***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 Trastuzumab , a monoclonal antibody against human epidermal growth factor receptor 2 ( HER2 ; also known as ERBB2 ) , was investigated in combination with chemotherapy for first-line treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer . METHODS ToGA ( Trastuzumab for Gastric Cancer ) was an open-label , international , phase 3 , r and omised controlled trial undertaken in 122 centres in 24 countries . Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumours showed overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation . Participants were r and omly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine plus cisplatin or fluorouracil plus cisplatin given every 3 weeks for six cycles or chemotherapy in combination with intravenous trastuzumab . Allocation was by block r and omisation stratified by Eastern Cooperative Oncology Group performance status , chemotherapy regimen , extent of disease , primary cancer site , and measurability of disease , implemented with a central interactive voice recognition system . The primary endpoint was overall survival in all r and omised patients who received study medication at least once . This trial is registered with Clinical Trials.gov , number NCT01041404 . FINDINGS 594 patients were r and omly assigned to study treatment ( trastuzumab plus chemotherapy , n=298 ; chemotherapy alone , n=296 ) , of whom 584 were included in the primary analysis ( n=294 ; n=290 ) . Median follow-up was 18.6 months ( IQR 11 - 25 ) in the trastuzumab plus chemotherapy group and 17.1 months ( 9 - 25 ) in the chemotherapy alone group . Median overall survival was 13.8 months ( 95 % CI 12 - 16 ) in those assigned to trastuzumab plus chemotherapy compared with 11.1 months ( 10 - 13 ) in those assigned to chemotherapy alone ( hazard ratio 0.74 ; 95 % CI 0.60 - 0.91 ; p=0.0046 ) . The most common adverse events in both groups were nausea  ( trastuzumab plus chemotherapy , 197 [ 67 % ] vs chemotherapy alone , 184 [ 63 % ] ) , vomiting ( 147 [ 50 % ] vs 134 [ 46 % ] ) , and neutropenia ( 157 [ 53 % ] vs 165 [ 57 % ] ) . Rates of overall grade 3 or 4 adverse events ( 201 [ 68 % ] vs 198 [ 68 % ] ) and cardiac adverse events ( 17 [ 6 % ] vs 18 [ 6 % ] ) did not differ between groups . INTERPRETATION Trastuzumab in combination with chemotherapy can be considered as a new st and ard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer . FUNDING F Hoffmann-La Roche The optimal adjuvant treatment for gastric cancer remains controversial . We compared the efficacy of a docetaxel and platinum adjuvant chemotherapy regimen , in patients with high-risk gastric cancer , with that of the same chemotherapy plus radiation therapy ( RT ) . In addition , we evaluated the prognostic and /or predictive value of a panel of molecular markers . Patients with histologically proven , radically resected gastric cancer , stage ≥T3 and /or N+ were r and omized to 6 cycles of docetaxel with cisplatin , both at 75 mg/m2 every 3 weeks ( arm A ) or the same treatment with RT ( arm B ; 45 Gy ) . Due to excessive nausea and vomiting , cisplatin was substituted by carboplatin at AUC ( area under the curve ) of 5 after the first 45 patients ( 22 group A , 23 group B ) . The prognostic value of EGFR , ERCC1 , HER2 , MET/HGFR , MAP-Tau , and PTEN expression was also studied in a subset of 67 patients using immunohistochemistry on tissue microarrays ( TMAs ) . A total of 147 patients were r and omized . After a median follow-up of 53.7 months , no differences in overall ( OS ) and disease-free survival ( DFS ) were found between the two arms . The most common grade 3/4 toxicities for arms A and B ( excluding alopecia ) were non-febrile neutropenia ( 11 and 17 % , respectively ) , febrile neutropenia ( 9 and 7 % ) and diarrhea ( 7 and 4 % , respectively ) . Patients with ERCC1 positive tumors had significantly longer median DFS ( 33.1 vs. 11.8 months , Wald P = 0.016 ) and OS ( 63.2 vs. 18.8 months , Wald P = 0.046 ) . Our results indicate that the addition of RT to platinum/docetaxel adjuvant chemotherapy does not appear to improve survival in high-risk , radically resected gastric cancer . However , the possibility that a benefit by the addition of RT was not detected due to decreased power of the study should not be excluded PURPOSE Amplification of the MET proto-oncogene in gastroesophageal cancer ( GEC ) may constitute a molecular marker for targeted therapy . We examined a GEC cohort with follow-up and reported the clinical response of four additional patients with MET-amplified tumors to the small molecule inhibitor crizotinib  as part of an exp and ed phase I cohort study . PATIENTS AND METHODS From 2007 to 2009 , patients with GEC were genetically screened as a consecutive series of 489 tumors ( stages 0 , I , and II , 39 % ; III , 25 % ; IV , 36 % ; n = 222 esophageal , including n = 21 squamous carcinomas ) .  MET , EGFR , and HER2 amplification status was assessed by using fluorescence in situ hybridization . RESULTS Ten ( 2 % ) of 489 patients screened harbored MET amplification ; 23 ( 4.7 % ) harbored EGFR amplification ; 45 ( 8.9 % ) harbored HER2 amplification ; and 411 ( 84 % ) were wild type for all three genes ( ie , negative ) . MET-amplified tumors were typically high- grade adenocarcinomas that presented at advanced stages ( 5 % ; n = 4 of 80 ) . EGFR-amplified tumors showed the highest fraction of squamous cell carcinoma ( 17 % ; n = 4 of 23 ) . HER2 , MET , and EGFR amplification were , with one exception ( MET and EGFR positive ) , mutually exclusive events . Survival analysis in patients with stages III and IV disease showed substantially shorter median survival in MET/EGFR-amplified groups , with a rank order for all groups by median survival ( from most to least aggressive ) : MET ( 7.1 months ; P < .001 ) less than EGFR ( 11.2 months ; P = .16 ) less than HER2 ( 16.9 months ; P = .89 ) when compared with the negative group ( 16.2 months ) . Two of four patients with MET-amplified tumors treated with crizotinib experienced tumor shrinkage ( -30 % and -16 % ) and experienced progression after 3.7 and 3.5 months . CONCLUSION MET amplification defines a small and aggressive subset of GEC with indications of transient sensitivity to the targeted MET inhibitor crizotinib ( PF-02341066 ) PURPOSE To investigate whether prognosis of patients with high-risk gastric cancer may depend on MET copy number gain ( CNG ) or an activating truncation within a deoxyadenosine tract element ( DATE ) in the promoter region of the MET lig and HGF . PATIENTS AND METHODS A single-institution cohort of 230 patients with stage II/III gastric cancer was studied .  Formalin-fixed paraffin-embedded tumor specimens were used for DNA extraction . Quantitative polymerase chain reaction ( qPCR ) for MET CNG and sequencing for HGF DATE truncation ( < 25 deoxyadenosines instead of 30 ) were used . Results were analyzed for association with disease-free survival ( DFS ) and overall survival ( OS ) . To assess the reliability of the qPCR measurement , a r and om sample of cases was reanalyzed using an alternative assay ( fluorescent in situ hybridization [ FISH ] ) with calculation of the intracorrelation coefficient ( ICC ) . RESULTS In 216 assessable patients , MET CNG five or more copies and homozygous HGF-truncated DATE occurred in 21 patients ( 10 % ) and 30 patients ( 13 % ) , respectively . Patients with MET CNG five or more copies ( MET-positive ) showed significantly worse prognosis with multivariate hazard ratio ( HR ) of 3.02 ( 95 % CI , 1.71 to 5.33 ; P < .001 ) for DFS and multivariate HR of 2.91 ( 95 % CI , 1.65 to 5.11 ; P < .001 ) for OS . The agreement between qPCR and FISH was high , with ICC = 0.9 % ( 95 % CI , 0.81 % to 0.95 % ; the closer the ICC is to 1 , the greater is the agreement ) . HGF-truncated DATE did not show relevant prognostic effect . CONCLUSION In this study , qPCR revealed approximately 10 % of white patients with gastric cancer harboring MET CNG of five or more copies . This marker was significantly associated with unfavorable prognosis . This information is relevant to the current clinical development of anti-MET compounds 
    Output:
    
The findings from present study indicated that higher MET gene amplification and expression in gastric cancer was an indicator of poor prognosis