***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 St and ardized conditions to distinguish sub population s of colorectal cancer ( CRC ) patients more and less sensitive to cetuximab therapy remain undefined . MATERIAL S AND METHODS We retrospectively analyzed epidermal growth factor receptor ( EGFR ) copy number by fluorescence in situ hybridization ( FISH ) in paraffin-embedded tumor blocks from 85 chemorefractory CRC patients treated with cetuximab .  Results were analyzed according to different score systems previously reported in colorectal and lung cancers . The primary end point of the study was identification of the EGFR FISH score that best associates with response rate ( RR ) . RESULTS Using receiver operating characteristic ( ROC ) analysis , the cut-off that best discriminated responders versus nonresponders to cetuximab was a mean of 2.92 EGFR gene copies per cell . This model showed sensitivity of 58.6 % [ 95 % confidence interval ( CI ) = 47.1 - 70.1 ) and specificity of 93.3 % ( 95 % CI = 80.6 - 100 ) . EGFR FISH-positive patients ( N = 43 , 50.6 % ) had significantly higher RR ( P = 0.0001 ) and significantly longer time to disease progression ( P = 0.02 ) than EGFR FISH negative ( N = 42 , 49.4 % ) . Other scoring systems result ed less accurate in discriminating patients with the highest likelihood of response to cetuximab therapy . CONCLUSIONS CRC patients with high EGFR gene copy number have an increased likelihood to respond to cetuximab therapy . Prospect i ve clinical trials with a careful st and ardization of assay conditions and pattern interpretation are urgently needed BACKGROUND The antiepidermal growth factor receptor ( antiEGFR ) monoclonal antibodies cetuximab and panitumumab have good clinical activity in about 10 % of patients with metastatic colorectal cancer that is resistant to chemotherapy . The molecular mechanisms underlying clinical response or resistance to these agents are unknown . METHODS Tumours from 31 patients with metastatic colorectal cancer who had either an objective response ( n=10 ) or stable disease or progressive disease ( n=21 ) after treatment with cetuximab or panitumumab  were screened for genetic changes in EGFR or its immediate intracellular effectors . Specifically , we assessed the EGFR copy number and the mutation profile of the EGFR catalytic domain and of selected exons in KRAS , BRAF , and PIK3CA . RESULTS Eight of nine of patients with objective responses who were assessable by fluorescence in-situ hybridisation ( FISH ) had an increased EGFR copy number . By contrast , one of 21 non-responders assessable by FISH had an increased EGFR copy number ( p<0.0001 for responders vs non-responders , Fisher 's exact test ) . The mutation status of the EGFR catalytic domain and its immediate downstream effectors PIK3CA , KRAS , and BRAF did not correlate with disease response . In colorectal-cancer cell lines , the concentration of cetuximab that completely inhibited proliferation of cells with amplified EGFR copy number did not affect proliferation of cells with unamplified EGFR . INTERPRETATION We propose that the response to antiEGFR treatment has a genetic basis and suggest that patients might be selected for treatment on the basis of EGFR copy number BACKGROUND A large proportion of colorectal cancer patients does not benefit from the use of anti-epidermal growth factor receptor ( EGFR ) treatment although in the absence of a mutation of the K-RAS gene . Preliminary observations suggested that HER-3 , insulin-like growth factor-1 ( IGF-1 ) , nuclear factor-kB ( NF-kB ) and EGFR gene copy number ( GCN ) might identify patients not likely to benefit from anti-EGFR therapy . We tested the interaction between HER-3 , IGF-1 , NF-kB , EGFR GCN and K-RAS mutational analysis to verify the relative ability of these variables to identify a subgroup of patients more likely to benefit from EGFR-targeted treatment among those harbouring a K-RAS wild-type status . PATIENTS AND METHODS We retrospectively collected tumours from 168 patients with metastatic colorectal cancer treated with irinotecan-cetuximab .  K-RAS was assessed with direct sequencing , EGFR amplification was assessed by chromogenic in situ hybridisation ( CISH ) and HER-3 , IGF-1 and NF-kB were assessed by immunohistochemistry . RESULTS In patients with K-RAS wild-type tumours , the following molecular factors result ed independently associated with response rate : HER-3 [ odds ratio (OR)=4.6 , 95 % confidence interval ( CI ) 1.8 - 13.6 , P=0.02 ] , IGF-1 ( OR=4.2 , 95 % CI 2 - 10.2 , P=0.003 ) and EGFR GCN ( OR=4.1 , 95 % CI 1.9 - 26.2 , P=0.04 ) . These factors also independently correlated with overall survival as follows : HER-3 [ hazard ratio (HR)=0.4 , 95 % CI 0.28 - 0.85 , P=0.008 ] , IGF-1 ( HR=0.47 , 95 % CI 0.24 - 0.76 , P<0.0001 ) and EGFR GCN ( HR=0.59 , 95 % CI 0.22 - 0.89 , P=0.04 ) . DISCUSSION We believe that our data may help further composing the molecular mosaic of EGFR-resistant tumours . The role of HER-3 , IGF-1 and CISH EGFR GCN should be prospect ively vali date d in clinical trials investigating anti-EGFR treatment strategies in colorectal cancer patients 
    Output:
    
It was also shown that EGFR GCN is independent of other factors such as KRAS status .
Among the anti-EGFR-treated patients , increased EGFR GCN appears to be associated with improved survival outcomes .
The effect on survival appears to be related to patients receiving the line of treatment