Search

Introduction About 50% of patients with non-small cell lung cancers (NSCLC) are diagnosed with brain metastases during treatment, and stereotactic radiosurgery (SRS) is an important treatment for brain oligometastasis. Some patients with brain metastases have cerebral edema before treatment, and radiation therapy may also cause, or aggravate brain edema. Vascular endothelial growth factor (VEGF) promotes angiogenesis and increase vascular permeability, and previous studies have shown that anti-VEGF treatment can reduce brain edema. We hypothesized that anlotinib hydrochloride can reduce perilesional edema around brain metastases, create conditions for subsequent SRS, increase local control rate and improve patient prognosis. Methods From one week before stereotactic radiosurgery, patients begin to receive anlotinib once a day (12 mg) from day 1-14 of a 21 day cycle, with two cycles in total. Brain magnetic resonance imaging (MRI) scan is taken before treatment, one week and one month after medication. A total of 50 patients will be included in this study. The primary endpoint is the Edema Index, and the secondary endpoints are intracranial objective response rate (iORR), intracranial progression-free survival (iPFS), objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and the rate of SRS after anlotinib treatment. Discussion This study is a multicenter, prospective, single-arm, phase II clinical study, and explores the efficacy and tolerability of SRS with anlotinib in NSCLC patients with limited brain metastases. The aim of the study is to provide new treatment options for NSCLC patients with brain metastases.

BackgroundUltra-central lung cancer (UCLC) is difficult to achieve surgical treatment. Over the past few years, stereotactic ablative radiotherapy (SABR) or stereotactic body radiotherapy (SBRT) obviously improved the clinical efficacy and survival of UCLC patients. However, the adapted scheme of radiation therapy is still controversial. For this, a single arm retrospective analysis was performed on UCLC patients treated with SBRT.Material and MethodsWe retrospectively studied primary UCLC patients who were treated with SBRT of 56 Gy/6-8f between 2010 and 2018. UCLC was defined as planning target volume (PTV) touching or overlapping the proximal bronchial tree, trachea, esophagus, heart, pulmonary vein, or pulmonary artery within 2 cm around the bronchial tree in all directions.ResultsA total of 58 patients whose median age was 68 years (range, 46-85) were included in our study, 79.3% of whom did not undergo any previous therapy. The median dose of the PTV was 77.8 Gy (range, 43.3-91.8), and the median PTV of tumors was 6.2 cm3 (range, 12.9-265.0). With a median follow-up of 57 months (range, 6-90 months), the median cumulative overall survival (OS) rate was 58 months (range, 2-105). In addition, the 1-year, 2-year and 5-year OS rates were 94.7%, 75.0% and 45.0%, respectively. In our univariable analysis (p=0.020) and multivariate analysis (p=0.004), the OS rate was associated with the PTV. The 5-year OS rates for PTV 3 and PTV ≥53.0 cm3 were 61.6% and 37.4%, respectively. Regarding toxicity after SBRT, there were two cases (3.5%) with grade ≥3 adverse events, of which 1 case died of sudden severe unexplained hemoptysis.ConclusionsPatients with UCLC can benefit from SBRT at a dose of 56 Gy/6-8f. On the other hand, smaller PTV was associated with superior outcomes, and the cure difference needs to be validated by prospective comparative trials.

Background Our previous research found that YAP1 may have a role in multidrug resistance (MDR) in small cell lung cancer (SCLC). However, its underlying mechanism is unknown. Methods In this study, we investigated the expression of YAP1 using immunohistochemical staining and assessed the relationship between the expression of YAP1 and overall survival in patients with SCLC. We established H69 stable cell lines that overexpressed constitutively active YAP1 and H446 stable cell lines that dominate negative YAP1. We conducted CCK‐8, flow cytometric analysis, and in vivo chemosensitivity experiments to evaluate the function of YAP1 in drug sensitivity apoptosis in vitro and in vivo. Results The results indicated that patients with high YAP1 expression have shorter survival rates and more advanced disease stage than those with low YAP1 expression. YAP1 may induce MDR by inhibiting the apoptosis of SCLC. YAP1 induced MDR when YAP1 was hyperactivated, and drug sensitivity increased when YAP1 was inhibited in vitro and in vivo. CD74 was significantly correlated with YAP1 in SCLC samples. Inhibition of CD74 using ISO‐1 increased drug sensitivity significantly. Conclusions The expression of YAP1 is significantly correlated with overall survival and disease stage in patients with SCLC. YAP1 may play an important role in these patients. We were the first to report that YAP1 can induce MDR in SCLC in vitro and in vivo. CD74 may be involved in YAP1‐induced MDR., The expression of YAP1 is significantly correlated with overall survival and disease stage in patients with SCLC. We were the first to report that YAP1 can induce MDR in SCLC in vitro and in vivo. CD74 may modulate the MDR of YAP1.

As a secretory cell transcription factor, muscle intestine stomach expression 1 (Mist1) is associated with serous secretory cell development and gastric chief cell maturation. Here, we focus on the function of Mist1 in gastric adenocarcinoma carcinogenesis. Based on clinical data and a mouse model of gastric cancer, we found that Mist1 expression was reduced in gastric cancer. Then, we overexpressed Mist1 using a lentivirus system and found that overexpression of Mist1 could inhibit gastric cancer cell proliferation, migration and invasion in vitro. Additionally, in vivo, we assessed the function of Mist1 in a gastric cancer xenograft model and distant pulmonary metastasis model. Overexpression of Mist1 decreased tumour growth and distant metastasis in vivo, suggesting that Mist1 acts as a tumour suppressor in gastric carcinogenesis. Furthermore, Mist1 overexpression inhibited epithelial-mesenchymal transition (EMT) in gastric cancer by suppressing β-catenin transcription activity and then the Wingless and INT-1 (Wnt)/β-catenin signalling pathway, which could be reversed by a Wnt/β-catenin-specific agonist. In conclusion, this study indicated that overexpression of Mist1 could reverse EMT in gastric carcinogenesis by inhibiting the Wnt/β-catenin signalling pathway and that Mist1 might be a novel marker for early gastric cancer screening.

Background In order to obtain a high dose conformal index of tumor and steep dose fall-off in healthy tissues for brain metastasis stereotactic radiosurgery (SRS), the aim of this study was to investigate SRS planning optimization by comparing one multiple-lesions plan (MLP) with multiple single-lesion plans (SLPs) for patients with multiple brain metastases using the Cyberknife (CK) system. Methods Fifty non-small cell lung cancer (NSCLC) patients (28 males and 22 females) with 2–4 brain metastases, inter-tumour distances less than 3 cm, were retrospectively replanned with the original prescription dose (12–32 Gy) in the original fractions (1–3). Two different clinical CK SRS plans (SLPs and MLP) were generated for the same patients with the same collimator and prescription isodose line (62–68%) by the CK Multiplan System. Both SLPs and MLP were able to achieve > 95% PTV volume covered prescription dose and met the Timmerman 2011 organs at risk (brainstem, optic nerve and pituitary) constraints. Results Compared with those in the SLPs, the maximum dose (Dmax) and mean dose (Dmean) of brainstem in the MLP were reduced 0.22–3.13% (2.62%) and 2.71–12.56% (5.57%), respectively, all P < 0.05. Meanwhile, the volumes of the whole brain minus the tumors that received a single dose equivalent of 8–16 Gy (V8Gy-V16Gy) were effectively reduced in the MLP. The treatment time parameters, the total number of beams and monitor units, of the MLP were reduced by 3.31 and 1.47% (P < 0.05), respectively. Although there were a few differences in the conformity index (CI) and homogeneity index (HI) between the two treatment plans, the differences were not statistically significant (P = 2.94 and 1.08 > 0.05). Conclusion One multiple-lesions plan for brain metastases could achieve higher precision in the target and lower doses in healthy tissue while shortening the treatment time and improving the treatment efficiency over multiple single-lesion plans.

BackgroundPart of gastric cancer (GC) patients in early stages still endure early relapse after systematic treatment. This study was designed to identify the value of d-dimer reflecting the bad phenotype in early GC patients. MethodsFrom January 1st 2009 to January 1st 2019, 467 primary GC patients with TNM stage I-II after R0 resection were enrolled, tumor stage was classified by the national comprehensive cancer network guideline 2019. Plasma D-dimer and associated factors were reviewed and analyzed with clinic-pathological characteristics, regularly follow up was proceed when first determined. ResultsThe median follow up is 33 months, and 381/467 GC patient survived after ten years follow up. Although D-dimer was significantly elevated in old age and vascular cancer emboli positive patients. Noteworthy, D-dimer levels displayed an increase in 48/467 GC patients when the cut-off values was 1.5 mg/ml based on the ROC curve in our previous study, log-rank and Cox hazard model analysis showed D-dimer is an independent risk factor for overall survival and disease free survival in this classification. ConclusionPlasma D-dimer represents an easy measurement and lower cost marker for the routine testing to predict highmalignancy phenotype in stage I-II gastric cancer after R0 resection.Clinical registrationChiCTR1900028178

Hui Wang,* Xiaoye Liu,* Xuechao Jiang, Yongchun Song, Xiaoguang Wang, Jingsheng Wang, Yang Dong, Fengtong Li, Zhiqiang Wu, Yuhan Zhang, Zhiyong Yuan Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China *These authors contributed equally to this work Purpose: Traditionally, radiosurgery was considered less effective for patients with cystic brain metastases. However, comparisons of prognosis between cystic and solid brain metastases in cancer patients have been seldom reported. We aimed to compare the survival between cystic and solid brain metastases and assess risk factors for overall survival after brain metastases (BMOS) in patients who underwent radiosurgery treatment. Patients and methods: The Kaplan–Meier method and multivariate Cox regression analysis were used to compare survival time and evaluate risk factors for BMOS. Results: A total of 356 patients (including 498 brain metastases) were analyzed in our study, including 67 patients (67/356, 18.8%) with 75 cystic brain metastases. There is no statistical significance in BMOS between patients with cystic (17 months, range: 3–64 months) and solid (17.5 months, range: 1–65 months) brain metastases (P=0.148). However, the volume of cystic brain metastases decreased more slowly than solid brain metastases (P

Developing rapidly from the cecal diverticulum in a 5-week-old embryo, the cecum, which is developed from the caudal limb of the midgut loop, is different from the ascending colon. The aim of this study was to analyze the different clinicopathological and biological characteristics of patients with carcinoma of the cecum and ascending colon. We accessed data for 59,035 patients with adenocarcinomas of the cecum and ascending colon from the Surveillance, Epidemiology and End Results database to explore the potential associations between the clinicopathological characteristics and overall survival. Furthermore, we analyzed the differences in gene expression between the two segments in the Gene Expression Omnibus database. The results were validated in The Cancer Genome Atlas database, as well as with another independent dataset from the First Affiliated Hospital of Xi'an Jiaotong University. The results of this study revealed the potential prognostic differences between adenocarcinoma of the cecum and ascending colon, which may be caused by the differential expression levels of the SLCO1B3 gene. When including the expression levels of SLCO1B3 in intraoperatively examined lymph nodes, 8 factors were found able to predict the prognosis of patients with carcinomas of the cecum and ascending colon. As regards the surgical therapeutic strategies, the resection of >15 local lymph nodes is appropriate for improving the prognosis of patients.

p38 mitogen-activated protein kinase (MAPK) signaling has been implicated in the cancer development and progression. However, the precise mechanism of this association remains unknown. The aim of the present study was to evaluate the association between p38 and cancer progression, including investigations into the effects on cell proliferation, resistance to thalidomide, indoleamine 2,3-dioxygenase (IDO) expression and prognosis in patients with esophageal cancer. The present retrospective study included patients with stage I-III esophageal cancer. A total of 228 patients with esophageal cancer were recruited to analyze the expression of phosphorylated (p)-p38 and IDO in tumor, and normal tissues through immunohistochemistry. Depression status was measured using the Zung Self-Rating Depression Scale. P38 cDNA was transfected into esophageal cancer cells to assess tumor cell viability, sensitivity to thalidomide treatment and IDO gene expression. Western blotting and flow cytometry was used to analyze protein expression alterations, and apoptosis in esophageal cancer cells. P-p38 protein was expressed in 68.9% of cancer tissues, and was significantly associated with depressive symptoms, tumor recurrence and poor survival of patients. In vitro experiments revealed that the expression of p-p38 induced esophageal cancer Eca-109 and TE-1 cell viability, and resistance to thalidomide treatment, as well as in the expression of IDO without the application of lipopolysaccharides. Further follow-up of patients revealed that depression was also an independent factor for early recurrence and overall survival rate. Altered p38 MAPK expression was associated with poor outcome in patients with esophageal cancer. p38 may be a potential biomarker for the prediction of depressive symptoms and prognosis in patients with esophageal cancer.

Jingsheng Wang, Fengtong Li, Yang Dong, Yongchun Song, Zhiyong Yuan Department of Radiation Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China Background: The aim of this study was to investigate the adrenal tumor motion law and influence factors in the treatment of adrenal gland tumor and provide a reference value basis for determining the planning target volume margins for therapy. Materials and methods: The subjects considered in this study were 38 adrenal tumor patients treated with CyberKnife with the placement of 45 gold fiducials. Fiducials were implanted into each adrenal tumor using β-ultrasonic guidance. Motion amplitudes of gold fiducials were measured with a Philips SLS simulator and motion data in the left–right, anterior–posterior, and cranio–caudal directions were obtained. Multiple linear regression models were used to analyze influencing factors. t-Test was used for motion amplitude comparison of different tumor locations along the z-axis. Results: The motion distances were 0.1–0.4 cm (0.27±0.07 cm), 0.1–0.5 cm (0.31±0.11 cm), and 0.5–1.2 cm (0.87±0.21 cm) along the x-, y-, and z-axes, respectively. Motion amplitude along the z-axis may be affected by tumor location, but movement along the other axes was not affected by age, height, body mass, location, and size. Conclusion: The maximum motion distance was along the z-axis. Therefore, this should be the main consideration when defining the planning target volume safety margin. Due to the proximity of the liver, adrenal gland tumor motion amplitude was smaller on the right than the left. This study analyzed adrenal tumor motion amplitude data to evaluate how motion and other factors influence the treatment of adrenal tumor with a goal of providing a reference for stereotactic radiotherapy boundary determination. Keywords: adrenal gland, gold fiducial, law of motion, CyberKnife, influence factors

Background Chemoradiotherapy (CRT) plays a central role in the treatment of esophageal squamous cell carcinoma (ESCC). However, no effective biomarkers have been identified for predict CRT sensitivity and prognosis of patients with ESCC. The aim of this study was to investigate cytokine profiles of epidermal growth factor (EGF) and urokinase plasminogen activator receptor (uPAR) in 68 ESCC patients, and to evaluate the clinical utility of these markers. Methods This pilot study enrolled 68 patients who received neoadjuvant CRT followed by radical surgery or definitive CRT between 2015 and 2017. Serum specimen was obtained from each patient before treatment and at the time of administration of total doses of 40 Gy. Cytokines expression analyses were performed in pre- and post-treatment serum using human cytokine antibody arrays which contained 120 known tumor-related cytokines. Results Seven differentially expressed cytokines identified by cytokine antibody arrays in pre- and post-treatment serum from 4 patients with CRT sensitivity and 4 patients with CRT resistance. Of these, up-regulation of EGF and uPAR in serum at the doses of 40 Gy were associated with adverse clinical outcomes. The predictive value of EGF and uPAR were further assessed in a second set of 60 ESCCs. A total of 68 patients enrolled in this study. The median follow-up duration of these patients was 15.87 months (range, 6.21-23.85 months). Cox multivariate survival analyses revealed that high uPAR ratio after CRT independently predicted progression-free survival (PFS) (HR =3.999, 95% CI: 1.503-10.639, P=0.006) and patients with elevated levels of EGF after CRT exhibited significantly worse overall survival (OS) (HR =2.574, 95% CI: 1.046-6.335, P=0.040). Of note, uPAR expression was significantly positive correlation with EGF expression in pre- and post-treatment serum (P=0.0001, P=0.0038). Patients with both high EGF and uPAR ratios had an inferior PFS and OS, compared to patients with a high EGF ratio only or uPAR ratio only or neither (1-year PFS rate 44.2% vs. 61.4%, 1-year OS rate 64.2% vs. 83.4%, P=0.033 and 0.029, respectively). Conclusions The levels of EGF and uPAR in serum are reliable and predictive biomarkers for survival in ESCC patients. Further prospective validation in larger independent cohorts is necessary to fully assess its predictive power. We present the following article in accordance with the REMARK reporting checklist.

Zhi Wang,1,2,* Zhangjian Zhou,1,* Wenxing Li,1 Wei Wang,3 Xin Xie,1 Jincheng Liu,2 Yongchun Song,1 Chengxue Dang,1 Hao Zhang1 1Division of Surgical Oncology, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Division of Surgery, Shaanxi Tuberculosis Hospital, Changan District, Xi’an, Shaanxi, People’s Republic of China; 3Division of Gynaecology and Obstetrics, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China *These authors contributed equally to this work Objective: The prevalence of breast cancer in elderly women (older than 80years) is expected to rise more dramatically than its incidence. In this study, we evaluated the evidence for treatment guidelines for elderly breast cancer patients.Patients and methods: All included patients were enrolled from 2010 to 2013 from the Surveillance, Epidemiology, and End Results (SEER) database. The Akaike information criterion (AIC) and Harrell’s C statistic were used to perform comparisons. In addition, a propensity score analysis was used to avoid bias caused by data selection criteria. Prognostic factors were selected as nomogram parameters to develop a model to predict survival.Results: A total of 16998 patients included in the SEER database from 2010 to 2013 had breast cancer and fulfilled the study criteria. Of whom, 13007 patients underwent surgery. Overall survival and cancer-specific survival were significantly better in patients who underwent surgery and/or radiotherapy than in those who did not (P

// Hongqing Zhuang 1 , Xiangkun Yuan 2 , Joe Y. Chang 3 , Yongchun Song 1 , Junjie Wang 4 , Zhiyong Yuan 1 , Xiaoguang Wang 1 and Ping Wang 1 1 Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin, China 2 Department of Radiotherapy, Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine (Cangzhou No. 2 Hospital), Hebei, China 3 Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America 4 Department of Radiotherapy, Peking University 3rd Hospital, Beijing, China Correspondence to: Hongqing Zhuang, email: // Keywords : bevacizumab, brain necrosis, recurrence Received : November 27, 2015 Accepted : February 08, 2016 Published : February 26, 2016 Abstract Objective: The aim of the paper was to investigate the recurrence and its causes of radiation brain necrosis following bevacizumab discontinuation. Methods: This study included 14 patients with radiation brain necrosis (confirmed through imaging) after stereotactic radiotherapy for a primary or metastatic brain tumor and who received bevacizumab treatment from June 2011 through December 2014. The patients received bevacizumab at 5 mg/kg, q3-4w, for at least 3 cycles. The T1 signal intensity from enhanced MRI images was used as the evaluation criteria for the brain necrosis treatment efficacy. Results: brain necrosis improved in 13 of the 14 cases (92.9%). However, during follow-up, 10 of the 13 responsive patients (76.9%) exhibited a recurrence in brain necrosis, and a multiple linear regression analysis shows that brain necrosis recurrence was related to the follow-up time after the initial bevacizumab treatment discontinuation. Conclusion: bevacizumab produced good short-term effects for radiation brain necrosis; however, most of the patients would recurrence after bevacizumab is discontinued. Thus, brain necrosis was irreversible.

The occurrence of chemotherapy-induced alterations in markers of haemostasis during chemotherapy has been reported previously. However, the change of the haemostasis markers in the cyclophosphamide, epirubicin and fluorouracil (CEF) regimen remains unclear. The aim of the present study was to identify the change of the haemostasis markers during systemic chemotherapy (600 mg/m2 cyclophosphamide, 80 mg/m2 epirubicin and 500 mg/m2 fluorouracil; four courses over 21 days) to investigate its influence on the haemostasis markers of breast cancer patients and to discuss the requirement of anticoagulation therapy. D-dimer, activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrinogen (FIB) values were obtained before chemotherapy and on days 1, 4, 7 and 21. The results show that PT, D-dimer and FIB were not prolonged prior to chemotherapy compared to that under the control. APTT was prolonged until day 4. The levels of D-dimer and APTT were significantly higher compared to those of the breast cancer patients before receiving chemotherapy and controls on days 1, 4, 7 and 21 after chemotherapy. Alteration of the haemostasis markers occurred in the breast cancer patients under the CEF chemotherapy regimen. As there is an increased risk of deep vein thrombosis and pool prognosis of cancer patients, anticoagulant therapy should be considered.

Objective: To investigate the relationship between the timing of SRS intervention and the complications of cerebral radiation necrosis(CRN) and its impact on the cognitive function and quality of life (QOL) in patients with brain metastases of EGFR-mutated NSCLC who received TKI treatment. Methods: A total of 361 targets from 257 patients with brain oligo-metastases of EGFR-mutated NSCLC who received Cyberknife treatment between 2010 and 2017 were collected from three Cyberknife centers. The difference in brain necrosis between patients with or without TKI application was statistically counted. Logistic regression analysis was used to analyze the effect of applying TKI on the occurrence of CRN in patients, and the effect of SRS before and after TKI resistance on CRN. The effects of CRN on the cognitive function and quality of life of surviving patients were analyzed. Results: The rate of CRN in the TKI group was significantly higher than that in the non-TKI group. The incidence of brain necrosis in patients undergoing SRS after drug resistance was significantly higher than that in patients undergoing SRS before drug resistance. Regression analysis showed that combination of TKI with SRS, and SRS after TKI resistance were important influencing factors for CRN. The follow-up results of currently surviving patients showed that the occurrence of brain necrosis seriously affected the cognitive function and QOL of patients. Conclusion: Long-term radiation-induced brain damage needs to be seriously monitored in NSCLC patients with EGFR mutation brain metastasis undergoing combination of radiotherapy and TKI. Clinicians need to pay attention to this problem and make reasonable recommendations for radiotherapy and TKI treatment. Funding Statement: This Paper was supported by Clinical key project of Peking University Third Hospital (BYSY2017030). Declaration of Interests: We declared that there were no any financial and personal relationships with other people or organizations that could inappropriately influence the work. Ethics Approval Statement: The study was approved by the Ethics Committee of the Peking University Third Hospital and completed under its supervision. It was in accordance with all the ethical requirements.

Background/Aims: Elevated pretreatment plasma D-dimer level has been reported as an unfavorable prognostic indicator in several malignancies. The aim of this meta-analysis was to evaluate the prognostic value of elevated D-dimer level in solid tumors. Methods: A comprehensive search of electronic databases up to June 10, 2017 was carried out by two independent reviewers. We included studies exploring the association between pretreatment plasma D-dimer level and patients’ survival outcomes in solid tumors. Overall survival (OS) was regarded as primary outcome and progression-free survival (PFS), disease-free survival (DFS) as well as cancer-specific survival (CSS) were chosen as secondary outcomes. Hazard ratio and 95% confidence interval (CI) were extracted directly or indirectly from included studies. Results: 49 studies with 13001 patients were included in our meta-analysis. Elevated D-dimer was markedly associated with poor OS (pooled HR = 1.90, 95% CI = 1.63 - 2.20, P < 0.001). The effect was observed in all different tumor sites, disease stages, cut-off values and ethnicities. Meanwhile, patients with a high plasma D-dimer had a shorter PFS (HR = 1.46, 95% CI = 1.22–1.76; P < 0.001), DFS (HR = 2.02, 95% CI = 1.56–2.62) and CSS (HR = 2.04, 95% CI= 1.58 – 2.64). Conclusions: Analysis of the pretreatment plasma D-dimer might provide useful information to predict prognosis in patients with solid tumors.

Background Fibrinogen (FIB) is an important source of fibrin, which plays a crucial role in circulating tumor cells (CTCs) extravasation and distant metastasis development. We hypothesize it’s stable final product, plasma D-dimer, may be associated with CTCs appearance and can reflect the metastatic phenotype in cancer patients. Methods We first verified our hypothesis in different murine gastric cancer metastasis models in vivo, plasma D-dimer and fibrinogen as well as its degradation products were directly examined in three metastasis immune-deficient mouse models and in controls. Next, we gathered and analyzed the result of plasma D-dimer levels and CTCs numbers in 41 advanced primary gastric cancer (GC) patients. A follow-up study was conducted in these patients. Results In three in vivo murine metastasis models, plasma D-dimer levels were extremely elevated in a hematogenous and intraperitoneal murine model of metastasis compared with a subcutaneous tumor model and the control group, supporting our previous hypothesis. While in 41 GC patients, the result displayed that plasma D-dimer levels were remarkably increased in patients with distant metastases, especially in visceral metastases patients. Additionally, linear association was shown between D-dimer level and CTCs numbers (R 2 = 0.688, p

Yongchun Song, Zhiyong Yuan, Fengtong Li, Yang Dong, Hongqing Zhuang, Jingsheng Wang, Huaming Chen, Ping Wang Department of Radiation Oncology and CyberKnife Center, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin, People’s Republic of China Objective: To evaluate the efficacy and safety of CyberKnife® treatment for locally-advanced pancreatic cancer (LAPC).Methods: The efficacy of CyberKnife® treatment was analyzed in 59 LAPC patients treated between October 2006 and September 2014. The median tumor volume was 27.1 mL (13.0–125.145 mL). The median prescribed dose was 45 Gy (35–50 Gy), delivered in 5 fractions (3–8 fractions). The overall survival (OS) rates and freedom from local progression (FFLP) rates were estimated using the Kaplan–Meier survival curve.Results: The median follow-up for all patients was 10.9 months (3.2–48.7 months) and 15.6 months (3.9–37.6 months) among surviving patients. The median OS was 12.5 months, and the 1-year and 2-year survival rates were 53.9% and 35.1%, respectively. The 1-year FFLP rate was 90.8% based on the computed tomography (CT) evaluation. Grade 1–2 acute and late-stage gastrointestinal (GI) reactions were observed in 61% of the patients. One patient experienced grade 3 toxicity.Conclusion: Excellent clinical efficacy was obtained after treatment of LAPC using CyberKnife®, with minimal toxicity. Keywords: pancreatic cancer, stereotactic body radiotherapy, CyberKnife®, local control, toxicity&nbsp

Background The aim of this study is to develop a prognostic nomogram for patients with adenocarcinoma of esophagogastric junction and compare its predictive accuracy with the traditional tumor-node-metastasis (TNM) malignant staging system. Methods Patients from the Surveillance, Epidemiology, and End Results Program (from 1988 to 2011) and the First Affiliated Hospital of Xi’an Jiaotong University (from 2005 to 2010) were collected retrospectively. Preselected multiple potential interactions were tested irrespective of significance as nomogram parameters. And the Harrell’s C-index was used to estimate the accuracy of the nomogram system. Model validation was performed using bootstrap to quantify our modeling strategy. Results In our study, six clinical associated factors (age, sex, depth of invasion, metastasized lymph nodes, examined lymph nodes, histological grade) were evaluated in the nomogram. In the training set, the nomogram exhibited superior discrimination power compared with the American Joint Committee on Cancer (AJCC) TNM classification (Harrell’s C-index, 0.69 and 0.63, respectively). Calibration of the nomogram predicted survival was similar to the actual overall survival. In the validation set, the discrimination of nomogram was also better than the AJCC TNM staging system (C-index, 0.75 and 0.65, respectively), and the calibration of nomogram predicted survival was within a 10 % margin of actual overall survival. Conclusions Based on the patients with adenocarcinoma of esophagogastric junction from a Western and an Eastern database, the nomogram provided significantly improved discrimination than the traditional AJCC TNM classification and also provided an accurate individualized prediction of the survival. Electronic supplementary material The online version of this article (doi:10.1186/s12957-015-0613-7) contains supplementary material, which is available to authorized users.

Explore potential screening biomarkers for noninvasive diagnosis of colorectal cancer (CRC) by testing methylation of the miR-34a and miR-34b/c promoter in CRC patients’ tissue and stool samples. Methylation-specific PCR analyses were performed on sample DNAs: 82 pairs of normal/cancer samples, 82 CRC patients’ stool samples, 40 healthy volunteer stool samples, and 20 healthy volunteer blood samples were recruited. miR-34a has been found methylated in 65 of 82 (79.3 %) the CRC tissue samples, but only 36 of 82 (43.9 %) in corresponding normal samples. And when testing miR-34a in stool, 63 of 82 (76.8 %) CRC stool samples were observed methylated, and 2 of 40 (5 %) healthy samples were observed methylated. The methylation for miR-34b/c has been found in 80 of 82 (97.5 %) CRC tissue samples, 49 of 82 (59.8 %) corresponding CRC normal samples, and 74 of 79 (93.6 %) CRC stool samples. Yet we did not detect any methylation from healthy volunteers stool samples or healthy adult blood samples. Results indicated 76.8 % sensitivity and 93.6 % specificity of the miR-34a methylation test for detecting CRC using stool samples. Meanwhile, the sensitivity and specificity of miR-34b/c were 95 and 100 %, respectively. Moreover, our results revealed that abnormal DNA methylation of miR-34a was correlated with lymph metastasis (P = 0.010). Abnormal methylation of miR-34a and miR-34b/c genes might be regarded as potential biomarkers for noninvasive screening and diagnosis of colorectal cancer.

The aim of this study was to evaluate hypermethylation of the spastic paraplegia-20 promoter as a potential biomarker and prognostic factor in gastric cancer. Four human gastric cancer cell lines, 41 primary gastric cancer tissue samples and corresponding peripheral blood samples, and blood samples of 21 healthy individuals were analyzed using methylation-specific polymerase chain reaction. Additionally, the expression of Spartin, the protein product encoded by spastic paraplegia-20, was analyzed in tissues from 119 gastric cancer patients who underwent radical gastrectomy at Xi’an Jiaotong University between 2005 and 2010. Hypermethylation of the spastic paraplegia-20 promoter was observed in 26 of 41 (63.4 %) primary tumors and 1 of 35 (2.9 %) adjacent normal gastric tissues (P < 0.001). Among matched peripheral blood samples from gastric cancer patients, 48.8 % exhibited hypermethylation of the spastic paraplegia-20 promoter. In contrast, no methylation of the spastic paraplegia-20 promoter was observed in blood samples from 21 healthy individuals (P < 0.001). Additionally, demethylation by 5-aza-dC treatment led to gene reactivation in gastric cancer cells exhibiting hypermethylation of the spastic paraplegia-20 promoter. Finally, immunohistochemical staining indicated that low expression of Spartin was a prognostic factor predicting poor outcomes in gastric cancer patients (P = 0.037). These findings suggested that hypermethylation of the spastic paraplegia-20 promoter occurred frequently in gastric cancer and could represent a novel prognostic factor. Furthermore, detection of this molecular feature in the peripheral blood of gastric cancer patients suggested that evaluation of the methylation state of the spastic paraplegia-20 promoter may be used as a noninvasive screening method.

Zhiyong Yuan,* Lijun Tian,* Ping Wang, Yongchun Song, Yang Dong, Hongqing Zhuang Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China *These authors contributed equally to this work Objective: To retrospectively analyze and compare the outcomes of patients with hepatocellular carcinoma treated with either surgical excision or CyberKnife® from September 2006 to August 2011. Materials and methods: Local control and toxicity were the primary endpoints, followed by local progression-free survival, progression-free survival, and overall survival as the secondary endpoints. Response Evaluation Criteria In Solid Tumors were the evaluation criteria for efficacy; Common Toxicity Criteria 3.0 were the evaluation criteria for adverse events. Local control was calculated using the direct method (nonactuarial). The survival curves were drawn using the Kaplan–Meier method along with log-rank test analysis. Results: The research included 26 patients treated with tumor-free cutting edge (R0) surgical excision and 22 patients treated with CyberKnife treatment. The results showed that the adverse effects of CyberKnife were milder, with 1-, 2-, and 3-year local control rates of 92.9%, 90.0%, and 67.7%, respectively. The overall survival rates of the surgical treatment were 88.5%, 73.1%, and 69.2% for the same periods, while those of CyberKnife treatment were 72.7%, 66.7%, and 57.1%, respectively. In this study, surgical excision appeared to prolong overall survival to a greater extent, but with no statistical significance; no statistical difference was observed in the tumor-specific overall survival and progression-free survival between the two cohorts. Conclusion: According to this preliminary study, with its mild toxicity, the efficacy of CyberKnife treatment for early hepatocellular carcinoma was on par with that of surgical resection. Keywords: hepatic carcinoma, stereotactic body radiation therapy, hepatectomy

Prior studies have demonstrated that analysis of gene promoter methylation in stool samples may be a potential biomarker for noninvasive colorectal cancer detection. Aberrant methylation in gene promoter is common in various cancers, and epigenetic alterations can result in down-regulation or silence of gene expression. Recently, hypermethylation of fibrillin-1 (FBN1) was reported to be associated with colorectal cancer (CRC). In this study, we examined the methylation status of FBN1 in stool samples to test CRC. For the purpose of colorectal cancer detection, we investigated FBN1 hypermethylation in the tissue and stool samples of colorectal cancer patients using methylation-specific polymerase chain reaction. The result is that out of 75 patients with colorectal cancer, 59 (78.7%) exhibited hypermethylated FBN1 in their tumor tissue DNA. We next detected the methylation status of FBN1 in the stool DNA of these patients. The hypermethylated FBN1 occurred in 72% (54/75) of these patients in their stool samples and occurred in 6.7% (2/30) of healthy people (P < 0.001). The results indicated 72.0% sensitivity and 93.3% specificity of the test for detecting CRC by using stool samples. So, the study reveals that hypermethylation status in the promoter of FBN1 is a high specific and sensitive biomarker for colorectal cancer, and detecting hypermethylated FBNI in stool samples is a noninvasive and useful method for screening colorectal cancer.

We conducted a meta-analysis to explore the relationships between p14ARF gene methylation and clinicopathological features of colorectal cancer (CRC). Databases, including Pubmed, Embase and Cochrane Library, were searched and, finally, a total of 18 eligible researches encompassing 1988 CRC patients were selected. Combined odds ratios (ORs) with 95% confidence intervals (95% CIs) were evaluated under a fixed effects model for absence of heterogeneity. Significant associations were observed between p14ARF gene methylation and tumor location (OR = 2.35, 95% CI: 1.55–3.55, P = 0.001), microsatellite instability (MSI) status (OR = 3.28, 95% CI: 2.12–5.07, P

Results: Transcatheter arterial chemoembolization (TACE) combined with EBRT constitutes an improved therapeutic strategy for unresectable but confined intrahepatic HCC. We found that EBRT can improve survival of HCC patients with PV tumor thrombi, and decreases the mortality of HCC patients with abdominal LNM, prolonging median survival to 8.4 months. EBRT also shrinks adrenal and lung metastatic HCC lesions, resulting in median survival times of 13.6 and 13.4 months, respectively. For patients with bone metastases from HCC, EBRT significantly relieved the symptoms, although median survival time for these patients was 7.4 months. EBRT is effective for treatment of intermediate/advanced stages of HCC. Although our finding is based only on retrospective analysis, no therapeutic option that provides better treatment than EBRT in this indication has thus far been identified. Because sorafenib has been recommended as a treatment strategy by the NCCN for HCC, we compared the survival after EBRT with sorafenib treatment on the basis of published clinical data in the Table and found that EBRT was more effective than sorafenib for improving patient survival when tested on tumors of comparable metastatic size. Conclusion: EBRT should be included in the NCCN guideline as a treatment strategy for intermediate/advanced HCC. Author Disclosure: Z. Zeng: None.

Background The incidence of adenocarcinoma of the esophagogastric junction is increasing. This study aims to evaluate the clinicopathological features of Chinese patients with adenocarcinoma of the esophagogastric junction and to define prognostic factors. Methods We retrospectively reviewed a database of 382 consecutive patients with adenocarcinoma of the esophagogastric junction at the First Affiliated Hospital of Xi’an Jiaotong University from January 2005 to March 2010. All patients were classified according to the Siewert’s classification and staged according to the latest edition of the American Joint Committee on Cancer categories. Results Six of the 382 patients had type I adenocarcinoma, 220 had type II, and 156 had type III. There was no significant difference in the overall survival of different Siewert subtypes. According to the multivariate analysis, pathological lymph node stage, age, and the existence of lymphovascular invasion were the independent factors of prognosis of adenocarcinoma of the esophagogastric junction following surgery. Conclusions On the data, the distribution of the three types of tumor was found to be different from that reported in Western countries. Lymph node metastasis, lymphovascular invasion, and age were significant and independent factors for poor prognosis after R0 resection for adenocarcinoma of the esophagogastric junction.