***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: Objective : To establish evidence -based recommendations for the molecular analysis of lung cancers that are that are required to guide EGFR- and ALK-directed therapies , addressing which patients and sample s should be tested , and when and how testing should be performed . Participants : Three cochairs without conflicts of interest were selected , one from each of the 3 sponsoring professional societies : College of American Pathologists , International Association for the Study of Lung Cancer , and Association for Molecular Pathology . Writing and advisory panels were constituted from additional experts from these societies . Evidence : Three unbiased literature search es of electronic data bases were performed to capture articles published published from January 2004 through February 2012 , yielding 1533 articles whose abstract s were screened to identify 521 pertinent articles that were then review ed in detail for their relevance to the recommendations . Evidence was formally grade d for each recommendation . Consensus Process : Initial recommendations were formulated by the cochairs and panel members at a public meeting . Each guideline section was assigned to at least 2 panelists . Drafts were circulated to the writing panel ( version 1 ) , advisory panel ( version 2 ) , and the public ( version 3 ) before su bmi ssion ( version 4 ) . Conclusions : The 37 guideline items address 14 subjects , including 15 recommendations ( evidence grade A/B ) . The major recommendations are to use testing for EGFR mutations and ALK fusions to guide patient selection for therapy with an epidermal growth factor receptor ( EGFR ) or anaplastic lymphoma kinase ( ALK ) inhibitor , respectively , in all patients with advanced-stage adenocarcinoma , regardless of sex , race , smoking history , or other clinical risk factors , and to prioritize EGFR and ALK testing over other molecular predictive tests . As scientific discoveries and clinical practice outpace the completion of r and omized clinical trials , evidence -based guidelines developed by expert practitioners are vital for communicating emerging clinical st and ards . Already , new treatments targeting genetic alterations in other , less common driver oncogenes are being evaluated in lung cancer , and testing for these may be addressed in future versions of these guidelines Introduction : PIONEER ( NCT01185314 ) was a prospect i ve , multinational , epidemiological study of epidermal growth factor receptor ( EGFR ) mutations in patients from Asia with newly diagnosed advanced lung adenocarcinoma . Methods : Eligible patients ( aged ≥20 years ) had untreated stage IIIB/IV adenocarcinoma . The EGFR mutation status ( primary end point : positive , negative , or undetermined ) of tumor sample s ( biopsy , surgical specimen , or cytology ) was determined ( Scorpion amplification refractory mutation system ) . EGFR mutation frequency was calculated and compared between demographic and clinical subgroups . Results : Of 1482 patients from seven Asian regions , 43.4 % of patients were female , median age was 60 years ( range , 17–94 ) , and 52.6 % of patients were never-smokers . EGFR mutation status was evaluable in tumors from 1450 patients ( 97.8 % ) ( 746 [ 51.4 % ] positive ; 704 [ 48.6 % ] negative ) . Country , sex , ethnicity , smoking status , pack-years ( all p < 0.001 ) , disease stage ( p = 0.009 ) , and histology type ( p = 0.016 ) correlated significantly with EGFR mutation frequency . Mutation frequency was 61.1 % in females , 44.0 % in males ; lower in patients from India ( 22.2 % ) compared with other areas ( 47.2%–64.2 % ) ; highest among never-smokers ( 60.7 % ) ; and decreased as pack-year number increased ( > 0–10 pack-years , 57.9 % ; > 50 pack-years , 31.4 % ) ( similar trend by sex ) . Ethnic group ( p < 0.001 ) and pack-years ( p < 0.001 ) had statistically significant associations with mutation frequency ( multivariate analysis ) ; sex was not significant when adjusted for smoking status . Conclusion : PIONEER is the first prospect i ve study to confirm high EGFR mutation frequency ( 51.4 % overall ) in tumors from Asian patients with adenocarcinoma . The observed high mutation frequency in demographic/ clinical subgroups compared with white population s suggests that mutation testing should be considered for all patients with stage IIIB/IV adenocarcinoma , even males and regular smokers , among Asian population Background Concurrent chemoradiotherapy is the st and ard of care for inoperable stage III non-small cell lung cancer ( NSCLC ) for patients who can tolerate it . We explored if adding erlotinib would increase the effectiveness of chemoradiotherapy  without increasing toxicity in a single-arm prospect i ve phase II trial . Methods Forty-eight patients with previously untreated NSCLC received intensity-modulated radiation therapy ( 63 Gy/35 fractions ) on Monday – Friday , with chemotherapy ( paclitaxel 45 mg/m2 , carboplatin AUC=2 ) on Mondays , for 7 weeks . All patients also received the epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor erlotinib ( 150 mg orally 1/day ) on Tuesday – Sunday for 7 weeks followed by consolidation paclitaxel – carboplatin . The primary endpoint was time to progression ; secondary endpoints were overall survival ( OS ) , toxicity , response , and disease control and whether any endpoint differed by EGFR mutation status . Results Of 46 patients evaluable for response , 40 were former or never-smokers and 41 were evaluable for EGFR mutations ( 37 wild-type [ wt ] and 4 [ mutated ; all adenocarcinoma ] ) . Median time to progression was 14.0 months and did not differ by EGFR status . Toxicity was acceptable ( no grade 5 , one grade 4 , eleven grade 3 ) . Twelve patients ( 26 % ) had complete responses ( 10 wt , 2 mutated ) , 27 ( 59 % ) partial ( 21 wt , 2 mutated , 4 unknown ) , and 7 ( 15 % ) none ( 6 wt , 2 mutated , 1 unknown ) ( P=0.610 ) . At 37.0 months ’ follow-up ( range 3.6–76.5 months ) for all patients , median OS time was 36.5 months and 1- , 2- , and 5-year OS rates were 82.6 % , 67.4 % , and 35.9 % ; none differed by mutation status . Twelve patients had no progression and 34 had local and /or distant failure . Eleven of 27 distant failures were in the brain ( 7 wt , 3 mutated , 1 unknown ) . Conclusions Toxicity and OS were promising , but time to progression did not meet expectations . The prevalence of distant failures underscores the need for effective systemic therapy Introduction : This study evaluated the addition of gefitinib to sequential or concurrent chemoradiotherapy ( CRT ) in unresectable stage III non-small cell lung cancer . Methods : Between May 2002 and April 2005 , 63 patients were entered before the study closing early . All received two cycles paclitaxel 200 mg/m2 and carboplatin area under the curve 6 intravenous plus gefitinib 250 mg daily . Poor risk stratum 1 ( ≥5 % weight loss and /or performance status 2 ) received radiotherapy 200 cGy for 33 fractions ( 6600 cGy ) and gefitinib 250 mg daily . Good-risk stratum 2 ( performance status : 0–1weight loss and < 5 % ) received the same RT with gefitinib 250 mg daily and weekly paclitaxel 50 mg/m2 plus carboplatin AUC 2 . Consolidation gefitinib until progression was started after all toxicities were grade ≤2 . Results : Acute high- grade infield toxicities were not clearly increased compared with historical CRT data . Poor-risk ( N = 21 ) median progression-free survival was 13.4 months ( 95 % confidence interval [ CI ] : 6.4–25.2 ) and median overall survival 19.0 months ( 95 % CI : 9.9–28.4 ) . Good-risk ( N = 39 ) median progression-free survival was 9.2 months ( 95 % CI : 6.7–12.2 ) , and median overall survival was 13 months ( 95 % CI : 8.5–17.2 ) . Thirteen of 45 tumors analyzed had activating epidermal growth factor receptor ( EGFR ) mutations , and 2 of 13 also had T790 M mutations . Seven tumors of 45 had KRAS mutations . There was no apparent survival difference with EGFR-activating mutations versus wild type or KRAS mutation versus wild type . Conclusions : Survival of poor-risk patients with wild type or mutated EGFR receiving sequential CRT with gefitinib was promising . Survival for good-risk patients receiving concurrent CRT plus gefitinib was disappointing even for tumors with activating EGFR mutations 
    Output:
    
Conclusions The presence of EGFR sensitizing mutations may improve tumour response rate but not survival in patients with localized NSCLC treated with definitive thoracic radiation therapy with or without chemotherapy