human
***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: This study determined whether expression levels of a panel of biologically relevant microRNAs can be used as prognostic or predictive biomarkers in patients who participated in the International Adjuvant Lung Cancer Trial ( IALT ) , the largest r and omized study conducted to date of  adjuvant chemotherapy in patients with radically resected non-small cell lung carcinoma ( NSCLC ) . Expression of miR-21 , miR-29b , miR-34a/b/c , miR-155 , and let-7a was determined by quantitative real-time PCR in formalin-fixed paraffin-embedded tumor specimens from 639 IALT patients . The prognostic and predictive values of microRNA expression for survival were studied using a Cox model , which included every factor used in the stratified r and omization , clinicopathologic prognostic factors , and other factors statistically related to microRNA expression . Investigation of the expression pattern of microRNAs in situ was performed . We also analyzed the association of TP53 mutation status and miR-34a/b/c expression , epidermal growth factor receptor and KRAS mutation status , and miR-21 and Let-7a expression . Finally , the association of p16 and miR-29b expression was assessed . Overall , no significant association was found between any of the tested microRNAs and survival , with the exception of miR-21 for which a deleterious prognostic effect of lowered expression was suggested . Otherwise , no single or combinatorial microRNA expression profile predicted response to adjuvant cisplatin-based chemotherapy . Together , our results indicate that the microRNA expression patterns examined were neither predictive nor prognostic in a large patient cohort with radically resected NSCLC , r and omized to receive adjuvant cisplatin-based chemotherapy versus follow-up only PURPOSE Adjuvant cisplatin-based chemotherapy ( ACT ) is now an accepted st and ard for completely resected stage II and III A non-small-cell lung cancer ( NSCLC ) . Long-term follow-up is important to document persistent benefit and late toxicity . We report here up date d overall survival ( OS ) and disease-specific survival ( DSS ) data . PATIENTS AND METHODS Patients with completely resected stage IB ( T2N0 , n = 219 ) or II ( T1 - 2N1 , n = 263 ) NSCLC were r and omly assigned to receive 4 cycles of vinorelbine/cisplatin or observation . All efficacy analyses were performed on an intention-to-treat basis . Results Median follow-up was 9.3 years ( range , 5.8 to 13.8 ; 33 lost to follow-up ) ; there were 271 deaths in 482 r and omly assigned patients . ACT continues to show a benefit ( hazard ratio [ HR ] , 0.78 ; 95 % CI , 0.61 to 0.99 ; P = .04 ) . There was a trend for interaction with disease stage ( P = .09 ; HR for stage II , 0.68 ; 95 % CI , 0.5 to 0.92 ; P = .01 ; stage IB , HR , 1.03 ; 95 % CI , 0.7 to 1.52 ; P = .87 ) . ACT result ed in significantly prolonged DSS ( HR , 0.73 ; 95 % CI , 0.55 to 0.97 ; P = .03 ) . Observation was associated with significantly higher risk of death from lung cancer ( P = .02 ) , with no difference in rates of death from other causes or second primary malignancies between the arms . CONCLUSION Prolonged follow-up of patients from the JBR.10 trial continues to show a benefit in survival for adjuvant chemotherapy . This benefit appears to be confined to N1 patients . There was no increase in death from other causes in the chemotherapy arm BACKGROUND Whether adjuvant chemotherapy improves survival of patients with non-small-cell lung cancer ( NSCLC ) is not known . We aim ed to compare the effect of adjuvant vinorelbine plus cisplatin versus observation on survival in patients with completely resected NSCLC . METHODS 840 patients with stage IB-IIIA NSCLC from 101 centres in 14 countries were r and omly assigned to observation ( n=433 ) or to 30 mg/m(2 ) vinorelbine plus 100 mg/m(2 ) cisplatin ( n=407 ) . Postoperative radiotherapy was not m and atory and was undertaken according to every centre 's policy . The primary endpoint was overall survival . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N95053737 . FINDINGS 367 patients in the chemotherapy group and 431 in the control group received their assigned treatment . 301 ( 36 % ) patients had stage IB disease , 203 ( 24 % ) had stage II disease , and 325 ( 39 % ) had stage IIIA disease . Tolerance to chemotherapy mainly included neutropenia in 335 ( 92 % ) patients and febrile neutropenia in 34 ( 9 % ) ; seven ( 2 % ) toxic deaths were also recorded . Compliance was greater with cisplatin than with vinorelbine ( median dose intensity 89 % [ range 17 - 108 ] vs 59 % [ 17 - 100 ] ) . After a median follow-up of 76 months ( range 43 - 116 ) , median survival was 65.7 months ( 95 % CI 47.9 - 88.5 ) in the chemotherapy group and 43.7 ( 35.7 - 52.3 ) months in the observation group . Adjusted risk for death was significantly reduced in patients assigned chemotherapy compared with controls ( hazard ratio 0.80 [ 95 % CI 0.66 - 0.96 ] ; p=0.017 ) . Overall survival at 5 years with chemotherapy improved by 8.6 % , which was maintained at 7 years ( 8.4 % ) . INTERPRETATION Adjuvant vinorelbine plus cisplatin extends survival in patients with completely resected NSCLC , better defining indication of adjuvant chemotherapy Purpose We conducted a phase III r and omized controlled trial ( RCT ) to investigate the efficacy of postsurgical adjuvant immunotherapy combined with chemotherapy . The immunotherapy targets were residual micrometastases and clones resistant to chemotherapy . Patients and methods Between April 2007 and July 2012 , 103 postsurgical non-small cell lung cancer patients were r and omly assigned to receive either chemo-immunotherapy ( group A ) or chemotherapy ( group B ) . The immunotherapy consisted of the adoptive transfer of autologous activated killer T cells and dendritic cells obtained from the lung cancer patients ’ own regional lymph nodes . Results The 2-year overall survival rates in groups A and B were 93.4 and 66.0 % , and the 5-year rates were 81.4 and 48.3 % , respectively . The differences were statistically significantly better in group A. The hazard ratio ( HR ) was 0.229 ( p = 0.0013 ) . The 2- and 5-year recurrence-free survival rates were 68.5 , 41.4 and 56.8 , 26.2 % in groups A and B , respectively . Those differences were also statistically significant ( log-rank test p = 0.0020 ) . The HR was 0.423 ( p = 0.0027 ) in favor of group A. As for adverse reactions to immunotherapy , of a total of 762 courses , 52 ( 6.8 % ) were accompanied with chills and shivering , and 47 ( 6.2 % ) , with fever ( > 38 ° C ) . Conclusions Immunotherapy has the potential to improve the postsurgical prognosis of lung cancer patients , but a large-scale multi-institutional RCT is awaited for further confirmation of this study OBJECTIVE Surgery constitutes the mainstay of treatment in stage I non-small cell lung cancer ( NSCLC ) . However , a significant fraction of patients after surgical resection die mainly due to systemic relapse . Nonetheless , the best adjuvant treatment to improve survival and decrease relapse rate remains as an ever controversial issue . Therefore , we conducted a r and omized trial to determine whether postoperative adjuvant chemotherapy is beneficial in prolonging survival and decreasing recurrence in patients with completely resected stage I NSCLC . METHODS It was design ed as a r and omized , prospect i ve two-armed study with  surgery only ( control group , 59 patients ) versus surgery plus adjuvant MVP ( mitomycin C , vinblastin and cisplatin ) chemotherapy ( study group , 59 patients ) . RESULTS Data for all the patients were complete . Twenty-four patients in the control group and nine patients in the study group experienced tumor recurrence during the follow-up . Neither histological type nor surgical extent correlated with recurrence . However , the addition of adjuvant MVP chemotherapy could decrease the rate of recurrence and the incidence of cancer-related death after surgery in the patients of stage I NSCLC ( P<0.05 ) . We followed up at least 5 years , and the duration of mean follow-up was 7.3 years . The rates of the loco-regional and distant metastases were 3.4 and 40.7 % in the control group , and 3.4 and 11.9 % in the study group , respectively . The 5- and 10-year survival rates were 74.6 and 56.3 % in the control group , and 81.4 and 65.0 % in the study group , respectively ( P=0.19 , log-rank test ) . The 5- and 10-year disease-free survival rates were 64.8 and 54.8 % in the control group , and 88.8 and 76.8 % in the study group , respectively ( P=0.002 , log-rank test ) . CONCLUSIONS Our results suggest that the addition of adjuvant MVP chemotherapy may reduce the incidence of distant metastasis and prolong the disease-free survival of the patients with stage I NSCLC after surgery We evaluated the therapeutic usefulness of adjuvant chemotherapy in patients with completely resected non-small cell lung cancer ( NSCLC ) . We also examined the relation between DNA ploidy pattern and the response to chemotherapy .  A total of 267 patients with NSCLC ( pathologically documented stage I , II , or IIIA ) underwent complete resection , and DNA ploidy pattern was analysed . Patients with stage I disease ( n=172 ) were r and omly assigned to receive surgery alone ( group A ) or surgery followed by adjuvant chemotherapy ( UFT ( oral anti-cancer drug , a combination of Uracil and Tegaful ) 400 mg day−1 for 1 year after surgery ; group B ) . Stage II or IIIA disease patients ( n=95 ) were r and omly assigned to surgery alone ( group C ) or surgery followed by chemotherapy ( two 28-day courses of cisplatin 80 mg m−2 on day 1 plus vindesine 3 mg m−2 on days 1 and 8 , followed by UFT 400 mg day−1 for at least 1 year ; group D ) . Eight-year overall survival rate in patients with stage I disease was 74.2 % ( 95 % confidence interval ( CI ) : 64.4–84.0 % ) in group B and 57.6 % ( 95 % CI : 46.4–68.8 % ) in group A ( P=0.045 by log-rank test ) . In patients with stage II and IIIA disease , no difference was found between groups C and D. Analysis according to DNA ploidy pattern revealed no difference between the groups . Postoperative chemotherapy with UFT was suggested to be useful in patients with completely resected stage I NSCLC . No difference was seen in relation to DNA pattern in any treatment group BACKGROUND On the basis of a previous meta- analysis , the International Adjuvant Lung Cancer Trial was design ed to evaluate the effect of cisplatin-based adjuvant chemotherapy on survival after complete resection of non-small-cell lung cancer . METHODS We r and omly assigned patients either to three or four cycles of cisplatin-based chemotherapy or to observation . Before r and omization , each center determined the pathological stages to include , its policy for chemotherapy ( the dose of cisplatin and the drug to be combined with cisplatin ) , and its postoperative radiotherapy policy . The main end point was overall survival . RESULTS A total of 1867 patients underwent r and omization ; 36.5 percent had pathological stage I disease , 24.2 percent stage II , and 39.3 percent stage III . The drug allocated with cisplatin was etoposide in 56.5 percent of patients , vinorelbine in 26.8 percent , vinblastine in 11.0 percent , and vindesine in 5.8 percent . Of the 932 patients assigned to chemotherapy , 73.8 percent received at least 240 mg of cisplatin per square meter of body-surface area . The median duration of follow-up was 56 months . Patients assigned to chemotherapy had a significantly higher survival rate than those assigned to observation ( 44.5 percent vs. 40.4 percent at five years [ 469 deaths vs. 504 ] ; hazard ratio for death , 0.86 ; 95 percent confidence interval , 0.76 to 0.98 ; P<0.03 ) 
    Output:
    
agent
***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: This study determined whether expression levels of a panel of biologically relevant microRNAs can be used as prognostic or predictive biomarkers in patients who participated in the International Adjuvant Lung Cancer Trial ( IALT ) , the largest r and omized study conducted to date of  adjuvant chemotherapy in patients with radically resected non-small cell lung carcinoma ( NSCLC ) . Expression of miR-21 , miR-29b , miR-34a/b/c , miR-155 , and let-7a was determined by quantitative real-time PCR in formalin-fixed paraffin-embedded tumor specimens from 639 IALT patients . The prognostic and predictive values of microRNA expression for survival were studied using a Cox model , which included every factor used in the stratified r and omization , clinicopathologic prognostic factors , and other factors statistically related to microRNA expression . Investigation of the expression pattern of microRNAs in situ was performed . We also analyzed the association of TP53 mutation status and miR-34a/b/c expression , epidermal growth factor receptor and KRAS mutation status , and miR-21 and Let-7a expression . Finally , the association of p16 and miR-29b expression was assessed . Overall , no significant association was found between any of the tested microRNAs and survival , with the exception of miR-21 for which a deleterious prognostic effect of lowered expression was suggested . Otherwise , no single or combinatorial microRNA expression profile predicted response to adjuvant cisplatin-based chemotherapy . Together , our results indicate that the microRNA expression patterns examined were neither predictive nor prognostic in a large patient cohort with radically resected NSCLC , r and omized to receive adjuvant cisplatin-based chemotherapy versus follow-up only PURPOSE Adjuvant cisplatin-based chemotherapy ( ACT ) is now an accepted st and ard for completely resected stage II and III A non-small-cell lung cancer ( NSCLC ) . Long-term follow-up is important to document persistent benefit and late toxicity . We report here up date d overall survival ( OS ) and disease-specific survival ( DSS ) data . PATIENTS AND METHODS Patients with completely resected stage IB ( T2N0 , n = 219 ) or II ( T1 - 2N1 , n = 263 ) NSCLC were r and omly assigned to receive 4 cycles of vinorelbine/cisplatin or observation . All efficacy analyses were performed on an intention-to-treat basis . Results Median follow-up was 9.3 years ( range , 5.8 to 13.8 ; 33 lost to follow-up ) ; there were 271 deaths in 482 r and omly assigned patients . ACT continues to show a benefit ( hazard ratio [ HR ] , 0.78 ; 95 % CI , 0.61 to 0.99 ; P = .04 ) . There was a trend for interaction with disease stage ( P = .09 ; HR for stage II , 0.68 ; 95 % CI , 0.5 to 0.92 ; P = .01 ; stage IB , HR , 1.03 ; 95 % CI , 0.7 to 1.52 ; P = .87 ) . ACT result ed in significantly prolonged DSS ( HR , 0.73 ; 95 % CI , 0.55 to 0.97 ; P = .03 ) . Observation was associated with significantly higher risk of death from lung cancer ( P = .02 ) , with no difference in rates of death from other causes or second primary malignancies between the arms . CONCLUSION Prolonged follow-up of patients from the JBR.10 trial continues to show a benefit in survival for adjuvant chemotherapy . This benefit appears to be confined to N1 patients . There was no increase in death from other causes in the chemotherapy arm BACKGROUND Whether adjuvant chemotherapy improves survival of patients with non-small-cell lung cancer ( NSCLC ) is not known . We aim ed to compare the effect of adjuvant vinorelbine plus cisplatin versus observation on survival in patients with completely resected NSCLC . METHODS 840 patients with stage IB-IIIA NSCLC from 101 centres in 14 countries were r and omly assigned to observation ( n=433 ) or to 30 mg/m(2 ) vinorelbine plus 100 mg/m(2 ) cisplatin ( n=407 ) . Postoperative radiotherapy was not m and atory and was undertaken according to every centre 's policy . The primary endpoint was overall survival . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N95053737 . FINDINGS 367 patients in the chemotherapy group and 431 in the control group received their assigned treatment . 301 ( 36 % ) patients had stage IB disease , 203 ( 24 % ) had stage II disease , and 325 ( 39 % ) had stage IIIA disease . Tolerance to chemotherapy mainly included neutropenia in 335 ( 92 % ) patients and febrile neutropenia in 34 ( 9 % ) ; seven ( 2 % ) toxic deaths were also recorded . Compliance was greater with cisplatin than with vinorelbine ( median dose intensity 89 % [ range 17 - 108 ] vs 59 % [ 17 - 100 ] ) . After a median follow-up of 76 months ( range 43 - 116 ) , median survival was 65.7 months ( 95 % CI 47.9 - 88.5 ) in the chemotherapy group and 43.7 ( 35.7 - 52.3 ) months in the observation group . Adjusted risk for death was significantly reduced in patients assigned chemotherapy compared with controls ( hazard ratio 0.80 [ 95 % CI 0.66 - 0.96 ] ; p=0.017 ) . Overall survival at 5 years with chemotherapy improved by 8.6 % , which was maintained at 7 years ( 8.4 % ) . INTERPRETATION Adjuvant vinorelbine plus cisplatin extends survival in patients with completely resected NSCLC , better defining indication of adjuvant chemotherapy Purpose We conducted a phase III r and omized controlled trial ( RCT ) to investigate the efficacy of postsurgical adjuvant immunotherapy combined with chemotherapy . The immunotherapy targets were residual micrometastases and clones resistant to chemotherapy . Patients and methods Between April 2007 and July 2012 , 103 postsurgical non-small cell lung cancer patients were r and omly assigned to receive either chemo-immunotherapy ( group A ) or chemotherapy ( group B ) . The immunotherapy consisted of the adoptive transfer of autologous activated killer T cells and dendritic cells obtained from the lung cancer patients ’ own regional lymph nodes . Results The 2-year overall survival rates in groups A and B were 93.4 and 66.0 % , and the 5-year rates were 81.4 and 48.3 % , respectively . The differences were statistically significantly better in group A. The hazard ratio ( HR ) was 0.229 ( p = 0.0013 ) . The 2- and 5-year recurrence-free survival rates were 68.5 , 41.4 and 56.8 , 26.2 % in groups A and B , respectively . Those differences were also statistically significant ( log-rank test p = 0.0020 ) . The HR was 0.423 ( p = 0.0027 ) in favor of group A. As for adverse reactions to immunotherapy , of a total of 762 courses , 52 ( 6.8 % ) were accompanied with chills and shivering , and 47 ( 6.2 % ) , with fever ( > 38 ° C ) . Conclusions Immunotherapy has the potential to improve the postsurgical prognosis of lung cancer patients , but a large-scale multi-institutional RCT is awaited for further confirmation of this study OBJECTIVE Surgery constitutes the mainstay of treatment in stage I non-small cell lung cancer ( NSCLC ) . However , a significant fraction of patients after surgical resection die mainly due to systemic relapse . Nonetheless , the best adjuvant treatment to improve survival and decrease relapse rate remains as an ever controversial issue . Therefore , we conducted a r and omized trial to determine whether postoperative adjuvant chemotherapy is beneficial in prolonging survival and decreasing recurrence in patients with completely resected stage I NSCLC . METHODS It was design ed as a r and omized , prospect i ve two-armed study with  surgery only ( control group , 59 patients ) versus surgery plus adjuvant MVP ( mitomycin C , vinblastin and cisplatin ) chemotherapy ( study group , 59 patients ) . RESULTS Data for all the patients were complete . Twenty-four patients in the control group and nine patients in the study group experienced tumor recurrence during the follow-up . Neither histological type nor surgical extent correlated with recurrence . However , the addition of adjuvant MVP chemotherapy could decrease the rate of recurrence and the incidence of cancer-related death after surgery in the patients of stage I NSCLC ( P<0.05 ) . We followed up at least 5 years , and the duration of mean follow-up was 7.3 years . The rates of the loco-regional and distant metastases were 3.4 and 40.7 % in the control group , and 3.4 and 11.9 % in the study group , respectively . The 5- and 10-year survival rates were 74.6 and 56.3 % in the control group , and 81.4 and 65.0 % in the study group , respectively ( P=0.19 , log-rank test ) . The 5- and 10-year disease-free survival rates were 64.8 and 54.8 % in the control group , and 88.8 and 76.8 % in the study group , respectively ( P=0.002 , log-rank test ) . CONCLUSIONS Our results suggest that the addition of adjuvant MVP chemotherapy may reduce the incidence of distant metastasis and prolong the disease-free survival of the patients with stage I NSCLC after surgery We evaluated the therapeutic usefulness of adjuvant chemotherapy in patients with completely resected non-small cell lung cancer ( NSCLC ) . We also examined the relation between DNA ploidy pattern and the response to chemotherapy .  A total of 267 patients with NSCLC ( pathologically documented stage I , II , or IIIA ) underwent complete resection , and DNA ploidy pattern was analysed . Patients with stage I disease ( n=172 ) were r and omly assigned to receive surgery alone ( group A ) or surgery followed by adjuvant chemotherapy ( UFT ( oral anti-cancer drug , a combination of Uracil and Tegaful ) 400 mg day−1 for 1 year after surgery ; group B ) . Stage II or IIIA disease patients ( n=95 ) were r and omly assigned to surgery alone ( group C ) or surgery followed by chemotherapy ( two 28-day courses of cisplatin 80 mg m−2 on day 1 plus vindesine 3 mg m−2 on days 1 and 8 , followed by UFT 400 mg day−1 for at least 1 year ; group D ) . Eight-year overall survival rate in patients with stage I disease was 74.2 % ( 95 % confidence interval ( CI ) : 64.4–84.0 % ) in group B and 57.6 % ( 95 % CI : 46.4–68.8 % ) in group A ( P=0.045 by log-rank test ) . In patients with stage II and IIIA disease , no difference was found between groups C and D. Analysis according to DNA ploidy pattern revealed no difference between the groups . Postoperative chemotherapy with UFT was suggested to be useful in patients with completely resected stage I NSCLC . No difference was seen in relation to DNA pattern in any treatment group BACKGROUND On the basis of a previous meta- analysis , the International Adjuvant Lung Cancer Trial was design ed to evaluate the effect of cisplatin-based adjuvant chemotherapy on survival after complete resection of non-small-cell lung cancer . METHODS We r and omly assigned patients either to three or four cycles of cisplatin-based chemotherapy or to observation . Before r and omization , each center determined the pathological stages to include , its policy for chemotherapy ( the dose of cisplatin and the drug to be combined with cisplatin ) , and its postoperative radiotherapy policy . The main end point was overall survival . RESULTS A total of 1867 patients underwent r and omization ; 36.5 percent had pathological stage I disease , 24.2 percent stage II , and 39.3 percent stage III . The drug allocated with cisplatin was etoposide in 56.5 percent of patients , vinorelbine in 26.8 percent , vinblastine in 11.0 percent , and vindesine in 5.8 percent . Of the 932 patients assigned to chemotherapy , 73.8 percent received at least 240 mg of cisplatin per square meter of body-surface area . The median duration of follow-up was 56 months . Patients assigned to chemotherapy had a significantly higher survival rate than those assigned to observation ( 44.5 percent vs. 40.4 percent at five years [ 469 deaths vs. 504 ] ; hazard ratio for death , 0.86 ; 95 percent confidence interval , 0.76 to 0.98 ; P<0.03 ) 
    Output:
    