AUTHOR=Tang Peng , Tan Chen , Pang Qingsong , Chi Chih-Wen , Wang Yuwen , Yuan Zhiyong , Huang Yu-Chuen , Chen Yu-Jen 

TITLE=Combination of 35-Gene Mutation Profile and Radiotherapy Dosimetry Predicts the Therapeutic Outcome of Definitive Chemoradiation in Patients With Esophageal Squamous Cell Carcinoma

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.729418

DOI=10.3389/fonc.2021.729418

ISSN=2234-943X

ABSTRACT=<p>Esophageal cancer is a common malignancy worldwide and a leading cause of cancer-related mortality. Definitive concurrent chemoradiotherapy (CCRT) has been widely used to treat locally advanced esophageal squamous cell carcinoma (ESCC). In this study, we evaluated the predictive power of a 35-gene mutation profile and radiation parameters in patients with ESCC. Data from 44 patients with ESCC who underwent definitive CCRT were retrospectively reviewed. A 35-gene mutation profile, derived from reported ESCC-specific next-generation sequencing results, and radiation dosimetry parameters were examined using the Kaplan–Meier curve and Cox proportional hazards model. All patients were native Chinese and underwent CCRT with a median follow-up time of 22.0 months. Significant prognostic factors affecting progression-free survival in the multivariable Cox regression model were clinical nodal staging ≥2 (hazard ratio, HR: 2.52, 95% CI: 1.15–5.54, <italic>p</italic> = 0.022), ≥10% lung volume receiving ≥30 Gy (V30) (HR: 2.36, 95% CI: 1.08–5.17, <italic>p</italic> = 0.032), and mutation of fibrous sheath interacting protein 2 (<italic>FSIP2</italic>) (HR: 0.08, 95% CI: 0.01–0.58, <italic>p</italic> = 0.013). For overall survival, significant prognostic factors in the multivariable Cox regression model were lung V30 ≥10% (HR: 3.71, 95% CI: 1.48–9.35, <italic>p</italic> = 0.005) and mutation of spectrin repeat containing nuclear envelope protein 1 (<italic>SYNE1</italic>) (HR: 2.95, 95% CI: 1.25–6.97, <italic>p</italic> = 0.014). Our cohort showed higher <italic>MUC17</italic> (79.5% vs. 5.7%), <italic>FSIP2</italic> (18.2% vs. 6.2%), and <italic>SYNE1</italic> (38.6% vs. 11.0%) mutation rates and lower <italic>TP53</italic> (38.6% vs. 68.7%) mutation rates than the ESCC cohorts from The Cancer Genome Atlas. In conclusion, by using a combination of a 35-gene mutation profile and radiotherapy dosimetry, mutations in <italic>FSIP2</italic> and <italic>SYNE1</italic> as well as lung V30 were identified as potential predictors for developing a prediction model for clinical outcomes in patients with ESCC administered definitive CCRT.</p>