***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 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 The study aim ed to investigate whether polymorphisms in genes of the EGFR signaling pathway are associated with clinical outcome in advanced colorectal cancer ( CRC ) patients treated with single-agent Cetuximab .  Polymorphisms of interest in the EGFR pathway include : cyclin D1 ( CCND1 ) A870 G , cyclooxygenase 2 ( Cox-2 ) G-765C , epidermal growth factor ( EGF ) A61 G , epidermal growth factor receptor ( EGFR ) codon R497 K , EGFR CA dinucleotide repeat in intron 1 , interleukin (IL)-8 T-251A and vascular endothelial growth factor ( VEGF ) C936 T gene polymorphisms . Thirty-nine metastatic CRC patients were enrolled in the IMCL-0144 trial and treated with single-agent Cetuximab .  Using the polymerase chain reaction-restriction fragment length polymorphism method , gene polymorphisms of CCND1 , COX-2 , EGF , EGFR , IL-8 and VEGF were assessed from genomic DNA extracted from blood sample s. A significant association was found between the CCND1 A870 G polymorphism and overall survival in our 39 CRC subjects . Patients with the AA homozygous genotype survived for a median of 2.3 months [ 95 % confidence interval (CI)=2.1–5.7 ] , whereas those with any G allele ( AG , GG genotype ) survived for a median of 8.7 months ( 95 % CI=4.4–13.5 ) ( P=0.019 , log-rank test ) . When we analysed the cyclin D1 and EGF polymorphisms together , patients with favourable genotypes ( EGF any A allele and CCND1 any G allele ) showed a median survival time of 12 months ( 95 % CI=4.8–15.2 ) , whereas patients with any two unfavourable genotypes ( EGF GG or CCND1 AA ) showed a median survived time of 4.4 months ( 95 % CI=2.1–5.7 ) ( P=0.004 , log-rank test ) . The findings of this pilot study suggest that the cyclin D1 A870 G and the EGF A61 G polymorphisms may be useful molecular markers for predicting clinical outcome in CRC patients treated with single-agent Cetuximab Despite years of research and hundreds of reports on tumor markers in oncology , the number of markers that have emerged as clinical ly useful is pitifully small . Often initially reported studies of a marker show great promise , but subsequent studies on the same or related markers yield inconsistent conclusions or st and in direct contradiction to the promising results . It is imperative that we attempt to underst and the reasons why multiple studies of the same marker lead to differing conclusions . A variety of method ological problems have been cited to explain these discrepancies . Unfortunately , many tumor marker studies have not been reported in a rigorous fashion , and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of study results . The development of guidelines for the reporting of tumor marker studies  was a major recommendation of the National Cancer Institute – European Organisation for Research and Treatment of Cancer ( NCI – EORTC ) First International Meeting on Cancer Diagnostics in 2000 . As for the successful CONSORT initiative for r and omized trials and for the STARD statement for diagnostic studies , we suggest guidelines to provide relevant information about the study design , preplanned hypotheses , patient and specimen characteristics , assay methods , and statistical analysis methods . In addition , the guidelines provide helpful suggestions on how to present data and important elements to include in discussion s. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and underst and the context in which the conclusions apply 
    Output:
    
This meta- analysis showed that mCRC patients harboring GG genotype of EGF A61 G polymorphism inclined to have a better response rate with cetuximab treatment