***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 The mechanisms of paraneoplastic thrombocytosis in ovarian cancer and the role that platelets play in abetting cancer growth are unclear . METHODS We analyzed clinical data on 619 patients with epithelial ovarian cancer to test associations between platelet counts and disease outcome . Human sample s and mouse models of epithelial ovarian cancer were used to explore the underlying mechanisms of paraneoplastic thrombocytosis . The effects of platelets on tumor growth and angiogenesis were ascertained . RESULTS Thrombocytosis was significantly associated with advanced disease and shortened survival . Plasma levels of thrombopoietin and interleukin-6 were significantly elevated in patients who had thrombocytosis as compared with those who did not . In mouse models , increased hepatic thrombopoietin synthesis in response to tumor-derived interleukin-6 was an underlying mechanism of paraneoplastic thrombocytosis . Tumor-derived interleukin-6 and hepatic thrombopoietin were also linked to thrombocytosis in patients . Silencing thrombopoietin and interleukin-6 abrogated thrombocytosis in tumor-bearing mice . Anti-interleukin-6 antibody treatment significantly reduced platelet counts in tumor-bearing mice and in patients with epithelial ovarian cancer . In addition , neutralizing interleukin-6 significantly enhanced the therapeutic efficacy of paclitaxel in mouse models of epithelial ovarian cancer . The use of an antiplatelet antibody to halve platelet counts in tumor-bearing mice significantly reduced tumor growth and angiogenesis . CONCLUSIONS These findings support the existence of a paracrine circuit wherein increased production of thrombopoietic cytokines in tumor and host tissue leads to paraneoplastic thrombocytosis , which fuels tumor growth . We speculate that countering paraneoplastic thrombocytosis either directly or indirectly by targeting these cytokines may have therapeutic potential . ( Funded by the National Cancer Institute and others . ) PURPOSE This study attempted to determine the prognostic value for survival of various pretreatment characteristics in patients with nonresectable non-small-cell lung cancer in the context of more than 10 years of experience of a European Cooperative Group . PATIENTS AND METHODS We included in the analysis all eligible patients ( N = 1,052 ) with advanced non-small-cell lung cancer registered onto one of seven trials conducted by the European Lung Cancer Working Party ( ELCWP ) during one decade . The patients were treated by chemotherapy regimens based on platinum derivatives . We prospect ively collected 23 variables and analyzed them by univariate and multivariate methods . RESULTS The global estimated median survival time was 29 weeks , with a 95 % confidence interval of 27 to 30 weeks . After univariate analysis , we applied two multivariate statistical techniques . In a Cox regression model , the selected explanatory variables were disease extent , Karnofsky performance status , WBC and neutrophil counts , metastatic involvement of skin , serum calcium level , age , and sex . These results were confirmed by application of recursive partitioning and amalgamation algorithms ( RECPAM ) , which led to classification of the patients into four homogeneous subgroups . CONCLUSION We confirmed by our analysis the role of well-known independent prognostic factors for survival , but also identified the effect of the neutrophil count , rarely studied , with the use of two methods : a classical Cox regression model and a RECPAM analysis . The classification of patients into the four subgroups we obtained needs to be vali date d in other series We have evaluated the prognostic value of 22 pretreatment attributes in 436 small cell lung cancer ( SCLC ) patients included in a prospect i ve multicenter study with a minimum 5-year follow-up . Pretreatment clinical and laboratory parameters were registered . Possible prognostic factors were evaluated by univariate analysis ( log rank test ) and by the Cox multivariate regression model . In the univariate analysis of all patients , only age , nodal metastasis , and skin metastasis were not associated with survival . The multivariate Cox model identified gender , extent of disease , performance status ( PS ) , weight loss , platelet count , LDH , and NSE as independent prognostic factors . In subset multivariate analyses according to extent of disease , we found haemoglobin level , PS , NSE , and total WBC as significant prognostic indicators for survival in limited-stage disease ( LD-SCLC ) , while PS , weight loss , LDH , number of metastases , liver metastases , and brain metastases were identified as independent prognostic factors in extensive-stage disease ( ED-SCLC ) . There was a significant correlation between serum LDH and NSE levels . In conclusion , gender , extent of disease , PS , weight loss , haemoglobin , WBC count , platelet count , LDH , and NSE were all found to be independent prognostic factors for SCLC survival . However , the prognostic value of these factors depends highly on whether all or subsets of SCLC patients are studied There is a sub clinical activation of coagulation and fibrinolysis system in lung cancer . Alterations in hemostatic system are seen frequently in lung cancer correlated with the prognosis of disease . In this prospect i ve study , our purpose was to investigate the prognostic significance of hemostatic markers in patients with lung cancer . The study comprised 58 patients ( 22 squamous cell carcinoma , 16 adenocarcinoma , 20 small cell carcinoma ) . There were 55 men ( 95 % ) and 3 women ( 5 % ) with a mean age of 61 years range ( 36 - 74 ) .  Plasma level of platelets ( PLT ) , prothrombin time ( PT ) , active partial thromboplastin time ( aPTT ) , antithrombin III ( AT III ) , fibrinogen ( F ) and D-dimer level were measured before the initiation of any therapy . Patients were followed up for 17 ( 12 - 20 ) months . The median survival was determined as 6.4 months . Three histopathologic groups ; squamous cell carcinoma , adenocarcinoma and small cell carcinoma were compared for the hemostatic parameters . There were no statistically significant differences among the histopathologic types for any of the parameters ( P > 0.05 ) . Patients were divided into two groups as patients without distant metastasis ( stages I , II , III ) and with distant metastasis ( stage IV ) . The group with distant metastasis had higher level of D-dimer than the other group ( P < 0.05 ) . However , there were no statistically significant differences for D-dimer level between stages IIIB and IV ( P > 0.05 ) . Patients having high D-dimer and low AT III level had poor survival in our study . Thus , high level of D-dimer and low AT III level were determined as correlated with short survival ( P < 0.05 ) . These results suggest that elevated plasma level of D-dimer and low AT III level might be a sign of poor prognosis in patients with lung cancer INTRODUCTION FRAME was a prospect i ve observational study that captured real-world data on patients with advanced or metastatic non-small cell lung cancer ( NSCLC ) receiving platinum-based chemotherapies as first-line treatment ( FLT ) across Europe . As previously reported , most patients observed in the study had initiated FLT with either pemetrexed , gemcitabine , vinorelbine or taxanes in combination with a platinum . Baseline patient and disease characteristics including age , performance status , and histology varied ( all p<0.01 ) across cohorts . METHODS Consenting adult patients initiating FLT for advanced or metastatic NSCLC with platinum-based chemotherapy , with or without a targeted agent , entered the study between April 2009 and February 2011 . The choice of FLT was left to physicians ' discretion per routine clinical practice . The primary objective was to evaluate overall survival ( OS ) across platinum-based doublet chemotherapy cohorts and key secondary objectives included the evaluation of OS in patients with different histological subtypes of NSCLC . Survival outcomes were assessed using Kaplan-Meier analysis , and unadjusted estimates are presented . RESULTS Median OS in months was 10.3 across cohorts ( n=1524 ) , 10.7 for pemetrexed ( n=569 ) , 10.0 for gemcitabine ( n=360 ) , 9.1 for taxanes ( n=295 ) , and 10.7 for vinorelbine ( n=300 ) . For patients with non-squamous NSCLC who received cisplatin ( n=616 , 40 % of total ) , median OS in months was 10.6 across the cohorts , 11.6 for pemetrexed , 8.4 for gemcitabine , 9.6 for taxanes , and 9.9 for vinorelbine . CONCLUSIONS FRAME describes real-world treatment patterns and survival for patients initiating FLT for advanced or metastatic NSCLC between 2009 and 2011 across Europe Background : The aim of the present study was to investigate any prognostic value of pre-treatment anemia , leukocytosis and thrombocytosis in patients with advanced pretreated NSCLC . Methods : A r and omized , multicenter phase II study comparing the IGF-1R modulator AXL with st and ard docetaxel in the treatment of previously treated stage IIIB or IV NSCLC patients was conducted in 2011 - 2013 . Clinical and laboratory data were collected , including serum values for hemoglobin ( Hgb ) , white blood cells ( WBC ) and platelets ( Plt ) at baseline . These hematological parameters were studied in relation to overall survival using Kaplan – Meier product-limit estimates and multivariate Cox proportional hazards regression models . Results : The median overall survival for all patients was 8.9 months . Patients with  leukocytosis  ( WBC > 9 x 109/L ) had a significantly shorter median overall survival ( 4.2 months ) as compared with those with a WBC ≤ 9 x 109/L at baseline ( 12.3 months ) with a corresponding of HR 2.10 ( 95 % CI : 1.29 - 3.43 ) . Patients with anemia ( Hgb < 110 g/L ) had a non-significant ( p = 0.097 ) shorter median overall survival ( 6.1 months ) as compared with their counterparts with Hgb ≥ 110 g/L at baseline ( 9.4 months ) . As for thrombocytosis ( Plt > 350 x 109/L ) , there was no statistically significant impact on overall survival . Leukocytosis retained its prognostic significance in a multivariate model where other clinical factors such as age , sex and WHO performance status were taken into consideration ( HR : 1.83 , 95 % CI : 1.06 - 3.13 , p = 0.029 ) . Conclusion : Pre-treatment leukocytosis is a strong and independent prognostic marker for shorter overall survival in previously treated stage IIIB or IV NSCLC patients receiving docetaxel or AXL1717 . Combined use of pre-treatment leukocytosis assessment s together with established prognostic factors such as performance status could be of help when making treatment decisions in this clinical setting AIMS An elevated plasma D-dimer level indicates the activation of coagulation and fibrinolysis . In the present study , we investigated the association of pre-treatment haemostatic parameters ( D-dimer , fibrinogen and prothrombin fragment 1 + 2 ) with clinicopathological parameters and outcome in patients with lung cancer . MATERIAL S AND METHODS  Plasma levels of D-dimer  and other parameters were measured in 78 evaluable patients with lung cancer ( 60 non-small cell lung cancers , 18 small cell lung cancers ) . At diagnosis , 35 patients ( 44.9 % ) were locally advanced stage ( IIIA/B ) and 43 patients ( 55.1 % ) had metastatic disease ( IV ) . Multivariate statistical analysis was carried out using Cox 's proportional hazards model . The receiver operating characteristic curve was used to determine the cut-off values for D-dimer , fibrinogen and prothrombin fragment 1 + 2 . RESULTS The median survival for all patients was 264 days ( 95 % confidence interval 200 - 328 days ) . A significant association between the plasma levels of D-dimer and the response to chemotherapy  was observed ( P=0.03 ) . With the univariate analysis , tumour stage , pre-treatment plasma levels of D-dimer , fibrinogen , platelet count , lactate dehydrogenase concentration and Karnofsky performance status were predictive for survival . With the multivariate analysis ( P < or = 0.1 ) , the plasma level of D-dimer ( P<0.001 ) , tumour stage ( P=0.01 ) and Karnofsky performance status ( P=0.02 ) were identified as independent predictive factors . The median survival times were 405 days ( 95 % confidence interval 165 - 644 days ) and 207 days ( 95 % confidence interval 146 - 267 days , P<0.001 ) , respectively , for patients with a low D-dimer level ( < or = 0.65 microg/ml ) and a high D-dimer level ( > 0.65 microg/ml ) . CONCLUSIONS Elevated plasma levels of D-dimer in patients with lung cancer are associated with decreased survival and a poor response to treatment . Pre-treatment for the D-dimer level may be useful in the prediction of survival 
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In subgroup analyses , elevated pretreatment platelet counts were also associated with poorer OS and DFS/PFS/TTP in most subgroups .
This meta- analysis revealed that elevated pretreatment platelet counts were an independent predictor of OS and DFS/PFS/TTP in lung cancer patients .