***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: Introduction : As a result of recent publications , we hypothesized that period of 8 weeks after initiation of treatment is a useful l and mark point for cytotoxic agents for advanced non-small cell lung cancer ( NSCLC ) . To test this hypothesis , we conducted l and mark analyses with clinical trials employing cytotoxic agents . Our goal was to assess the proper design of clinical trials with cytotoxic agents for NSCLC for maximizing patients ’ benefit . Methods : We conducted l and mark analyses of a phase II study of pemetrexed in locally advanced or metastatic NSCLC and a phase III study of Four-Arm Cooperative Study for advanced NSCLC . A total of 806 patients who received chemotherapy ( pemetrexed , cisplatin and irinotecan , paclitaxel and carboplatin , cisplatin and gemcitabine , cisplatin and vinorelbine )  were included in this assessment . Results : Tumor-shrinkage rate at 8 weeks was significantly associated with longer survival in the study with pemetrexed ( p = 0.043 ) , whereas tumor-shrinkage rate at 4 weeks did not correlated with survival ( p = 0.139 ) . Similarly , using the Four-Arm Cooperative Study data , the optimal l and mark point was 8 weeks ( p = 0.002 ) , not 4 weeks ( p = 0.190 ) . Conclusion : The l and mark point for NSCLC was 8 weeks with all cytotoxic agents in our analysis when the therapy was given as a frontline or subsequent therapy . Our result suggests the concept of a disease-specific l and mark point , which may lead to a change of phase II/III clinical study design to evaluate cytotoxic agents and clinical investigators , and their sponsors may consider an early look to assess the efficacy of cytotoxic agents for NSCLC Background : Bevacizumab , the anti-vascular endothelial growth factor agent , provides clinical benefit when combined with platinum-based chemotherapy in first-line advanced non-small-cell lung cancer . We report the final overall survival ( OS ) analysis from the phase III AVAiL trial . Patients and methods : Patients ( n = 1043 ) received cisplatin 80 mg/m2 and gemcitabine 1250 mg/m2 for up to six cycles plus bevacizumab 7.5 mg/kg ( n = 345 ) , bevacizumab 15 mg/kg ( n = 351 ) or placebo ( n = 347 ) every 3 weeks until progression . Primary end point was progression-free survival ( PFS ) ; OS was a secondary end point . Results : Significant PFS prolongation  with bevacizumab compared with placebo was maintained with longer follow-up { hazard ratio ( HR ) [ 95 % confidence interval ( CI ) ] 0.75 ( 0.64–0.87 ) , P = 0.0003 and 0.85 ( 0.73–1.00 ) , P = 0.0456 } for the 7.5 and 15 mg/kg groups , respectively . Median OS was > 13 months in all treatment groups ; nevertheless , OS was not significantly increased with bevacizumab [ HR ( 95 % CI ) 0.93 ( 0.78–1.11 ) , P = 0.420 and 1.03 ( 0.86–1.23 ) , P = 0.761 ] for the 7.5 and 15 mg/kg groups , respectively , versus placebo . Most patients ( ∼62 % ) received multiple lines of post study treatment . Up date d safety results are consistent with those previously reported . Conclusions : Final analysis of AVAiL confirms the  efficacy of bevacizumab when combined with cisplatin – gemcitabine . The PFS benefit did not translate into a significant OS benefit , possibly due to high use of efficacious second-line therapies Categorizations of best response observed at week 8 ( between week 3 and 14 ) of first-line treatment in two studies of bevacizumab plus chemotherapy in Western ( 878 patients ) and Chinese ( 198 patients ) patients with non-small cell lung cancer were assessed together with baseline prognostic factors in multivariate parametric models to predict overall survival ( OS ) and progression free survival ( PFS ) . Predictive performances of the models were assessed by simulating multiple replicates of the studies . Disease control rate ( DCR ) was the best response categorization to predict OS and PFS . In the OS model , DCR fully captured bevacizumab effect . For PFS , DCR did not fully capture  bevacizumab treatment effect . The models adequately predicted OS and PFS distributions in each arm as well as bevacizumab hazard ratio ( HR ) for OS and PFS , for example , in Western patients ( model prediction [ 95 % prediction interval ] : 0.84 [ 0.71 - 0.98 ] vs. observed : 0.77 for OS and 0.59 [ 0.49 - 0.72 ] vs. observed : 0.58 for PFS ) . Covariates in the models captured endpoint differences seen in Chinese patients . There was no impact of Chinese ethnicity on the DCR relationship to OS or PFS . DCR predicted OS benefit with bevacizumab in first-line NSCLC patients . Western data can be used to inform design of studies in Chinese patients PURPOSE A traditional end point for colon adjuvant clinical trials is overall survival ( OS ) , with 5 years demonstrating adequate follow-up . A shorter-term end point providing convincing evidence to allow treatment comparisons could significantly speed the translation of advances into practice . METHODS Individual patient data were pooled from 18 r and omized phase III colon cancer adjuvant clinical trials . Trials included 43 arms , with a pooled sample size of 20,898 patients . The primary hypothesis was that disease-free survival ( DFS ) , with 3 years of follow-up , is an appropriate primary end point to replace OS with 5 years of follow-up . RESULTS The recurrence rates for years 1 through 5 were 12 % , 14 % , 8 % , 5 % , and 3 % , respectively . Median time from recurrence to death was 12 months . Eighty percent of recurrences were in the first 3 years ; 91 % of patients with recurrence by 3 years died before 5 years . Correlation between 3-year DFS and 5-year OS was 0.89 . Comparing control versus experimental arms within each trial , the correlation between hazard ratios for DFS and OS was 0.92 . Within-trial log-rank testing using both DFS and OS provided the same conclusion in 23 ( 92 % ) of 25 cases . Formal measures of surrogacy were satisfied . CONCLUSION In patients treated on phase III adjuvant colon clinical trials , DFS and OS are highly correlated , both within patients and across trials . These results suggest that DFS after 3 years of median follow-up is an appropriate end point for adjuvant colon cancer clinical trials of fluorouracil-based regimens , although marginally significant DFS improvements may not translate into significant OS benefits Background Following publication of the PRISMA statement , the UK Centre for Review s and Dissemination ( CRD ) at the University of York in Engl and began to develop an international prospect i ve register of systematic review s with health-related outcomes . The objectives were to reduce unplanned duplication of review s and provide transparency in the review process , with the aim of minimizing reporting bias . Methods An international advisory group was formed and a consultation undertaken to establish the key items necessary for inclusion in the register and to gather views on various aspects of functionality . This article describes the development of the register , now called PROSPERO , and the process of registration . Results PROSPERO offers free registration and free public access to a unique prospect i ve register of systematic review s across all areas of health from all around the world . The dedicated web-based interface is electronically search able and available to all prospect i ve registrants . At the moment , inclusion in PROSPERO is restricted to systematic review s of the effects of interventions and strategies to prevent , diagnose , treat , and monitor health conditions , for which there is a health-related outcome .Ideally , registration should take place before the research ers have started formal screening against inclusion criteria but review s are eligible as long as they have not progressed beyond the point of completing data extraction .The required data set captures the key attributes of review design as well as the administrative details necessary for registration .Su bmi tted registration forms are checked against the scope for inclusion in PROSPERO and for clarity of content before being made publicly available on the register , rejected , or returned to the applicant for clarification . The public records include an audit trail of major changes to planned methods , details of when the review has been completed , and links to result ing publications when provided by the authors . Conclusions There has been international support and an enthusiastic response to the principle of prospect i ve registration of protocol s for systematic review s and to the development of PROSPERO .In October 2011 , PROSPERO contained 200 records of systematic review s being undertaken in 26 countries around the world on a diverse range of interventions BACKGROUND Whether progression-free survival ( PFS ) or overall survival ( OS ) is the more appropriate endpoint in clinical trials of metastatic cancer is controversial . In some disease and treatment setting s , an improvement in PFS does not result in an improved OS . METHODS We partitioned OS into two parts and expressed it as the sum of PFS and survival postprogression ( SPP ) . We simulated r and omized clinical trials with two arms that had respective medians for PFS of 6 and 9 months . We assumed no treatment difference in median SPP . We found the probability of a statistically significant benefit in OS for various median SPP and observed P values for PFS . We compared the sample sizes required for PFS vs OS for various median SPP . We compare our results with the literature regarding surrogacy of PFS for OS by use of the correlation between hazard ratios for PFS and OS . All statistical tests were two-sided . RESULTS For a trial with observed P value for improvement in PFS of .001 , there was a greater than 90 % probability for statistical significance in OS if median SPP was 2 months but less than 20 % if median SPP was 24 months . For a trial requiring 280 patients to detect a 3-month difference in PFS  , 350 and 2440 patients , respectively , were required to have the same power for detecting a real difference in OS that is carried over from the 3-month benefit in PFS when the median SPP was 2 and 24 months . CONCLUSIONS Addressing SPP is important in underst and ing treatment effects . For clinical trials with a PFS benefit , lack of statistical significance in OS does not imply lack of improvement in OS , especially for diseases with long median SPP . Although there may be no treatment effect on SPP , its variability so dilutes the OS comparison that statistical significance is likely lost . OS is a reasonable primary endpoint when median SPP is short but is too high a bar when median SPP is long , such as longer than 12 months BACKGROUND Many more phase II studies have favorable outcomes than the subsequent phase III trials . We used historical data from phase II and phase III studies for patients with extensive-stage small-cell lung cancer ( SCLC ) to generate a statistical model to provide assistance in selecting chemotherapy regimens from phase II studies for subsequent use in phase III r and omized studies . METHODS Information from 21 phase III trials for patients with extensive-stage SCLC initiated during the period from 1972 through 1990 was review ed to identify those that were preceded by phase II studies of the same regimen . We used data from all the trial pairs to develop a statistical model in which the number of patients , the median survival of patients , and the number of deaths observed in the phase II trial are used to estimate the statistical power of the subsequent phase III trial . All statistical tests were two-sided . RESULTS Nine phase II studies were identified that preceded phase III trials of the same regimen . The regimens from two phase II studies with the greatest expected power in the phase III trial ( 0 . 62 and 0.58 ) both demonstrated significantly prolonged survival when compared with st and ard treatment in subsequent phase III trials ( P<. 001 and P = .002 , respectively ) . The regimens from six of the other phase II studies , for which the median power expected in the phase III trial was 0.28 ( range , 0.19 - 0.52 ) , showed no difference when compared with st and ard treatment in a phase III trial . CONCLUSIONS Phase II studies for particular regimens that have an expected power of greater than 0.55 provide a reasonable basis for proceeding with a phase III trial This paper is an overview of the new response evaluation criteria in solid tumours :  revised RECIST guideline ( version 1 . 1 ) , with a focus on up date d contents Several challenging and often controversial issues arise in oncology trials with the use of the end point  progression-free survival  ( PFS ) , defined to be the time to detection of progressive disease or death . While this end point does not directly measure how a patient feels , functions , or survives , it does provide insights about whether an intervention affects the tumor burden process , the intended mechanism through which it is hoped that most anticancer agents will provide benefit . However , simply achieving statistically significant effects on PFS is insufficient to obtaining reliable evidence of important clinical benefit , and even is insufficient to justifying the conclusion that the experimental intervention is " reasonably likely to provide clinical benefit . " The magnitude of the effect on PFS in addition to the statistical strength of evidence is of great importance in interpreting the reliability of the evidence regarding clinical efficacy . PFS has several important properties , including being a direct measure of the effect of treatment on the tumor burden process , being sensitive to cytostatic as well as cytotoxic mechanisms of interventions , and incorporating the clinical ly relevant event of death , increasing its sensitivity to influential harmful mechanisms and avoiding substantial bias that arises when deaths are censored . To obtain reliable evidence about the effect of an intervention on PFS and patient survival , 
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ORrr , followed by HRpfs , had the strongest association with HRos at the trial level .
However , these measures were not strong enough to replace OS