***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: There is an increasing dem and for accurate prognostication for colorectal cancer ( CRC ) . This study sought to assess prognostic potentials of methylation targets in the serum of CRC patients . A total of 165 CRC patients were enrolled in this prospect i ve study . Promoter methylation levels of seven genes in pre-operative sera and matched tumor tissues were evaluated by quantitative methylation-specific PCR . Kaplan-Meier test , and univariate and multivariate Cox proportional hazards regression models were used for survival analyses . After a median follow-up of 56 months , 43 patients ( 28.7 % ) experienced tumor recurrence . In univariate survival analyses , serum methylation levels of SST and MAL were significantly predictive of cancer-specific death ( P<0.005 for both ) . The former was also a significant predictor for tumor recurrence ( P=0.007 ) . Independent prognostic effects of serum methylation levels of SST were revealed by multivariate Cox regression model ( P=0.031 and P=0.003 for cancer death and recurrence , respectively ) . When focusing on stage II and III patients , prognostication with serum methylated SST remained significant . Methylated SST detected in all serum sample s can be traced back to the matched primary tumor tissues . We believe that methylated SST detected in the pre-operative sera of CRC patients appear to be a novel promising prognostic marker and probably can be auxiliary to tumor staging system and serum carcinoembryonic antigen towards better risk stratification Background Regorafenib , a multi-kinase inhibitor , is used in the treatment of patients with metastatic colorectal cancer refractory to st and ard therapy . However , this benefit was limited to 1.4 months improvement in overall survival , with more than half of patients experiencing grade 3 to 4 adverse events . We aim to eluci date the pharmacodynamic effects of regorafenib in metastatic colorectal cancer and discover potential biomarkers that may predict clinical benefit . Methods Patients with metastatic colorectal adenocarcinoma refractory to st and ard therapy with tumours amenable to biopsy were eligible for the study .  Regorafenib was administered orally at 160 mg daily for 3 out of 4 weeks with tumour assessment every 2 cycles .  Metabolic response was assessed by FDG PET-CT scans ( pre-treatment and day 15 ) ; paired tumour biopsies ( pre-treatment and day 21 post-treatment ) were sample d for immunohistochemistry and proteomic profiling analyses . Plasma circulating cell free DNA was quantified serially before and after treatment . Results There were 2(6 % ) partial responses out of 35 patients , and 8(23 % ) patients had stable disease for more than 7 months . Adverse event profile was similar to reported data . Recurrent somatic mutations in K-RAS , PIK3CA and BRAF were detected in plasma circulating cell free DNA in 14 patients ; some mutations were not found in archival tumour . Total plasma circulating cell free DNA inversely correlated with progression free survival ( PFS ) , and presence of KRAS mutations associated with shorter PFS . Immunohistochemistry of pre- and post- treatment biopsies showed majority of patients had downregulation of phosphorylated-VEGFR2 , podoplanin , phosphorylated-AKT , Ki-67 and upregulation of the MEK-ERK axis , phosphorylated-C-MET , phosphorylated-SRC , phosphorylated-STAT3 and phosphorylated-JUN . Proteomic analysis of fine needle tumour aspirates showed down-regulation of PI3 K was associated with longer PFS . Conclusion Plasma circulating cell free DNA may yield potential predictive biomarkers of regorafenib treatment . Downregulation of the PI3K-AKT axis may be an important predictor of clinical benefit Purpose : Blood-based circulating-free ( cf ) tumor DNA may be an alternative to tissue-based EGFR mutation testing in NSCLC . This exploratory analysis compares matched tumor and blood sample s from the FASTACT-2 study . Experimental Design : Patients were r and omized to receive six cycles of gemcitabine/platinum plus sequential erlotinib or placebo .  EGFR mutation testing was performed using the cobas tissue test and the cobas blood test ( in development ) . Blood sample s at baseline , cycle 3 , and progression were assessed for blood test detection rate , sensitivity , and specificity ; concordance with matched tumor analysis ( n = 238 ) , and correlation with progression-free survival ( PFS ) and overall survival ( OS ) . Results : Concordance between tissue and blood tests was 88 % , with blood test sensitivity of 75 % and a specificity of 96 % . Median PFS was 13.1 versus 6.0 months for erlotinib and placebo , respectively , for those with baseline EGFR mut+ cfDNA [ HR , 0.22 ; 95 % confidence intervals ( CI ) , 0.14–0.33 , P < 0.0001 ] and 6.2 versus 6.1 months , respectively , for the EGFR mut− cfDNA subgroup ( HR , 0.83 ; 95 % CI , 0.65–1.04 , P = 0.1076 ) . For patients with EGFR mut+ cfDNA at baseline  , median PFS was 7.2 versus 12.0 months for cycle 3 EGFR mut+ cfDNA versus cycle 3 EGFR mut− patients , respectively ( HR , 0.32 ; 95 % CI , 0.21–0.48 , P < 0.0001 ) ; median OS by cycle 3 status was 18.2 and 31.9 months , respectively ( HR , 0.51 ; 95 % CI , 0.31–0.84 , P = 0.0066 ) . Conclusions : Blood-based EGFR mutation analysis is relatively sensitive and highly specific . Dynamic changes in cfDNA EGFR mutation status relative to baseline may predict clinical outcomes . Clin Cancer Res ; 21(14 ) ; 3196–203 . © 2015 AACR BACKGROUND Despite the improvement in detection and surgical therapy in the last years , the outcome of patients affected by colorectal carcinoma ( CRC ) remains limited by metastatic relapse . The aim of this study was to investigate the presence of free tumor DNA in the plasma of CRC patients in order to underst and its possible prognostic role . PATIENTS AND METHODS  Ki-Ras , TP53 mutations and p16(INK4A ) methylation status were prospect ively evaluated in tumor tissues and plasma of 66 CRC patients . RESULTS In 50 of the 66 primitive tumor cases ( 76 % ) at least one significant alteration was identified in Ki-Ras and /or TP53 and /or p16(INK4A ) genes .  Eighteen of the 50 patients presented the same alteration both in the plasma and in the tumor tissue . At univariate analysis , Ki-Ras mutations proved to be significantly related to quicker relapse ( P < 0.01 ) , whereas only a trend towards statistical significance ( P = 0.083 ) was observed for the TP53 mutations CONCLUSIONS Detection of Ki-Ras and TP53 mutation in plasma should be significantly related to disease recurrence . These data suggest that patients with a high risk of recurrence  can be identified by means of the analysis of tumor-derived plasma DNA with the use of fairly non-invasive techniques DNA hypermethylation is frequently found in colorectal cancer ( CRC ) . Methylation of helicase-like transcription factor ( HLTF ) and hyperplastic polyposis 1 ( HPP1 ) are potential and carcinoembryonic antigen ( CEA ) is an established prognostic factor in serum of patients with CRC . The aim of this study was to perform a direct comparison of the prognostic roles of these markers . Methylation status of HLTF and HPP1 was examined in pretherapeutic sera of 311 patients with CRC and matched primary tissues of 54 stage IV patients using methylation-specific quantitative PCR .  CEA  was determined using an immunoenzymometric assay . Methylation of HLTF and HPP1 DNA in serum significantly correlated with tumor size , stage , grade and metastatic disease . HPP1 methylation correlated with nodal status . Overall survival was shortened in case of methylation of HLTF or HPP1 or elevated levels of CEA ( p < 0.0001 for all ) . In stage IV , patients survival was impaired if HLTF ( p = 0.0005 ) or HPP1 ( p = 0.0003 ) were methylated or CEA was above the median of 27 ng/ml ( p = 0.002 ) . Multivariate analysis revealed that methylation of HLTF [ hazard ratio ( HR ) 1.8 , p = 0.0438 ] , HPP1 ( HR 1.6 , p = 0.0495 ) and CEA > 27 ng/ml ( HR 1.7 , p = 0.0317 ) were independent prognostic factors in stage IV . The combination of any two or all three of these factors outperformed each marker on its own . In conclusion , the presence of methylated DNA of the genes HLTF or HPP1 in serum are independent prognostic factors in metastasized CRC . Prospect i ve validation is required to determine their usefulness in clinical routine along with the established marker CEA OBJECTIVES : While promoter hypermethylation is a common molecular alteration of human colorectal cancer that could be detected in the bloodstream , we tested the feasibility of quantitative detection of aberrant DNA methylation in multiple genes in the serum sample s of colorectal cancer patients . METHODS : The  pre-therapeutic serum sample s  of 49 colorectal cancer patients and 41 age-matched controls with normal colonoscopy were examined . The presence of methylated DNA in APC ( adenomatous polyposis coli ) , hMLH1 ( human MutL homolog 1 ) , and HLTF ( helicase-like transcription factor ) was detected by quantitative methylation-specific PCR ( MethyLight ) . RESULTS : There was a significant difference in the concentration of methylated serum DNA between cancer patients and controls for HLTF ( p = 0.015 ) and hMLH1 ( p = 0.0001 ) genes , but not for APC gene ( p = 0.21 ) . In total , 28 patients with colorectal cancer and 4 controls had methylated DNA detected in at least one marker , which gave a sensitivity of 57 % and specificity of 90 % . All patients with methylation in two methylation markers had advanced ( stage III/IV ) cancer ( p = 0.006 ) and patients with methylation in at least one marker tended to have a lower probability of survival ( p = 0.08 ) . CONCLUSION : The quantitative detection of aberrant DNA methylation in serum may be a promising high-throughput approach for the noninvasive screening and monitoring of colorectal cancer Detection of circulating tumor DNA in patients with resected stage II colon cancer provides evidence of residual disease . Footprints of persistent cancer Stage II colon cancer , which has spread through the wall of the colon but has not metastasized to the lymph nodes , can present a therapeutic dilemma . On one h and , these tumors can usually be completely removed by surgery , and the majority does not recur even without chemotherapy . On the other h and , it is difficult to determine which of these tumors will recur and to identify patients who would benefit from adjuvant chemotherapy after surgery . Tie et al. show that the presence of circulating tumor DNA in a patient ’s blood after surgery is a sign of persistent tumor and a greatly increased risk of relapse , suggesting that this group of patients may require chemotherapy to prevent recurrence . Detection of circulating tumor DNA  ( ctDNA ) after resection of stage II colon cancer may identify patients at the highest risk of recurrence and help inform adjuvant treatment decisions . We used massively parallel sequencing – based assays to evaluate the ability of ctDNA to detect minimal residual disease in 1046 plasma sample s from a prospect i ve cohort of 230 patients with resected stage II colon cancer . In patients not treated with adjuvant chemotherapy , ctDNA was detected postoperatively in 14 of 178 ( 7.9 % ) patients , 11 ( 79 % ) of whom had recurred at a median follow-up of 27 months ; recurrence occurred in only 16 ( 9.8 % ) of 164 patients with negative ctDNA [ hazard ratio ( HR ) , 18 ; 95 % confidence interval ( CI ) , 7.9 to 40 ; P < 0.001 ] . In patients treated with chemotherapy  , the presence of ctDNA after completion of chemotherapy was also associated with an inferior recurrence-free survival ( HR , 11 ; 95 % CI , 1.8 to 68 ; P = 0.001 ) . ctDNA detection after stage II colon cancer resection provides direct evidence of residual disease and identifies patients at very high risk of recurrence Assessment of KRAS status is m and atory in patients with metastatic colorectal cancer ( mCRC ) before applying targeted therapy . We describe here a blinded prospect i 
    Output:
    
This analysis provides evidence that ctDNA may be a prognostic biomarker , negatively correlated with the survival of patients with colorectal cancer