***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 : Tumor genotyping using cell-free plasma DNA ( cfDNA ) has the potential to allow noninvasive assessment of tumor biology , yet many existing assays are cumbersome and vulnerable to false-positive results . We sought to determine whether droplet digital PCR ( ddPCR ) of cfDNA would allow highly specific and quantitative assessment of tumor genotype . Experimental Design : ddPCR assays for EGFR , KRAS , and BRAF mutations were developed using plasma collected from patients with advanced lung cancer or melanoma of a known tumor genotype . Sensitivity and specificity were determined using cancers with nonoverlapping genotypes as positive and negative controls . Serial assessment of response and resistance was studied in patients with EGFR-mutant lung cancer on a prospect i ve trial of erlotinib . Results : We identified a reference range for EGFR L858R and exon 19 deletions in specimens from KRAS-mutant lung cancer , allowing identification of c and i date thresholds with high sensitivity and 100 % specificity . Received operative characteristic curve analysis of four assays demonstrated an area under the curve in the range of 0.80 to 0.94 . Sensitivity improved in specimens with optimal cfDNA concentrations . Serial plasma genotyping of EGFR-mutant lung cancer on erlotinib demonstrated pretreatment detection of EGFR mutations , complete plasma response in most cases , and increasing levels of EGFR T790 M emerging before objective progression . Conclusions : Noninvasive genotyping of cfDNA using ddPCR demonstrates assay qualities that could allow effective translation into a clinical diagnostic . Serial quantification of plasma genotype allows noninvasive assessment of response and resistance , including detection of resistance mutations up to 16 weeks before radiographic progression . Clin Cancer Res ; 20(6 ) ; 1698–705 . © 2014 AACR Background Circulating cell-free DNA ( cfDNA ) is emerging as a surrogate sample type for mutation analyses . To improve the clinical utility of cfDNA , we developed a sensitive peptide nucleic acid (PNA)-based method for analyzing EGFR and KRAS mutations in the plasma cfDNA of patients with advanced non-small cell lung cancer ( NSCLC ) . Methods Baseline tissue and plasma sample s were collected from treatment-naïve advanced NSCLC patients participated in a r and omized phase II study , which was registered with Clinical Trials.gov at Feb. 2009 ( NCT01003964 ) . EGFR and KRAS mutations in the plasma cfDNA were analyzed retrospectively using a PNA clamping-assisted fluorescence melting curve analysis . The results were compared with those obtained from tissue analysis performed using the direct sequencing . Exploratory analyses were performed to determine survival predicted by the plasma and tissue mutation status . Results Mutation analyses in matched tissue and plasma sample s were available for 194 patients for EGFR and 135 patients for KRAS . The mutation concordance rates were 82.0 % ( 95 % confidence interval [ CI ] , 76.5–87.4 ) for EGFR and 85.9 % ( 95 % CI , 80.1–91.8 ) for KRAS . The plasma EGFR mutation test sensitivity and specificity were 66.7 % ( 95 % CI , 60.0–73.3 ) and 87.4 % ( 95 % CI , 82.7–92.1 ) , respectively , and the plasma KRAS mutation test sensitivity and specificity were 50.0 % ( 95 % CI , 41.6–58.4 ) and 89.4 % ( 95 % CI , 84.2–94.6 ) , respectively . The predictive value of the plasma EGFR and KRAS mutation status with respect to survival was comparable with that of the tissue mutation status . Conclusions These data suggest that plasma EGFR and KRAS mutations can be analyzed using PNA-based real-time PCR methods and used as an alternative to tumor genotyping for NSCLC patients when tumor tissue is not available Non-small cell lung cancer ( NSCLC ) is one of the most common malignant tumours in the western world and is associated with a poor prognosis . Biomarkers predicting prognosis and therapeutic effects are highly required , and cell-free DNA ( cfDNA ) may be a feasible option . Genetic mutations can be analysed in plasma and may increase the scientific use of such measurements . In the present study , we investigated : i ) the dynamics of cfDNA and plasma mutated KRAS ( pmKRAS ) during the treatment of patients with advanced NSCLC ; and ii ) the prognostic value of baseline cfDNA and pmKRAS . Sixty‑nine patients were included in a prospect i ve biomarker trial . Inclusion criteria included advanced NSCLC , c and i date for first-line treatment , no previous cancer within the five years prior to this study . Blood sample s were drawn at baseline , day 8 and at progression . Analyses of cfDNA and KRAS mutations in plasma were performed using an in-house qPCR assay . Evaluation of the treatment effect and status at follow-up was performed according to RECIST 1.1 . The median levels of cfDNA were significantly higher at progression ( 9,250 alleles/ml ) than at baseline ( 5,450 alleles/ml ) . Overall survival and progression-free survival were both significantly shorter in patients with high levels of cfDNA ( above the 75th percentile ) compared to lower levels . Only few patients harboured KRAS mutations in plasma . Two patients had no KRAS mutations in plasma at baseline , but mutations appeared in the subsequent blood sample s. High baseline levels of cfDNA indicate a poor prognosis . The level changes during the treatment course with a significant increase at progression , suggesting a possible predictive value of cfDNA . The plasma KRAS status may change during treatment with potential implication s for treatment selection Pancreatic ductal adenocarcinoma ( PDAC ) remains one of the most lethal malignancies . The genomic l and scape of the PDAC genome features four frequently mutated genes ( KRAS , CDKN2A , TP53 , and SMAD4 ) and dozens of c and i date driver genes altered at low frequency , including potential clinical targets . Circulating cell-free DNA ( cfDNA ) is a promising re source to detect and monitor molecular characteristics of tumors . In the present study , we determined the mutational status of KRAS in plasma cfDNA using multiplex picoliter-droplet digital PCR in 259 patients with PDAC . We constructed a novel modified SureSelect-KAPA-Illumina platform and an original panel of 60 genes . We then performed targeted deep sequencing of cfDNA and matched germline DNA sample s in 48 patients who had ≥1 % mutant allele frequencies of KRAS in plasma cfDNA . Importantly , potentially targetable somatic mutations were identified in 14 of 48 patients ( 29.2 % ) examined by targeted deep sequencing of cfDNA . We also analyzed somatic copy number alterations based on the targeted sequencing data using our in-house algorithm , and potentially targetable amplifications were detected . Assessment of mutations and copy number alterations in plasma cfDNA may provide a prognostic and diagnostic tool to assist decisions regarding optimal therapeutic strategies for PDAC patients BACKGROUND Lung cancer is one of the most common malignant diseases worldwide and associated with considerable morbidity and mortality . New agents targeting the epidermal growth factor system are emerging , but only a subgroup of the patients will benefit from the therapy . Cell free DNA ( cfDNA ) in the blood allows for tumour specific analyses , including KRAS-mutations , and the aim of the study was to investigate the possible prognostic value of plasma mutated KRAS ( pmKRAS ) in patients with non-small cell lung cancer ( NSCLC ) . MATERIAL AND METHODS Patients with newly diagnosed , advanced NSCLC eligible for chemotherapy were enrolled in a prospect i ve biomarker trial . A pre-treatment blood sample was drawn and subsequently DNA was extracted and pmKRAS analysed . The patients received carboplatin ( AUC5 ) i.v . day 1 and vinorelbine ( 30mg/m(2 ) i.v . day 1 and 60mg/m(2 ) p.o . day 8) for a maximum of six cycles . Response to chemotherapy  was evaluated according to RECIST v.1.0 by CT scans of the chest and upper abdomen . The presence of pmKRAS at baseline was assessed by an in-house qPCR method . The primary endpoint was overall survival ( OS ) . Secondary end-points were progression free survival ( PFS ) and overall response rate . RESULTS The study included 246 patients receiving a minimum of 1 treatment cycle , and all but four were evaluable for response according to RECIST . Forty-three patients ( 17.5 % ) presented with a KRAS mutation . OS was 8.9 months and PFS by intention to treat 5.4 months . Patients with a detectable plasma-KRAS mutation had a significantly shorter OS and PFS compared to the wild type ( WT ) patients ( median OS 4.8 months versus 9.5 months , HR 1.87 , 95 % CI 1.23 - 2.84 , p=0.0002 and median PFS 3.0 months versus 5.6 months , HR 1.60 , 95 % CI 1.09 - 2.37 , p=0.0043 ) . A multivariate Cox regression analysis confirmed the independent prognostic value of pmKRAS in OS but not in PFS . The response rate to chemotherapy was significantly lower in the group of patients with a mutation compared to WT ( p<0.0001 ) . CONCLUSION The presence of KRAS mutations in plasma may be a marker of poor prognosis and may also hold predictive value . Further validation in an independent cohort is highly needed Purpose : Non – small cell lung cancer ( NSCLC ) with KRAS mutation may be resistant to epidermal growth factor receptor tyrosine kinase inhibitors ( EGFR-TKI ) . This study aims to evaluate a plasma-based KRAS mutation analysis and the clinical significance of plasma KRAS mutation as a predictive marker for tumor resistance to EGFR-TKIs in patients with NSCLC . Experimental Design : DNA extracted from plasma and matched tumor tissues were obtained from 273 patients with advanced stage NSCLC . Patients were followed up prospect ively for treatment outcomes . KRAS mutations in codon 12 and 13 were detected using PCR-restriction fragment length polymorphism .  Mutations in plasma and matched tumors were compared . Associations between KRAS mutation status and patients ' clinical outcomes were analyzed . Results : KRAS mutation was found in 35 ( 12.8 % ) plasma sample s and 30 ( 11.0 % ) matched tumor tissues . The consistency of KRAS mutations between plasma and tumors is 76.7 % ( 23 of 30 ; κ = 0.668 ; P < 0.001 ) . Among 120 patients who received EGFR-TKI treatment , the  response rate  was only 5.3 % ( 1 of 19 ) for patients with plasma KRAS mutation compared with 29.7 % for patients with no KRAS mutation in plasma DNA ( P = 0.024 ) . The median progression-free survival time of patients with plasma KRAS mutation was 2.5 months compared with 8.8 months for patients with wild-type KRAS ( P < 0.001 ) . Conclusions : KRAS mutation in plasma DNA correlates with the mutation status in the matched tumor tissues of patients with NSCLC . Plasma KRAS mutation status is associated with a poor tumor response to EGFR-TKIs in NSCLC patients and may be used as a predictive marker in selecting patients for such treatment . Clin Cancer Res ; 16(4 ) ; Noninvasive mutation tracking in plasma can detect circulating tumor DNA arising from residual micrometastatic disease and thus identify patients at high risk of recurrence . Risk of recurrence Predicting whether a cancer patient will relapse remains a formidable challenge in modern medicine . Fortunately , circulating tumor DNA ( ctDNA ) present in the blood may give clues on residual disease — cancer cells left behind to seed new tumors even after treatment . Garcia-Murillas et al. developed a personalized ctDNA assay based on digital polymerase chain reaction to track mutations over time in patients with early-stage breast cancer who had received apparently curative treatments , surgery , and chemotherapy . Mutation tracking in serial sample s accurately predicted metastatic relapse — in several instances , months before clinical relapse ( median of ~8 months ) . Such unprecedented early prediction could allow for intervention before the reappearance of cancer in high-risk patients . In addition , the authors were able to shed light on the genetic events driving such metastases , by massively parallel sequencing of the ctDNA , which could inform new drug-based therapies on the basis of the patients ’ individual mutations . The identification of early-stage breast cancer patients at high risk of relapse would allow tailoring of adjuvant therapy approaches . We assessed whether analysis of circulating tumor DNA ( ctDNA ) in plasma can be used to monitor for minimal residual disease ( MRD ) in breast cancer . In a prospect i ve cohort of 55 early breast cancer patients receiving neoadjuvant chemotherapy  , detection of ctDNA in plasma after completion of apparently curative treatment — either at a single postsurgical time point or with serial follow-up plasma 
    Output:
    
Briefly , KRAS mutation in cfDNA was a survival prognostic biomarker in cancer patients .
Its prognostic value was different in various types of cancer