You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Predictive and prognostic angiogenic markers in a gynecologic oncology group phase II trial of bevacizumab in recurrent and persistent ovarian or peritoneal cancer.
Abstract 1:
OBJECTIVE Potential predictive/prognostic angiogenic markers were prospect ively examined in a phase II trial of bevacizumab in epithelial ovarian cancer (EOC)/ primary peritoneal cancer ( PPC ) . METHODS Recurrent/persistent EOC/PPC patients were treated with bevacizumab ( 15 mg/kg IV q21days ) until disease progression . Vali date d-immunohistochemistry ( IHC ) assays were performed on pre-cycle 1/4 tumor biopsies for CD31-microvessel density ( MVD ) , VEGF-histoscore ( HS ) , p53-HS , and TSP1 image analysis score ( IA ) . Pre-cycle 1/4 serum and plasma VEGF were quantified using a vali date d-ELISA . RESULTS CD31-MVD and serum VEGF , evaluated pre-cycle 1 in 41/61 and 51/61 eligible patients , respectively , did not appear to be correlated . High CD31-MVD , categorized at the median , appeared to be associated with tumor response , a 13-month shorter median survival , and an increased risk of death ( unadjusted hazard ratio [ HR ] = 2.2 , 95 % confidence interval [ CI ] = 1.067 - 4.467 ) . In addition , each st and ard deviation ( SD ) increase in CD31-MVD appeared to be associated with worse survival in unadjusted and adjusted analyses . IHC and plasma biomarkers did not change with bevacizumab treatment except for serum VEGF , which appeared to decrease during bevacizumab treatment . This decrease was not associated with response . High pre-cycle 1 serum VEGF , categorized at the median , was associated with 22-month shorter median survival and an increased risk of death ( unadjusted HR = 2.7 , 95 % CI = 1.369 - 5.191 ) . Categorized p53 appeared to be associated with unadjusted survival and each SD increase in TSP1-IA appeared to be associated with a decreased risk of progression in unadjusted and adjusted analyses . CONCLUSIONS Despite the limitations in sample size and exploratory nature of the study , angiogenic markers in tumor and serum may provide prognostic value in recurrent/persistent EOC/PPC , and are being prospect ively evaluated in the GOG phase III trial of carboplatin , paclitaxel and bevacizumab/placebo in previously untreated EOC/PPC


Title 2:
Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma.
Abstract 2:
BACKGROUND Axillary lymph node status has been the most important prognostic factor in operable breast carcinoma , but it does not fully account for the varied disease outcome . More accurate prognostic indicators would help in selection of patients at high risk for disease recurrence and death who are c and i date s for systemic adjuvant therapy .  Our recent findings indicated that microvessel density ( count or grade ) in invasive breast carcinoma ( a measure of tumor angiogenesis ) is associated with metastasis and thus may be a prognostic indicator . PURPOSE This study was design ed to further define the relationship of microvessel density with overall and relapse-free survival and with other reported prognostic indicators in breast carcinoma . METHODS In a prospect i ve , blinded study of 165 consecutive patients , the microvessels within primary invasive breast carcinoma were highlighted by immunocytochemical staining to detect factor VIII-related antigen . Using light microscopy , we counted microvessels per 200x field in the most active areas of neovascularization and grade d microvessel density . These findings were correlated , by univariate and multivariate analyses , with overall and relapse-free survival , axillary node status , and other prognostic indicators ( median follow-up , 51 months ) . RESULTS There was a highly significant ( P < or = .001 ) association of microvessel density with overall survival and relapse-free survival in all patients , including node-negative and node-positive subsets . All patients with breast carcinomas having more than 100 microvessels per 200x field experienced tumor recurrence within 33 months of diagnosis , compared with less than 5 % of the patients with breast carcinoma having 33 or fewer microvessels per 200x field . Moreover , microvessel density was the only statistically significant predictor of overall survival among node-negative women ( P < .001 ) . Only microvessel density ( P < .001 ) and histologic grade ( P = .04 ) showed statistically significant correlations with relapse-free survival in the node-negative subset . CONCLUSIONS Microvessel density in the area of the most intense neovascularization in invasive breast carcinoma is an independent and highly significant prognostic indicator for overall and relapse-free survival in patients with early-stage breast carcinoma ( I or II by International Union Against Cancer criteria ) . IMPLICATION S Such an indicator would be useful in selection of those node-negative patients with breast carcinoma who are at high risk for having occult metastasis at presentation . These patients could then be given systemic adjuvant therapy


Title 3:
Language bias in randomised controlled trials published in English and German
Abstract 3:
BACKGROUND Some r and omised controlled trials ( RCTs ) done in German-speaking Europe are published in international English- language journals and others in national German- language journals . We assessed whether authors are more likely to report trials with statistically significant results in English than in German . METHODS We studied pairs of RCT reports , matched for first author and time of publication , with one report published in German and the other in English . Pairs were identified from reports round in a manual search of five leading German- language journals and from reports published by the same authors in English found on Medline .  Quality of methods and reporting were assessed with two different scales by two investigators who were unaware of authors ' identities , affiliations , and other characteristics of trial reports . Main study endpoints were selected by two investigators who were unaware of trial results . Our main outcome was the number of pairs of studies in which the levels of significance ( shown by p values ) were discordant . FINDINGS 62 eligible pairs of reports were identified but 19 ( 31 % ) were excluded because they were duplicate publications . A further three pairs ( 5 % ) were excluded because no p values were given . The remaining 40 pairs were analysed . Design characteristics and quality features were similar for reports in both language s. Only 35 % of German- language articles , compared with 62 % of English- language articles , reported significant ( p < 0.05 ) differences in the main endpoint between study and control groups ( p = 0.002 by McNemar 's test ) . Logistic regression showed that the only characteristic that predicted publication in an English- language journal was a significant result . The odds ratio for publication of trials with significant results in English was 3.75 ( 95 % CI 1.25 - 11.3 ) . INTERPRETATION Authors were more likely to publish RCTs in an English- language journal if the results were statistically significant . English language bias may , therefore , be introduced in review s and meta-analyses if they include only trials reported in English . The effort of the Cochrane Collaboration to identify as many controlled trials as possible , through the manual search of many medical journals published in different language s will help to reduce such bias


Title 4:
Biostatistics primer: what a clinician ought to know: hazard ratios.
Abstract 4:
Hazard ratios ( HRs ) are used commonly to report results from r and omized clinical trials in oncology . However , they remain one of the most perplexing concepts for clinicians . A good underst and ing of HRs is needed to effectively interpret the medical literature to make important treatment decisions . This article provides clear guidelines to clinicians about how to appropriately interpret HRs . While this article focuses on the commonly used methods , the authors acknowledge that other statistical methods exist for analyzing survival data


Title 5:
Independent prognostic relevance of microvessel density in advanced epithelial ovarian cancer and associations between CD31, CD105, p53 status, and angiogenic marker expression: A Gynecologic Oncology Group study.
Abstract 5:
OBJECTIVES The aims of this study were to examine prognostic significance of  microvessel density ( MVD )  in previously-untreated , advanced epithelial ovarian cancer ( EOC ) and explore associations between MVD and factors that affect angiogenesis . METHODS  MVD  was determined by immunohistochemical expression of CD31 or CD105 in tumor sections from 106 women treated on GOG r and omized phase III trials .  Average MVD hotspots were quantified by light microscopy at high power ( x400 ) and categorized as low ( or = upper quartile ) . Immunoblot expression of MASPIN , THBS-1 , bFGF , VEGF , VEGFR-1 and p53 status ( mutation and overexpression ) was previously determined . RESULTS Of 106 evaluable cases , 25 % exhibited high  CD31-MVD  ( > 24.25 vessels/high power field [ HPF ] ) or high  CD105-MVD  ( > 19.25 vessels/HPF ) . After adjusting for age and stratifying by GOG performance status , stage , cell type , grade , debulking status and treatment regimen , high versus low CD105-MVD was associated with increased risk of disease progression ( hazard ratio [HR]=1.873 ; 95 % confidence interval [ CI ] : 1.102 - 3.184 ; p=0.020 ) , but not death ( HR=1.125 ; 95 % CI : 0.654 - 1.935 ; p=0.670 ) whereas CD31-MVD was not associated with risk of disease progression ( HR=1.578 ; 95 % CI=0.918 - 2.711 ; p=0.099 ) or death ( HR=1.678 ; 95 % CI=0.957 - 2.943 ; p=0.071 ) . CD31-MVD was correlated with CD105-MVD ( p=0.001 ) and MASPIN ( p=0.016 ) . Neither CD31-MVD nor CD105-MVD was associated with p53 status , THBS-1 , bFGF , VEGF or VEGFR-1 . CONCLUSIONS High MVD assessed using CD105 , a marker of proliferating endothelial cells and neoangiogenesis , but not CD31 a pan-endothelial marker , appeared to be an independent prognostic factor for worse progression-free survival in women with advanced EOC after adjusting for prognostic clinical covariates
The OS and PFS with high MVD were significant poorer than with low MVD in ovarian cancer patients .
However , high MVD detected by CD34 seems to be more associated with survival for patients without pre-chemotherapy