***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 : Sorafenib , a multikinase inhibitor targeting Raf and VEGFR , has shown activity in unselected patients with non – small-cell lung cancer ( NSCLC ) . At present there are no vali date d biomarkers indicative of sorafenib activity . Experimental Design : Patients received sorafenib 400 mg BID daily to determine activity and tolerability and to measure its biological effects . KRAS mutation status ( N = 34 ) , angiogenesis markers ( VEGF , bFGF , FLT-1 , PLGF-1 ) and imaging with DCE-MRI ( dynamic contrast enhanced MRI ) to determine early changes in tumor vascular characteristics were evaluated . Three parameters Ktrans , Kep , and Ve were measured by DCE-MRI at baseline and day 14 of cycle 1 . Cytokine analysis was done on days 0 , 14 , 28 , and 54 . Results : Thirty-seven patients with previously treated stage IV NSCLC were enrolled in this single-center phase II trial . In 34 evaluable patients , 2 had partial responses and 20 had stable disease for 3 to 17 months , a disease control rate of 65 % . The median progression-free survival ( PFS ) was 3.4 months , and median overall survival ( OS ) was 11.6 months . Toxicity was consistent with the known side effects of sorafenib . KRAS ( 32 % ) and EGFR mutations ( 22 % ) showed no correlation with response , PFS , or OS . Kep , was significant in predicting an improvement in OS ( P = 0.035 ) and PFS ( P = 0.029 ) . Cytokine analysis demonstrated an improved OS for bFGF day 0 ( < 6 vs. > 6 pg/mL ; P = 0.042 ) , whereas a PFS benefit was seen with bFGF at day 28 ( < 6 vs. > 6 ; P = 0.028 ) . Conclusions : KRAS and EGFR mutational status showed no correlation with response , PFS , or OS . Radiologic and cytokine changes may act as biomarkers indicative of early angiogenesis inhibition . Clin Cancer Res ; 17(5 ) ; 1190–9 . © 2011 AACR Introduction : Avastin Biomarkers In lunG And 3D Innovative anaLysis ( ABIGAIL ) , which is a phase II , open-label , r and omized study , investigated correlations between biomarkers and best overall response to bevacizumab plus platinum-doublet chemotherapy for patients with advanced/recurrent non – small-cell lung cancer . Methods : Patients received  bevacizumab ( 7.5 or 15 mg/kg , 3-weekly until disease progression/unacceptable toxicity ) plus carboplatin/gemcitabine or carboplatin/paclitaxel ( maximum six cycles ) . Plasma sample s ( baseline/throughout treatment ) were analyzed for vascular endothelial growth factor (VEGF)-A ( baseline only ) , VEGF receptors ( VEGFR-1/VEGFR-2 ) , basic fibroblast growth factor , E-selectin , intercellular adhesion molecule-1 , and placental growth factor ( baseline only ) . Tumor sample s ( primary specimen ) were analyzed for VEGF-A , VEGFR-1/VEGFR-2 , neuropilin ( NRP ) , and CD31 . Response was evaluated at baseline and every 6 weeks ( Response Evaluation Criteria in Solid Tumors ) . Results : Patients were r and omized to receive chemotherapy plus 7.5 mg/kg ( n = 154 ) or 15 mg/kg ( n = 149 ) bevacizumab .  For the primary analysis , none of the baseline plasma biomarkers correlated with best overall response . Exploratory analyses showed that low VEGF-A levels were associated with longer progression-free survival ( 7.4 versus 6.1 months ; hazard ratio , 1.57 ; 95 % confidence intervals , 1.17 to 2.09 ; p = 0.002 ) and overall survival ( 19.8 versus 11.1 months ; hazard ratio , 1.57 ; 95 % confidence interval , 1.15–2.13 ; p = 0.004 ) compared with these in high baseline plasma VEGF-A levels . No plasma biomarkers changed significantly over time . No significant correlations were observed between tumor biomarkers and clinical outcomes . No new safety signals were observed . Conclusion : Baseline and /or dynamic changes in plasma basic fibroblast growth factor , E-selectin , intercellular adhesion molecule-1 , placental growth factor , VEGFR-1 and VEGFR-2 , and tumor biomarkers did not correlate statistically with treatment outcomes for bevacizumab plus chemotherapy . Only baseline plasma VEGF-A was significantly correlated with progression-free survival/overall survival PURPOSE To investigate the efficacy and safety of bevacizumab plus cisplatin and etoposide in patients with extensive-stage disease , small-cell lung cancer ( ED-SCLC ) . PATIENTS AND METHODS In this phase II trial , 63 patients were treated with bevacizumab 15 mg/kg plus cisplatin 60 mg/m(2 ) and etoposide 120 mg/m(2 ) , which was followed by bevacizumab alone until death or disease progression occurred . The primary end point was the proportion of patients alive at 6 months without disease progression ( ie , progression-free survival [ PFS ] ) . Secondary end points included overall survival ( OS ) , objective response rate , and toxicity . Correlative studies were performed to explore the relationship between baseline and changes in plasma vascular endothelial growth factor ( VEGF ) , soluble cell adhesion molecules ( ie , vascular cell adhesion molecule [ VCAM ] , intercellular cell adhesion molecule [ ICAM ] , and E-selectin ) and basic fibroblast growth factor and outcome . RESULTS The 6-month PFS was 30.2 % , the median PFS was 4.7 months , and OS was 10.9 months . The response rate was 63.5 % . The most common adverse event was neutropenia ( 57.8 % ) . Only one patient had grade 3 pulmonary hemorrhage . Patients who had high baseline VCAM had a higher risk of progression or death compared with those who had low baseline VCAM levels . No relationships between outcome and any other biomarkers were seen . CONCLUSION The addition of bevacizumab to cisplatin and etoposide in patients with ED-SCLC results in improved PFS and OS relative to historical controls who received this chemotherapy regimen without bevacizumab . This regimen appears to be well tolerated and has minimal increase in toxicities compared with chemotherapy alone . Baseline VCAM levels predicted survival , but no other relationships among treatment , biomarkers , and outcome were identified BACKGROUND The formation of new microvessels from the existing vascular bed is known as angiogenesis and is normally under the tight regulatory control of angiogenic factors . This control is lost in malignant tumours . Previous studies have correlated increased microvessel density with poor prognosis in patients with primary lung cancer . MATERIAL S AND METHODS Our group measured levels of  vascular endothelial growth factor ( VEGF ) and basic fibroblast growth factor ( bFGF )  in sera from 68 patients with non-small cell lung cancer ( NSCLC ) and compared elevated levels of VEGF and bFGF with clinical outcome . Serum basic FGF and VEGF  were measured using commercially available enzyme- linked immunosorbent assays ( R & D Systems Inc. , Minneapolis , MN USA ) . RESULTS In 26/68 ( 38 % ) patients we found that elevated circulating levels of bFGF and in 27/68 ( 39 % ) serum sample s levels of VEGF were elevated . Elevated bFGF values in sera was a statistically significant good prognostic factor , p- value = 0.048 , when adjusted to stage and there was a trend in that patients with elevated levels of bFGF had a higher fraction of adenocarcinomas compared with squamous epithelial carcinomas ( chi 2 = 2.0 ) . No significant correlations could be demonstrated when elevated levels of VEGF in serum was present . Elevated levels of both VEGF and bFGF was present in 45 % of the patients . CONCLUSIONS We found that elevated levels of bFGF is a good prognostic factor when measured in sera from NSCLC patients . As this result disagrees with earlier studies on other malignancies the results from our study needs to be further investigated in a prospect i ve study Basic fibroblast growth factor ( bFGF ) is a secreted multifunctional cytokine and a potent stimulator of angiogenesis . We measured bFGF concentrations from serum sample s taken from 103 patients with small cell lung cancer at the time of diagnosis .  Serum concentration of bFGF ( S-bFGF )  ranged from undetectable to 54 pg/ml ( median , 6 pg/ml ) . S-bFGF was not associated with age , sex , performance status , or stage . A high pretreatment S-bFGF was associated with poor overall survival . The 1- and 2-year survival rates of the patients within the highest quartile of S-bFGF ( > or=17 pg/ml ) were only 26 % and 11 % , respectively , in contrast to the 49 % and 20 % 1- and 2-year survival rates of those patients with S-bFGF < 17 pg/ml ( P = 0.013 ) . The 1- and 2-year survival rates of the patients with extensive-stage disease were 33 % and 10 % , respectively ( P = 0.0091 ) . Interestingly , S-bFGF provided additional prognostic information to the stage because the 1- and 2-year survival rates of patients with extensive-stage disease and a high S-bFGF ( > or=17 pg/ml ) were as low as 16 % and 5 % , respectively ( P = 0.0026 ) . Similarly , in the multivariate model of survival analysis , patients with both extensive-stage disease and a high S-bFGF ( > or=17 pg/ml ) were found to have a particularly poor prognosis ( relative risk of death , 2.1 ; 95 % confidence interval , 1.2 - 3.6 ; P = 0.0057 ) . We conclude that a high S-bFGF at diagnosis is associated with poor outcome in small cell lung cancer , possibly reflecting active angiogenesis and rapid tumor growth , and may complement prognostic information obtained by staging Background : E4599 was a phase II/phase III trial , in which 878 patients with advanced non – small cell lung cancer were r and omized to carboplatin + paclitaxel ( PC arm ) or PC + bevacizumab ( BPC arm ) . Survival and progression-free survival were superior on the BPC arm . The rationale for markers used in this correlative study was based on elevated vascular endothelial growth factor ( VEGF ) , basic fibroblast growth factor ( bFGF ) , soluble intercellular adhesion molecule ( ICAM ) and E-selectin in a variety of malignances and changes in response to endothelial cell apoptosis . Material s and Methods : Prospect i ve correlates included measurements of pretreatment plasma VEGF , as well as pretreatment and week 7 , bFGF , ICAM , and E-selectin . Low and high levels were defined as less than or equal to or more than the median . Results : E-selectin ( P < 0.0001 ) showed a decrease and bFGF showed an increase ( P = 0.004 ) from baseline at week 7 , which were similar in both arms . Baseline ICAM showed significant associations with response and survival in both groups . Patients with low baseline ICAM had a higher response rate ( 32 % versus 14 % ; P = 0.02 ) , better overall survival ( P = 0.00005 ) , and better 1-year survival ( 65 % versus 25 % ) than those with high ICAM , respectively , regardless of treatment arm . Patients with high VEGF levels were more likely to respond to BPC compared with PC , but this was not predictive of survival . The results also suggest a benefit from bevacizumab for patients with low baseline ICAM levels ( 53 % reduction in the progression-free survival hazard rate ) . Conclusions : In this study , baseline ICAM levels were prognostic for survival and predictive of response to chemotherapy with or without bevacizumab .  VEGF levels were predictive of response to bevacizumab but not survival 
    Output:
    
There was no significant impact of bFGF expression on survival in advanced NSCLC .
This meta- analysis showed that  bFGF overexpression is a potential indicator of worse prognosis for patients with operable NSCLC and SCLC , but is not associated with outcome in advanced NSCLC .
The data suggests that high bFGF expression is highly related to poor prognosis .
Nevertheless , more high- quality studies should be performed in order to provide additional evidence for the prognostic value of bFGF in lung cancer