Honglei Pei

Prognostic role of tissue and circulating microRNA-200c in malignant tumors: a systematic review and meta-analysis.

Background: Recently, many studies have shown that microRNAs (miRNA) exhibit altered expression in various cancers and may serve as prognostic biomarkers. We performed a systematic review and meta-analysis to evaluate the prognostic role of miR-200c expression in different cancers. Methods: Studies were recruited by searching PubMed, Embase and the Cochrane Library (last search update was May 2014) and assessed by further quality evaluation. Results: A total of 25 studies dealing with various carcinomas were identified for systematic review. Among them, 18 studies were ultimately included in the meta-analysis. Our results indicated that the expression of tissue miR-200c was not associated with OS and PFS in various carcinomas; however, downregulation of tissue miR-200c did predict poor OS of patients with stage I disease (HR=0.41, 95% CI 0.25-0.68, P=0.001). Furthermore, overexpression of blood miR-200c was significantly related to poor OS and PFS (HR=3.07 95% CI 1.58-5.96 P=0.001, HR=2.26 95% CI 1.66-3.08 P<0.001, respectively), especially in patients with advanced disease. Conclusion: This systematic review and meta-analysis clarified that low expression of miR-200c in primary tissue was significantly associated with poor survival in cancer patients at early stage, whereas a high level of blood miR-200c predicted poor prognosis in patients with advanced tumors.

Single arc volumetric-modulated arc therapy is sufficient for nasopharyngeal carcinoma: a dosimetric comparison with dual arc VMAT and dynamic MLC and step-and-shoot intensity-modulated radiotherapy

BackgroundThe performance of single arc VMAT (VMAT1) for nasopharyngeal carcinoma (NPC) on the Axesse linac has not been well described in previous studies. The purpose of this study is to assess the feasibility of VMAT1 for NPC by comparing the dosimetry, delivery efficiency, and accuracy with dual arc VMAT (VMAT2), dynamic MLC intensity-modulated radiotherapy (dIMRT), and step-and-shoot intensity-modulated radiotherapy (ssIMRT).MethodsTwenty consecutive patients with non-metastatic NPC were selected to be planned with VMAT1, VMAT2, dIMRT and ssIMRT using Monaco 3.2 TPS on the Axesse™ linear accelerator. Three planning target volumes (PTVs), contoured as high risk, moderate risk and low risk regions, were set to receive median absorbed-dose (D50%) of 72.6 Gy, 63.6 Gy and 54 Gy, respectively. The Homogeneity Index (HI), Conformity Index (CI), Dose Volume Histograms (DVHs), delivery efficiency and accuracy were all evaluated.ResultsMean HI of PTV72.6 is better with VMAT1(0.07) and VMAT2(0.07) than dIMRT(0.09) and ssIMRT(0.09). Mean HI of PTV63.6 is better with VMAT1(0.21) and VMAT2(0.21) than dIMRT and ssIMRT. Mean CI of PTV72.6 is also better with VMAT1(0.57) and VMAT2(0.57) than dIMRT(0.49) and ssIMRT(0.5). Mean CI of PTV63.6 is better with VMAT1(0.76) and VMAT2(0.76) than dIMRT(0.73) and ssIMRT(0.73). VMAT had significantly improved homogeneity and conformity compared with IMRT. There was no significant difference between VMAT1 and VMAT2 in PTV coverage. Dose to normal tissues was acceptable for all four plan groups. VMAT1 and VMAT2 showed no significant difference in normal tissue sparring, whereas the mean dose of the parotid gland of dIMRT was significantly reduced compared to VMAT1 and VMAT2. The mean delivery time for VMAT1, VMAT2, dIMRT and ssIMRT was 2.7 min, 3.9 min, 5.7 min and 14.1 min, respectively. VMAT1 reduced the average delivery time by 29.8%, 51.1% and 80.8% compared with VMAT2, dIMRT and ssIMRT, respectively. VMAT and IMRT could all be delivered accurately based on our quality assurance standards.ConclusionsIn the treatment of NPC using the Axesse™ linear accelerator, single arc VMAT has shown superiority to double arc VMAT, dIMRT and ssIMRT in delivery efficiency, without compromise to the PTV coverage. However, there is still room for improvement in terms of OAR sparing.

Computed tomography-guided permanent brachytherapy for locoregional recurrent gastric cancer.

BackgroundLocoregional recurrence is the typical pattern of recurrence in gastric cancer, and cannot be removed by surgery in most of the patients. We aimed to evaluate the feasibility and efficacy of computed tomography (CT)-guided brachytherapy for patients with locoregional recurrent gastric cancer.Materials and methodsWe reviewed the case histories of 28 patients with locoregional recurrent gastric cancer that were selected for CT- guided brachytherapy by a multidisciplinary team. The clinical data of the patients including patient characteristics, treatment parameters, short-term effects, and survival data were collected and analyzed.Results15-75 125I seeds were implanted into each patient to produce a minimal peripheral dose (MPD) 100-160 Gy. Median day 0 dosimetry was significant for the following: V100 (the volume treated with the prescription dose) 95.8% (90.2-120.5%) and D90 (prescription dose received by at least 90% of the volume) 105.2% (98.0-124.6%) of prescription dose. No serious complications occurred during the study. Two months after brachytherapy, complete response, partial response and progressive disease were observed in 50.0%, 28.6% and 21.4% of patients, respectively. The median survival time was 22.0 ± 5.2 months, and the 1, 2,and 3-year survival rate was 89 ± 6%, 52 ± 10% and 11 ± 7%, respectively. A univariate analysis showed that the tumor size was a significant predictor of overall survival (P = 0.034). Patients with tumors <3 cm had relatively higher complete response rate (66.7%), compared to those with tumors >3 cm (30.8%). The PTV (planning target volume) smaller than 45 cm3 was significantly correlated with achieving complete tumor eradication in the treated region (P = 0.020).ConclusionsFor selected patients with limited locoregional recurrent gastric cancer, CT-guided brachytherapy using 125I seeds implantation can provide a high local control rate, with minimal trauma.

Proposed Modification of Nodal Staging as an Alternative to the Seventh Edition of the American Joint Committee on Cancer Tumor-Node-Metastasis Staging System Improves the Prognostic Prediction in the Resected Esophageal Squamous-Cell Carcinoma.

Introduction: The 7th American Joint Committee on Cancer (AJCC) tumor-node-metastasis staging system for esophageal cancer defined N classification based on the number of metastatic lymph nodes (LNs). However, this classification might neglect the extent of LNs metastasis. This study aimed to revise N classification based on the extent of LNs metastasis and propose a modification to the current AJCC staging system for better representing the prognostic characteristics of Chinese esophageal squamous-cell carcinoma (ESCC). Methods: We retrospectively reviewed 1993 ESCC patients who underwent curative resection. The proposed N categories based on the number of LNs metastasis stations were compared with the current staging system by univariate and multivariate Cox regression analyses. Homogeneity, discriminatory ability, and monotonicity of gradients of two staging systems were compared using likelihood ratio &khgr;2 statistics and Akaike information criterion calculations. Results: The survival differences were not significant for N2 versus N3 category (p = 0.231) and stages IIIB versus IIIC (p = 0.713) based on the 7th AJCC staging system. When the modified staging system was adopted, the survival difference for N2 versus N3 and IIIB versus IIIC could be well discriminated. Statistical analysis showed that the modified staging system had higher likelihood ratio &khgr;2 scores and smaller Akaike information criterion values than the 7th AJCC staging system, which represented the optimum prognostic stratification. Conclusions: The modified staging system with the revised N categories based on the number of LNs metastasis stations better predicts the survival of Chinese ESCC population than the 7th AJCC staging system. Further studies are required to confirm this result.

Evaluating the Prognostic Value of microRNA-203 in Solid Tumors Based on a Meta-Analysis and the Cancer Genome Atlas (TCGA) Datasets

Background: It has been reported that miR-203 expression was aberrant in various types of cancers, and it could be used as a prognostic biomarker. Therefore, in this study, we aimed to evaluate the prognostic value of miR-203 expression in solid tumors by using meta-analysis and The Cancer Genome Atlas (TCGA) datasets. Methods: By doing a literature research in PubMed, Embase and the Cochrane Library (last update by December 2016), we were able to identify the studies assessing the prognostic role of miR-203 in various tumors. We then used TCGA datasets to validate the results of meta-analysis. Results:33 studies from 26 articles were qualified and enrolled in this meta-analysis. Pooled analyses showed that higher expression of miR-203 in tissues couldn’t predict poor overall survival (OS) and progression-free survival (PFS) in solid tumors. However, the results of subgroup analyses revealed that the upregulation of tissue miR-203 expression was associated with poor OS in colorectal cancer (hazard ratio (HR)=1.81, 95% confidence intervals (CI) 1.31-2.49; P<0.001), pancreatic cancer (HR=1.19, 95% CI 1.09-1.31; P<0.001) and ovarian cancer (HR=1.85, 95% CI 1.45-2.37; P<0.001); but it had opposite association in liver cancer (HR=0.52, 95% CI 0.28-0.97; P=0.040) and esophageal cancer (HR=0.41, 95% CI 0.25-0.66; P<0.001). Based on TCGA datasets, we found the same results for pancreatic cancer and esophageal cancer, but not for colorectal cancer and liver cancer. Moreover, patients with high circulating miR-203 in blood had significantly poor OS and PFS in colorectal cancer and breast cancer. Conclusion: Our study showed that the prognostic values of tissue miR-203 varied in different tumor types. In addition, the upregulation of circulating miR-203 in blood was associated with poor prognosis in colorectal cancer and breast cancer.

Prognostic nomogram integrated systemic inflammation score for patients with esophageal squamouscell carcinoma undergoing radical esophagectomy

Growing evidence indicates that nomogram combined with the biomarkers of systemic inflammation response could provide more accurate prediction than conventional staging systems in tumors. This study aimed to establish an effective prognostic nomogram for resectable thoracic esophageal squamouscell carcinoma (ESCC) based on the clinicopathological parameters and inflammation-based prognostic scores. We retrospectively investigated 916 ESCC patients who underwent radical esophagectomy. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve, and compared with the 6th and 7th AJCC TNM classifications. The neutrophil lymphocyte ratio (NLR), C-reactive protein albumin (CRP/Alb) ratio, histological grade, T stage and modified N stage were integrated in the nomogram. The C-index of the nomogram for predicting the survival was 0.72, which showed better predictive ability of OS than the 6th or 7th TNM stages in the primary cohort (P < 0.001). The calibration curve showed high consistency between the nomogram and actual observation. The decision curve analysis showed more potential of clinical application of the prediction models compared with TNM staging system. Moreover, our findings were supported by the validation cohort. The proposed nomogram showed more accurate prognostic prediction for patients with ESCC after radical esophagectomy.

Dosimetric comparison between step-shoot intensity-modulated radiotherapy and volumetric-modulated arc therapy for upper thoracic and cervical esophageal carcinoma

To compare and analyze the dosimetric characteristics of volumetric modulated arc therapy (VMAT) vs step-shoot intensity-modulated radiation therapy (sIMRT) for upper thoracic and cervical esophageal carcinoma. Single-arc VMAT (VMAT1), dual-arc VMAT (VMAT2), and 7-field sIMRT plans were designed for 30 patients with upper thoracic or cervical esophageal carcinoma. Planning target volume (PTV) was prescribed to 50.4Gy in 28 fractions, and PTV1 was prescribed to 60Gy in 28 fractions. The parameters evaluated included dose homogeneity and conformality, dose to organs at risk (OARs), and delivery efficiency. (1) In comparison to sIMRT, VMAT provided a systematic improvement in PTV1 coverage. The homogeneity index of VMAT1 was better than that of VMAT2. There were no significant differences among sIMRT, VMAT1, and VMAT2 in PTV coverage. (2) VMAT1 and VMAT2 reduced the maximum dose of spinal cord as compared with sIMRT (p < 0.05). The rest dose-volume characteristics of OARs were similar. (3) Monitor units of VMAT2 and VMAT1 were more than sIMRT. However, the treatment time of VMAT1, VMAT2, and sIMRT was (2.0 ± 0.2), (2.8 ± 0.3), and (9.8 ± 0.8) minutes, respectively. VMAT1 was the fastest, and the difference was statistically significant. In the treatment of upper thoracic and cervical esophageal carcinoma by the AXESSE linac, compared with 7-field sIMRT, VMAT showed better PTV1 coverage and superior spinal cord sparing. Single-arc VMAT had similar target volume coverage and the sparing of OAR to dual-arc VMAT, with shortest treatment time and highest treatment efficiency in the 3 kinds of plans.

Prognostic role of high Bmi-1 expression in Asian and Caucasian patients with solid tumors: A meta-analysis

Recently, many studies have shown that the B-cell-specific moloney leukemia virus insertion site 1 (Bmi-1) exhibits altered expression in various cancers and may serve as prognostic biomarkers. We performed a meta-analysis to evaluate the prognostic role of Bmi-1 expression in solid cancers. Studies were recruited by searching PubMed, Embase and the Cochrane Library. Thirty-nine articles including 40 studies were involved in this meta-analysis. Our results indicated that the Bmi-1 showed the opposite prognostic effect in Asian and Caucasian populations. High Bmi-1 expression as a negative predictor for overall survival (OS) in Asian patients (HR=1.96, 95% CI 1.62-2.36), but a positive predictor in Caucasian populations (HR=0.77, 95% CI 0.63-0.93). Furthermore, we took a further subgroup analysis based on tumor type in these two populations, respectively. In Asian cases, high expression of Bmi-1 was associated with poor OS in oesophageal carcinoma (HR=1.93, 95% CI 1.52-2.46), gastric cancer (HR=1.50, 95% CI 1.22-1.85), lung cancer (HR=1.73, 95% CI 1.05-2.85), cervical cancer (HR=2.80, 95% CI 2.26-3.47) and colorectal cancer (HR=3.36, 95% CI 2.19-5.15), rather than in breast cancer and HCC. In Caucasian populations, high expression of Bmi-1 was associated with better OS in breast cancer (HR=0.70, 95% CI 0.51-0.97), but it showed no significance in oesophageal carcinoma. In conclusion, high Bmi-1 expression was significantly associated with poor survival in Asian patients with oesophageal carcinoma, gastric cancer, lung cancer, colorectal cancer and cervical carcinoma, whereas high level of Bmi-1 can predict better prognosis in Caucasian patients with breast cancer.

Collimator rotation in volumetric modulated arc therapy for craniospinal irradiation and the dose distribution in the beam junction region

PurposeThe purpose of this study was to investigate the role of beam collimator rotation in Volumetric Modulated Arc Therapy (VMAT) for craniospinal irradiation (CSI), and the impact on dose distribution in the beam junctions.MethodsSix adult patients were selected for the study. Six VMAT plans with different collimator angles were generated for each patient. The patients were treated in supine position with two beam isocenters. The plans were evaluated by analysis of Dose-Volume Histogram (DVHs) data for planning target volume (PTV) and organs at risk (OAR), and conformity index (CI) and homogeneity index (HI) for the target. Dose distributions in the beam junctions were examined carefully and experimentally validated in phantom, with measurement using an ion chamber array and film.ResultsThe mean values of HI and CI for the plans with different beam collimator angles were not significantly different. The numbers of segments, monitor units (MUs) and the delivery time of the plans with 45° beam collimator were obviously higher than those in plans with other beam collimator angles. When collimator angle for both sets of beams were set at 0°, there was a 1 mm low dose gap measured in the junction region.ConclusionsBy setting the collimator angle to 45°, only two isocenters were needed for the treatment of a target with the length up to 90 cm. The HI and CI of the plans were almost the same, regardless if the collimator angles were at 0°. The collimator angles for at least one set of beams should be off 0° in order to avoid a dose gap in the beam junction region.

Frameless stereotactic body radiation therapy for multiple lung metastases

Two patients with multiple lung metastases (≥ 5) were treated using frameless stereotactic body radiation therapy (SBRT) on an Elekta Axesse linear accelerator equipped with an interdigitation‐capable multileaf collimator and four‐dimensional cone‐beam CT (4D CBCT). The technique and the early clinical outcomes were evaluated. Patient A with five lung metastases and Patient B with seven lung metastases underwent SBRT (48 Gy/8 fractions for Patient A, 42 Gy/7 fractions for Patient B). The treatments were administered using a 6 MV photon beam. The nominal dose rate was 660 MUs/min. Patients were positioned and immobilized using thermoplastic masks and image guidance was done using 4D CBCT. The targets were delineated on the images of the 4D CT, and the positron emission tomography‐computed tomography (PET‐CT) images were taken as references. A two‐step, volumetric‐modulated arc therapy (VMAT) plan was designed for each patient. Step 1: the lesions in one lung were irradiated by a 210° arc field; Step 2: the rest of the lesions in the other lung were irradiated by a 120° arc field. Plans were evaluated using conformity index (CI) and homogeneity index (HI). Patients were followed up and adverse events were graded according to the Common Terminology Criteria for Adverse Events v4.0 (CTCAE v4.0). The beam‐on time of each treatment was less than 10 min. The CI and HI for the two plans were 0.562, 0.0709 and 0.513, 0.0794, respectively. Pulmonary function deteriorated slightly in both patients, and the patient with seven lung lesions was confirmed to have Grade 1 radiation pneumonitis. The technique was fast, accurate, and well tolerated by patients, and the two‐step plan is a helpful design in reducing the dose to the lungs. PACS numbers: 87.55‐x, 87.56.J‐, 87.56.‐v, 87.56.nk, 87.57.qp