GASC1-Adapted Neoadjuvant Chemotherapy for Resectable Esophageal Squamous Cell Carcinoma: A Prospective Clinical Biomarker Trial

Abstract EN

Neoadjuvant chemotherapy (NCT) is a standard care for esophageal squamous cell carcinoma (ESCC), but the efficacy is unsatisfactory.

Cancer stem cells (CSCs) play key roles in chemotherapy resistance.

Gene amplified in squamous cell carcinoma 1 (GASC1) is a neoteric gene in stemness maintaining of ESCC.

We aimed to reveal whether GASC1 could be a predictive biomarker for NCT in ESCC.

ESCC patients (T2-4N0-2M0) were evaluated for GASC1 expression using immunohistochemical staining and classified as GASC1-low group (GLG) and GASC1-high group (GHG).

NCT was delivered in two cycles and then the surgery was completed.

Primary endpoints were tumor regression grade (TRG) and objective response rate (ORR); secondary endpoints were radical surgical resection (R0) rate and three-year overall survival (OS).

60 patients were eligible with evaluable outcomes: 24 in GHG and 36 in GLG.

Between GHG and GLG, TRG1, TRG2, TRG3, and TRG4 were 0 : 16.7%, 20.8% : 41.7%, 58.3% : 36.1%, and 20.8% : 5.6%, respectively (P=0.006); ORR and R0 rate were 33.3% : 69.4% (P=0.006) and 75% : 94.4% (P=0.046), respectively; the median OS was 20 : 32 (months) (P=0.0356).

No significant difference in the three-year OS was observed between GHG and GLG: 29.2% : 41.7% (P=0.24).

Furthermore, the GASC1 expression level was associated with poor OS independent of other factors by univariate and multivariate analyses.

Therefore, GASC1 might be a potential biomarker to predict NCT efficacy for ESCC.