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PurposeNeoadjuvant chemoradiotherapy (nCRT) is a standard treatment option for patients with stage III oesophageal cancer. Approximately 30% of oesophageal cancer patients will have a pathological complete response (pCR) after nCRT. However, available clinical methods cannot accurately predict pCR for patients. We aimed to find more indicators that could be used to predict the pathological response to nCRT.MethodA total of 84 patients with stage III oesophageal squamous cell cancer were enrolled in this study. Ten patients failed to have surgery as a result of progressive disease (PD). Among the patients who underwent surgery, 32 patients had a pathologic complete response (pCR), whereas 42 patients showed no or partial response (npCR) after nCRT. Routine blood test results and lymphocyte subset assessments before and after nCRT were retrospectively analysed. Univariate and multivariate analyses were used to identify independent predictors of the clinical curative effect of nCRT. Eventually, nomograms were established for predicting the PD and pCR rates.ResultsThe numbers of lymphocytes, B lymphocytes, T lymphocytes, Th lymphocytes, Ts lymphocytes, and NK cells and the percentages of B lymphocytes and NK cells were decreased significantly after nCRT (P < 0.0001), whereas the percentages of T lymphocytes and Ts lymphocytes increased (P < 0.0001). Univariate analysis showed that age, the length of the lesion, the level of haemoglobin before nCRT, and the amount of change in haemoglobin were related to PD, and the percentage of NK cells after nCRT was related to pCR. Multivariate logistic analysis demonstrated that the length of the lesion, the neutrophil-to-lymphocyte ratio (NLR) before nCRT, and the amount of change in haemoglobin were independent predictors of PD, whereas the percentage of NK cells after nCRT was an independent predictor of pCR.ConclusionLymphocyte subsets changed dramatically during nCRT, and these changes together with baseline and posttreatment lymphocyte subsets have predictive value in determining the response to nCRT for oesophageal cancer.

Background Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is a currently widely used strategy for locally advanced esophageal cancer (EC). However, the conventional imaging methods have certain deficiencies in the evaluation and prediction of the efficacy of nCRT. This study aimed to explore the value of functional imaging in predicting the response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced esophageal squamous cell carcinoma (ESCC). Methods Fifty-four patients diagnosed with locally advanced ESCC from August 2017 to September 2019 and treated with nCRT were retrospectively analyzed. DW-MRI scanning was performed before nCRT, at 10–15 fractions of radiotherapy, and 4–6 weeks after the completion of nCRT. 18F-FDG PET/CT scans were performed before nCRT and 4–6 weeks after the completion of nCRT. These 18F-FDG PET/CT and DW-MRI parameters and relative changes were compared between patients with pathological complete response (pCR) and non-pCR. Results A total of 8 of 54 patients (14.8%) were evaluated as disease progression in the preoperative assessment. The remaining forty-six patients underwent operations, and the pathological assessments of the surgical resection specimens demonstrated pathological complete response (pCR) in 10 patients (21.7%) and complete response of primary tumor (pCR-T) in 16 patients (34.8%). The change of metabolic tumor volume (∆MTV) and change of total lesion glycolysis (∆TLG) were significantly different between patients with pCR and non-pCR. The SUVmax-Tpost, MTV-Tpost, and TLG-Tpost of esophageal tumors in 18F-FDG PET/CT scans after neoadjuvant chemoradiotherapy and the ∆ SUVmax-T and ∆MTV-T were significantly different between pCR-T versus non-pCR-T patients. The esophageal tumor apparent diffusion coefficient (ADC) increased after nCRT; the ADCduring, ADCpost and ∆ADCduring were significantly different between pCR-T and non-pCR-T groups. ROC analyses showed that the model that combined ADCduring with TLG-Tpost had the highest AUC (0.914) for pCR-T prediction, with 90.0% and 86.4% sensitivity and specificity, respectively. Conclusion 18F-FDG PET/CT is useful for re-staging after nCRT and for surgical decision. Integrating parameters of 18F-FDG PET/CT and DW-MRI can identify pathological response of primary tumor to nCRT more accurately in ESCC.

Background Apatinib, a novel vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, has been approved for the treatment of metastatic gastric cancer and other tumors. Apatinib exerts antiproliferative and proapoptotic effects in different kinds of cancer cells. However, the molecular mechanisms by which apatinib effective against esophageal squamous cell carcinoma (ESCC) have only been partially researched and whether it has a sensitizing effect on paclitaxel remains unclear. Materials and methods The effects of apatinib or paclitaxel on endoplasmic reticulum (ER) stress, autophagy, apoptosis and proliferation of ESCC cell lines were evaluated. Western blot and immunohistochemistry analyses were performed to detect the expression of related genes. The weight and volume of xenograft tumors in mice were measured. Results In the current study, we elucidated the antiproliferative and ER-stress-mediated autophagy-inducing effects of apatinib on ECA-109 and KYSE-150 esophageal squamous cancer cells and identified the underlying mechanisms of its action. We demonstrated that apatinib not only inhibited the proliferation and induced the apoptosis of ESCC cells, but also activated ER stress and triggered protective autophagy. Moreover, inhibiting autophagy by chloroquine (CQ) enhanced the apatinib-induced apoptosis of ESCC cells through the IRE-1α–AKT–mTOR pathway. In addition, we showed, for the first time, the paclitaxel combined with apatinib and CQ exhibited the best antitumor effect on ESCC both in vivo and in vitro via the IRE-1α–AKT–mTOR pathway. Conclusions Our data showed that apatinib induced ER stress, autophagy and apoptosis in ESCC. Inhibiting autophagy by CQ enhanced apatinib-induced apoptosis. The combination of apatinib and CQ sensitized ESCC cells to paclitaxel to induce apoptosis through the IRE-1α–AKT–mTOR signaling pathway, thus providing the basis for its use in innovative anticancer therapeutic strategies. Graphic abstract