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Background Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematologic malignancies that mostly affect the elderly and have a poor prognosis. Azacitidine (AZA) and decitabine (DAC) are the most widely used hypomethylating agents. However, few randomized controlled trials (RCTs) have compared AZA and DAC head to head in MDS or AML. This study intended to conduct a network meta-analysis to compare the 2 drugs to provide more guidance using evidence-based medicine. Patients and Methods A comprehensive search for RCTs was performed till July 31, 2020. The network meta-analysis was conducted using the Markov chain Monte Carlo method. The primary endpoints were overall survival (OS) and the incidence of adverse events, and the secondary endpoints were complete remission (CR) rate, overall remission rate (ORR), and AML-free survival. There were 6 RCTs with 1072 MDS patients, and 3 RCTs with 1256 AML patients. Results In MDS, AZA showed better AML-free survival (hazard ratio = 0.62; 95% CI, 0.43-0.9), whereas DAC had the possibility of achieving better CR and ORR, and AZA had the possibility of obtaining better OS with lower toxicity. As for elderly AML patients, DAC had the possibility of achieving superior CR, ORR, and OS, while the toxicity was relatively higher. Furthermore, subgroup analysis for patients ≥ 75 years old or of high risk in MDS suggested that AZA achieved better OS. Conclusion For MDS, especially patients with intermediate or high risk disease with advanced age and poor general condition, AZA may be a better choice, while DAC may be of more benefit in elderly AML patients.

Background The present study aimed to explore the efficacy of easily obtained intratumoral heterogeneous parameters, other than regular semi-quantitative parameters, based on static O-(2-[18F]fluoroethyl)-l-tyrosine (18F-FET) positron emission tomography (PET) imaging in glioma grade and isocitrate dehydrogenase (IDH) gene 1 mutation prediction. Methods Fifty-eight adult patients with untreated glioma (grades II-IV) who underwent preoperative 18F-FET PET/computed tomography (CT) imaging were enrolled in the present study. Eight semi-automatically obtained static PET imaging parameters after lesion delineation were chosen for analysis. These were: maximal tumor-to-background ratio (TBRmax), peak tumor-to-background ratio (TBRpeak), mean tumor-to-background ratio (TBRmean), coefficient of variation (COV), heterogeneity index (HI), the standard deviation of lesion standardized uptake value (SUVsd), metabolic tumor volume (MTV), and total lesion tracer standardized uptake (TLU). Pathological and immunohistochemical results were used as a reference. The receiver-operating characteristic analysis was used to investigate the predictive efficacy of these parameters in glioma grade and IDH1 mutation status. Results TLU [area under the curve (AUC): 0.841, P

Aim To investigate the impact of biological subtypes in locoregional recurrence in Chinese breast cancer patients receiving postmastectomy radiotherapy (PMRT). Methods and Materials About 583 patients who received postmastectomy radiation between 2010 and 2012 were retrospectively analyzed. According to immunohistochemical staining profile, patients were classified into: Luminal A‐like, Luminal B‐like, HER2‐positive, and triple‐negative breast cancer (TNBC). Local and regional recurrence (LRR) cumulative incidences were calculated by competing risks methodology and the power of prognostic factors was examined by Gray's test and the test of Fine and Gray. Results The median follow‐up was 70.9 months. About 34 LRR events occurred. For Luminal A, Luminal B, HER2‐positive, and TNBC patients, the 5‐year LRR cumulative incidence rates were 1.57%, 4.09%, 10.74%, and 10.28%. Compared with Luminal A, HER2‐positive subtype and TNBC had a significant increased risk of LRR (HR was 5.034 and 5.188, respectively). In univariate analysis, predictive factors for higher LRR were HER2‐positive subtype (HR = 4.43, P .05) in HER2‐positive subtype patients, while LRR with trastuzumab was approximate to Luminal A (with vs Luminal A, P > .05). Additionally, endocrine therapy also significantly reduced LRR incidence in the luminal subtype cohort (without vs with therapy, 6.25% vs 2.89%, HR = 0.365, P, Our study demonstrated that biological subtype based on the classification standard from the St Gallen International Breast Cancer Conference (2013) Expert Panel serves as a reliable prognostic predictor for Chinese breast cancer patients receiving PMRT. Treatment with trastuzumab and endocrine therapy dramatically decreased the risk of LRR in HER2‐positive and hormonal receptor‐positive patients.

Background: A number of clinical trials were conducted to assess the efficacy and toxicity of shorter durations of adjuvant trastuzumab compared with 12-month standard duration. However, the results were controversial and the reduced time varied among trials. To assess the effect of treatment time of adjuvant trastuzumab on the clinical outcomes at trial level, we performed a systematic literature search and a trial-level meta-regression analysis to figure out the appropriate time for trastuzumab treatment. Methods: A comprehensive search of (neo)adjuvant trastuzumab in breast cancer in PUBMED and EMBASE databases from Jan 2000 to June 2019 was performed. We treated the “12-month trastuzumab” as the standard. The “shorter duration” is less than 12 months, including extreme value of 0-month for no trastuzumab. The primary clinical outcome is DFS. HR with 95% confidence intervals (CIs) should be reported. Shortened treatment time (months) and DFS outcome (expressed as HRs) were extracted from each trial. Meta-regression was performed using HR of DFS and shortened time of adjuvant trastuzumab in random-effects model. The coefficient of determination (R2) and the regression coefficient (β) were calculated. We also performed sensitivity analysis by omitting each study to find the potential outliers. Results: A final set of 12 trials was included in the analysis. Five studies compared the 12-month trastuzumab with shorter duration in a non-inferiority setting and 7 studies compared with no trastuzumab in a superiority design (Table 1). The between-study variance τ2 is 0.0062 and the adjusted R2 is 63.14%, which means 63% of the variability among the effects on DFS can be explained by the shortened time of adjuvant trastuzumab, and the remaining between-study variance appears small at 0.0062. We estimated the effects of different shortened times of trastuzumab on DFS and the regression coefficients β of shortened treatment time is 0.04 (P=0.038, 95% CI, 0.0029-0.0788), indicating for each month reduced, the ln(HR) of DFS events increased 0.04. If transferred to HR, the values were 1.042 (e0.04), indicating the risk of DFS would increase 4.2% for each month trastuzumab shortened. Similarly, if 3-month reduced, the risk increased 12.7% (e0.12=1.127); 6-month reduction would increase risk of 27.1%, and 9-month, 43.3% (Table 2). Further subgroup analyses according to estrogen receptor status and lymph nodes status yielded qualitatively similar results. Conclusion: We revealed a significant linear association between shortened time of trastuzumab and the risk of DFS events. These findings suggest that a shorter duration of trastuzumab might be appropriate for patients with lower-risk disease but unacceptable for those with high-risk disease. We believe that the duration of adjuvant trastuzumab should be tailored according to the risk, as well as toxicity and cost. Table 1. Summary of included studies.IDITT numberTrial designHazard marginHR with 95% CIShortened time (month)EndpointMedian Follow-up (year)PHARE1691non-inferiority1.151.08 (0.93-1.25)6DFS7.5HORG481non-inferiority1.531.57 (0.86-2.10)6DFS3Short-HER1253non-inferiority1.291.15 (0.87-1.53)9.9DFS5.2SOLD2174non-inferiority1.31.39 (1.08-1.80)9.9DFS5.2PERSEPHONE4088non-inferiority1.291.07 (0.90-1.27)6DFS5.4E2198227superiorityNA1.18 (0.56-2.44)12DFS6.4NCCTG N98311944superiorityNA1.72 (1.52-1.92)12DFS8.4NSABP B-312102superiorityNA1.72 (1.52-1.92)12DFS8.4HERA3401superiorityNA1.45 (1.27-1.69)12DFS8BCRIG-0062147superiorityNA1.39 (1.18-1.64)12DFS10.3PACS04528superiorityNA1.16 (0.82-1.64)12DFS3.9NOAH235superiorityNA1.69 (1.11-2.63)12EFS3.2 Table 2. Shortened time of adjuvant trastuzumab and increased risk of DFSShortened Time (Month)Change in ln(HR)Increased relative risk of DFS eventsPredicted DFS in APT trial (%)Predicted DFS in N9831/B31 trials (%)10.044%937330.1213%927160.2427%916790.3643%9063120.4862%8958 Citation Format: Ke-Da Yu, Zhi-Rui Zhou, Zhi-Ming Shao. Tailored duration of adjuvant trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-14-04.

The indication for internal mammary node irradiation (IMNI) after preoperative systemic therapy in breast cancer remains vague. This study was designed to evaluate the effect of IMNI in patients with clinical stage II-III breast cancer after preoperative systemic therapy and surgery.Between August 2005 and December 2013, 497 patients with clinical stage II-III breast cancer underwent anthracycline- or taxane-based preoperative systemic therapy, surgery, and postoperative radiation therapy. A median dose of 50 Gy (range, 46-60 Gy) in 25 fractions was delivered to the chest wall or breast with IMNI (n = 236) or without IMNI (n = 261). Disease-free survival (DFS) and overall survival (OS) rates with or without IMNI were evaluated using the Kaplan-Meier method and compared with the log-rank test. Propensity score matching was performed to adjust for the unbalanced characteristics between the 2 groups. Prognostic factors associated with survival were evaluated by univariate and multivariate analysis.The median follow-up time was 64 months. Patients with IMNI presented with more advanced clinical T stage, pathologic N stage, positive lymph-vascular invasion, and medically or centrally located disease (P .05). The 5-year DFS and OS rates were 73.7% and 86.3% in the IMNI group and 71.5% and 86.7% in the non-IMNI group, respectively (P .05). Multivariate analysis demonstrated that IMNI was an independent prognostic factor for DFS (P = .018) and resulted in a borderline improvement in OS (P = .067). After propensity score matching, characteristics were well balanced. The 5-year DFS rates of IMNI and non-IMNI group were 76.8% and 63.4%, respectively (P = .030), and the 5-year OS rates were 88.9% and 84.1%, respectively (P = .083). IMNI was independently prognostic for DFS (P = .014) and OS (P = .047) in matched patients.IMNI improves survival outcomes in patients with clinical stage II-III breast cancer after preoperative systemic therapy. Further prospective studies are warranted to identify the role of IMNI in the preoperative systemic therapy setting.

To evaluate the incidence of symptoms related to brachial plexus neuropathy (BPN) and the dose distribution to the brachial plexus (BP) in patients with breast cancertreated with supraclavicular (SCV) irradiation and boost.In this study, 117 patients with initial ipsilateral supraclavicular lymph node (SLN) metastasis and 39 with recurrent SLN metastasis between 2008 and 2018 in our cancer center were retrospectively analyzed. All patients were treated with 50 Gy of SCV irradiation in 25 fractions and a boost (median dose, 10 Gy; range, 10-16 Gy) to involved nodes in the SCV area. Symptoms related to BPN (including ipsilateral arm numbness, pain, and weakness) were recorded and graded according to the Common Terminology Criteria for Adverse Events, version 5.0. The BP was delineated on simulation computed tomography, and the dose distributions to the BP were evaluated. Meanwhile, 297 patients treated with SCV irradiation without boost during the same period were identified as a control group to compare the incidences of BPN-related symptoms and dosimetric data with patients who received an SCV boost.The 5-year overall survival rate was 80.3% for patients with initial SLN metastasis and 51.0% for patients with recurrent SLN metastasis. For patients who received an SCV boost, incidence rates of ipsilateral arm numbness, pain, and weakness were 23.9%, 18.3%, and 34.3%, respectively. Four patients (5.6%) developed grade 2 numbness and 3 (4.3%) developed grade 2 arm weakness. In the control group, incidence rates of arm numbness, pain, and weakness were 31.6%, 21.9%, and 36.0%, respectively. The incidence of BPN-related symptoms was not significantly different between the 2 groups. Symptoms of grade 3 were not observed in either cohort. The mean doses to the BP in patients who received boost and who did not were 56.8 and 46.8 Gy, respectively (P.001). The maximum doses to the BP in patients who received boost and who did not were 64.5 and 53.5 Gy, respectively (P.001). The BP volumes receiving at least 50 Gy, 60 Gy, 61 Gy, and 62 Gy were also significantly higher in the boosted group compared with the control group (P.001).This study found that an SCV boost of 10 Gy did not increase the incidence of BPN-related symptoms and that the toxicity to the BP was acceptable. Comprehensive treatment including SCV irradiation and boost led to satisfactory survival outcomes in patients with breast cancer who had SLN metastasis.

Radiotherapy is an important treatment for glioblastoma (GBM), but there is no consensus on the target delineation for GBM radiotherapy. The Radiation Therapy Oncology Group (RTOG) and European Organisation for Research and Treatment of Cancer (EORTC) each have their own rules. Our center adopted a target volume delineation plan based on our previous studies. This study focuses on the recurrence pattern of GBM patients whose target delineations did not intentionally include the T2/fluid-attenuated inversion recovery (FLAIR) hyperintensity area outside of the gross tumor volume (GTV). We prospectively collected 162 GBM cases and retrospectively analysed the clinical data and continuous dynamic magnetic resonance images (MRI) of 55 patients with recurrent GBM. All patients received concurrent radiotherapy and chemotherapy with temozolomide (TMZ). The GTV that we defined includes the postoperative T1-weighted MRI enhancement area and resection cavity. Clinical target volume 1 (CTV1) and CTV2 were defined as GTVs with 1 and 2 cm margins, respectively. Planning target volume 1 (PTV1) and PTV2 were defined as CTV1 and CTV2 plus a 3 mm margin with prescribed doses of 60 and 54 Gy, respectively. The first recurrent contrast-enhanced T1-weighted MRI was introduced into the Varian Eclipse radiotherapy planning system and fused with the original planning computed tomography (CT) images to determine the recurrence pattern. The median follow-up time was 15.8 months. The median overall survival (OS) and progression-free survival (PFS) were 17.7 and 7.0 months, respectively. Among the patients, 44 had central recurrences, two had in-field recurrences, one had marginal recurrence occurred, 11 had distant recurrences, and three had subependymal recurrences. Five patients had multiple recurrence patterns. Compared to the EORTC protocol, target delineation that excludes the adjacent T2/FLAIR hyperintensity area reduces the brain volume exposed to high-dose radiation (P = 0.000) without an increased risk of marginal recurrence. Therefore, it is worthwhile to conduct a clinical trial investigating the feasibility of intentionally not including the T2/FLAIR hyperintensity region outside of the GTV.

The aim of this study was to determine the impact of postmastectomy radiotherapy (PMRT) on reoperation rates in women with breast cancer undergoing mastectomy and breast reconstruction. Between June 2001 and December 2015, 832 breast cancer patients treated with mastectomy and breast reconstruction with (n = 159) or without (n = 673) PMRT were analyzed retrospectively. Reoperations following breast reconstruction were categorized into the following three types: anticipated, unanticipated, and others. Multivariable logistic regression models were used to evaluate the impact of PMRT on overall and unanticipated reoperations according to different breast reconstruction types after adjusting for relevant covariates. With a median follow-up of 58.5 months, a total of 1298 operations were performed in 832 breast cancer patients. The rates of overall and unanticipated reoperations were 46.2% and 7.7%, respectively. Multivariable analysis showed that PMRT was not associated with overall reoperations in either implant-based reconstruction patients (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.43–2.37, p = 0.995) or autologous reconstruction patients (OR 0.85, 95% CI 0.52–1.40, p = 0.533); however, the impact of PMRT on unanticipated reoperations differed by reconstruction type. In patients who received implant-based reconstructions, PMRT was associated with a 3.05-fold (95% CI 1.20–7.75, p = 0.019) higher odds of unanticipated reoperations, while there was no difference in patients who underwent autologous reconstruction (OR 1.17, 95% CI 0.51–2.66, p = 0.713). Delayed reconstruction or delayed–immediate reconstructions were associated with an increased risk of both overall and unanticipated reoperations in both reconstruction cohorts. PMRT appears to be associated with an increased risk of unanticipated reoperations among patients receiving implant-based reconstruction, but not among those receiving autologous reconstruction. The risk of reoperation should be taken into consideration when selecting the appropriate breast reconstruction type when PMRT is planned.

In the past, searching for effective radiotherapy sensitization molecular targets and improving the radiation sensitivity of malignant tumors was the hot topic for the oncologists, but with little achievements. We will summarize the research results about breast cancer irradiation sensitization molecular targets over the past two decades; we mainly focus on the following aspects: DNA damage repair and radiation sensitization, cell cycle regulation and radiation sensitization, cell autophagy regulation and radiation sensitization, and radiation sensitivity prediction and breast cancer radiotherapy scheme making. And based on this summary, we will put forward some of our viewpoints.

The aim of this study was to explore the independent prognostic factors related to postoperative recurrence‐free survival (RFS) in patients with breast phyllodes tumors (PTBs). A retrospective analysis was conducted in Fudan University Shanghai Cancer Center. According to histological type, patients with benign PTBs were classified as a low‐risk group, while borderline and malignant PTBs were classified as a high‐risk group. The Cox regression model was adopted to identify factors affecting postoperative RFS in the two groups, and a nomogram was generated to predict recurrence‐free survival at 1, 3, and 5 years. Among the 404 patients, 168 (41.6%) patients had benign PTB, 184 (45.5%) had borderline PTB, and 52 (12.9%) had malignant PTB. Fifty‐five patients experienced postoperative local recurrence, including six benign cases, 26 borderline cases, and 22 malignant cases; the three histological types of PTB had local recurrence rates of 3.6%, 14.1%, and 42.3%, respectively. Stromal cell atypia was an independent prognostic factor for RFS in the low‐risk group, while the surgical approach and tumor border were independent prognostic factors for RFS in the high‐risk group, and patients receiving simple excision with an infiltrative tumor border had a higher recurrence rate. A nomogram developed based on clinicopathologic features and surgical approaches could predict recurrence‐free survival at 1, 3, and 5 years. For high‐risk patients, this predictive nomogram based on tumor border, tumor residue, mitotic activity, degree of stromal cell hyperplasia, and atypia can be applied for patient counseling and clinical management. The efficacy of adjuvant radiotherapy remains uncertain.

BACKGROUND: Breast cancer risk prediction is often based on clinicopathological characteristics despite the high heterogeneity derived from gene expression. Metabolic alteration is a hallmark of cancer, and thus, the integration of a metabolic signature with clinical parameters is necessary to predict disease outcomes in breast cancers. METHODS: Metabolic genes were downloaded from the Gene Set Enrichment Analysis (GSEA) dataset. Genes with statistical significance in the univariate analysis were applied in the least absolute shrinkage and selection operator (LASSO) analysis to build a gene signature in the GSE20685 dataset. Clinicopathological characteristics and risk scores with prognostic significance were incorporated into the nomogram to predict the overall survival (OS) of patients. The Cancer Genome Atlas (TCGA) and GSE866166 datasets were used as the validation datasets. Time-dependent receiver operating characteristic (tROC) curves and calibration plots were used to assess the accuracy and discrimination of the model. RESULTS: A 55-gene metabolic gene signature (MGS) was constructed, and was significantly related to OS both in the discovery (P

// Zhi-Rui Zhou 1,2,3,* , Min Liu 3,* , Hui-Rong Lu 3 , Ye-Fei Li 3 , Shi-Xiong Liang 3,4 and Chun-Yan Zhang 5 1 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, P.R. China 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China 3 Department of Radiation Oncology, Cancer Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China 4 Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R. China 5 Department of Experimental Research, Cancer Hospital of Guangxi Medical University, Nanning, P.R. China * These authors have contributed equally to this work Correspondence to: Shi-Xiong Liang, email: // Chun-Yan Zhang, email: // Keywords : hepatocellular carcinoma, radiotherapy, cancer staging Received : September 20, 2016 Accepted : January 16, 2017 Published : January 28, 2017 Abstract There is no consensus on predicting prognosis for hepatocellular carcinoma patients undergoing radiotherapy. This study aims to evaluate the validity of different staging systems. Overall, 249 hepatocellular carcinoma patients were evaluated retrospectively. All patients were classified by different staging systems. The cumulative survival rates were calculated using the Kaplan-Meier method, and survival curves were compared using the log-rank test. Harrell’s concordance index (c-index) was calculated. The 1-, 3-, and 5-year overall survival rates were 58%, 31% and 20%, respectively. Significant differences in overall survival were observed between stages I and II of the Okuda staging system ( p =0.004), between scores of 3 and 4 of Cancer of the Liver Italian Program prognostic score ( p =0.009), between Chinese University Prognostic Index low-risk and intermediate-risk groups ( p =0.01), between 1 and 2 points of the Japan Integrated Staging score ( p =0.037), between stages III and IV of American Joint Committee on Cancer 1997 TNM staging system ( p =0.011), between stages II and III of American Joint Committee on Cancer 2002 TNM staging system ( p =0.026) and between stages I and II of Guangzhou 2001 staging system ( p =0.000). In conclusion, the Okuda staging system, Chinese University Prognostic Index, and Chinese Guangzhou 2001 staging system were more discriminative than the other staging systems in the prognostic stratification for hepatocellular carcinoma patients undergoing radiotherapy.

Background Genetic studies have shown that C9orf72 , SOD1 , TARDBP and FUS are the most common mutated genes in amyotrophic lateral sclerosis (ALS). Here, we performed a meta-analysis to determine the mutation frequencies of these major ALS-related genes in patients with ALS. Methods We performed an extensive literature research to identify all original articles reporting frequencies of C9orf72 , SOD1 , TARDBP and FUS mutations in ALS. The mutation frequency and effect size of each study were combined. Possible sources of heterogeneity across studies were determined by meta-regression, sensitivity analysis and subgroup analysis. Results 111 studies were included in the meta-analysis. The overall pooled mutation frequencies of these major ALS-related genes were 47.7% in familial amyotrophic lateral sclerosis (FALS) and 5.2% in sporadic ALS (SALS). A significant difference was identified regarding the frequencies of mutations in major ALS genes between European and Asian patients. In European populations, the most common mutations were the C9orf72 repeat expansions (FALS 33.7%, SALS 5.1%), followed by SOD1 (FALS 14.8%, SALS 1.2%), TARDBP (FALS 4.2%, SALS 0.8%) and FUS mutations (FALS 2.8%, SALS 0.3%), while in Asian populations the most common mutations were SOD1 mutations (FALS 30.0%, SALS 1.5%), followed by FUS (FALS 6.4%, SALS 0.9%), C9orf72 (FALS 2.3%, SALS 0.3%) and TARDBP (FALS 1.5%, SALS 0.2%) mutations. Conclusions These findings demonstrated that the genetic architecture of ALS in Asian populations is distinct from that in European populations, which need to be given appropriate consideration when performing genetic testing of patients with ALS.

Background: A retrospective analysis of diagnoses was performed in patients with phyllodes tumors of the breast (PTB) who received preoperative core needle biopsy (CNB) and had breast surgery at Fudan University Shanghai Cancer Center from January 1, 2002 to April 1, 2013. The resulting data allowed us to compare the accordance between CNB and excision diagnoses of PTB patients and evaluate the accuracy of CNB in preoperative diagnosis. Methods: Data from 128 patients with PTB who had undergone preoperative CNB and breast surgery were retrospectively analyzed. We reviewed the medical history, clinical follow-up data, and CNB diagnostic data. A diagnostic test was used to evaluate the sensitivity and specificity of CNB in diagnosing benign, borderline, and malignant phyllodes tumors. Results: The accuracy of CNB for diagnosing PTB was 13.3% (17/128). Of the remaining patients, 98 (75.5% of the PTB patients) were diagnosed with fibroadenoma or fibroepithelial lesions. The sensitivity of CNB at diagnosing benign, borderline, and malignant phyllodes tumors were 4.9% (2/41), 4.2% (3/71), and 25.0% (4/16), respectively, whereas the corresponding specificity were 92.0%, 98.2%, and 100%, respectively. Some clinical features, such as large tumor size, rapid growth, or surgical history of fibroadenomas, were indicative of an increased possibility of PTB. Conclusions: CNB provides a pathological basis for the preoperative diagnosis of PTB, but it has a poor accuracy and offers limited guidance for surgical decisions. Considering CNB along with multiple histologic features may improve the ability to accurately diagnose PTB. An integrated assessment using CNBs in combination with clinical data and imaging features is suggested as a reliable strategy to assist PTB diagnosis.

Postoperative radiotherapy plays an important role in the multidisciplinary treatment of breast cancer. However, it remains a controversy whether it is necessary to carry out prophylactic internal mammary nodes irradiation (IMNI). This review will focus on this topic. In our opinion, the total risk of relapse should be considered during the decision-making on IMNI; in particular, IMNI is recommended for high-risk patients whose tumor is located at the central/medial area or in patients with positive axillary lymph nodes.

// Zhi-Rui Zhou 1,2,3,* , Qing Han 3,* , Shi-Xiong Liang 3,4 , Xiao-Dong He 4 , Nu-Yun Cao 5 and Ying-Jie Zi 3 1 Department of Radiation Oncology, Fudan University, Shanghai Cancer Center, Shanghai, P.R.China 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R.China 3 Department of Radiation Oncology, Cancer Hospital of Guangxi Medical University, Nanning, P.R.China 4 Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R.China 5 College of Mathematics and Information Science, Guangxi University, Nanning, P.R.China * These authors have contributed equally to this paper Correspondence to: Shi-Xiong Liang, email: // Keywords : intensity modulated radiotherapy; normal tissue complication probability; radiation-induced lung injury; breast cancer Received : September 16, 2016 Accepted : October 24, 2016 Published : October 28, 2016 Abstract To investigate the relationship between dosimetric factors, including Lyman normal-tissue complication (NTCP) parameters and radiation-induced lung injury (RILI), in postoperative breast cancer patients treated by intensity modulated radiotherapy (IMRT). 109 breast cancer patients who received IMRT between January 2012 and December 2013 were prospectively enrolled. A maximum likelihood analysis yielded the best estimates for Lyman NTCP parameters. Ten patients were diagnosed with RILI (primarily Grade 1 or Grade 2 RILI); the rate of RILI was 9.17% (10/109). Multivariate analysis demonstrated that ipsilateral lung V 20 was an independent predictor ( P =0.001) of RILI. Setting V 20 =29.03% as the cut-off value, the prediction of RILI achieved high accuracy (94.5%), with a sensitivity of 80% and specificity of 96%. The NTCP model parameters for 109 patients were m=0.437, n =0.912, and TD 50 (1)=17.211 Gy. The sensitivity of the modified Lyman NTCP model to predict the RILI was 90% (9/10), the specificity was 69.7% (69/99), and the accuracy was 71.6% (78/109). The RILI rate of the NTCP 9.62% in patients with breast cancer was 23.08% (9/39), ( P =0.001). In conclusion, V 20 is an independent predictive factor for RILI in patients with breast cancer treated by IMRT; V 20 =29.03% could be a useful dosimetric parameter to predict the risk of RILI. The Lyman NTCP model parameters of the new value (m=0.437, n =0.912, TD50 (1) =17.211 Gy) can be used as an effective biological index to evaluate the risk of RILI.

// Jing Hou 1, * , Zhirui Zhou 2, 3, * , Xingxing Chen 2, 3, * , Ruping Zhao 4 , Zhaozhi Yang 2, 3 , Na Wei 1 , Qing Ni 1 , Yan Feng 2, 3 , Xiaoli Yu 2, 3 , Jinli Ma 2, 3 , Xiaomao Guo 2, 3 1 Department of Breast surgery, Guizhou Provincial People's Hospital, Guiyang 550002, Guizhou Province, China 2 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China 3 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China 4 Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou 310006, Zhejiang, China * These authors contributed equally to this work Correspondence to: Xiaomao Guo, email: guoxm1800@163.com Jinli Ma, email: jinlima_c@yahoo.com Keywords: breast cancer, radiosensitivity, HER2, focal adhesion kinase, anoikis Received: March 06, 2016 Accepted: May 17, 2016 Published: June 07, 2016 ABSTRACT Growing evidence has demonstrated that human epidermal growth factor receptor 2 (HER2) is involved in the radiation response to breast cancer. However, the underlying mechanism remains elusive. Therefore, we investigated if HER2 overexpression is associated with radiosensitivity of breast cancer. We constructed breast cancer cell lines differing in HER2 expression by transducing HER2 cDNA or short hairpin RNA against HER2. We then assessed the radiosensitivity and investigated the potential mechanism by using cell proliferation assay, cell adhesion assays, anoikis assays, colony formation assays, and western blotting analyses. We found that HER2 introduction in breast cancer cell lines MCF-7 (low HER2 expression) and MDA-MB-231 (HER2 is not expressed) promoted cell proliferation and invasion and enhanced cell adhesion and resistance to anoikis. Moreover, HER2 reduced radiosensitivity in these two cells compared with the corresponding control. The opposite results were observed when HER2 was silenced in breast cancer cell lines ZR-7530 and SK-BR-3 (both cells with high expression of HER2) using HER2 shRNA. In addition, animal experiment results showed HER2 could enhance the radioresistance of xenograft tumors. Further studies showed HER2 promoted the phosphorylation of focal adhesion kinase (Fak) and thereby up-regulated the expression of proteins associated with the epithelial-to-mesenchymal transition such as Claudin-1, ZO-1, and ZEB-1. The inhibition of Fak activity using the Fak inhibitor (PF-562281) restored the radiosensitivity in HER2-overexpressing cells. In conclusion, HER2 reduces the radiosensitivity of breast cancer by activating Fak in vitro and in vivo . Fak might be a potential target for the radiosensitization of HER2-overexpressed breast cancer.

// Yong-Jing Yang 1, * , Ling Cao 1, * , Zhi-Wen Li 2 , Ling Zhao 1 , Hong-Fen Wu 1 , Dan Yue 1 , Jin-Lei Yang 1 , Zhi-Rui Zhou 3 , Shi-Xin Liu 1 1 Department of Radiation Oncology, Cancer Hospital of Jilin Province, Changchun, 130012, People’s Republic of China 2 Department of Anesthesiology, The First Hospital Affiliated to Jilin University, Changchun, 130012, People’s Republic of China 3 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China * These authors contribute equally to this work Correspondence to: Shi-Xin Liu, email: liushixin1964@126.com Zhi-Rui Zhou, email: zzr3711@163.com Keywords: rectal neoplasms, neoadjuvant chemoradiotherapy, oxaliplatin, meta-analysis Received: March 06, 2016 Accepted: June 03, 2016 Published: June 14, 2016 ABSTRACT To measure the safety and efficacy of oxaliplatin (OX) application in neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC), EMBASE, PubMed, Cochrane Library, and Web of Science were used for a literature search. Cochrane’s risk of bias tool of randomized controlled trials (RCTs) was used for quality evaluation. The statistical analyses were performed using RevMan 5.3. In addition, 95% confidence intervals (CIs) and pooled risk ratios (RRs) were calculated. Seven RCTs were included in our meta-analysis. After adding OX to fluoropyrimidine (FU), a marginal significant improvement in disease-free survival was noted compared with FU alone (RR = 0.89, 95% CI: 0.78–1.00; P = 0.05). Neoadjuvant CRT with OX significantly decreased the distant metastasis rate (RR = 0.79, 95% CI: 0.67–0.94, P = 0.007). However, no improvement in the local recurrence rate (RR = 0.86, 95% CI: 0.68–1.08; P = 0.19) was noted. In addition, neoadjuvant CRT with OX also significantly increased the pathologic complete response (RR = 1.24, 95% CI: 1.02–1.51; P = 0.03). Grade 3–4 acute toxicity and grade 3–4 diarrhea was considerably higher for OX/FU compared with FU alone. In conclusion, the use of OX on the basis of FU/capecitabine in preoperative CRT is feasible. LARC patients are likely to benefit from CRT regimens with OX.

Transcutaneous electrical nerve stimulation (TENS) has been reported to relieve pain and improve function in patients with knee osteoarthritis. The purpose of this systematic review and meta-analysis was to evaluate the efficacy of TENS for the management of knee osteoarthritis.We searched Embase, PubMed, CENTRAL, SIGLE, PEDro, and clinicaltrials.gov, up to June 2014 for literature related to TENS used for the treatment of knee osteoarthritis. Two authors independently screened the searched records based on the title and abstract. Information including the authors, study design, mean age, sex, study population, stimulation frequency (of TENS), outcome measures, and follow-up periods were extracted by the 2 authors.Eighteen trials were included in the qualitative systematic review, and 14 were included in the meta-analysis. TENS significantly decreased pain (standard mean difference, -0.79; 95% confidence interval [CI], -1.31 to -0.27; P0.00001) compared with control groups. There was no significant difference in the Western Ontario and McMaster Universities Osteoarthritis Index (standard mean differences, -0.13; 95% CI, -0.35 to 0.1; P=0.09) or the rate of all-cause discontinuation (risk ratio, 0.77; 95% CI, 0.48 to 1.22; P=0.94) between the TENS and control groups.TENS might relieve pain due to knee osteoarthritis. Further randomized-controlled trials should focus on large-scale studies and a longer duration of follow-up.

BACKGROUND: To build the triple-negative breast cancer (TNBC) radiation resistance model in vitro and vivo, and screen the molecular markers that related to radiation resistance. METHODS: We used X-ray to irradiate MDA-MB-231 cells repeatedly to build radioresistant cell (231-RR), then select one gemcitabine-resistance of MDA-MB-231 cell (231-GEM). We screen differentially expressed genes of these cell lines. Then, we would select 2 genes of them associated with DNA damage repair or cell cycle, and build RNAi lentivirus vector to knock down related gene. We also used X-rays repeatedly exposure TNBC tumor xenograft to build tumor with radioresistance properties, and then verify previously screening differentially expressed genes using IHC. Finally, we used The Cancer Genome Atlas (TCGA) database to validate the relationships between radioresistance related genes and the prognosis of breast cancer. RESULTS: We got 161 up-regulated genes and 156 down-regulated genes from three cell lines. Cellular results show the 231-cell with knock-down CDKN1A or SOD2 gene, its radiation sensitivity was significantly enhanced. We successfully got the TNBC xenograft tumor with radioresistance properties. Immunohistochemical results show that the radioresistance of tumor tissue with higher p21 (CDKN1A encoding protein) and SOD2 expression (P

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effectiveness of chemotherapy in patients with newly diagnosed inoperable brain metastases (BM) from non‐small cell lung cancer (NSCLC) in terms of brain response rate, overall survival (OS), progression‐free survival (PFS), health‐related quality of life (HRQoL) and treatment related toxic events.

Objective Most comprehensive treatments for PBC include UDCA, combination of methotrexate (MTX), corticosteroids (COT), colchicine (COC) or bezafibrate (BEF), cyclosporin A (CYP), D-penicillamine (DPM), methotrexate (MTX), or azathioprine (AZP). Since the optimum treatment regimen remains inconclusive, we aimed to compare these therapies in terms of patient mortality or liver transplantation (MOLT) and adverse event (AE). Methods We searched PubMed, Embase, Scopus and the Cochrane Library for randomized controlled trials until August 2014. We estimated HRs for MOLT and ORs for AE. The sensitivity analysis based on dose of UDCA was also performed. Results The search identified 49 studies involving 12 different treatment regimens and 4182 patients. Although no statistical significance can be found in MOLT, COT plus UDCA was ranked highest for efficacy outcome amongst all the treatment regimes. While for AEs, compared with OBS or UDCA, monotherapy with COC (OR 5.6, P < 0.001; OR 5.89, P < 0.001), CYP (OR 3.24, P < 0.001; OR 3.42, P < 0.001), DPM (OR 8.00, P < 0.001; OR 8.45, P < 0.001) and MTX (OR 5.31, P < 0.001; OR 5.61, P < 0.001) were associated with statistically significant increased risk of AEs. No significant differences were found for other combination regimes. Effect estimates from indirect comparisons matched closely to estimates derived from pairwise comparisons. Consistently, in the sensitivity analysis, results closely resembled our primary analysis. Conclusions COT plus UDCA was the most efficacious among treatment regimens both for MOLT and AEs.

// Li Zhang 1,* , Zhao-zhi Yang 1,* , Xing-xing Chen 1,* , Jeffrey Tuan 3 , Jin-li Ma 1 , Xin Mei 1 , Xiao-li Yu 1 , Zhi-rui Zhou 1 , Zhi-min Shao 2 , Guang-yu Liu 2 and Xiao-mao Guo 1 1 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China 2 Department of Breast Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China 3 Department of Radiation Oncology, National Cancer Centre Singapore, Singapore * These authors have contributed equally to this work Correspondence to: Guang-yu Liu, email: // Xiao-mao Guo, email: // Keywords : breast cancer; positive sentinel lymph nodes, radiotherapy, intensity modulated radiation therapy, axillary level Received : March 27, 2015 Accepted : May 18, 2015 Published : May 27, 2015 Abstract Purpose: This study was designed to evaluate the dose coverage of axillary areas during whole breast irradiation with simplified intensity modulated radiation therapy (s-IMRT) and field-in-field IMRT (for-IMRT) in early stage breast cancer patients. Methods: Sixty-one consecutive patients with breast-conserving surgery and sentinel lymph node biopsy were collected. Two plans were created for each patient: the s-IMRT and for-IMRT plan. Dosimetric parameters of axillary areas were compared. Results: The average of mean doses delivered to the axillary level I areas in s-IMRT and for-IMRT plan were 27.7Gy and 29.1Gy ( p = 0.011), respectively. The average of V47.5Gy, V45Gy and V40Gy (percent volume receiving≥ 47.5Gy, 45Gy and 40Gy) of the axillary level I in s-IMRT plan was significantly lower than that in for-IMRT plan ( p 19.3cm and body width >31.9cm had significantly higher mean dose in axillary level I area ( p = 0.002, 0.007, 0.001, respectively). Conclusion: Compared with for-IMRT plan, the s-IMRT plan delivered lower dose to axillary level I area. For centers using s-IMRT technique, caution should be exercised when selecting to omit axillary lymph node dissection for patients with breast conserving surgery and limited positive SLNs.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To evaluate the efficacy and toxicity of induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy with or without adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma.

Background and Purpose: Radiotherapy is the mainstay of treatment modality for human nasopharyngeal carcinoma (NPC), but in some cases, the disease is radioresistant. This study aimed to identify proteins potentially responsible for radioresistance of NPC by a proteomic approach. Material and Methods: The radioresistant human NPC cell line CNE-2R and its parental cell line CNE-2 were analyzed by two-dimensional gel electrophoresis and matrix-assisted laser desorption/time-of-flight mass spectrometry analysis. The candidate proteins were validated by Western blot analysis. Results: In total, 16 differentially expressed proteins were identified; among them, Nm23 H1 was significantly increased, while Annexin A3 was significantly downregulated in CNE-2R cells, compared to CNE-2 cells. Conclusions: Our findings provide a platform for further characterization of the proteins implicated in radioresistance and suggest that these proteins could be exploited as a biomarker for predicting the NPC response t...

To compare the efficacy and safety of short-term versus long-term hormonotherapy (HT) plus radiotherapy (RT) or prostatectomy (RP) for prostate cancer. Literatures were searched from Embase, PubMed, Web of science and Cochrane Library up to October, 2012. Quality of the study was evaluated according to the Cochrane’s risk of bias of randomized controlled trial (RCT); the Grading of Recommendations Assessment, Development and Evaluation System was used to rate the level of evidence. RevMan 5.1 was used for statistical analysis. Two comparisons were of interest: RT plus short-term HT versus RT plus long-term HT and RP plus short-term HT versus RP plus long-term HT. Pooled risk ratio or standardized mean differences were calculated; HT adverse reactions were descriptively evaluated. Nine RCTs (total 4,743 patients) were included, 7 RCTs compared RT plus short-term HT with RT plus long-term HT, 2 RCTs compared RP plus short-term HT with RP plus long-term HT. Meta-analysis showed there was no significant difference in overall survival, disease-free survival and PSA level before RP; long-term was superior to short-term hormonotherapy in biochemical failure rate, clinical progression rate, prostate cancer-specific mortality, positive surgical margin rate and prostate volume before RP. Systematic review demonstrated adverse events caused by the increased length of HT were more common. Long-term HT plus RT showed a trend toward improved overall survival; long-term HT plus RP declined positive surgical margin rate and prostate volume before RP. So, long-term HT may benefit more, but it did not significantly improve the patients’ overall survival, and the adverse reactions are inevitable.

Radiotherapy has been applied in the treatment for lung cancer patients for many years, especially those with advanced stage disease who cannot be treated with surgery. However, if these advanced stage patients should be treated with standard dosage therapy (60 Gy) or high dosage therapy (>60 Gy) remains a hot debated point. Literature related to this topic would be reviewed here. We believe standard dosage therapy should be strongly recommended, and high dosage therapy might benefit patients with high risk factors patients.

MK-8776 is a recently described inhibitor that is highly selective for checkpoint kinase 1 (Chk1), which can weaken the DNA repair capacity in cancer cells to achieve chemo-sensitization. A number of studies show that MK-8776 enhances the cytotoxicity of hydroxyurea and gemcitabine without increasing normal tissue toxicities. Thus far, there is no evidence that MK-8776 can be used as a radiotherapy sensitization agent. In this study, we investigated the effects of MK-8776 on the radiosensitivity of 3 human triple-negative breast cancer (TNBC) cell lines MDA-MB-231, BT-549 and CAL-51. MK-8776 dose-dependently inhibited the proliferation of MDA-MB-231, BT-549 and CAL-51 cells with IC50 values of 9.4, 17.6 and 2.1 μmol/L, respectively. Compared with irradiation-alone treatment, pretreatment with a low dose of MK-8776 (100–400 nmol/L) significantly increased irradiation-induced γH2A.X foci in the 3 TNBC cell lines, suggesting enhanced DNA damage by MK-8776, inhibited the cell proliferation and increased the radiosensitivity of the 3 TNBC cell lines. Similar results were obtained in MDA-MB-231 xenograft tumors in nude mice that received MK-8776 (15 or 40 mg/kg, ip) 26 d after irradiation. To explore the mechanisms underlying the radio-sensitization by MK-8776, we used TEM and found that irradiation significantly increased the numbers of autophagosomes in the 3 TNBC cell lines. Moreover, irradiation markedly elevated the levels of Atg5, and promoted the transformation of LC3-I to LC3-II in the cells. Pretreatment with the low dose of MK-8776 suppressed these effects. The above results suggest that MK-8776 increases human TNBC radiosensitivity by inhibiting irradiation-induced autophagy and that MK-8776 may be a potential agent in the radiosensitization of human TNBC.

Purpose: The main objective of the present study was to evaluate the efficacy and toxicity of concurrent chemoradiotherapy followed by adjuvant chemotherapy compared with concurrent chemoradiotherapy alone in the treatment of locoregionally advanced nasopharyngeal carcinoma. Methods: The search strategy included Pubmed, Embase, the Cochrane Library, China National Knowledge Internet Web, Chinese Biomedical Database and Wanfang Database. We also searched reference lists of articles and the volumes of abstracts of scientific meetings. Randomized controlled trials (RCTs) that compared concurrent chemoradiotherapy followed by adjuvant chemotherapy with concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma were included. Meta-analysis was performed with RevMan 5.1.0. The Grading of Recommendations Assessment, Development, and Evaluation system (GRADE) was used to rate the level of evidence. Results: Five studies were included. Risk ratios of 1.02 (95%CI 0.89-1.15), 0.93 (95%CI 0.72-1.21), 1.07 (95%CI 0.87-1.32), 0.95 (95%CI 0.80-1.13) were observed for 3 years overall survival, 5 years failure-free survival, 5 years locoregional failure-free survival and 5 years distant metastasis failure-free survival. There were no treatment-related deaths in both groups of five studies. Hematologic and gastrointestinal toxicity were the most significant for patients during adjuvant chemotherapy. The level of evidence was low. Conclusion: Compared with concurrent chemoradiotherapy alone, concurrent chemotherapy followed by adjuvant chemotherapy did not improve prognosis. More toxicity was found during adjuvant chemotherapy.

Background High prevalence of erectile dysfunction (ED) has been observed in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). However, whether or not CP/CPPS is a risk factor of ED remains unknown and controversial. Therefore, we conducted this systematic review and meta-analysis to evaluate the relationship between CP/CPPS and ED. Methods PubMed, Embase, Web of Science, and The Cochrane Library were searched up to November 11, 2014 to identify studies reporting the association between CP/CPPS and ED. Case–control, cohort and cross-sectional studies were included. Quality of the included studies was assessed. The odds ratio of ED and the mean difference of five-item International Index of Erectile Function (IIEF-5) score were pooled using a random effects model. Subgroup analysis and sensitivity analyses were performed. Results Three cross-sectional studies, two case–control studies, and four retrospective studies with 31,956 participants were included to calculate the pooled odds ratio of ED, and two studies with 1499 participants were included to calculate the pooled mean difference of IIEF-5 scores. A strong correlation was found between CP/CPPS and ED (pooled odds ratio: 3.02, 95% CI: 2.18–4.17, P < 0.01), with heterogeneity across studies (I2 = 65%; P < 0.01). A significant decrease in the IIFE-5 score was observed in the CP/CPPS group (pooled mean difference: −4.54, 95% CI: −5.11–−3.98; P < 0.01). Conclusion Our study indicates that patients with CP/CPPS have an increased risk of suffering from ED. Assessment of erectile function is necessary for the therapy of patients with CP/CPPS. Further evidence is necessary to confirm the relationship between CP/CPPS and ED.

Supplemental Digital Content is available in the text, Major ursodeoxycholic acid (UDCA)-based therapies for primary biliary cirrhosis (PBC) include UDCA only, or combined with either methotrexate (MTX), corticosteroids (COT), colchicine (COC), or bezafibrate (BEF). As the optimum treatment regimen is unclear and warrants exploration, we aimed to compare these therapies in terms of patient mortality or liver transplantation (MOLT) and adverse events (AE). PubMed, the Cochrane Library, and Scopus were searched for randomized controlled trials up to August 31, 2014. We estimated the hazard ratios (HRs) for MOLT and odds ratios (ORs) for AE. A sensitivity analysis based on the dose of UDCA was also executed. Thirty-one eligible articles were included. Compared with COT plus UDCA, UDCA (HR 0.38, 95% confidence interval [CI] 0.09–1.39), BEF plus UDCA (HR 0.29, 95% CI 0.02–4.83), COC plus UDCA (HR 0.39, 95% CI 0.07–2.25), MTX plus UDCA (HR 0.28, 95% CI 0.05–1.63), or OBS (HR 0.49, 95% CI 0.11–2.01) all provided an increased risk of MOLT. With respect to drug AE profile, although not differing appreciably, BEF plus UDCA was associated with more AEs compared with UDCA (OR 3.16, 95% CI 0.59–20.67), COT plus UDCA (OR 2.27, 95% CI 0.15–33.36), COC plus UDCA (OR 1.00, 95% CI 0.09–12.16), MTX plus UDCA (OR 2.03, 95% CI 0.23–17.82), or OBS (OR 3.00, 95% CI 0.53–20.75). The results of sensitivity analyses were highly consistent with previous analyses. COT plus UDCA was the optimal UDCA-based regimen for both MOLT and AEs. BEF plus UDCA was most likely to cause AEs, whereas monotherapy with UDCA and coadministriation of COT plus UDCA appeared to be associated with the fewest AEs for PBC treatment.

Introduction Although most prostate cancers initially respond to castration with luteinizing hormone- releasing analogues or bilateral orchiectomy, progression eventually occurs. Based on the exciting results of several randomized controlled trials (RCTs), it seems that patients with metastatic castration-resistant prostate cancer (mCRPC) might benefit more from treatment withabiraterone. Therefore we conducted a systematic review to evaluate the efficacy and toxicity of abiraterone in the treatment of mCRPC. Methods Literature was searched from Embase, PubMed, Web of Science, and Cochrane Library up to July, 2013. Quality of the study was evaluated according to the Cochrane's risk of bias of randomized controlled trial (RCT) tool, then the Grading of Recommendations Assessment, Development and Evaluation (GRADE) System was used to rate the level of evidence. Stata 12.0 was used for statistical analysis. Summary data from RCTs comparing abiraterone plus prednisone versus placebo plus prednisone for mCRPC were meta-analyzed. Pooled hazard ratios (HRs) for overall survival (OS), radiographic progression-free survival (RPFS) and time to PSA progression (TTPP); Pooled risk ratios (RR) for PSA response rate, objective response rate and adverse event were calculated. Results Ten trials were included in the systematic review; Data of 2,283 patients (1,343 abiraterone; 940 placebo) from two phase 3 trials: COU-AA-301 and COU-AA-302 were meta-analyzed. Compared with placebo, abiraterone significantly prolonged OS (HR, 0.74; 95% confidence interval [CI], 0.66 to 0.84), RPFS (HR, 0.59; 95% CI, 0.48 to 0.74) and time to PSA progression (HR, 0.55; 95% CI, 0.43 to 0.70); it also significantly increased PSA response rate (RR, 3.63; 95% CI, 1.72 to 7.65) and objective response rate (RR, 3.05; 95% CI, 1.51 to 6.15). This meta-analysis suggested that the adverse events caused by abiraterone are acceptable and can be controlled. CONCLUTIOS: Abiraterone significantly prolonged OS, RPFS and time to progression patients with mCRPC, regardless of prior chemotherapy or whether chemotherapy-naive, and no unexpected toxicity was evident. Abiraterone can serve as a new standard therapy for mCRPC.

This updated meta-analysis investigated whether operative treatment is superior to nonoperative treatment in complex proximal humeral fractures. The authors searched the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE. Randomized controlled trials that evaluated operative vs nonoperative treatment for exclusively 3- or 4-part proximal humeral fractures were considered. Six studies with a total of 287 patients who had proximal humeral fractures were included. According to the meta-analysis, no statistically significant differences were found between operative and nonoperative treatment in Constant-Murley shoulder scores (Constant scores); Disabilities of the Arm, Shoulder, and Hand scores; total complication events; mortality; infection; nonunion; avascular necrosis; osteoarthritis; redisplacement of fractures; or dislocation or resorption of tuberosity. For health-related quality of life, EuroQol-5D (EQ-5D) favored operative treatment, but 15D scores showed no significant difference. Compared with nonoperative treatment, open reduction and internal fixation required significantly more additional surgeries (risk ratio, 6.50; 95% confidence interval, 1.54–27.50; P =.01), and more penetrations into joint space occurred (risk ratio, 9.56; 95% confidence interval, 2.27–40.13; P =.002). The limited evidence suggests that no convincing findings support the use of either open reduction and internal fixation or hemiarthroplasty for the treatment of complex proximal humeral fractures. The findings of the current study should be interpreted cautiously because of the modest sample size and the short follow-up period.

To evaluate the value of 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) and pretherapeutic Ki67 in predicting pathologic response in locally advanced breast cancer (LABC) after neoadjuvant chemotherapy (NAC). As a training set, total 301 LABC patients treated with NAC were retrospectively analyzed to evaluate the potential predictive value of pretherapeutic Ki67 for pathologic complete response (pCR) after NAC. Another 60 LABC patients were prospectively included as a validation set to evaluate the value of Ki67 combined PET/CT as pCR predictors. Ki67 was assessed in pretherapy core needle biopsy specimens and PET/CT scans were performed at baseline (before initiating NAC), after the 2nd, and 4th cycle of NAC. Maximum standardized uptake value (SUVmax) and its changes relative to baseline (ΔSUVmax%) were used as parameters of PEC/CT. In the training set, Ki67 was a predictor of pCR to NAC, with area under the curve (AUC) of 0.624 (P = 0.003) in receiver-operating characteristic (ROC) analysis. In the validation set, Ki67 alone did not show significant value in predicting pCR in the validation set. ΔSUVmax% after then 2nd or 4th course are predictors of pCR to NAC with the AUC of 0.774 (P = 0.002) and 0.791 (P = 0.002), respectively. When combined with ΔSUVmax% after the 2nd and 4th course NAC, Ki67 increased the value of ΔSUVmax% in predicting pCR with the AUC of 0.824 (P = 0.001). Baseline SUVmax and after 2nd, 4th course NAC had no predictive value for pCR, but SUVmax after the 2nd and 4th course showed remarkable predictive value for nonpathologic response (Grade 1 in Miller-Payne Grading System) with the AUC of 0.898 (P = 0.0001) and 0.801 (P = 0.003). Both PET/CT and Ki67 can predict pCR to NAC in LABC patients in the early phases of treatment. PET/CT combined Ki67 is a better pCR predictor for response to NAC. This helps the physician to predict the probability of pCR, and facilitates the optimization of individual treatment plan in case of ineffective and/or excessive chemotherapy.

Chemotherapy plays a critical and venturous role against the co-morbidity of nonsmall cell lung cancer and interstitial lung disease (NSCLC-ILD).We performed a Bayesian meta-analysis and systematic review to evaluate the safety and efficacy of the chemotherapy in NSCLC-ILD patients.EMBASE, PubMed, the Cochrane Central Register of Controlled Trials, and clinicaltrials.gov (up to January 2015).We included all study designs except case reports, all studies with NSCLC-ILD patients and all the possible chemotherapy regimens.Quality was assessed by a components approach. We derived summary estimates using Bayesian method through WinBUGS (version 1.4.3, MRC Biostatistics Unit, Cambridge, UK).Seven studies involving 251 patients with NSCLC-ILD were included in the meta-analysis. The treatment response (complete remission, 0; [partial remission, 39.1%; 95% credible interval [CrI], 32.6-45.7]; [stable disease, 36%; 95% CrI, 29.6-42.2]; [PD, 15.4%; 95% CrI, 11.3-19.8]; [nonevaluable, 6.4%; 95% CrI, 2.7-10.1]; [overall response rate, 41.3%; 95% CrI, 35.3-47.4]; [disease control rate, 77.7%; 95% CrI, 72.2-82.7]) were comparable to that of patients with NSCLC alone; the survival outcomes (median overall survival, median progression-free survival, and 1-year survival rate) were slightly worse, especially the lower 1-year survival rate. Platinum-based doublets as first-line chemotherapy may be related to higher incidence of acute exacerbation-ILD in first line chemotherapy (AE, 8.47%; 95% CrI, 5.04-12.6).The data selection bias and small patient number make the meta-analysis of treatment response and conclusions generated from these data inaccurate.The present meta-analysis suggests that chemotherapy might be an effective therapy for patients with NSCLC-ILD, but it might be associated with higher incidence of acute exacerbation.

Context The preferred treatment for osteoporosis in men is debated, and pairwise meta-analysis cannot obtain hierarchies of these treatments. Objective The objective of this study was to integrate the evidence and provide hierarchies of eight drugs based on their effect on the bone mineral density in the lumbar spine (BMD in LS) and the fracture rate. Data Sources Eligible studies were identified by searching Amed, British Nursing Index, EMBASE, PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar, SIGLE, the National Technical Information Service, the National Research Register (UK), and the Current Controlled Trials databases. Study Selection RCTs or quasi-RCTs reporting at least two drugs (two active drugs or one active drug and a placebo) used to treat osteoporosis in men were selected by two authors. Data Extraction Two authors independently extracted the data. Data Synthesis Thirteen studies involving 3647 patients were included. Compared with placebo therapy, zoledronate (SMDs 13.48, 95% credible intervals 11.88-15.08) yielded the most significant effect on increasing the BMD in LS, followed by alendronate (11.04, 9.68-12.41), teriparatide (20mcg) + risedronate (10.98, 8.55-13.48), risedronate (10.33, 8.68-12.01), teriparatide (20mcg) (9.33, 6.87-11.76), strontium ranelate (8.88, 7.51-10.24), ibandronate (5.49, 3.82-7.16), parathyroid hormone (1-84) (4.89, 3.12-6.62) and alfacalcidol (3.42, 1.7-5.2). Placebo therapy had a significantly higher fracture rate in contrast to risedronate (OR 2.51, 95% CrI 1.23-4.24) or zoledronate (2.92, 1.29-5.62) or teriparatide (20mcg) (4.04, 1.36-8.49) or teriparatide (40mcg) (3.5, 1.14-8.34). Zoledronate ranked first for increasing the BMD in LS, and teriparatide (20mg) was ranked first for decreasing the fracture rate. Conclusions Zoledronate might be the best choice to increase the BMD in LS and teriparatide (20mg) might lead to the lowest fracture rate.

Context Alendronate may relate to the incidence of cancers, especially esophageal and colon cancer. But the results are inconsistent in different studies. Objective To quantify the association between the use of alendronate and the occurrence of different types of cancer. Data Sources We searched Embase, Pubmed, CENTRAL, SIGLE and clinicaltrials.gov, up to 2014 June. Study Selection Cohort studies reporting association between alendronate or bisphosphonate therapy including alendronate in patients with osteoporosis and risk of cancer were selected by two authors. Data Extraction Two authors independently extracted the data. The Chi-square test and the I-square test were used for testing heterogeneity between studies. Data Synthesis Eight cohort studies were included in the meta-analysis. Meta-analysis result manifested that alendronate significantly increased the incidence of lung cancer (HR 1.23, 95%CI 1.03 to 1.47, P value = 0.03), nevertheless, there was no significant difference after we excluded either Lee’s 2012 study (HR 1.17, 95%CI 0.95 to 1.44, P value = 0.13) or Chiang’s 2012 study (HR 1.47, 95%CI 1 to 2.17, P value = 0.05). For the incidence of colorectal cancer, no significant difference occurred (HR 0.91, 95%CI 0.74 to 1.13, P value = 0.39), but there was a positive relationship when we used fixed model (HR 0.85, 95%CI 0.78 to 0.93, P value = 0.004). For the incidence of liver cancer, there was no significant difference (HR 1.36, 95%CI 0.9 to 2.04, P value = 0.14), however, the result changed after we excluded Chiang’s 2012 study (HR 1.69, 95%CI 1.03 to 2.77, P value = 0.04). There was no significant difference in other types of cancer. Conclusion Based on current evidences, alendronate therapy may be associated with a high risk of lung cancer, may with an excess risk of liver cancer, a low risk of colorectal and no related risk of other cancers.