***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 Polychemotherapy and biological drugs have increased therapeutic options and outcomes of advanced colorectal cancer ( CRC ) . We examined the relation between progression-free survival ( PFS ) , post-progression survival ( PPS ) and overall survival ( OS ) in trials of  modern ( oxaliplatin- and irinotecan-based ) chemotherapy alone or with targeted therapies for advanced CRC . We also evaluated surrogacy of PFS and OS . PATIENTS AND METHODS A PubMed search identified 34 r and omized trials . We split the OS , PFS and PPS and evaluated the correlation between OS and either PFS or PPS . RESULTS The median PPS and PFS were 10.75 and 8.4 months , respectively . For all trials , PPS was strongly associated with OS [ regression coefficient (R2)=0.8 ; Spearman 's rank correlation coefficient (r)=0.88 ] , whereas PFS was moderately associated with OS (R2)=0.43 ; r=0.64 ) . In trials with targeted therapies , the correlation of PPS with OS was 0.88 . However , across all trials , correlation between differences in median PFS ( ΔPFS ) and median OS ( ΔOS ) is 0.59 ( P=0.0007 ) , confirming PFS/OS surrogacy . CONCLUSION Our findings indicate that in recent first-line , phase III , trials , OS becomes more associated with PPS than PFS . However , improvements in PFS are strongly associated with improvements in OS . In this setting so , PFS may be an appropriate surrogate for OS PURPOSE Mutations affecting the KRAS gene are established predictive markers of outcome with anti-epithelial growth factor receptor ( EGFR ) antibodies in advanced colorectal cancer ( CRC ) . The relevance of these markers for anti-vascular endothelial growth factor ( VEGF ) therapy is controversial . This analysis was performed to assess the predictive and prognostic impact of KRAS and BRAF gene mutation status in patients receiving capecitabine with bevacizumab ( CG ) or capecitabine without bevacizumab in the phase III AGITG MAX ( Australasian Gastrointestinal Trials Group MAX ) study . PATIENTS AND METHODS Mutation status was determined for 315 ( 66.9 % ) of the original 471 patients . Mutation status was correlated with efficacy outcomes ( response rate , progression-free survival [ PFS ] , and overall survival [ OS ] ) , and a predictive analyses was undertaken . RESULTS Mutations in KRAS and BRAF genes were observed in 28.8 % and 10.6 % of patients , respectively . KRAS gene mutation status ( wild type [ WT ] v mutated [ MT ] ) had no prognostic impact for PFS ( hazard ratio [ HR ] , 0.89 ; CI , 0.69 to 1.14 ) or OS ( HR , 0.97 ; CI , 0.73 to 1.28 ) . BRAF mutation status ( WT v MT ) was not prognostic for PFS ( HR , 0.80 ; CI , 0.54 to 1.18 ) but was prognostic for OS ( HR , 0.49 ; CI , 0.33 to 0.73 ; P = .001 ) . By using the comparison of capecitabine versus capecitabine and bevacizumab ( CB ) and CB plus mitomycin ( CBM ) , KRAS gene mutation status was not predictive of the effectiveness of  bevacizumab for PFS or OS ( test for interaction P = .95 and 0.43 , respectively ) . Similarly , BRAF gene mutation status was not predictive of the effectiveness of bevacizumab for PFS or OS ( test for interaction P = .46 and 0.32 , respectively ) . CONCLUSION KRAS gene mutation status was neither prognostic for OS nor predictive of bevacizumab outcome in patients with advanced CRC . BRAF gene mutation status was prognostic for OS but was not predictive of outcome with bevacizumab We assessed Ki-ras mutations by single-str and conformation polymorphism followed by DNA sequencing , p53 expression by immunohistochemistry , ploidy status , and S-phase fraction in 66 stage II and 163 stage III colon cancer patients enrolled on a r and omized trial of surgery followed by observation or adjuvant levamisole or 5-fluorouracil ( 5FU ) plus levamisole ( Intergroup Trial 0035 ) to see whether these factors were independently associated with survival or with differential effects of adjuvant therapy . A Cox proportional hazards survival model was used to describe marker effects and therapy by marker interactions , with adjustment for the clinical covariates affecting survival . A Bonferroni adjustment was used to account for multiple testing . Mutation of the Ki-ras gene was found in 41 % of the cancers and was associated with a poor prognosis in stage II but not stage III . In stage II , 7-year survival was 86 % versus 58 % in those with wild type versus Ki-ras mutations . After adjustment for treatment and clinical variables , the hazard ratio ( HR ) for death was 4.5 ; 95 % confidence interval ( CI ) , 1.7 - 12.1 ( P = 0.012 ) . p53 overexpression was found in 63 % of cancers and was associated with a favorable survival in stage III but not stage II . Seven-year survival in stage III was 56 % with p53 overexpression versus 43 % with no p53 expression ( HR , 2.2 ; 95 % CI , 1.3 - 3.6 ; P = 0.012 ) . Aneuploidy was more common in stage III than in stage II ( 66 versus 47 % ; P = 0.009 ) but was not independently related to survival in either group . The proliferative rate was greater in aneuploid than in diploid cancers but was not related to survival . There was no benefit of adjuvant therapy in stage II nor in any of the stage II subgroups defined by mutational status . In stage III , adjuvant therapy with 5FU plus levamisole improved 7-year survival in patients with wild-type Ki-ras ( 76 versus 44 % ; HR , 0.4 ; 95 % CI , 0.2 - 0.8 ) and in those without p53 overexpression ( 64 versus 26 % ; HR , 0.3 ; 95 % CI , 0.1 - 0.7 ) . Adjuvant therapy did not benefit those with Ki-ras mutations or p53 overexpression . The effects of adjuvant therapy did not differ according to ploidy status or proliferative rate . Ki-ras mutation is a significant risk factor for death in stage II , and the absence of p53 expression is a significant risk factor for death in stage III colon cancer after adjustment for treatment and clinical covariates . Exploratory analyses suggest that patients with stage III colon cancer with wild-type Ki-ras or no p53 expression benefit from adjuvant 5FU plus levamisole , whereas those with Ki-ras mutations or p53 overexpression do not . An independent study will be required to determine whether response to  adjuvant therapy in colon cancer depends on mutational status BACKGROUND Mutations involving the oncogene K-ras in colorectal cancer may be related to tumor aggressiveness . However , the value of K-ras gene determination as a prognostic marker has not been clearly established . PATIENTS AND METHODS The results from 98 patients recruited in a prospect i ve study analyzing the effect of a K-ras mutation as a prognostic factor in colorectal cancer are reported . RESULTS Disease-free ( P = 0.02 ) and overall survival ( P = 0.03 ) were significantly reduced for patients harboring a K-ras mutation . Two specific mutations demonstrated a significantly increased risk of disease recurrence , namely , 12-TGT ( P = 0.04 ) and 13-GAC substitutions ( P = 0.002 ) . Patients with either of these substitutions had a 2-year disease-free survival rate of 37 % compared with that of 67 % for the group of patients harboring any other mutation type or a wild-type status ( P = 0.01 ) . CONCLUSIONS The results herein presented suggest that K-ras acts as a prognostic factor in colorectal cancer and that this effect is probably related to a limited number of defined mutations BACKGROUND Despite the consistent clinical results demonstrated by studies on anti-angiogenic drugs targeted against the vascular endothelial growth factor in metastatic colorectal cancer ( mCRC ) patients , no specific direct/indirect biomarker of their efficacy has been vali date d. In this field , circulating endothelial cells ( CECs ) and endothelial progenitor cells ( CEPs ) have recently been proposed as noninvasive biomarkers . PATIENTS AND METHODS The absolute numbers of CEPs , total CECs ( tCECs ) and their resting ( rCECs ) and activated subsets were evaluated by multiparameter flow cytometry in 40 mCRC patients at baseline and before the administration of the third and sixth course of a bevacizumab-based first-line treatment . Fifty healthy subjects were utilized as control . RESULTS The overall response rate was 80 % , overall clinical benefit was 90 % and median progression-free survival ( PFS ) was 13.8 months . In our patients , tCECs and rCECs were significantly increased compared with healthy subjects . The patients who achieved a radiological  response  showed , at baseline , a significant decrease of rCECs and a trend in decrease of tCECs in comparison with patients not achieving response . Finally , a baseline absolute number of tCEC and rCEC < 40 cells/ml was evidence d in patients with a longer PFS . No correlation was found regarding CEP . CONCLUSIONS Our study suggests significant correlations between both tCEC and rCEC baseline levels and the antitumor efficacy of a bevacizumab-based combination therapy in mCRC patients , thus confirming that these biomarkers could be used in the clinical setting as an early predictor of tumor response PURPOSE Mutations in the K-ras gene are frequent in human cancer . ras activation in primary cells results in a cellular senescence phenotype that is precluded by inactivation of p16 . At the clinical level , this may imply a differential behavior for tumors with alternative or cooperative activation of K-ras function and impairment of p16 pathways . PATIENTS AND METHODS We have determined the presence of mutations in the K-ras gene and the methylation status of p16 promoter in a series of 119 prospect ively collected colorectal carcinomas .  p53 mutations and p14 alternative reading frame methylation status were also assessed . Associations with survival were investigated . RESULTS  K-ras mutations were present in 44 ( 38 % ) of 115 cases , and p16 methylation was present in 42 ( 37 % ) of 113 cases . p53 mutations were detected in 50 % ( 56 of 115 ) and p14 methylation in 29 % ( 32 of 112 ) of cases . K-ras and p16 alterations were independent genetic events . Presence of K-ras or p16 genetic alterations ( analyzed independently ) was associated with shorter survival , although differences were not statistically significant . Cox analysis of the two variables combined showed a diminished survival as the results of an interaction between p16 and K-ras . Alternative alteration of K-ras and p16 genes was an independent prognostic factor in human colorectal cancer in univariate and multivariate analysis . Differences were maintained when cases undergoing radical surgery and without distant metastases were considered . CONCLUSION These results suggest that the combined K-ras and p16 analyses may be of prognostic use in human colorectal cancer BACKGROUND Hypertension is associated with antivascular endothelial growth factor treatment , but the clinical implication s of hypertension are uncertain . To assess the prognostic and predictive value of bevacizumab-related hypertension , a comprehensive analysis of whether hypertension and efficacy outcomes are associated was conducted on seven company-sponsored placebo-controlled phase III studies of bevacizumab . METHODS Patient-specific data were available from 6,486 patients with metastatic colorectal , breast , non-small cell lung , pancreatic , and renal cell cancers . Primary hypertension endpoint was a blood pressure ( BP ) increase of > 20 mmHg systolic or > 10 mmHg diastolic within the first 60 days of treatment . Additional endpoints included other predefined thresholds of change in BP and severity of hypertension grade d using the National Cancer Institute 's Common Terminology Criteria for Adverse Events . To analyze the general prognostic importance of an early BP increase , multivariate Cox regression models were used to assess the correlation between BP changes and progression-free ( PFS ) and overall survival ( OS ) outcomes in the control groups . To analyze whether early BP increases could predict for benefit from bevacizumab , similar analyses were conducted in the bevacizumab-treated and control groups . RESULTS In six of seven studies , early BP increase was neither predictive of clinical benefit from bevacizumab nor prognostic for the course of the disease . For study AVF2107 g , early increased BP was associated with longer PFS and OS times in the bevacizumab group but shorter OS time in the control group . CONCLUSIONS 
    Output:
    
This pooled analysis of 12 published studies shows that KRAS wt status is a good prognostic factor for  B-based chemotherapy .
Also , KRAS wt CRC is associated with a better RR with B plus chemotherapy than mut counterpart