359. NFE2L2 MUTATIONS ARE PREDICTIVE AND PROGNOSTIC OF TREATMENT OUTCOME IN RESECTABLE ESOPHAGEAL SQUAMOUS CELL CARCINOMA PATIENTS
Josephine Ko, Chen Guo, Anthony Wing-Ip Lo, Lihua Tao, Simon Law, Ka-On Lam, Dora Lai-Wan Kwong, Ian Yu-Hong Wong, Claudia Lai-Yin Wong, Siu-Yin Chan, Kwan-Kit Chan, Tsz-Ting Law, Alvin Ka-Kiu Leung, Carissa Wing-Yan Wong, Wei Dai, Maria Li Lung- Gastroenterology
- General Medicine
Abstract
Background
The poor prognosis of resectable esophageal squamous cell carcinoma (ESCC) poses an unmet need to identify genomic early predictive and prognostic biomarkers to improve treatment outcome and risk stratification.
Methods
Retrospective targeted sequencing was performed on 80 ESCC formalin-fixed, paraffin-embedded (FFPE) tumor specimens from 37 good responders and 43 poor responders receiving neoadjuvant treatment. Somatic mutations and copy number variations (CNVs) were detected in 130 cancer druggable genes with TOMA Os-seq. Kaplan Meier curve and COX regression analysis were used to estimate the risk of relapse and survival.
Results
Twelve patients (12/80, 15%) with hot spot NFE2L2 mutations occurred with significantly higher frequency in poor responders (p = 0.0003) and in patients with non-complete pathological response (p = 0.007) in resectable ESCC treated by chemo-radiotherapy (CRT). These patients also had poorer prognosis with higher risk of death (HR = 1.942, p = 0.039) and relapse (HR = 1.817, p = 0.063) by COX analysis. The independent prognostic role of hot spot NFE2L2 mutations was validated by the presence of recurrent plasma cell-free (ct)-DNA NFE2L2 mutations in an independent prospective cohort of resectable ESCC patients.
Conclusions
In summary, our study now demonstrates the clinical usefulness of hot spot NFE2L2 mutations, as a potential predictive and prognostic biomarker associated with pre-surgery CRT responses, and provides novel insights for future therapeutic options targeting the NRF signaling in resectable ESCC treated by neoadjuvant CRT. The novel prognostic role of hot spot NFE2L2 mutations may be useful markers to guide clinicians for treatment decisions in resectable ESCC patients following pre-surgery treatment.