Capecitabine or Capecitabine Plus Oxaliplatin Versus Fluorouracil Plus Cisplatin in Definitive Concurrent Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma (CRTCOESC): A Multicenter, Randomized, Open-Label, Phase 3 Trial.

PURPOSE: This phase 3 trial aimed to compare the efficacy and safety of capecitabine or capecitabine plus oxaliplatin (XELOX) with those of fluorouracil plus cisplatin (PF) in definitive concurrent chemoradiotherapy (DCRT) for inoperable locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Patients were randomly assigned to receive two cycles of capecitabine, XELOX, or PF along with concurrent intensity-modulated radiation therapy. Patients in each arm were again randomly assigned to receive two cycles of consolidation chemotherapy or not. The primary end points were 2-year overall survival (OS) rate and incidence of grade ≥3 adverse events (AEs). RESULTS: A total of 246 patients were randomly assigned into the capecitabine (n = 80), XELOX (n = 85), and PF (n = 81) arms. In capecitabine, XELOX, and PF arms, the 2-year OS rate was 75%, 66.7%, and 70.9% (capecitabine v PF: hazard ratio [HR], 0.91 [95% CI, 0.61 to 1.35]; nominal P = .637; XELOX v PF: 0.86 [95% CI, 0.58 to 1.27]; P = .444); the median OS was 40.9 (95% CI, 34.4 to 49.9), 41.9 (95% CI, 28.6 to 52.1), and 35.4 (95% CI, 30.4 to 45.4) months. The incidence of grade ≥3 AEs during the entire treatment was 28.8%, 36.5%, and 45.7%, respectively. Comparing the consolidation chemotherapy with the nonconsolidation chemotherapy groups, the median OS was 41.9 (95% CI, 34.6 to 52.8) versus 36.9 (95% CI, 28.5 to 44) months (HR, 0.71 [95% CI, 0.52 to 0.99]; nominal P = .0403). CONCLUSION: Capecitabine or XELOX did not significantly improve the 2-year OS rate over PF in DCRT for inoperable locally advanced ESCC. Capecitabine showed a lower incidence of grade ≥3 AEs than PF did.

Chemoradiation versus oesophagectomy for locally advanced oesophageal cancer in Chinese patients: study protocol for a randomised controlled trial.

BACKGROUND: Surgery is the gold standard treatment for local advanced disease, while definitive concurrent chemoradiotherapy (DCRT) is recommended for those who are medically unable to tolerate major surgery or medically fit patients who decline surgery. The primary aim of this trial is to compare the outcomes in Chinese patients with oesophageal squamous cell cancer with locally advanced resectable disease who have received either surgery or DCRT. METHODS/DESIGN: One hundred ninety-six patients with T1bN + M0 or T2-4aN0-2 M0 oesophageal squamous cell cancer will be randomised to the DCRT group or the surgery group. In the DCRT group, patients will be given intensity-modulated radiation therapy (IMRT) with 50 Gy/25 fractions and basic chemotherapy with 5-fluorouracil regimens. In the surgery group, patients will receive neoadjuvant chemoradiotherapy (NCRT) and standard oesophagectomy. Five years of follow-up will be scheduled for patients. The primary endpoints are 2-year/5-year overall survival; the secondary endpoints are 2-year/5-year progression-free survival, treatment-related adverse events and the patients' quality of life. The main evaluation methods include oesophagoscopy, endoscopic ultrasonography and biopsy, oesophageal barium meal, computed tomography, positron emission tomography-computed tomography, blood tests and questionnaires. DISCUSSION: The preponderant oesophageal cancer pathology type is dramatically different in western Caucasian and Asian oesophageal cancer patients: Caucasian patients present with 80% adenocarcinomas, and Asians patients present with 95% squamous cell carcinomas. This phenomenon needs more in-depth studies to elucidate the differences in these populations. Based on the results of this study, we will show whether DCRT will benefit patients more than oesophagectomy. This study will contribute more evidence to the management of oesophageal squamous cell cancer. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02972372 . Registered on 26 November 2016.

GASC1 Promotes Stemness of Esophageal Squamous Cell Carcinoma via NOTCH1 Promoter Demethylation.

The highest incidence of esophageal squamous cell carcinoma (ESCC) occurs in China. Cancer stem cells play key roles for tumor progression. Gene amplified in squamous cell carcinoma 1 (GASC1) is essential to maintain self-renewal and differentiation potential of embryonic stem cells. This study aimed to reveal the effect and mechanism of GASC1 on ESCC stemness. The biological function of GASC1 in ESCC was evaluated both in vitro and in vivo. ChIP assay was performed to determine the molecular mechanism of GASC1 in epigenetic regulation of NOTCH1. We found that GASC1 expression was increased in poor differentiated ESCC cells and tissues. ESCC patients with a high level of GASC1 presented a significantly worse survival rate. GASC1 expression in purified ALDH+ ESCC cells was significantly higher than that in ALDH- cells. The stemness of ESCC was dramatically decreased after GASC1 blockade. Furthermore, blockade of GASC1 decreased NOTCH1 expression via increase of NOTCH1 promoter H3K9me2 and H3K9me3. Moreover, the impaired stemness after blockade of GASC1 could be reversed after transfection of NOTCH1 overexpression lentiviral vector. GASC1 promoted stemness in ESCC cells via NOTCH1 promoter demethylation. Therefore, GASC1/NOTCH1 signaling might be a potential therapeutic target for the treatment of ESCC patients.

Efficacy and safety of biapenem in treatment of infectious disease: a meta-analysis of randomized controlled trials.

BACKGROUND: Biapenem is a parenteral carbapenem antibiotic that has powerful antibacterial activity. The aim of this study is to evaluate the efficacy and safety of biapenem for the treatment of infection diseases. METHODS: We performed a meta-analysis of published randomized-controlled trials (RCTs) identified in Embase, PubMed, and Cochrane library that compared the efficacy and safety of biapenem with other antibiotic regimes for the treatment of patients with infections. RESULTS: Eight RCTs were included in the meta-analysis, involving totally 1685 patients with lower respiratory tract infections (LRTIs), complicated urinary tract infections (cUTIs), and complicated intra-abdominal infections (cIAIs). There was no difference found between the patients with LRTIs, cUTIs, or cIAIs treated with biapenem and comparators, regarding treatment success and adverse events. CONCLUSION: This meta-analysis provides evidence that biapenem can be used as effectively and safely as imipenem-cilstatin or meropenem, for the treatment of patients with LRTIs, cUTIs, and cIAIs. It may be a considerable option for the treatment of these infections.

Efficacy and safety of capecitabine-based first-line chemotherapy in advanced or metastatic breast cancer: a meta-analysis of randomised controlled trials.

We sought to evaluate the efficacy and safety of capecitabine-based therapy as first-line chemotherapy in advanced breast cancer. Randomised controlled trials of capecitabine monotherapy or combined treatment were included in the meta-analysis. PubMed, EMBASE, the Cochrane Library database and important meeting summaries were searched systematically. Outcomes were progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and grades 3-4 drug-related adverse events.Nine trials with 1798 patients were included. The results indicated a significant improvement with capecitabine-based chemotherapy compared with capecitabine-free chemotherapy in ORR (relative risk [RR] 1.14, 95% confidence interval [CI] 1.03 to 1.26, P = 0.013) and PFS (hazard ratio [HR] 0.77, 95% CI 0.69 to 0.87, P < 0.0001). Overall survival favoured capecitabine-based chemotherapy, but this was not significant. There were more incidences of neutropenia and neutropenic fever in the capecitabine-free chemotherapy group and more vomiting, diarrhoea and hand-foot syndrome in the capecitabine-based chemotherapy group. There were no significant differences in nausea, fatigue, cardiotoxicity or mucositis/stomatitis between the two treatment regimens.Capecitabine-based chemotherapy significantly improves ORR and PFS in patients with advanced breast cancer, but has no demonstrable impact on OS. Capecitabine-based regimens are suitable as first-line treatment for patients with advanced breast cancer.

[Repeatability of three-dimensional measurements based on cone-beam CT images].

OBJECTIVE: To investigate the repeatability of three-dimensional (3-D) cephalometric measurements for the clinical application of 3-D cephalometry. METHODS: Forty-nine measurements that widely used in traditional cephalometric analyses were defined in 3-D cone-beam CT (CBCT) images. Three examiners identified landmarks on CBCT images of 17 subjects with normal occlusion, respectively, and 3-D measurements were exported automatically by software SimPlant. Inter-examiner reliability correlation coefficients (ICC) were obtained for all measurements. RESULTS: Repeatability of 36 measurements was high (ICC value greater than 0.9), including SNA, SNB. Repeatability of 11 measurements was moderate (ICC value between 0.8 and 0.9), including CoL-GoL, CoL-MSP. Repeatability of 2 measurements was low (ICC value lower than 0.8), including Gn-MSP and MPR-MSP. CONCLUSIONS: Most 3-D cephalometric measurements based on CBCT had high repeatability. However, some 3-D cephalometric measurements had limited repeatability.