***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: PURPOSE To explore whether progression-free survival ( PFS ) or biochemical PFS can be used as a predictor of overall survival ( OS ) and to investigate the dependence between PFS and OS in men with castrate-resistant prostate cancer . PATIENTS AND METHODS Data from nine Cancer and Leukemia Group B trials that enrolled 1,296 men from 1991 to 2004 were pooled . Men were eligible if they had prostate cancer that had progressed during and rogen deprivation therapy and did not receive prior treatment with chemotherapy , immunotherapy , or other nonhormonal therapy .  L and mark analyses of PFS at 3 and 6 months from r and omization/ registration were performed to minimize lead time bias . The proportional hazards model was used to assess the significance effect of PFS rate at 3 and at 6 months in predicting OS . In addition , biochemical progression using the definitions of Prostate-Specific Antigen Working Group ( PSAW ) Criteria PSAWG1 and PSAWG2 were analyzed as time-dependent covariates in predicting OS . RESULTS The median survival time among men who experienced progression at 3 months was 9.2 months ( 95 % CI , 8.0 to 10.0 months ) compared with 17.8 months in men who did not experience progression at 3 months ( 95 % CI , 16.2 to 20.4 months ; P < .0001 ) . Compared with men who did not progress at 3 and at 6 months , the adjusted hazard ratios for death were 2.0 ( 95 % CI , 1.7 to 2.4 ; P < .001 ) and 1.9 ( 95 % CI , 1.6 to 2.4 ; P < .001 ) for men who experienced progression at 3 and 6 months , respectively . In addition , biochemical progression at 3 months predicted OS . The association between PFS and OS was 0.30 ( 95 % confidence limits = 0.26 , 0.32 ) . CONCLUSION PFS at 3 and 6 months and biochemical progression at 3 months predict OS . These observations require prospect i ve validation Summary  Progression-free survival ( PFS ) and time to progression ( TTP )  have been reported to correlate with overall survival ( OS ) in several types of cancers . To our knowledge , however , their use in the evaluation of new agents for AGC has not been investigated . We evaluated the potential of PFS and TTP to act as surrogates of OS in clinical trial setting s. R and omized trials of systemic chemotherapy for advanced gastric cancer were identified by comprehensive electronic and manual search . Correlations between PFS/TTP and OS were evaluated . Thirty-six trials with a total of 83 treatment arms and 10,484 patients were selected for analysis .  The nonparametric Spearman rank correlation coefficient ( ρ ) between median PFS/TTP and OS was 0.70 ( 95 % CI , 0.59 to 0.82 ) and the correlation coefficient between hazard ratios in PFS/TTP and OS was 0.80 ( 95 % CI , 0.68 to 0.92 ) . Correlation tended to be higher in trials reporting PFS ( ρ = 0.85 ; 0.72–0.97 ) than in those reporting TTP ( ρ = 0.60 ; 0.24–0.97 ) , trials in Non-Asian countries ( ρ = 0.80 ; 0.61–0.99 ) than Asia ( ρ = 0.67 ; 0.39–0.94 ) , trials in patients with measurable lesions only ( ρ = 0.91 ; 0.77–1.00 ) than in those including non-measurable lesions ( ρ = 0.71 ; 0.50–0.93 ) , albeit that none of these differences was significant . Our results indicate that improvements in PFS/TTP in advanced gastric cancer strongly correlate with improvements in OS . Further research is needed to clarify the surrogacy of PFS/TTP for OS or the role of PFS as the true end point in future r and omized clinical trials of chemotherapy for AGC Background : The correlation between efficacy end points in r and omized controlled trials ( RCTs ) of systemic therapy for non-Hodgkin 's lymphoma ( NHL ) was investigated to identify an appropriate surrogate end point for overall survival ( OS ) . Methods : RCTs of previously untreated NHL published from 1990 to 2009 were identified . Associations between absolute differences in efficacy end points were determined using nonparametric Spearman 's rank correlation coefficients ( rs ) . Results : Thirty-eight RCTs representing 85 treatment arms for aggressive NHL and 20 RCTs representing 42 arms for indolent NHL were included . For aggressive NHL , differences in 3-year progression-free survival (PFS)/event-free survival ( EFS ) were high correlated with differences in 5-year OS { rs of 0.90 [ 95 % confidence interval ( CI ) 0.73–0.96 ] } and linear regression determined that a 10 % improvement in 3-year EFS or PFS would predict for a 7 % ± 1 % improvement in 5-year OS . For indolent histology disease , differences in complete response were strongly correlated with differences in 3-year EFS [ rs 0.86 ( 95 % CI 0.35–0.97 ) ] , but there was no correlation between 3-year time-to-event end points and 5-year OS . Conclusions : Improvements in 3-year EFS/PFS are highly correlated with improvements in 5-year OS in aggressive NHL and should be explored as a c and i date surrogate end point . Definition of these relationships may inform future clinical trial design and interpretation of interim trial data We assessed six-month progression-free survival ( PFS ) as an alternative primary efficacy endpoint to overall survival in newly diagnosed glioblastoma multiforme ( GBM ) patients receiving temozolomide ( TMZ ) . A total of 183 patients with newly diagnosed GBM enrolled in 3 phase II protocol s at the University of California-San Francisco were included . Patients were treated with interventions based on the Stupp regimen , each with the added component of a second oral agent given concurrently with radiotherapy and TMZ , followed by its coadministration with adjuvant TMZ . We examined whether progression status at 2 , 4 , and 6 months predicted subsequent survival using the l and mark analysis . The hazard ratios of death as a function of progression status were estimated based on the Cox proportional hazards model after adjustment for putative prognostic factors . Progression status at 2 , 4 , and 6 months were all consistently found to be strong predictors of subsequent survival in all studies . The study -specific hazard ratios associated with progression status at 6 months ranged from 2.03 to 3.39 . The hazard ratios associated with the earlier time points ( 2- and 4-month progression ) all exceeded 2 in magnitude , ranging from 2.29 to 4.73 . P-values were statistically significant for all time points . In this report , we demonstrated a strong association between the endpoints of PFS at 2 , 4 , and 6 months and survival . Patients who showed the signs of early progression were at significantly higher risk of earlier death . Our analysis suggests that 6-month PFS may be an appropriate primary endpoint in the context of phase II upfront GBM trials in the TMZ era Background It is controversial for the use of survival surrogate end points including response rate ( RR ) , disease control rate ( DCR ) , time to progression , and progression-free survival ( PFS ) in trials of molecular targeted agents . Our aim was to determine the correlations of these surrogates with survival in the treatment of advanced non-small-cell lung cancer ( ANSCLC ) with epidermal growth factor receptor tyrosine kinase inhibitors ( EGFR-TKIs )  , gefitinib and erlotinib . Methods Summary data of  median survival time ( MST )  and surrogates from prospect i ve trials of  EGFR-TKIs  in ANSCLC were identified . Patient- or trial-related characteristics were introduced as covariates . Simple and multivariate linear regression models were fitted for MST and each surrogate , respectively . And the significance of each surrogate as a survival marker was compared by calculating the area under their receiver operating characteristic ( ROC ) curves . Results Sixty eligible trials ( 9,903 patients ) were enrolled .  RR , DCR , and PFS were all strongly associated with MST . In their simple linear regression models , the coefficient of determination ( R2 ) was 0.83 ( p < 0.000001 ) , 0.58 ( p < 0.0001 ) , and 0.70 ( p < 0.0001 ) , respectively . And in their multivariate linear regression models , the st and ard coefficient was 0.71 ( p < 0.001 ) , 0.40 ( p < 0.001 ) , and 0.74 ( p < 0.001 ) , respectively , while RR and PFS were the preferred survival predictors in the ROC analysis . Conclusion RR or PFS may serve as an appropriate survival surrogate in the clinical trials of EGFR-TKIs for ANSCLC OBJECTIVES Our aim was to review the recommendations given by health technology assessment ( HTA ) institutions in their method ological guidelines concerning the use of surrogate outcomes in their assessment s. In a second step , we aim ed at quantifying the role surrogate parameters take in assessment reports . METHODS We analyzed method ological papers and guidelines from HTA agencies with International Network of Agencies for Health Technology Assessment membership as well as from institutions related to pharmaceutical regulation ( i.e. , reimbursement , pricing ) . We analyzed the use of surrogate outcomes in a sample of HTA reports r and omly drawn from the HTA data base . We checked methods , results ( including evidence tables ) , and conclusions sections and extracted the outcomes reported . We report descriptive statistics on the presence of surrogate outcomes in the reports . RESULTS We identified thirty-four method ological guidelines , twenty of them addressing the issue of outcome parameter choice and the problematic of surrogate outcomes . Overall HTA agencies call on caution regarding the reliance on surrogate outcomes . None of the agencies has provided a list or catalog of acceptable and vali date d surrogate outcomes . We extracted the outcome parameter of 140 HTA reports . Only around half of the reports determined the outcomes for the assessment prospect ively .  Surrogate outcomes  had been used in 62 percent of the reports . However , only 3.6 percent were based upon  surrogate outcomes  exclusively . All of them assessed diagnostic or screening technologies and the surrogate outcomes were predominantly test characteristics . CONCLUSIONS HTA institutions seem to agree on a cautious approach to the use of  surrogate outcomes  in technology assessment . Thorough assessment of health technologies should not rely exclusively on surrogate outcomes Progression-free  survival ( PFS )  is an increasingly important end-point in cancer drug development . However , several concerns exist regarding the use of PFS as a basis to compare treatments . Unlike survival , the exact time of progression is unknown , so progression times might be over-estimated ( or under-estimated ) and , consequently , bias may be introduced when comparing treatments . In addition , the assessment of progression is subject to measurement variability which may introduce error or bias . Ideally trials with PFS as the primary end-point should be r and omised and , when feasible , double-blinded . All patients eligible for study should be evaluable for the primary end-point and thus , in general , have measurable disease at baseline . Appropriate definitions should be provided in the protocol and data collected on the case-report forms , if patients with only non-measurable disease are eligible and /or clinical , or symptomatic progression are to be considered progression events for analysis . Protocol defined assessment s of disease burden should be obtained at intervals that are symmetrical between arms . Independent review of imaging may be of value in r and omised phase II trials and phase III trials as an auditing tool to detect possible bias 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 Common end points for phase II trials in patients with glioblastoma multiforme ( GBM ) are six-month progression-free survival ( PFS6 ) and 12-month overall survival ( OS12 ) . OS12 can be accurately measured but may be confounded with subsequent therapies upon progression , whereas the converse is true for PFS6 . Our goal was to assess the relationship between these end points separately for phase II trials in patients with newly diagnosed GBM and patients with recurrent GBM . Data were pooled from 11 North Central Cancer Treatment Group trials for patients with newly diagnosed GBM ( n = 1348 ) . All patients received radiotherapy and pharmaceutical therapy ( before , during , or after radiotherapy ) . Data were pooled from 16 trials that used various pharmaceuticals in treating patients for recurrent GBM ( n = 345 ) . All trial regimens were declared nonefficacious by predefined criteria . Overall per-patient concordance was estimated with a kappa statistic . The relationship between OS12 and PFS6 across study arms was assessed by weighted linear regression and Pearson 's correlation . Simulation was used to determine the agreement of study outcomes when using PFS6 versus OS12 end points . Cox models with progression status as a time-dependent variable and Kaplan-Meier estimators were used to ascertain the association between progression-free survival status and overall survival . At present 
    Output:
    
Not in all solid tumors the treatment-level association between PFS or TTP and OS has been investigated .
According to IQWiG 's framework , only PFS achieved acceptable evidence of surrogacy in metastatic colorectal and ovarian cancer treated with cytotoxic agents .