e.g. endoscopic biopsy) may misclassify non-pCR as cCR. In this study, we investigate the value of two kinds of ctDNA analysis strategies in predicting tumor response and residual disease after nCRT in ESCC, including personalized panel and tumor-naïve fixed panel (TNFP) analyses. Methods This is a side study of preSINO trial (NCT03937362). After nCRT completion, patients underwent clinical response evaluations (CREs) before planned surgery. CRE-1 was 4–6 weeks after nCRT. CRE-2 was 10–12 weeks after nCRT for patients without histological evidence of residual tumor at CRE-1. Individual tumors and matched white blood cells prior to nCRT (B0) were whole-exome sequenced for somatic mutations selection. Serial plasma samples were analyzed by brPROPHET personalized panel and 168-gene TNFP respectively at three timepoints: B0, CRE-1, CRE-2. We correlated ctDNA status with pCR and major locoregional residual disease (MLRD) (>10% residual cancer or any residual nodal disease). Results A total of 55 ESCC patients who received per-protocol treatments underwent ctDNA detection. The pCR rate was 27% (15/55). 98.38% of variants selected for brPROPHET panel design were private to a specific patient, only 3.1% of variants were included in the TNFP (Fig. A-B). ctDNA positive rates of brPROPHET were significantly higher than TNFP assay at three timepoints (Fig. C). Importantly, the brPROPHET achieved higher sensitivity than TNFP in predicting non-pCR and MLRD owing to its ability to detect extremely low ctDNA fractions (Fig. D). Moreover, combining brPROPHET with CREs could further improve the sensitivity (Fig. E). Conclusion Personalized ctDNA analysis exhibited superior sensitivity and predictive performance than TNFP assay. What’s more, personalized ctDNA analysis can supplement the clinical assessment to decrease the false negative rate in identifying patients with residual disease after nCRT, and might become useful in the ‘Watch and Wait’ strategy for the management of ESCC.