***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 Somatic mutations in EGFR and K-RAS may predict for sensitivity and resistance to EGFR tyrosine kinase inhibitors ( TKIs ) . Whether EGFR and K-RAS mutations could also predict clinical outcome of non-small cell lung cancer ( NSCLC ) patients following front-line chemotherapy  has not yet been established . PATIENTS AND METHODS One hundred and sixty-two chemotherapy-naïve patients with locally advanced/metastatic NSCLC who received front-line chemotherapy  were included in this retrospective study and their clinical outcome data was analyzed according to EGFR and K-RAS mutation status of their tumors . RESULTS Classical activating EGFR and K-RAS mutations were found in 8.2 and 22.6 % of patients respectively and were not associated with patients ' clinicopathological characteristics . Patients with classical EGFR mutations had a higher probability of response to front-line chemotherapy as compared to those with wild type EGFR ( p=0.023 ) . Multivariate analysis showed that the presence of activating EGFR mutations was an independent factor associated with response to front-line chemotherapy ( HR=4.85 ; 95 % CI : 1.13 - 20.83 , p=0.034 ) . K-RAS mutation status was not associated with response to front-line chemotherapy . The presence of activating EGFR but not of K-RAS mutations was associated with a significantly higher overall survival compared to patients without mutations treated with platinum-based front-line chemotherapy ( p=0.043 ) . CONCLUSIONS The data indicate that EGFR mutation status could be predictive for response to cytotoxic front-line chemotherapy in patients with NSCLC . Additional prospect i ve studies are needed in order to vali date this observation and to define whether these patients should be preferentially treated with front-line TKIs or chemotherapy PURPOSE The phase III , r and omized , placebo-controlled Sequential Tarceva in Unresectable NSCLC ( SATURN ; BO18192 ) study found that erlotinib maintenance therapy extended progression-free survival ( PFS ) and overall survival in patients with advanced non-small-cell lung cancer ( NSCLC ) who had nonprogressive disease following first-line platinum-doublet chemotherapy .  This study included prospect i ve analysis of the prognostic and predictive value of several biomarkers . PATIENTS AND METHODS M and atory diagnostic tumor specimens were collected before initiating first-line chemotherapy and were tested for epidermal growth factor receptor ( EGFR ) protein expression by using immunohistochemistry ( IHC ) , EGFR gene copy number by using fluorescent in situ hybridization ( FISH ) , and EGFR and KRAS mutations by using DNA sequencing . An EGFR CA simple sequence repeat in intron 1 ( CA-SSR1 ) polymorphism was evaluated in blood . RESULTS All 889 r and omly assigned patients provided tumor sample s.  EGFR IHC , EGFR FISH , KRAS mutation , and EGFR CA-SSR1 repeat length status were not predictive for erlotinib efficacy . A profound predictive effect on PFS of erlotinib relative to placebo was observed in the EGFR mutation-positive subgroup ( hazard ratio [ HR ] , 0.10 ; P < .001 ) . Significant PFS benefits were also observed with erlotinib in the wild-type EGFR subgroup ( HR , 0.78 ; P = .0185 ) . KRAS mutation status was a significant negative prognostic factor for PFS . CONCLUSION This large prospect i ve biomarker study found that patients with activating EGFR mutations derive the greatest PFS benefit from erlotinib maintenance therapy . No other biomarkers were predictive for outcomes with erlotinib , although the study was not powered for clinical outcomes in biomarker subgroups other than EGFR IHC-positive [ corrected ] . KRAS mutations were prognostic for reduced PFS . The study demonstrated the feasibility of prospect i ve tissue collection for biomarker analyses in NSCLC BACKGROUND Because there is no clear consensus as to the predictive value of K-ras gene mutation for survival in patients with lung cancer , we examined the occurrence of K-ras mutations in a large , prospect i ve case series of non-small-cell lung cancer ( NSCLC ) . Our goals were to define the patient characteristics associated with K-ras mutation and to determine whether mutation of this gene might be a biomarker of patient prognosis . METHODS Consecutive , newly diagnosed patients with lung cancer treated with potentially curative resection over a 4-year period were recruited for study . The mutation status of K-ras codon 12 in each patient 's tumor DNA was determined by means of polymerase chain reaction-restriction fragment length polymorphism analysis of archived pathology specimens . Analyses were restricted to adenocarcinoma . RESULTS There was a statistically significant association between female sex and K-ras mutation after adjustment for carcinogen exposures ( odds ratio = 3.3 ; 95 % confidence interval [ CI ] = 1.3 - 7.9 ) ; mutations were found only in smokers . Comparison of Kaplan-Meier curves indicated a strong association between K-ras mutation and decreased patient survival ( two-sided P = .009 ) ; analysis stratified by pathologic staging groups revealed that this association was statistically significant only for stage I tumors ( two-sided P = .002 ) . Cox proportional hazards modeling indicated that K-ras codon 12 mutation was a statistically significant predictor of patient survival , after adjustment for the effects of age , sex , and stage ( risk ratio = 1.8 ; 95 % CI = 1.1 - 3.1 ) . CONCLUSIONS After adjustment for environmental exposures , non-small-cell lung tumors in women appear to be more likely than those in men to harbor K-ras mutations , suggesting a possible role of estrogen exposure in either the initiation or the selection of K-ras mutant clones in adenocarcinoma . In addition , our data suggest that K-ras codon 12 mutation is a marker of aggressive NSCLC , as evidence d by its association with decreased patient survival , particularly for early-stage disease Background . The main attention regarding prognostic and predictive markers in NSCLC directs towards the EGFR-targeted pathway , where the most studied genetic alterations include EGFR mutations , EGFR copy number , and KRAS mutations . We wanted to explore the prognostic impact of mutated KRAS in the stage III setting treated with high-dose radiochemotherapy . Methods . Sample s were obtained from patients participating in two prospect i ve studies of locally advanced NSCLC receiving combined radiochemotherapy :  the RAKET study , a r and omized phase II study where patients were treated with induction chemotherapy ( carboplatin/paclitaxel ) followed by concurrent radiochemotherapy , and the Satellite trial , a phase II study with induction chemotherapy ( cisplatin/docetaxel ) followed by radiotherapy concurrent cetuximab . The sample s were analysed regarding KRAS mutations , EGFR mutations , and EGFR FISH positivity . Results . Patients with mutated KRAS had a significantly inferior survival , which maintained its significance in a multivariate analysis when other possible prognostic factors were taken into account . The prevalence of KRAS mutations , EGFR mutations , and EGFR FISH positivity were 28.8 % , 7.5 % , and 19.7 % , respectively . Conclusion . Mutated KRAS is an independent negative prognostic factor for survival in NSCLC stage III disease treated with combined radiochemotherapy . The prevalence of KRAS mutations and EGFR mutations are as expected in this Sc and inavian population Introduction : Relationships between clinical outcomes and epidermal growth factor receptor (EGFR)-related tumor markers were investigated in patients with advanced non-small cell lung cancer . Methods : Patients with stage IIIB/IV non-small cell lung cancer ( 0–2 prior regimens ) received erlotinib ( 150 mg PO per day ) .  Response and survival were evaluated , and tumor sample s were assessed by immunohistochemistry ( EGFR , phosphorylated mitogen-activated protein kinase , and phosphorylated AKT protein expression ) , fluorescence in situ hybridization ( FISH ; EGFR gene copy number ) , and DNA sequencing ( EGFR , KRAS gene mutations ) . Results : Among 311 patients , 8 % had a complete/partial response ; the disease control rate was 66 % . Median Overall survival ( OS ) was 6.1 months ; 1-year survival rate was 27.2 % . Two of 4 patients with EGFR mutations had tumor responses , versus 2/68 with wild-type EGFR ( p = 0.014 ) . Progression-free survival ( PFS ) ( HR = 0.31 ) and OS ( HR = 0.33 ) were significantly prolonged in patients with EGFR mutations . Response rate was significantly higher in patients with EGFR FISH-positive ( 17 % ) than FISH-negative tumors ( 6 % ) , and both PFS ( HR = 0.58 ) and OS ( HR = 0.63 ) significantly favored patients with EGFR FISH-positive tumors ; median OS was 8.6 months in the EGFR FISH-positive group . None of 17 patients with a KRAS mutation had a tumor response , but the impact of KRAS mutation status on survival outcomes was of borderline statistical significance . Neither phosphorylated mitogen-activated protein kinase nor phosphorylated AKT immunohistochemistry status had a significant effect on PFS and OS with erlotinib . Conclusions : The presence of EGFR mutations and EGFR FISH-positive tumors may predispose patients to achieving better outcomes on erlotinib , but may have a beneficial impact on prognosis ( irrespective of treatment ) . Prospect i ve , placebo-controlled studies are needed to determine the predictive value of the putative biomarkers A prospect i ve study was performed in patients with non-small cell lung cancer ( NSCLC ) to evaluate the prognostic importance of multiple molecular marker ( p53 , c-Ki-ras , c-erbB-2 ) testing . 103 patients with potentially curative resections ( RO resection ) for NSCLC in histopathological stages I – IIIA were included .  SSCP analysis and DNA sequencing for p53 and c-Ki-ras genes  were performed on paired tumour and normal lung tissue sample s and immunohistochemistry ( c-erbB-2 ) was done on frozen tissue sections with a specific anti-c-erbB-2 monoclonal antibody . 46/103 ( 44.6 % ) NSCLC showed p53 mutations and 17/103 ( 16.5 % ) c-Ki-ras mutations including 12/37 ( 32.4 % ) adenocarcinomas . Overexpression of c-erbB-2 ( p185 ) was detected in 56/103 ( 54.4 % ) tumours . 24/103 ( 23.3 % ) NSCLC were negative for alterations in all 3 parameters ( c-Ki-ras , p53 and p185 ) whereas 79/103 ( 76.7 % ) were positive for at least one of the 3 parameters . In a regression model including a multiple molecular marker parameter ( negative for all 3 markers versus positive for at least one marker ) , histopathological stage ( P < 0.00001 ) , respectively the pT ( P < 0.01 ) and pN ( P < 0.00001 ) categories and the multiple molecular marker parameter ( P < 0.01 ) were of significant prognostic importance . This study demonstrates that testing 3 molecular markers ( c-Ki-ras , p53 and c-erbB-2 ) improves estimation of prognosis compared to single marker testing and appears to define low ( 82.6 % ± 7.9 % 5-year survival ) and high risk ( 40.2 % ± 5.5 % 5-year survival ) groups for treatment failure in potentially curative ( RO ) resected NSCLC . © 2000 Cancer Research Introduction : Although mutation of the epidermal growth factor receptor ( EGFR ) gene is predictive for the response to EGFR-tyrosine kinase inhibitor , its prognostic impact for patients without EGFR-tyrosine kinase inhibitor treatment remains controversial . We examined for EGFR , KRAS or TP53 mutations in a consecutive large cohort of patients with lung adenocarcinoma , and evaluated their prognostic impact . Methods : We analyzed 397 patients with lung adenocarcinoma who underwent potentially curative pulmonary resection . Total ribonucleic acid was extracted and direct sequencing of each gene was performed after reverse transcription-polymerase chain reaction . Results : We found that 196 patients ( 49 % ) had EGFR mutations . Of these , 83 were exon 19 deletions ( 42 % ) and 92 were L858R ( 47 % ) . Univariate analysis showed that patients with EGFR mutations survived for a longer period than those without mutations ( p = 0.0046 ) . However , there was no difference in overall survival between the patients with exon 19 deletion and those with L858R ( p = 0.4144 ) . Patients with KRAS mutations or TP53 mutations tended to survive for a shorter period ( p = 0.2183 and 0.0230 , respectively ) . Multivariate analysis using the Cox proportional hazards model revealed that smoking status ( p = 
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In conclusion , this meta- analysis suggests that K-RAS mutations are associated with a worse overall survival in patients with NSCLC , especially in patients with adenocarcinoma and early stage