Author：Xiaofeng Wang, Xinying Shi, Xu Yang, Wenqing Wang, Lei Deng, Lili Zhao, Wanning Yang, Beibei Mao, Henghui Zhang, Jun Liang

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant diseases in the world and especially in China. The combined modality therapy neoadjuvant chemoradiation therapy (nCRT) has become the new standard of care. This study was aimed to investigate the molecular features in cell-free DNA (cfDNA) that is related with the response to nCRT in the local advanced ESCC. 

Methods: 24 eligible ESCC patients with received nCRT were included and baseline blood were collected from Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. 14 patients had response and the other 10 patients had no response to nCRT, respectively. Both cfDNA fragments and fragmented genomic DNA were extracted for enrichment of a 0.96M size panel covering exon regions of 1,408 genes. Gene alterations were analyzed to explore the relationship between genetic characterizations of cfDNA and response to nCRT. 

Results: The most common mutated genes were NOTCH1, IRS1, TP53. The somatic alternation of NOTCH1, IRS1, ZFHX4 occurred more frequently in response group than in non-response group. On the contrary, patients with response to nCRT had significantly less mutations of PDE11A, STK11. Moreover, the tumor mutation burden (TMB) of cfDNA in response group was significantly higher than non-response group(p = 0.024). 

Conclusions: The molecular features in cfDNA of patients with response to nCRT were different from those without response. Five genes’ mutational profile could identify the response and non-response patients with local advanced ESCC. However, prospective studies are needed to validate our findings.