***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: UNLABELLED In a major study that showed a treatment advantage for induction chemotherapy followed by radiation therapy ( CALGB 8433 ) , there was a significantly ( P = 0.02 ) lower proportion of patients dying within 105 days of registration in the chemotherapy/radiation arm than the radiation therapy arm ; without this difference , the overall survival was marginally better ( P = 0.059 ) for the chemotherapy/radiation group . A retrospective analysis of RTOG trials sought explanations for the phenomenon . MATERIAL S AND METHODS Patients who fit the CALGB eligibility criteria and received radiation therapy alone in four prospect i ve trials of the RTOG conducted between 1983 and 1989 were analyzed to determine factors that distinguished patients dying within 105 days from longer survivors . Two were trials of altered fractionation and two used st and ard fractionation . Of 683 patients identified , 107 ( 15.7 % ) died within 105 days after registration . The log linear model was used to evaluate relationships between death within 105 days and known prognostic factors . Karnofsky performance status ( KPS ) , < 90 vs. > or = 90 , was the only factor significantly related to death within 105 days ( P = 0.0052 ) . A Cox model with the same factors plus fractionation and total dose found KPS and T-stage associated with overall survival ( P = 0.0005 and 0.025 , respectively ) . The choice of the hyperfractionation arm ( HFX ) for Phase III study ( 69.6 Gy at 1.2 Gy b.i.d . ) was based in part on comparison with st and ard fractionation ( STD ) from a concurrent RTOG protocol , 8321 . Review of early deaths showed that this HFX arm had a lower proportion of patients dying within 105 days ( 7.9 % ) than STD in 8321 ( 21.0 % ) . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND CYFRA 21 - 1 , a serum cytokeratin 19 fragment , and neuron specific enolase ( NSE ) , the gamma-subunit of enolase , are putative markers of lung cancer . Their clinical applicability as prognostic factors in non-small cell lung cancer ( NSCLC ) would need an appraisal by simultaneous evaluation of other known survival determinants in a large population followed over a long period . AIM To determine the prognostic value of different clinical and routine biological variables at presentation with particular attention paid to the above-mentioned markers . METHODS 621 histologically proven and previously untreated NSCLC patients have been prospect ively studied ( seven were lost to follow-up ) . Median follow-up was 4 years and 2 months . At presentation , 16 clinical and biological variables were recorded .  Serum NSE and CYFRA 21 - 1  were assayed blind without any clinical information given . RESULTS The serum CYFRA 21 - 1 distribution differed significantly according to histology , disease stage and performance status , with the highest levels observed in squamous cell carcinomas , metastatic stage , positive mediastinal nodal status and poor performance status . However , the respective " receiver operating characteristic " curves showed that the  CYFRA 21 - 1 serum level did not accurately predict tumour stage . Serum NSE distribution correlated neither with tumour stage nor with performance index and its sensitivity in the whole NSCLC was low . In the Cox proportional hazard model , the following variables were independent determinants of a poor outcome : performance status 2 or 3 , hazard ratio ( HR ) : 2.25 ; Nodal status N(2 - 3 ) , HR : 1.84 ; Metastatic disease , HR : 1.73 ; NSE>12.5 ng/ml , HR : 1.52 ; CYFRA 21 - 1>3.6 ng/ml , HR : 1.41 and Tumour status T(3 - 4 ) , HR : 1.31 . When the survival analysis was restricted to the 274 patients affected by a metastatic stage , we observed that performance status , nodal status , NSE and CYFRA 21 - 1 remained prognostic determinants with similar hazard ratios . CONCLUSION The prognostic information given by a high serum CYFRA 21 - 1 level is independent from other well-known variables such as performance status and disease stage and is perennial throughout extended follow-up period . A high NSE level also prognosticates a poor outcome probably by reflecting tumour heterogeneity and underestimated neuroendocrine differentiation The aim of this study was the assessment of the predictive value for survival of an antitumoral response to three courses of chemotherapy in association with various pretreatment characteristics in patients with non-resectable non-small cell lung cancer treated by cisplatin- ( or carboplatin)-based combination regimens . Patients considered for this study were eligible patients with advanced non-small cell lung cancer registered in one of the seven trials conducted by the European Lung Cancer Working Party from December 1980 to August 1991 . All these trials tested chemotherapy regimens with platinum derivatives ( cisplatin and /or carboplatin ) . In this population of 1052 eligible patients , 752 were assessed in this analysis . Data were prospect ively collected on 23 pretherapeutic variables and objective response after three chemotherapy cycles . The predictive value of response to chemotherapy on survival ( measured from the time of response assessment i.e. 12 weeks after registration in the trial ) was studied by univariate analysis as well as by multivariate methods ( adjustment of the impact of several covariates simultaneously on the dependent variable ) with adjustment for the pretreatment prognostic variables . After three cycles of chemotherapy , the global estimated median survival time was 24 weeks with a 95 % confidence interval of 22 - 25 weeks . By univariate analysis , we identified an objective response to chemotherapy as a highly significant discriminant marker ( P < 0.0001 ) for further survival with estimated median survival times of 41 weeks ( 95 % CI : 38 - 46 ) and 19 weeks ( 95 % CI : 17 - 20 ) , respectively , for the responding and non-responding patients . In a Cox regression model fitted to the data using a forward stepwise procedure , this variable was the first selected explanatory variable . Its effect was adjusted by the introduction in the model of initial disease extent , Karnofsky performance status , serum calcium level and white blood cell count . These results were consistent with those obtained by application of recursive partitioning and amalgamation algorithms ( RECPAM ) which led to a classification of the patients into three homogeneous subgroups . Our results , using a classical Cox regression model consistent with those highlighted by application of a RECPAM analysis , found an objective response to chemotherapy to be a predominant predictive factor for further survival , although it did not allow any conclusion about a causal relationship . The RECPAM results led to a classification of the patients into three subgroups which needs to be vali date d in other series Levels of the tumour markers neurone specific enolase ( NSE ) , lactate dehydrogenase ( LDH ) ,  chromogranin A ( ChrA ) and carcinoembryonic antigen ( CEA ) were measured in serum taken at presentation and during treatment , remission and relapse from 154 patients who received chemotherapy for small cell lung cancer at a single centre over a 6 year period . At presentation NSE was the most frequently elevated marker , being raised in 81 % of patients and significantly higher in extensive as opposed to limited disease , as were LDH and ChrA. The response rate to therapy was best correlated with presentation level of ChrA , being 79 % for those whose levels were within twice the upper limit of normal and 51 % above ( P < 0.01 ) . Multivariate regression analysis showed NSE , performance status and albumin at presentation to be the best independent predictors of survival . Patients with NSE below twice the upper limit of normal , Karnofsky performance status of 80 or above and albumin 35 g l-1 or above had a median survival of 15 months with 25 % alive at 2 years , whilst those with NSE above twice normal , Karnofsky below 80 and albumin less that 35 g l-1 had all died by 8 months . Changes in marker levels during therapy were of low predictive value for outcome although the finding of rising NSE during chemotherapy after an initial fall correlated with significantly reduced duration of remission . There was a strong inverse correlation between the NSE level at the time of response and duration of remission ( P < 0.0001 ) . Prediction of relapse was most reliable with ChrA , 52 % of patients having rising levels before clinical evidence of disease recurrence BACKGROUND The predictive and prognostic role of neuron-specific enolase ( NSE ) in non-small cell lung cancer ( NSCLC ) is still under debate . PATIENTS AND METHODS To study these aspects ,  serum NSE  was prospect ively measured at baseline of first-line chemotherapy treatment and tested for correlation with clinical outcome in 129 advanced NSCLC patients . RESULTS An objective response was achieved in 27 out of 65 ( 41.5 % ) patients with NSE < 8.6 ng/ml and in 38 out of 64 ( 59.4 % ) patients with NSE > or = 8.6 ng/ml ( p = 0.05 ) . Logistic analysis confirmed the positive association between objective response and NSE values > or = 8.6 ng/ml ( odds ratio = 1.69 ; 95 % confidence interval : 1.09 - 2.63 ; p = 0.02 ) . Overall median survival was 10.8 months . A statistically significant prognostic effect on survival was found for performance status , stage and response to treatment , but not for baseline NSE value . CONCLUSION Based on these data , baseline circulating tumor NSE levels appear to have a weak predictive role , but not a prognostic significance in patients with advanced NSCLC su bmi tted to st and ard chemotherapy Several studies have suggested that biochemical or molecular markers examined in non-small cell lung cancer carry prognostic or treatment response information . Non-small cell lung cancer patients whose tumors have neuroendocrine ( NE ) features may be more responsive to chemotherapy . In addition , increased expression of HER2 ( c-erbB-2 ) , a membrane-bound receptor with tyrosine kinase activity , has been associated with shortened survival . The Cancer and Leukemia Group B ( CALGB ) performed a study of patients with stage IIIA ( N2 nodes positive ) non-small cell lung cancer in which patients received initial chemotherapy followed by surgery , then post-operative therapy consisting of sequential chemotherapy and radiation therapy . Since all patients underwent mediastinoscopy , this provided an opportunity to compare pre- and post-chemotherapy tumor specimens to test the hypothesis that these proteins would predict treatment response . In particular , we hypothesized that the post-chemotherapy specimens would be enriched for NE marker negative cells because of the increased sensitivity of NE positive cells to chemotherapy . We performed immunohistochemical analysis for a panel of NE markers [ neuron-specific enolase ( NSE ) , Leu-7 , chromogranin A ( ChrA ) , synaptophysin ( Syn ) ] , HER2 and CEA to determine if there was an effect of therapy on the percentage of cells expressing these markers . Secondary endpoints were a correlation with chemotherapy response and survival . Slides were scored for intensity ( 0 - 4 ) and percentage of cells positive ( 0 - 4 ) . Of 61 eligible patients , there were 38 with both pre- and post-chemotherapy specimens . When both intensity of staining and percentage of positive cells were considered , post-chemotherapy specimens had a higher percentage of positive NE markers compared with pre-chemotherapy . In addition , there was no correlation between NE marker , HER2 or CEA expression ( prior to or post treatment ) and response to chemotherapy or survival . These data do not support the hypothesis that NE positive tumor cells are preferentially killed by chemotherapy in patients with stage IIIA non-small cell lung cancer To evaluate the impact of non-small cell lung cancer ( NSCLC ) histological subtypes on survival , we performed a retrospective multivariate analysis of survival in 361 patients with a NSCLC diagnosed in 1987 and 1988 at the University Hospital in Strasbourg , France . There were 262 ( 73 % ) squamous cell carcinomas ( SQ ) , 59 ( 16 % ) adenocarcinomas other than bronchioloalveolar carcinoma ( ADOBAC ) , 24 ( 7 % ) bronchioloalveolar carcinoma ( BAC ) and 16 ( 4 % ) large cell carcinomas ( LC ) . The proportion of metastatic disease was significantly higher in the ADOBAC group than in the SQ group ( 30 % vs. 15 % , P < 0.001 ) . In operated patients , only extent of disease and age were independent prognostic factors . In patients with unresectable NSCLC , extent of disease had also the heaviest impact on survival . However , in these unresected patients , ADOBAC had a pejorative impact on survival , in contrast to BAC which was of better prognosis . If these results are confirmed by prospect i ve studies , this will support stratification according to histological subtypes in clinical trials involving inoperable NSCLC patients OBJECTIVE To assess the value of Cyfra 21 - 1 , carcino-embryonic antigen ( CEA ) and neuron-specific enolase ( NSE ) combined , all three together as prognostic factors in advanced stage non-small cell lung cancer ( NSCLC ) patients . PATIENTS AND METHODS Serum sample s from untreated NSCLC patients were prospect ively collected . All assays were performed using commercial kits blind to clinical information . Serum levels of CEA , NSE and Cyfra 2 
    Output:
    
The present study indicated that serum NSE level is of no prognostic significance in patients with NSCLC