Autologous culture method improves retention of tumors' native properties.

No current in vitro tumor model replicates a tumor's in vivo microenvironment. A culturing technique that better preserves a tumor's pathophysiological conditions is needed for some important clinical applications, including personalized drug-sensitivity/resistance assays. In this study, we utilized autologous serum or body fluid to build a 3D scaffold and grow a patient's tumor. We named this technique "3D-ACM" (autologous culture method). Forty-five clinical samples from biopsies, surgically removed tumor tissues and malignant body fluids were cultured with 3D-ACM. Traditional 3D-FBS (fetal bovine serum) cultures were performed side-by-side for comparison. The results were that cells cultured in 3D-ACM rebuilt tissue-like structures, and retained their immuno-phenotypes and cytokine productions. In contrast, the 3D-FBS method promoted mesenchymal cell proliferation. In preliminary chemo drug-sensitivity assays, significantly higher mortality was always associated with FBS-cultured cells. Accordingly, 3D-ACM appears to more reliably preserve a tumor's biological characteristics, which might improve the accuracy of drug-testing for personalized cancer treatment.

Prognostic Significance of Baseline Neutrophil Count and Lactate Dehydrogenase Level in Patients With Esophageal Squamous Cell Cancer Treated With Radiotherapy.

Background: This present study aimed to explore the prognostic value of pretreatment neutrophil and lactate dehydrogenase (LDH) and to develop a prognostic risk scoring model to predict prognosis in esophageal squamous cell cancer (ESCC) patients treated with definitive radiotherapy. Methods: Retrospectively collected data of patients who received definitive radiotherapy for ESCC at Shantou Central Hospital between January 2009 and December 2015 were included for the analysis. The association between the level of LDH and neutrophil and clinicopathological characteristics were analyzed. We performed univariate and multivariate analyses to identify the prognostic predictors for patients with ESCC. Based on the results, we also developed a prognostic risk scoring model and assessed its predictive ability in the subgroups. Results: A total of 567 patients who received definitive radiotherapy for ESCC were included in the present study. The optimal cutoff values were 4.5 × 109/L, 3.25, and 220 U/L for neutrophil, neutrophil-to-lymphocyte ratio (NLR), and LDH, respectively. A high level of LDH was significantly associated with advanced N stage (p = 0.031), and neutrophil count was significantly associated with gender (p = 0.001), T stage (p < 0.001), N stage (p = 0.019), clinical stage (p < 0.001), and NLR (p < 0.001). Multivariate survival analysis identified gender (p = 0.006), T stage (p < 0.001), N stage (p = 0.008), treatment modality (p < 0.001), LDH level (p = 0.012), and neutrophil count (p = 0.038) as independent prognostic factors for overall survival. Furthermore, a new prognostic risk scoring (PRS) model based on six prognostic factors was developed, in which the patients were divided into three groups with distinct prognosis (χ2 = 67.94, p < 0.0001). Conclusions: Elevated baseline LDH level and neutrophil count predicted poor prognosis for ESCC patients treated with definitive radiotherapy. A PRS model comprised of LDH, neutrophil count, and other prognostic factors would help identify the patients who would benefit the most from definitive radiotherapy.

Effect of modern high-dose versus standard-dose radiation in definitive concurrent chemo-radiotherapy on outcome of esophageal squamous cell cancer: a meta-analysis.

BACKGROUND AND OBJECTIVES: Radiation Therapy Oncology Group (RTOG) 94-05 has demonstrated that higher dose radiation didn't improve outcome of patients with esophageal cancer (EC). However, several retrospective studies showed that a higher dose radiation based on modern radiotherapy techniques could improve overall survival (OS) and local control rate (LCR) of patients with EC, especially esophageal squamous cell cancer (ESCC). As trials have provided updated and controversial data, we performed this updated meta-analysis to investigate whether high-dose (> = 60 Gy) radiotherapy in definitive concurrent chemo-radiotherapy (CCRT) could yield benefit compared to standard dose radiotherapy. METHODS: A systematic literature search was carried out in the database of MEDLINE, PubMed and Embase. All studies published between 1 January 1990 and 31 December 2018 on the association between radiation dose and curative efficiency in EC were included in this meta-analysis. The hazard ratio (HR) was used to evaluate the time-to-event data employing RevMan version 5.3. RESULTS: Eight articles with a total of 3736 patients were finally included. Results indicated that there was a significant benefit in favor of high dose radiotherapy (HD-RT) regarding OS (HR = 0.78, 95%CI: 0.72-0.84, p < 0.001; 2-year OS risk ratio (RR) = 1.25, 95%CI: 1.14-1.37, p < 0.001), progression-free survival (PFS) (P = 0.001, HR = 0.7, 95%CI: 0.57-0.87) and LRFS (P < 0.001, HR = 0.52, 95%CI: 0.36-0.74) . CONCLUSIONS: HD-RT (> = 60 Gy) based on modern radiotherapy techniques in definitive CCRT appears to improve OS, PFS amd LRFS compared to the SD-RT in patients with ESCC.

Prognostic value of tumor length and diameter for esophageal squamous cell cancer patients treated with definitive (chemo)radiotherapy: Potential indicators for nonsurgical T staging.

PURPOSE: The aim of this work was to evaluate the prognostic value of tumor length and diameter for patients with esophageal squamous cell cancer (ESCC) treated with definitive (chemo)radiotherapy to identify potential indicators for separate nonsurgical T staging, which are needed in clinical practice. MATERIALS AND METHODS: A total of 682 patients with ESCC who underwent definitive (chemo)radiotherapy between 2009 and 2015 were reviewed. Esophageal tumor length and diameter were determined by barium esophagography and computed tomography before treatment. Univariate and multivariate analyses were used to assess the impact of tumor length and diameter on long-term overall survival (OS) and progression-free survival (PFS). Propensity score matching (PSM) analysis was also used to control intergroup heterogeneity. RESULTS: The median OS and PFS were 22.2 months and 15.4 months, respectively, in the tumor length ≤ 6 cm group, which were significantly longer than those in the tumor length > 6 cm group (13.4 and 8.5 months, respectively). The median OS and PFS were 23.3 months and 15.9 months, respectively, in the tumor diameter ≤ 3.5 cm group, which were also significantly longer than those in the tumor diameter > 3.5 cm group (13.3 and 8.8 months, respectively). Similar results were found after PSM. Univariate and multivariate analyses showed that tumor length and diameter were both independent predictors of long-term survival. CONCLUSION: Tumor length and diameter are both independent prognostic factors for ESCC patients treated with definitive (chemo)radiotherapy. These two imaging parameters have the potential for development and use in nonsurgical T staging.

Impact of sex on the prognosis of patients with esophageal squamous cell cancer underwent definitive radiotherapy: a propensity score-matched analysis.

BACKGROUND: The impact of sex on prognosis of patients with esophageal squamous cell cancer (ESCC) who underwent definitive radiotherapy remained unclear. The present study aimed to determine the impact of sex on the prognosis of patients with ESCC underwent definitive radiotherapy. METHODS: Between January 2009 and December 2015, patients with ESCC underwent definitive radiotherapy in Shantou Central Hospital were included in this study. The Progression-free survival (PFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. The PFS and OS were compared between female and male patients. The Cox regression model was used to identify prognostic factors. Propensity score-matched analysis was performed to balance baseline characteristics between female and male patients. RESULTS: A total of 683 ESCC patients treated with definitive radiotherapy were included, with 497 male and 186 female patients. In the whole cohort, female patients had a significantly longer median PFS (14.0 months vs 10.6 months, P = 0.0001, HR = 0.688, 95% CI, 0.567-0.836) and OS (20.8 months vs 15.9 months, P = 0.0005, HR = 0.702, 95% CI, 0.575-0.857). In the matched cohort, female patients still had a significantly longer median PFS (13.5 months vs 11.6 months) and OS (19.6 months vs 16.1 months). Multivariate analysis showed that sex was an independent prognostic factor for PFS (HR = 0.746, 95% CI, 0.611-0.910, P = 0.004) and OS (HR = 0.755, 95% CI, 0.615-0.926, P = 0.007). CONCLUSIONS: This present study indicated that sex was an independent prognostic factor in Chinese patients with ESCC underwent definitive radiotherapy, with better survival outcome for women than men. Efforts should be made to investigate the underlying biological mechanism.

Analysis of definitive chemo-radiotherapy for esophageal cancer with supra-clavicular node metastasis based on CT in a single institutional retrospective study: a propensity score matching analysis.

BACKGROUND: The prognostic value of supra-clavicular lymph node (SCLN) metastases in esophageal cancer (EC) is still not clear. METHOD: From January 2009 to December 2015, a survival analysis was performed to retrospectively identify the prognostic value of SCLN metastasis on survival on 751 patients with EC treated with definitive chemo-radiotherapy (dCRT). RESULTS: The median follow-up duration for living patients was 56.6 months. The median overall survival (OS) for all patients was 16.6 months. Patients with SCLN metastasis had a much poorer prognosis for OS (χ2 = 17.342, P < 0.001), distant metastasis-free survival (DMFS) (χ2 = 24.793, P < 0.001) and progression-free survival (PFS) (χ2 = 25.802, P < 0.001) than those without SCLN metastasis. The same results were found after propensity score matching. Nonetheless, the prognosis of patients with cervical or upper thoracic EC metastasis in SCLN was better than those of patients with middle or lower thoracic EC metastasis in SCLN for OS (χ2 = 4.516, P = 0.038), DMFS (χ2 = 8.326, P = 0.004) and PFS (χ2 = 6.255, P = 0.012). Univariate analysis showed that gender, middle or lower thoracic EC with SCLN metastasis, tumor length, tumor diameter, concurrent chemo-radiotherapy (CCR) and number of lymph nodes were prognostic factors for PFS. Gender, age, middle or lower thoracic EC with SCLN metastasis, tumor diameter, tumor length, and number of lymph nodes were prognostic factors for DMFS. According to the multivariate analysis, only middle or lower thoracic EC with SCLN metastasis and number of lymph nodes were independent prognostic factors for DMFS and PFS. CONCLUSION: For patients with cervical or upper thoracic EC, metastasis in SCLN should be considered to be regional lymph nodes and treated with curative intent if the total number of lymph nodes is limited. However, for patients with middle or lower thoracic EC, metastasis should be considered to be a higher level N stage or M1 stage, and it is thus necessary to provide consolidation chemotherapy after dCRT.

Efficacy of Stereotactic Body Radiotherapy for Recurrent or Residual Hepatocellular Carcinoma after Transcatheter Arterial Chemoembolization.

AIM: To evaluate the efficacy and toxicity of hypofractionated stereotactic body radiotherapy (SBRT) for patients with recurrent or residual hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). METHODS: Between June 2008 and July 2015, thirty-three patients with HCC were treated by SBRT. There were 63 lesions in 33 patients. A total dose of 39-45 Gy/3-5 fractions was delivered to the 70-80% isodose line. RESULTS: Objective response rate (CR + PR) was 84.8% at 6 months. The overall survival rate was 87.9%, 75.8%, 57.6%, and 45.5% at 6, 12, 18, and 24 months, respectively. Median overall survival was 19 months. At 3 months, AFP decreased by more than 75% in 51.5% of patients (17/33). Overall survival was significantly different (P < 0.001) between the group of patients for whom AFP decreased more than 75% and the group for whom AFP decreased by less than 75%. The AFP-negative rate was 48.5% (16/33) after 6 months. Eight patients (24.2%) had grade 1-2 transient fatigue, and 11 patients (33.3%) had grade 1-2 gastrointestinal reactions within 1 month. CONCLUSION: SBRT is a promising noninvasive and palliative treatment with acceptable toxicity for recurrent or residual HCC after TACE.

Zoledronic acid suppresses metastasis of esophageal squamous cell carcinoma cells through upregulating the tight junction protein occludin.

We have previously demonstrated the radio-sensitizing effect of zoledronic acid (ZOL), a third generation bisphosphonate, on human esophageal squamous cell carcinoma (ESCC) cells. Here we show that ZOL suppresses metastatic progression of ESCC cells mainly through up-regulating the tight junction protein occludin. Exposure to ZOL at lower concentrations dramatically reduced migration and invasion of ESCC cells. In addition, ZOL treatment decreased the expression of mesenchymal markers, vimentin and N-cadherin, while increased the expression of the tight junction protein occludin. Moreover, ectopic expression of Slug, a well-known transcriptional repressor of occludin, partially but significantly abrogated the effect of ZOL on occludin expression and subsequently rescued the malignant metastatic phenotype, suggesting that Slug is one of the mediators underlying the anti-metastatic effect of ZOL. The present study is the first to report the significance of ZOL on ESCC metastasis. These data are promising for the future application of this drug regimen in patients with ESCC.