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: 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 BACKGROUND Results from phase II studies in patients with stage IIIA non-small-cell lung cancer with ipsilateral mediastinal nodal metastases ( N2 ) have shown the feasibility of resection after concurrent chemotherapy and radiotherapy with promising rates of survival . We therefore did this phase III trial to compare concurrent chemotherapy and radiotherapy followed by resection with st and ard concurrent chemotherapy and definitive radiotherapy without resection . METHODS Patients with stage T1 - 3pN2M0 non-small-cell lung cancer were r and omly assigned in a 1:1 ratio to  concurrent induction chemotherapy  ( two cycles of cisplatin [ 50 mg/m(2 ) on days 1 , 8 , 29 , and 36 ] and etoposide [ 50 mg/m(2 ) on days 1 - 5 and 29 - 33 ] ) plus radiotherapy ( 45 Gy ) in multiple academic and community hospitals . If no progression , patients in group 1 underwent resection and those in group 2 continued radiotherapy uninterrupted up to 61 Gy . Two additional cycles of cisplatin and etoposide were given in both groups . The primary endpoint was overall survival ( OS ) . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00002550 . FINDINGS 202 patients ( median age 59 years , range 31 - 77 ) were assigned to group 1 and 194 ( 61 years , 32 - 78 ) to group 2 .  Median OS was 23.6 months ( IQR 9.0-not reached ) in group 1 versus 22.2 months ( 9.4 - 52.7 ) in group 2 ( hazard ratio [ HR ] 0.87 [ 0.70 - 1.10 ] ; p=0.24 ) . Number of patients alive at 5 years was 37 ( point estimate 27 % ) in group 1 and 24 ( point estimate 20 % ) in group 2 ( odds ratio 0.63 [ 0.36 - 1.10 ] ; p=0.10 ) . With N0 status at thoracotomy , the median OS was 34.4 months ( IQR 15.7-not reached ; 19 [ point estimate 41 % ] patients alive at 5 years ) . Progression-free survival ( PFS ) was better in group 1 than in group 2 , median 12.8 months ( 5.3 - 42.2 ) vs 10.5 months ( 4.8 - 20.6 ) , HR 0.77 [ 0.62 - 0.96 ] ; p=0.017 ) ; the number of patients without disease progression at 5 years was 32 ( point estimate 22 % ) versus 13 ( point estimate 11 % ) , respectively . Neutropenia and oesophagitis were the main grade 3 or 4 toxicities associated with chemotherapy plus radiotherapy in group 1 ( 77 [ 38 % ] and 20 [ 10 % ] , respectively ) and group 2 ( 80 [ 41 % ] and 44 [ 23 % ] , respectively ) . In group 1 , 16 ( 8 % ) deaths were treatment related versus four ( 2 % ) in group 2 . In an exploratory analysis , OS was improved for patients who underwent lobectomy , but not pneumonectomy , versus chemotherapy plus radiotherapy . INTERPRETATION Chemotherapy plus radiotherapy with or without resection ( preferably lobectomy ) are options for patients with stage IIIA(N2 ) non-small-cell lung cancer . FUNDING National Cancer Institute , Canadian Cancer Society , and National Cancer Institute of Canada PURPOSE To evaluate mediastinal nodal clearance ( MNC ) rates after induction chemotherapy and concurrent , full-dose radiation therapy ( RT ) in a phase II trimodality trial ( Radiation Therapy Oncology Group protocol 0229 ) . PATIENTS AND METHODS Patients ( n=57 ) with stage III non-small cell lung cancer ( pathologically proven N2 or N3 ) were eligible .  Induction chemotherapy consisted of weekly carboplatin ( AUC = 2.0 ) and paclitaxel 50 mg/m(2 ) . Concurrent RT was prescribed , with 50.4 Gy to the mediastinum and primary tumor and a boost of 10.8 Gy to all gross disease . The mediastinum was pathologically reassessed after completion of chemoradiation . The primary endpoint of the study was MNC , with secondary endpoints of 2-year overall survival and postoperative morbidity/mortality . RESULTS The grade 3/4 toxicities included hematologic 35 % , gastrointestinal 14 % , and pulmonary 23 % . Forty-three patients ( 75 % ) were evaluable for the primary endpoint . Twenty-seven patients achieved the primary endpoint of MNC ( 63 % ) . Thirty-seven patients underwent resection . There was a 14 % incidence of grade 3 postoperative pulmonary complications and 1 30-day , postoperative grade 5 toxicity ( 3 % ) . With a median follow-up of 24 months for all patients , the 2-year overall survival rate was 54 % , and the 2-year progression-free survival rate was 33 % . The 2-year overall survival rate was 75 % for those who achieved nodal clearance , 52 % for those with residual nodal disease , and 23 % for those who were not evaluable for the primary endpoint ( P=.0002 ) . CONCLUSIONS This multi-institutional trial confirms the ability of neoadjuvant concurrent chemoradiation with full-dose RT to sterilize known mediastinal nodal disease The role of post-operative radiotherapy for patients with non-small-cell lung cancer ( NSCLC ) is unclear despite five previous r and omised trials . One deficiency with these trials was that they did not include adequate TNM staging , and so the present r and omised trial was design ed to compare surgery alone ( S ) with surgery plus post-operative radiotherapy ( SR ) in patients with pathologically staged T1 - 2 , N1 - 2 . M0 NSCLC . Between July 1986 and October 1993 , 308 patients ( 154 S , 154 SR ) were entered from 16 centres in the UK . The median age of the patients was 62 years , 74 % were male , > 85 % had normal or near normal levels of general condition , activity and breathlessness , 68 % had squamous carcinoma , 52 % had had a pneumonectomy , 63 % had N1 disease and 37 % N2 disease . SR patients received 40 Gy in 15 fractions starting 4 - 6 weeks post-operatively . Overall there was no advantage to either group in terms of survival , although definite local recurrence and bony metastases appeared less frequently and later in the SR group . In a subgroup analysis , in the N1 group no differences between the treatment groups were seen , but in the N2 group SR patients appeared to gain a one month survival advantage , delayed time to local recurrence and time to appearance of the bone metastases . There is , therefore , no clear indication for post-operative radiotherapy in N1 disease , but the question remains unresolved in N2 disease BACKGROUND We have used doses of 60Gy or higher for neoadjuvant chemoradiotherapy for select patients with advanced non-small cell lung cancer ( NSCLC ) , including patients with N2 disease and those with Pancoast lesions , to avoid gaps in radiotherapy in case surgery is ultimately not offered . METHODS A retrospective cohort study using a prospect i ve data base . Patients underwent initial staging with CT , PET/CT and lymph node biopsy ( mediastinoscopy , endoscopic esophageal ultrasound and endobronchial ultrasound ) and then received neoadjuvant high dose radiotherapy and chemotherapy , followed by thoracotomy with intent to cure . RESULTS Between January 1998 and June 2008 there were 216 patients who were eligible for this study . The median dose of radiation was 60Gy ( range 60 - 72Gy ) . Lobectomy was performed in 152 patients ( 70 % ) about 7 weeks after radiotherapy finished ( mean 51 days , range 34 - 89 days).The bronchus was buttressed with an intercostal muscle flap in 97 % patients . Median hospital stay was 4.5 days ( range 2 - 57 ) . Major morbidity occurred in 17 % . There were five ( 2.3 % ) deaths . There were no bronchial-pleural fistulas after lobectomy , but two occurred after right pneumonectomy . Predictors of morbidity were FEV(1 ) < 50 % ( p<0.001 ) , DLCO < 60 % ( p<0.001 ) and age > 75 years ( p=0.008 ) . The overall 5-year Kaplan-Meier survival was 34 % . It was 42 % for those who underwent R0 resection , 3 
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agent
RESULTS For patients who have undergone surgical resection , high-level evidence suggests that use of postoperative RT does not influence survival , but optimizes local control for patients with N2 involvement , and its use in the setting of positive margins or gross primary /nodal residual disease is recommended .
No high-level evidence exists for the routine use of preoperative induction chemoradiation therapy ; however , modern surgical series and a post-hoc Intergroup 0139 clinical trial analysis suggest that a survival benefit may exist if patients are properly selected and surgical techniques/postoperative care is optimized .
***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: 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 BACKGROUND Results from phase II studies in patients with stage IIIA non-small-cell lung cancer with ipsilateral mediastinal nodal metastases ( N2 ) have shown the feasibility of resection after concurrent chemotherapy and radiotherapy with promising rates of survival . We therefore did this phase III trial to compare concurrent chemotherapy and radiotherapy followed by resection with st and ard concurrent chemotherapy and definitive radiotherapy without resection . METHODS Patients with stage T1 - 3pN2M0 non-small-cell lung cancer were r and omly assigned in a 1:1 ratio to  concurrent induction chemotherapy  ( two cycles of cisplatin [ 50 mg/m(2 ) on days 1 , 8 , 29 , and 36 ] and etoposide [ 50 mg/m(2 ) on days 1 - 5 and 29 - 33 ] ) plus radiotherapy ( 45 Gy ) in multiple academic and community hospitals . If no progression , patients in group 1 underwent resection and those in group 2 continued radiotherapy uninterrupted up to 61 Gy . Two additional cycles of cisplatin and etoposide were given in both groups . The primary endpoint was overall survival ( OS ) . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00002550 . FINDINGS 202 patients ( median age 59 years , range 31 - 77 ) were assigned to group 1 and 194 ( 61 years , 32 - 78 ) to group 2 .  Median OS was 23.6 months ( IQR 9.0-not reached ) in group 1 versus 22.2 months ( 9.4 - 52.7 ) in group 2 ( hazard ratio [ HR ] 0.87 [ 0.70 - 1.10 ] ; p=0.24 ) . Number of patients alive at 5 years was 37 ( point estimate 27 % ) in group 1 and 24 ( point estimate 20 % ) in group 2 ( odds ratio 0.63 [ 0.36 - 1.10 ] ; p=0.10 ) . With N0 status at thoracotomy , the median OS was 34.4 months ( IQR 15.7-not reached ; 19 [ point estimate 41 % ] patients alive at 5 years ) . Progression-free survival ( PFS ) was better in group 1 than in group 2 , median 12.8 months ( 5.3 - 42.2 ) vs 10.5 months ( 4.8 - 20.6 ) , HR 0.77 [ 0.62 - 0.96 ] ; p=0.017 ) ; the number of patients without disease progression at 5 years was 32 ( point estimate 22 % ) versus 13 ( point estimate 11 % ) , respectively . Neutropenia and oesophagitis were the main grade 3 or 4 toxicities associated with chemotherapy plus radiotherapy in group 1 ( 77 [ 38 % ] and 20 [ 10 % ] , respectively ) and group 2 ( 80 [ 41 % ] and 44 [ 23 % ] , respectively ) . In group 1 , 16 ( 8 % ) deaths were treatment related versus four ( 2 % ) in group 2 . In an exploratory analysis , OS was improved for patients who underwent lobectomy , but not pneumonectomy , versus chemotherapy plus radiotherapy . INTERPRETATION Chemotherapy plus radiotherapy with or without resection ( preferably lobectomy ) are options for patients with stage IIIA(N2 ) non-small-cell lung cancer . FUNDING National Cancer Institute , Canadian Cancer Society , and National Cancer Institute of Canada PURPOSE To evaluate mediastinal nodal clearance ( MNC ) rates after induction chemotherapy and concurrent , full-dose radiation therapy ( RT ) in a phase II trimodality trial ( Radiation Therapy Oncology Group protocol 0229 ) . PATIENTS AND METHODS Patients ( n=57 ) with stage III non-small cell lung cancer ( pathologically proven N2 or N3 ) were eligible .  Induction chemotherapy consisted of weekly carboplatin ( AUC = 2.0 ) and paclitaxel 50 mg/m(2 ) . Concurrent RT was prescribed , with 50.4 Gy to the mediastinum and primary tumor and a boost of 10.8 Gy to all gross disease . The mediastinum was pathologically reassessed after completion of chemoradiation . The primary endpoint of the study was MNC , with secondary endpoints of 2-year overall survival and postoperative morbidity/mortality . RESULTS The grade 3/4 toxicities included hematologic 35 % , gastrointestinal 14 % , and pulmonary 23 % . Forty-three patients ( 75 % ) were evaluable for the primary endpoint . Twenty-seven patients achieved the primary endpoint of MNC ( 63 % ) . Thirty-seven patients underwent resection . There was a 14 % incidence of grade 3 postoperative pulmonary complications and 1 30-day , postoperative grade 5 toxicity ( 3 % ) . With a median follow-up of 24 months for all patients , the 2-year overall survival rate was 54 % , and the 2-year progression-free survival rate was 33 % . The 2-year overall survival rate was 75 % for those who achieved nodal clearance , 52 % for those with residual nodal disease , and 23 % for those who were not evaluable for the primary endpoint ( P=.0002 ) . CONCLUSIONS This multi-institutional trial confirms the ability of neoadjuvant concurrent chemoradiation with full-dose RT to sterilize known mediastinal nodal disease The role of post-operative radiotherapy for patients with non-small-cell lung cancer ( NSCLC ) is unclear despite five previous r and omised trials . One deficiency with these trials was that they did not include adequate TNM staging , and so the present r and omised trial was design ed to compare surgery alone ( S ) with surgery plus post-operative radiotherapy ( SR ) in patients with pathologically staged T1 - 2 , N1 - 2 . M0 NSCLC . Between July 1986 and October 1993 , 308 patients ( 154 S , 154 SR ) were entered from 16 centres in the UK . The median age of the patients was 62 years , 74 % were male , > 85 % had normal or near normal levels of general condition , activity and breathlessness , 68 % had squamous carcinoma , 52 % had had a pneumonectomy , 63 % had N1 disease and 37 % N2 disease . SR patients received 40 Gy in 15 fractions starting 4 - 6 weeks post-operatively . Overall there was no advantage to either group in terms of survival , although definite local recurrence and bony metastases appeared less frequently and later in the SR group . In a subgroup analysis , in the N1 group no differences between the treatment groups were seen , but in the N2 group SR patients appeared to gain a one month survival advantage , delayed time to local recurrence and time to appearance of the bone metastases . There is , therefore , no clear indication for post-operative radiotherapy in N1 disease , but the question remains unresolved in N2 disease BACKGROUND We have used doses of 60Gy or higher for neoadjuvant chemoradiotherapy for select patients with advanced non-small cell lung cancer ( NSCLC ) , including patients with N2 disease and those with Pancoast lesions , to avoid gaps in radiotherapy in case surgery is ultimately not offered . METHODS A retrospective cohort study using a prospect i ve data base . Patients underwent initial staging with CT , PET/CT and lymph node biopsy ( mediastinoscopy , endoscopic esophageal ultrasound and endobronchial ultrasound ) and then received neoadjuvant high dose radiotherapy and chemotherapy , followed by thoracotomy with intent to cure . RESULTS Between January 1998 and June 2008 there were 216 patients who were eligible for this study . The median dose of radiation was 60Gy ( range 60 - 72Gy ) . Lobectomy was performed in 152 patients ( 70 % ) about 7 weeks after radiotherapy finished ( mean 51 days , range 34 - 89 days).The bronchus was buttressed with an intercostal muscle flap in 97 % patients . Median hospital stay was 4.5 days ( range 2 - 57 ) . Major morbidity occurred in 17 % . There were five ( 2.3 % ) deaths . There were no bronchial-pleural fistulas after lobectomy , but two occurred after right pneumonectomy . Predictors of morbidity were FEV(1 ) < 50 % ( p<0.001 ) , DLCO < 60 % ( p<0.001 ) and age > 75 years ( p=0.008 ) . The overall 5-year Kaplan-Meier survival was 34 % . It was 42 % for those who underwent R0 resection , 3 
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