***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 Lung cancer patients with mutations in the epidermal growth factor receptor ( EGFR ) are primary c and i date s for EGFR-targeted therapy . Reliable analyses of such mutations have previously been possible only in tumour tissue . Here , we demonstrate that mutations can be detected in plasma sample s with allele-specific PCR assays . Methods Pairs of the diagnostic biopsy and plasma obtained just prior to start of erlotinib treatment were collected from 199 patients with adenocarcinoma of non-small-cell lung cancer . DNA from both sample types was isolated and examined for the presence of mutations in exons 18–21 of the EGFR gene , employing the cobas ® EGFR Tissue Test and cobas ® EGFR Blood Test ( in development , Roche Molecular Systems , Inc. , CA , USA ) . Results Test results were obtained in all 199 ( 100 % ) plasma sample s and 196/199 ( 98 % ) of the biopsies . EGFR-activating mutations were identified in 24/199 ( 12 % ) plasma sample s and 28/196 ( 14 % ) biopsy sample s , and 17/196 ( 9 % ) matched pairs contained the same mutation . Six EGFR mutations were present only in plasma sample s but not in the biopsy sample s. The overall concordance of the EGFR gene mutations detected in plasma and biopsy tissue was 179/196 ( 91 % ) ( kappa value : 0.621 ) . Conclusion Mutational analysis of the EGFR gene in plasma sample s is feasible with allele-specific PCR assays and represents a non-invasive supplement to biopsy analysis .Trial registration M-20080012 from March 10 , 2008 and reported to Clinical Trials.gov : NCT00815971 Cases of non – small-cell lung cancer ( NSCLC ) carrying the somatic mutation of epidermal growth factor receptor ( EGFR ) have been shown to be hyperresponsive to the EGFR tyrosine kinase inhibitor gefitinib ( IRESSA ) . If EGFR mutations can be observed in serum DNA , this could serve as a noninvasive source of information on the genotype of the original tumor cells that could influence treatment and the ability to predict patient response to gefitinib .  Serum genomic DNA was obtained from Japanese patients with NSCLC before first-line gefitinib monotherapy . Scorpion Amplified Refractory Mutation System technology was used to detect EGFR mutations . Wild-type EGFR was detected in all of the 27 serum sample s. EGFR mutations were detected in 13 of 27 ( 48.1 % ) patients and two major EGFR mutations were identified ( E746_A750del and L858R ) . The EGFR mutations were seen significantly more frequently in patients with a partial response than in patients with stable disease or progressive disease ( P = 0.046 , Fisher 's exact test ) . The median progression-free survival was significantly longer in patients with EGFR mutations than in patients without EGFR mutations ( 200 versus 46 days ; P = 0.005 , log-rank test ) . The median survival was 611 days in patients with EGFR mutations and 232 days in patients without EGFR mutations ( P > 0.05 ) . In pairs of tumor and serum sample s obtained from 11 patients , the EGFR mutation status in the tumors was consistent with those in the serum of 8 of 11 ( 72.7 % ) of the paired sample s. Thus , EGFR mutations were detectable using Scorpion Amplified Refractory Mutation System technology in serum DNA from patients with NSCLC . These results suggest that patients with EGFR mutations seem to have better outcomes with gefitinib treatment , in terms of progression-free survival , overall survival , and response , than those patients without EGFR mutations Introduction : In IPASS ( IRESSA Pan-Asia Study ) , clinical ly selected patients with pulmonary adenocarcinoma received first-line gefitinib or carboplatin/paclitaxel . This preplanned , exploratory analysis was conducted to increase underst and ing of the use of surrogate sample s , such as serum , versus tumor biopsy sample s for determining EGFR mutation status in the Japanese cohort ( n = 233 ) . Methods : EGFR mutations were assessed using tumor tissue-derived DNA ( n = 91 ) and circulating free ( cf ) DNA from pretreatment serum sample s ( n = 194 ) . Results : Fewer patients were  EGFR mutation positive when assessed using pretreatment cfDNA ( 23.7 % ) versus tumor tissue-derived DNA ( 61.5 % ) . cfDNA results identified no false positives but a high rate of false negatives ( 56.9 % ) . There was a significant interaction between cfDNA EGFR mutation status and treatment for progression-free survival ( PFS ) ( p = 0.045 ) . PFS was significantly longer and objective response rate ( ORR ) higher with gefitinib than carboplatin/paclitaxel in the cfDNA EGFR mutation-positive subgroup ( PFS : hazard ratio [ HR ] , 0.29 ; 95 % confidence interval [ CI ] , 0.14–0.60 ; p < 0.001 ; ORR : odds ratio [ OR ] , 1.71 ; 95 % CI , 0.48–6.09 ; 75.0 % versus 63.6 % ; p = 0.40 ) . There was a slight numerical advantage in PFS and ORR for gefitinib over carboplatin/paclitaxel in the cfDNA EGFR mutation-negative subgroup , likely due to the high rate of false negatives within this subgroup . Conclusions : These results merit further investigation to determine whether alternative sources of tumor DNA , such as cfDNA in serum , could be used for determining EGFR mutation status in future ; currently , where a sample is available , analysis of tumor material is recommended PURPOSE Mutations in the epidermal growth factor receptor ( EGFR ) kinase domain can predict tumor response to tyrosine kinase inhibitors ( TKIs ) in non-small-cell lung cancer ( NSCLC ) . However , obtaining tumor tissues for mutation analysis is challenging . We hypothesized that plasma-based EGFR mutation analysis is feasible and has value in predicting tumor response in patients with NSCLC . PATIENTS AND METHODS Plasma DNA sample s and matched tumors from 230 patients with stages IIIB to IV NSCLC were analyzed for EGFR mutations in exons 19 and 21 by using denaturing high-performance liquid chromatography . We compared the mutations in the plasma sample s and the matched tumors and determined an association between EGFR mutation status and the patients ' clinical outcomes prospect ively . RESULTS In 230 patients , we detected 81 EGFR mutations  in 79 ( 34.3 % ) of the patients ' plasma sample s. We detected the same mutations in 63 ( 79.7 % ) of the matched tumors . Sixteen plasma ( 7.0 % ) and fourteen tumor ( 6.1 % ) sample s showed unique mutations . The mutation frequencies were significantly higher in never-smokers and in patients with adenocarcinomas ( P = .012 and P = .009 , respectively ) . In the 102 patients who failed platinum-based treatment and who were treated with gefitinib  , 22 ( 59.5 % ) of the 37 with EGFR mutations in the plasma sample s , whereas only 15 ( 23.1 % ) of the 65 without EGFR mutations , achieved an objective response ( P = .002 ) . Patients with EGFR mutations had a significantly longer progression-free survival time than those without mutations ( P = .044 ) in plasma . CONCLUSION EGFR mutations can be reliably detected in plasma DNA of patients with stages IIIB to IV NSCLC and can be used as a biomarker to predict tumor response to TKIs Background : The authors evaluate the efficacy and safety of gefitinib monotherapy in chemotherapy-naive patients with advanced non – small-cell lung cancer ( NSCLC ) . A secondary endpoint is to evaluate the relationship between clinical manifestations and epidermal growth factor receptor ( EGFR ) mutation status . Methods : Japanese chemotherapy-naive NSCLC patients were enrolled . They had measurable lesions , Eastern Cooperative Oncology Group performance status of 0 to 2 , and adequate organ and bone marrow function . Patients received 250 mg of oral gefitinib daily . EGFR mutations in exon 18 , 19 , and 21 of DNA extracted from tumor and serum were analyzed by genomic polymerase chain reaction and direct sequence . Results : All 30 patients were eligible for the assessment of efficacy and safety . An objective response and stable disease were observed in 10 patients ( 33.3 % ) and nine patients ( 30.0 % ) , respectively . The median time to progression was 3.3 months and the median overall survival was 10.6 months . The 1-year survival rate was 43.3 % . Grade 3 toxicities were observed in seven patients . EGFR mutation was observed in four of 13 ( 30.8 % ) tumors , and two of them achieved partial response . In serum sample s , three of 10 patients with EGFR mutations in the serum before treatment had a response to gefitinib .  EGFR mutation was observed in 10 of 27 and significantly more frequently observed in the posttreatment sample s from patients with a partial response or stable disease than in those from patients with progressive disease ( p = 0.006 ) . Conclusions : Gefitinib monotherapy in chemotherapy-naive NSCLC patients was active , with acceptable toxicities . These results warrant further evaluation of gefitinib monotherapy as a first-line therapy . The EGFR mutation in serum DNA may be a biomarker for monitoring the response to gefitinib during treatment 
    Output:
    
Conclusions : Although blood had a better specificity for detecting EGFR mutations , the absence of blood positivity should not necessarily be construed as confirmed negativity .