Background: The aim of this study was to investigate the feasibility of involved-field irradiation (IFI) for the treatment of cervical and upper-thoracic esophageal cancer with concurrent chemoradiation. Patients and Methods: 102 eligible patients with cervical or upper-thoracic esophageal cancer were treated with concurrent chemoradiation and randomized to either an IFI or elective nodal irradiation (ENI) group. Results: Adverse events included infection (27.4 vs. 64.7%) and nausea (25.4 vs. 54.9%), with a statistically significant difference between the IFI and the ENI group (p = 0.008 and 0.028, respectively). No difference was seen for late radiation reaction. The cumulative incidence of local/regional failure (13.7 vs. 17.6%) and regional lymph failure (7.8 vs. 9.8%) showed no statistically significant difference between the IFI versus the ENI group (p = 0.837 and 0.837, respectively). A nodal out-field relapse rate of only 2% was seen in the IFI group. 3-year survival rates for the ENI and IFI group were 41.3 and 32.0%, respectively (p = 0.58), and 3-year local control rates were 85.7 and 80.1%, respectively (p = 0.34). Conclusion: IFI was acceptable for cervical and upper-thoracic esophageal cancer with a decrease in acute toxicities and no increase in lymph node failure.

BackgroundThis study aimed to investigate risk factors for esophageal fistula in patients with locally advanced esophageal carcinoma receiving chemoradiotherapy.Subjects and methodsThe study prospectively enrolled 212 esophageal carcinoma patients undergoing chemoradiotherapy and evaluated 16 clinical parameters. The best cut-off values were determined by receiver operating characteristics curves. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated by the Cox proportional hazards model. Kaplan–Meier analysis was used to evaluate the cumulative probability.ResultsIn total, 22 patients (10.38%) developed esophageal fistula, of whom 9 experienced fistula during treatment and the other 13 patients developed fistula after chemoradiotherapy. The median time until occurrence was 5.75 months (range 0.6–8 months). In univariate analysis, the evaluated significant factors were Karnofsky performance status, smoking status, esophageal stenosis, T stage, fraction dose, and carcinoembryonic antigen (CEA). In addition, esophageal stenosis (HR=4.089, 95% CI 1.451–11.527, p=0.008), T stage (HR=2.663, 95% CI 1.019–6.960, p=0.046), and CEA (HR=0.309, 95% CI 0.124–0.768, p=0.011) were revealed as risk parameters in further multivariate analysis.ConclusionThis is the first prospective study to evaluate factors associated with fistula formation in patients with esophageal carcinoma receiving chemoradiotherapy. More attention should be given to patients with esophageal stenosis, stage T4 disease, and high levels of CEA.

Tumor metastasis leads to high mortality; therefore, understanding the mechanisms that underlie tumor metastasis is crucial. Generally seen as a secretory protein, osteopontin (OPN) is involved in multifarious pathophysiological events. Here, we present a novel pro-metastatic role of OPN during metastatic colonization. Unlike secretory OPN (sOPN), which triggers the epithelial–mesenchymal transition (EMT) to initiate cancer metastasis, intracellular/nuclear OPN (iOPN) induces the mesenchymal–epithelial transition (MET) to facilitate the formation of metastases. Nuclear OPN is found to interact with HIF2α and impact the subsequent AKT1/miR-429/ZEB cascade. In vivo assays confirm that the progression of metastatic colonization is accompanied by the nuclear accumulation of OPN and the MET process. Furthermore, evidence of nuclear OPN in the lung metastases is exhibited in clinical specimens. Finally, VEGF in the microenvironment was shown to induce the translocation of OPN into the nucleus through a KDR/PLCγ/PKC-dependent pathway. Taken together, our results describe the pleiotropic roles of OPN in the tumor metastasis cascade, which indicate its potential as an effective target for both early and advanced tumors.