Background: The aim of the present study was to identify the potential long non-coding (lnc.)-RNA and its associated molecular mechanisms involved in the regulation of the radiosensitivity of esophageal squamous cell cancer (ESCC) in order to assess whether it could be a biomarker for the prediction of the response to radiotherapy and prognosis in patients with ESCC. Methods: Microarrays and bioinformatics analysis were utilized to screen the potential lncRNAs associated with radiosensitivity in radiosensitive (n = 3) and radioresistant (n = 3) ESCC tumor tissues. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed in 35 ESCC tumor tissues (20 radiosensitive and 15 radioresistant tissues, respectively) to validate the lncRNA that contributed the most to the radiosensitivity of ESCC (named the candidate lncRNA). MTT, flow cytometry, and western blot assays were conducted to assess the effect of the candidate lncRNA on radiosensitivity in vitro in ECA109/ECA109R ESCC cells. A mouse xenograft model was established to confirm the function of the candidate lncRNA in the radiosensitivity of ESCC in vivo. The putative downstream target genes regulated by the candidate lncRNA were predicted using Starbase 2.0 software and the TargetScan database. The interactions between the candidate lncRNA and the putative downstream target genes were examined by Luciferase reporter assay, and were confirmed by PCR. Results: A total of 113 aberrantly expressed lncRNAs were identified by microarray analysis, of which family with sequence similarity 201-member A (FAM201A) was identified as the lncRNA that contributed the most to the radiosensitivity of ESCC. FAM201A was upregulated in radioresistant ESCC tumor tissues and had a poorer short-term response to radiotherapy resulting in inferior overall survival. FAM201A knockdown enhanced the radiosensitivity of ECA109/ECA109R cells by upregulating ataxia telangiectasia mutated (ATM) and mammalian target of rapamycin (mTOR) expression via the negative regulation of miR-101 expression. The mouse xenograft model demonstrated that FAM201A knockdown improved the radiosensitivity of ESCC. Conclusion: The lncRNA FAM201A, which mediated the radiosensitivity of ESCC by regulating ATM and mTOR expression via miR-101 in the present study, may be a potential biomarker for predicting radiosensitivity and patient prognosis, and may be a therapeutic target for enhancing cancer radiosensitivity in ESCC.

Esophageal cancer is the eighth most common malignancy and sixth most fatal disease worldwide. However, it is the fourth most common cause of death in China. Although surgery is currently the recommended course of treatment, there are some patients that do not receive radical treatment due to the presence of distant organ or lymph node metastasis. There is at present no established treatment standard for esophageal cancer patients with distant organ metastasis. The purpose of this study was to investigate the prognostic factors involved in determining survival of esophageal cancer patients with distant organ metastasis at initial diagnosis, and to provide a reference for the planning of a clinical treatment strategy. The data of 57 evaluable esophageal squamous cell carcinoma patients with distant organ metastasis at initial diagnosis were studied retrospectively. The survival rate was calculated using the Kaplan-Meier method, and the log-rank test was used to test the differences. Multivariable analysis was performed using the Cox proportion hazards model. The median survival time for all patients was 6 months (range, 1-55 months), and the 1- and 2-year survival rates were 21.1% and 11.8%, respectively. The median survival time for patients with single metastasis was 10 months with 1- and 2-year survival rates of 47.4% and 28.1%, respectively. For patients with multiple metastases, the survival duration was 5 months, with 1- and 2-year survival rates of 7.9% and 3.9%, respectively (p < 0.001). The 1- and 2-year survival rates with multimodality treatment were 70% and 45%, respectively, which were significantly better than chemotherapy alone (13.3% and 8.9%, respectively, p = 0.003) and best supportive care (5.9% and 0%, p < 0.001), but there was no significant difference between the latter two groups (p = 0.061). For esophageal squamous cell carcinoma patients with distant organ metastasis upon initial diagnosis, the presence of a single metastasis appeared to favor overall survival compared to multiple metastases. Multimodality treatment may also improve patient survival, but chemotherapy alone has not been established as a favorable prognostic factor.

The aim of the present study was to assess the efficacy of adjuvant chemotherapy (AC) in patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy (CRT). The clinical data of patients with ESCC treated with chemoradiotherapy with or without AC were collected and retrospectively reviewed. The overall survival (OS), locoregional failure-free survival (LFFS) and distant failure-free survival (DFFS) rates were analyzed statistically. A total of 187 patients fulfilled the inclusion criteria, 98 of whom were treated with CRT-alone, while 89 were treated with CRT-AC. Patient characteristics did not significantly differ between the CRT-alone and CRT-AC groups, with the exception of sex and the number of cycles of concurrent chemotherapy. Following CRT, 50 patients achieved complete response (CR), 67 had partial response (PR), 63 patients maintained stable disease (SD) and 7 developed progression of disease (PD). The OS, LFFS and DFFS at 1, 2 and 5 years for the entire cohort were 67.5, 41.4 and 27.2%; 68.7, 57.9 and 52.4%; and 78.5, 68.9 and 63.9%, respectively. The clinical N-stage, M-stage, and short-term response to CRT were identified as significant factors that influenced patient prognosis. No significant differences in OS, LFFS or DFFS were observed between the CRT-alone and CRT-AC groups for the entire cohort and for clinical N-stage, clinical M-stage and short-term response subgroups. The short-term response to CRT and the tumor clinical stage were significant prognosis factors for patients with ESCC treated with CRT. With current chemotherapy regimens, AC did not improve survival for patients with ESCC treated with CRT. The retrospective nature of the current study serves as a limitation; thus, further clinical trials are required to evaluate the efficacy of AC in patients with ESCC treated with CRT.

To validate and propose revision of the 8th edition American Joint Committee on Cancer (AJCC) clinical staging system for esophageal squamous cell cancer (ESCC) patients treated with definitive intensity-modulated radiation therapy combined with concurrent chemotherapy (Chemo-IMRT) based on computed tomography (CT) imaging. The clinical data of patients with ESCC treated with Chemo-IMRT were collected and retrospectively reviewed. All CT images were independently reevaluated and restaged according to the 8th edition AJCC staging system. The overall survival (OS) rates were analyzed statistically. ROC curves of the various parameters of the primary tumor and metastatic lymph nodes were generated in order to identify the cutoff values correlated to patient survival using the area under curve. The gross tumor volume of the primary tumor (GTV-prT) and the clinical N stage (cN) were independent factors that influenced OS. The 5-year OS rate of patients with GTV-prT ≤28 cm3, GTV-prT > 28 and ≤ 56 cm3, and GTV-prT > 56 cm3 were 54.6, 31.1 and 18.6%, respectively. The 5-year OS rate of patients with cN0, cN1 SLNM (−), cN2 SLNM (−), cN3 SLNM (−) and SLNM (+) were 62.8 (P < 0.001), 34.0 (P = 0.16), 20.0 (P = 0.785), 0 (P < 0.001) and 26.9%, respectively. After restaging the SLNM as regional MLNs, the 5-year OS rates of the patients with cN0, 1, 2 and 3 were 62.8, 36.3, 23.7 and 7.8%, respectively. Various GTV-prT were combined with the cN to establish a new clinical TNM staging system: I, GTV-prT1 and cN0; II, GTV-prT2 or 3 and cN0, GTV-prT1 and cN1; III, GTV-prT1 and cN2, GTV-prT2 and cN1,2; Iva, GTV-prT3 and cN1,2; IVb, GTV-prTany and cN3; IVc, TanyNanyM1. Subsequently, the OS differed significantly between the adjacent GTV-prT cN categories, except those of stage I vs. II. The SLNM should be dealt with as a regional rather than a distant disease in patients with ESCC when treated with CRT. The proposed nonsurgical staging system based on the GTV-prT and N appears to be a simple and accurate prognosis predictor for patients with ESCC who have undergone definitive Chemo-IMRT.

To assess the efficacy of neoadjuvant chemotherapy (NAC) in esophageal squamous cell carcinoma (ESCC) patients treated with definitive chemoradiotherapy (CRT). The clinical data of patients with ESCC treated with chemoradiotherapy with or without NAC were collected and retrospectively reviewed. The overall survival, locoregional failure-free survival, and distant failure-free survival were analyzed statistically. A total of 60 patients fulfilled the inclusion criteria, of which 41 were treated with NAC-CRT and 19 were treated with CRT-alone. Patient characteristics were well balanced between the NAC-CRT and CRT-alone groups, except for the ECOG scores. The tumor response to NAC included 11 patients (26.8%) with partial response (PR), 25 patients (61.0%) with stable disease (SD), 5 patients (12.2%) with progression disease (PD), and no patients with complete response (CR). After CRT, 21 patients achieved CR (14 after NAC-CRT and 7 after CRT-alone), 30 had PR (19 and 11, respectively), 6 maintained SD (5 and 1, respectively), and 3 patients (all in the NAC-CRT group) developed PD. Twenty-nine patients (18 in NAC-CRT and 11 in CRT-alone) succumbed to the disease from locoregional or distant failure, one patient in the NAC-CRT group died of radiation pneumonitis, one patient in the CRT-alone group died from unknown reasons, and 29 patients remained alive. The overall survival, locoregional failure-free survival, and distant failure-free survival at 1 and 2 years in all the patients were 64.9% and 40.5%, 58.6% and 52.0%, and 85.7% and 79.3%, respectively. The overall survival, locoregional failure-free survival, and distant failure-free survival between the NAC-CRT group and the CRT-alone group were not significantly different. In patients with ESCC treated with definitive CRT, NAC treatment using the current regimen does not prolong overall survival, locoregional failure-free survival or distant failure-free survival. Further development of NAC treatment is urgently needed.