***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Vascular endothelial growth factor ( VEGF ) promotes angiogenesis , a mediator of disease progression in cervical cancer . Bevacizumab , a humanized anti-VEGF monoclonal antibody , has single-agent activity in previously treated , recurrent disease . Most patients in whom recurrent cervical cancer develops have previously received cisplatin with radiation therapy , which reduces the effectiveness of cisplatin at the time of recurrence . We evaluated the effectiveness of bevacizumab and nonplatinum combination chemotherapy in patients with recurrent , persistent , or metastatic cervical cancer . METHODS Using a 2-by-2 factorial design , we r and omly assigned 452 patients to chemotherapy with or without bevacizumab at a dose of 15 mg per kilogram of body weight . Chemotherapy consisted of cisplatin at a dose of 50 mg per square meter of body-surface area , plus paclitaxel at a dose of 135 or 175 mg per square meter or topotecan at a dose of 0.75 mg per square meter on days 1 to 3 , plus paclitaxel at a dose of 175 mg per square meter on day 1 . Cycles were repeated every 21 days until disease progression , the development of unacceptable toxic effects , or a complete response was documented . The primary end point was overall survival ; a reduction of 30 % in the hazard ratio for death was considered clinical ly important . RESULTS Groups were well balanced with respect to age , histologic findings , performance status , previous use or nonuse of a radiosensitizing platinum agent , and disease status . Topotecan-paclitaxel was not superior to cisplatin-paclitaxel ( hazard ratio for death , 1.20 ) . With the data for the two chemotherapy regimens combined , the addition of bevacizumab to chemotherapy was associated with increased overall survival ( 17.0 months vs. 13.3 months ; hazard ratio for death , 0.71 ; 98 % confidence interval , 0.54 to 0.95 ; P=0.004 in a one-sided test ) and higher response rates ( 48 % vs. 36 % , P=0.008 ) . Bevacizumab , as compared with chemotherapy alone , was associated with an increased incidence of hypertension of grade 2 or higher ( 25 % vs. 2 % ) , thromboembolic events of grade 3 or higher ( 8 % vs. 1 % ) , and gastrointestinal fistulas of grade 3 or higher ( 3 % vs. 0 % ) . CONCLUSIONS The addition of bevacizumab to combination chemotherapy  in patients with recurrent , persistent , or metastatic cervical cancer was associated with an improvement of 3.7 months in median overall survival . ( Funded by the National Cancer Institute ; GOG 240 Clinical Trials.gov number , NCT00803062 . ) Cervical cancer is the second most commonly diagnosed cancer and the third leading cause of cancer death among females in less developed countries . There were an estimated 527 600 new cervical cancer cases and 265 700 deaths worldwide in 2012 [ 1 ] . Nearly 90 % of cervical cancer deaths occurred in developing parts of the world . The large geographic variation in cervical cancer rates reflects differences in the availability of screening ( which allows for the detection and removal of precancerous lesions ) and in human papillomavirus ( HPV ) infection prevalence . However , cervical cancer still represents a major public health problem even in developed countries : more than 58 000 new cases of cervical cancer are diagnosed and 24 000 patients die in Europe every year [ 2 ] . Five-year relative survival for European women diagnosed with cervical cancer in 2000–2007 was 62 % , ranging from 57 % in Eastern Europe to 67 % in Northern Europe . Survival was particularly low ( < 55 % ) in Bulgaria , Latvia and Pol and and highest in Norway ( 71 % ) [ 3 ] . Survival decreased with advancing age at diagnosis , from 81 % for 15–44-year olds to 34 % for women 75 years . Survival increased significantly from 61 % in 1999–2001 to 65 % in 2005–2007 . FIGO stage is one of the most important prognostic factors . The most significant cause of cervical cancer is persistent papillomavirus infection . HPV is detected in 99 % of cervical tumours , particularly the oncogenic subtypes such as HPV 16 and 18 . To date , three HPV vaccines are licensed and available : the bivalent HPV virus-like particle vaccine ( 2vHPV ) , the quadrivalent HPV virus-like particle vaccine ( 4vHPV ) and nine-valent HPV virus-like particle vaccine ( 9vHPV ) . All 3 vaccines provide protection against HPV 16 and 18 . 4vHPV also includes HPV 6 and 11 which cause 90 % of genital warts . Furthermore , 9vHPV covers 5 more oncogenic HPV viruses ( HPV 31 , 33 , 45 , 52 and 58 ) in addition to the types already included in 4vHPV , which cause an additional 15 % of HPV-related cancers in women and 4 % of those in men [ 4 ] . Both the 2vHPV and 4vHPV have significant cross-protective activity against other oncogenic viruses . All three are efficacious against related infection and cervical , vaginal , vulvar and anal dysplasia [ 5–7 ] . Post-licensure reports from countries with established HPV vaccination programs indicate that HPV vaccination has a beneficial effect at the population level as early as 3 years after the introduction of an HPV vaccination programme , including decreases in the incidence of high- grade cervical abnormalities , the prevalence of vaccine HPV types and the incidence of genital warts [ 8 , 9 ] . Prophylactic administration of HPV vaccine can effectively prevent infection and disease associated with the vaccine HPV types . The effect of vaccination on the burden of cancer remains to be determined but , according to surrogate markers , it is expected to prevent > 70 % of cervical cancers . For many years , the Papanicolaou ( Pap ) test has been the st and ard method for cervical cancer screening , reducing the incidence by 60%–90 % and the death rate by 90 % . However , the limitations of this cytology-based test are the sensitivity ( 50 % ) and significant proportion of inadequate specimens . More recently , an HPV test has been introduced as a screening tool as HPV deoxyribonucleic acid ( DNA ) is present in almost all cervical cancers and it has demonstrated higher sensitivity for high grade cervical intraepithelial neoplasia ( CIN2þ ) than that achieved by cytology in several studies . A pooled analysis of four r and omised controlled trials of HPV-based cervical screening versus conventional cytology showed that HPV-based cervical screening provides 60%–70 % greater protection against Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed PURPOSE To prospect ively assess the impact of treatment with cisplatin alone or in combination with topotecan ( CT ) on quality of life ( QOL ) in patients with advanced or recurrent cervical cancer , and to explore the prognostic value of baseline QOL scores . PATIENTS AND METHODS Patients entered on Gynecologic Oncology Group ( GOG ) Protocol 179 were expected to complete QOL assessment s at four time points using Functional Assessment of Cancer Therapy-General ( FACT-G ) , Cervix subscale ( Cx subscale ) , FACT/GOG-Neurotoxicity subscale ( NTX subscale ) , Brief Pain Inventory ( BPI ) , and UNISCALE ( UNI ) . Adjusting for patient age , baseline scores , and effects of time , we longitudinally examined treatment effect on QOL during and after chemotherapy . RESULTS Among patients r and omly allocated to receive cisplatin ( n = 146 ) or CT ( n = 147 ) , there were no statistically significant differences in QOL up to 9 months after r and omization despite more hematologic toxicity in the combination arm . QOL assessment s were completed at rates of 98 % , 85 % , 68 % , and 59 % , respectively , for the four time points , with similar rates and reasons for nonparticipation between regimens . Baseline FACT-G ( P = .0016 ) and BPI ( P = .0001 ) scores were significantly associated with patient age ; older patients had better QOL and less pain . Baseline UNI was positively correlated with FACT-G ( r = 0.66 ; P < .001 ) and Cx subscale ( r = 0.29 ; P < .001 ) , and negatively related to BPI ( r = -0.41 ; P < .0001 ) . Baseline FACT-Cx ( FACT-G + Cx subscale ) was associated with survival . CONCLUSION Despite increased toxicity , CT did not significantly reduce patient QOL when compared with cisplatin alone . Patient-reported QOL measures may be an important prognostic tool in advanced cervix cancer PURPOSE On the basis of reported activity of methotrexate , vinblastine , doxorubicin , and cisplatin ( MVAC ) or topotecan plus cisplatin in advanced cervix cancer , we undertook a r and omized trial comparing these combinations versus cisplatin alone , to determine whether survival is improved with either combination compared with cisplatin alone , and to compare toxicities and quality of life ( QOL ) among the regimens . PATIENTS AND METHODS Eligible patients were r and omly allocated to receive cisplatin 50 mg/m(2 ) every 3 weeks ( CPT ) ; cisplatin 50 mg/m(2 ) day 1 plus topotecan 0.75 mg/m(2 ) days 1 to 3 every 3 weeks ( CT ) ; or methotrexate 30 mg/m(2 ) days 1 , 15 , and 22 , vinblastine 3 mg/m(2 ) days 2 , 15 , and 22 , doxorubicin 30 mg/m(2 ) day 2 , and cisplatin 70 mg/m(2 ) day 2 every 4 weeks ( MVAC ) . Survival was the primary end point ; response rate and progression-free survival ( PFS ) were secondary end points . QOL data are reported separately . RESULTS The MVAC arm was closed by the Data Safety Monitoring Board after four treatment-related deaths occurred among 63 patients , and is not included in this analysis . Two hundred ninety-four patients enrolled onto the remaining regimens : 146 to CPT and 147 to CT . Grade 3 to 4 hematologic toxicity was more common with CT . Patients receiving CT had statistically superior outcomes to those receiving CPT , with median overall survival of 9.4 and 6.5 months ( P = .017 ) , median PFS of 4.6 and 2.9 months ( P = .014 ) , and response rates of 27 % and 13 % , respectively . CONCLUSION This is the first r and omized phase III trial to demonstrate a survival advantage for combination chemotherapy over cisplatin alone in advanced cervix cancer Objectives : The Gynecologic Oncology Group performed a r and omized phase II study to determine the antitumor activity and toxicity of two different schedules of administration of bryostatin-1 in patients with persistent or recurrent squamous cell carcinoma of the cervix . Methods : Eligible patients were r and omized to receive either bryostatin-1 25 μg/m2 as a 1-h infusion weekly for 3 weeks followed by a 1-week rest ( Regimen I ) or bryostatin-1 120 μg/m2 as a 72-h continuous infusion every 2 weeks ( Regimen II ) . Results : A total of 70 patients were enrolled on this study . There were 32 eligible patients on Regimen I and 33 eligible patients on Regimen II ; all but 4 had had prior chemotherapy . There were two partial responses ( one on each treatment arm ) among the 65 eligible patients ( response rates = 3.1 and 
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Conclusions The results of this network meta- analysis show that bevacizumab in combination with paclitaxel-topotecan or paclitaxel-cisplatin is likely to prolong OS over other non – bevacizumab-containing chemotherapies ( eg , paclitaxel-carboplatin ) , which were not included in the GOG240 trial .
In patients with advanced , persistent , and recurrent cervical cancer , cisplatin-paclitaxel-bevacizumab and topotecan-paclitaxel-bevacizumab showed the highest efficacy in all regimens investigated in this analysis