***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 Cancers rely on angiogenesis for their growth and dissemination . We hypothesized that thalidomide , an oral antiangiogenic agent , when combined with chemotherapy , and as maintenance treatment , would improve survival in patients with advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Seven hundred twenty-two patients were r and omly assigned to receive placebo or thalidomide capsules 100 to 200 mg daily for up to 2 years . All patients received gemcitabine and carboplatin every 3 weeks for up to four cycles . End points were overall survival ( OS ) , progression-free survival ( PFS ) , response rate , grade 3/4 toxicity , and quality of life ( QoL ) . RESULTS The median OS rates were 8.9 months ( placebo ) and 8.5 months ( thalidomide ) . The hazard ratio ( HR ) was 1.13 ( 95 % CI , 0.97 to 1.32 ; P = .12 ) . The 2-year survival rate was 16 % and 12 % in the placebo and thalidomide arms , respectively . The PFS results were consistent with those for OS . The risk of having a thrombotic event was increased by 74 % in the thalidomide group : HR of 1.74 ( 95 % CI , 1.20 to 2.52 ; P = .003 ) . There were no differences in hematologic toxicities , but a slight excess of rash and neuropathy in the thalidomide group . QoL scores were similar but thalidomide was associated with less insomnia , and more constipation and peripheral neuropathy . In a retrospective analysis , patients with nonsquamous histology in the thalidomide group had a poorer survival : 2-year risk difference of 10 % ( 95 % CI , 4 % to 16 % ; P < .001 ) . CONCLUSION In this large trial of patients with NSCLC , thalidomide in combination with chemotherapy did not improve survival overall , but increased the risk of thrombotic events . Unexpectedly , survival was significantly worse in patients with nonsquamous histology We present experience from a phase II r and omized clinical trial , comparing st and ard gemcitabine as monotherapy with low-dose gemcitabine in long infusion in a doublet with cisplatin at reduced dose for patients with non-small cell lung cancer ( NSCLC ) and who are unfit for st and ard platin-based chemotherapy . Eligible patients had microscopically confirmed NSCLC in stage IIIB ( wet ) or IV , were chemo-naive , and were in poor performance status or presented with significant comorbidity .  St and ard treatment with gemcitabine , 1250 mg/m2 in 20–30 min on days 1 and 8 as monotherapy ( arm A ) was compared with low-dose gemcitabine in long infusion ( 200 mg/m2 in 6 h on day 1 ) and cisplatin at 60 mg/m2 on day 2 ( arm B ) . Both treatment schedules were repeated every 3 weeks until disease progression , unacceptable toxicity , or to a maximum of six cycles . A total of 112 patients ( 83 male , 29 female , median age 66 years ) were r and omized between arm A ( 57 patients ) and B ( 55 patients ) . The two groups were balanced for prognostic factors . Fifty-three patients in arm A and 52 in arm B received at least one application of chemotherapy and were evaluable for toxicity and response . The median number of cycles was four and five for arms A and B , respectively . Except for grade 3 anemia ( one patient in arm A and two in arm B ) , no other major toxicity was seen . Regarding response to treatment , arm B was superior : 1 complete response and 13 partial remissions ( response rate 26.9 % ) as compared with five partial remissions ( response rate 9.4 % ) in arm A ( P<0.01 ) . The median time to progression was 3.8 and 5.6 months , and the median survival was 4.3 and 6.8 months for arms A and B , respectively ( P<0.05 ) . Treatment with low-dose gemcitabine in long infusion and cisplatin at reduced dose has very low toxicity , is effective , was found to be superior to monotherapy with gemcitabine in st and ard doses , and is suitable for patients with NSCLC who can not tolerate a st and ard platin-based doublet PURPOSE To determine the radiosensitizing effect of prolonged exposure of carboplatin in patients with locally unresectable non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Patients with histologically proven NSCLC , performance score < 2 , weight loss < 10 % , and normal organ functions were r and omized between carboplatin 840 mg/m2 administered continuously during 6 weeks of radiotherapy or thoracic radiotherapy alone ( both 60 Gy ) . Toxicity was evaluated with National Cancer Institute Common Toxicity Criteria ( NCI CTC ) and the Radiation Therapy Oncology Group ( RTOG ) criteria . Quality of life was measured with European Organization for Research and Treatment of Cancer ( EORTC ) QLQ-C30/LC13 question naires . RESULTS One-hundred and sixty patients were included . Pathologically confirmed persistent tumor was present in 53 % of patients in the combination arm versus 58 % in the radiotherapy alone arm ( P=0.5 ) . Median survival in the combination arm was 11.8 [ 95 % confidence interval ( CI ) 9.3 - 14.2 ] months and in the radiotherapy alone arm 11.7 ( 95 % CI 8.1 - 15.5 ) months ; progression-free survival was not different between arms [ 6.8 and 7.5 months , respectively ( P=0.28 ) ] . Acute toxicity was mild , late toxicity was radiation-induced cardiomyopathy ( three patients ) and pulmonary fibrosis ( five patients ) . Quality of life was not different between arms , but in all measured patients cough and dyspnea improved , pain became less , and slight paresthesia developed 3 months after treatment . CONCLUSION Addition of continuously administered carboplatin as radiosensitizer for locally unresectable NSCLC does not improve local tumor control or overall survival BACKGROUND AND PURPOSE To compare the course of symptoms and health-related quality -of-life ( HRQOL ) after immediate thoracic radiotherapy ( TRT ) between symptomatic ( S ) and non-symptomatic ( NS ) patients with advanced NSCLC . PATIENTS AND METHODS 407 stage III/IV patients were initially treated with immediate TRT  within a r and omised phase III trial comparing different fractionation schedules . At inclusion , patients were prospect ively stratified according to presence ( S ) or absence ( NS ) of tumour-related chest/airway symptoms to facilitate comparison between these groups . The EORTC QLQ-C30 and LC-13 were used for symptom and HRQOL assessment s at baseline and at regular intervals up to 1 year ( N=395 ) . RESULTS NS patients had significantly more favourable baseline characteristics when compared to S patients with a median survival of 11.8 versus 6.0 months ( P<0.0001 ) , respectively . At baseline , S patients demonstrated HRQOL scores inferior to those of NS patients ( P<0.01 ) for most scales . Until week 14 , NS patients developed more symptoms while S patients experienced symptom relief in most scales . After week 14 , no significant differences could be observed between the groups . CONCLUSION This study indicates that immediate TRT , given to patients with minimal/none chest symptoms , does not prevent development of disease-related symptoms and diminished HRQOL . A wait- and -see policy appears to be acceptable PURPOSE Gemcitabine plus carboplatin ( GC ) is active as front-line treatment for advanced non-small-cell lung cancer ( NSCLC ) . For patients without progression , timing of second-line chemotherapy for optimum clinical benefit remains uncertain . This phase III , r and omized trial assessed the efficacy and safety of docetaxel administered either immediately after GC or at disease progression . PATIENTS AND METHODS The chemotherapy-naïve patients enrolled had either stage IIIB NSCLC with pleural effusion or stage IV NSCLC .  Gemcitabine ( 1,000 mg/m(2 ) ) was administered on days 1 and 8 followed by carboplatin ( area under the curve = 5 ) on day 1 . After four 21-day cycles , patients who did not have progression were r and omly assigned either to an immediate docetaxel group ( docetaxel 75 mg/m(2 ) on day 1 every 21 days , with maximum of six cycles ) or to a delayed docetaxel group . The primary end point was overall survival ( OS ) measured from r and om assignment . Additional analyses included tumor response , toxicity , progression-free survival ( PFS ) , and quality of life ( QOL ) . RESULTS Enrollment totaled 566 patients ; 398 patients completed GC ; 309 patients were r and omly assigned equally to the two docetaxel treatment groups . Toxicity profiles were generally comparable for the docetaxel groups . Median PFS for immediate docetaxel ( 5.7 months ) was significantly greater ( P = .0001 ) than for delayed docetaxel ( 2.7 months ) . Median OS for immediate docetaxel ( 12.3 months ) was greater than for delayed docetaxel ( 9.7 months ) , but the difference was not statistically significant ( P = .0853 ) . QOL results were not statistically different ( P = .76 ) between docetaxel groups . CONCLUSION We observed a statistically significant improvement in PFS and a nonstatistically significant increase in OS when docetaxel was administered immediately after front-line GC , without increasing toxicity or decreasing QOL The purpose of our study was to compare progression-free survival and quality of life ( QOL ) after cisplatin – gemcitabine ( CG ) or epirubicin – gemcitabine ( EG ) in chemotherapy-naive patients with unresectable non-small-cell lung cancer . Patients ( n=240 ) were r and omised to receive gemcitabine 1125 mg m−2 ( days 1 and 8) plus either cisplatin 80 mg m−2 ( day 2 ) or epirubicin 100 mg m−2 ( day 1 ) every 3 weeks for a maximum of five cycles . Eligible patients had normal organ functions and Eastern Cooperative Oncology Group performance status ⩽2 .  QOL was measured with European Organisation for Research and Treatment of Cancer QLQ-C30 and LC13 question naires . There were no significant differences in median progression-free survival ( CG 26 weeks , EG 23 weeks ) , median overall survival ( CG 43 weeks , EG 36 weeks ) , or tumour response rates ( CG 46 % , EG 36 % ) . Toxicity was mainly haematologic . In the EG arm granulocytopenia occurred more frequently , leading to more febrile neutropenia . Also , elevation of serum transaminases , mucositis , fever , and decline in LVEF were more common in the EG arm . In the CG arm , more patients experienced elevated serum creatinine levels , sensory neuropathy , nausea , and vomiting . Global QOL was not different in both arms . Progression-free survival , overall survival , response rate , and QOL were not different between both arms ; however , overall toxicity was more severe in the EG arm Objective : Gemcitabine in low dose in prolonged infusion is a treatment with documented activity against a variety of tumors . We here report the first r and omized trial to compare st and ard brief and low-dose prolonged infusion of gemcitabine . Patients and Methods : Eligible patients had non-small cell lung cancer in stage IIIB ( wet ) or IV , Karnofsky performance status 100 to 70 ( Eastern Cooperative Oncology Group 0–2 ) , measurable disease , were chemonaïve and fulfilled the st and ard criteria for chemotherapy . In arm A ( st and ard treatment ) , gemcitabine was given at 1250 mg/m2 in 20 to 30 minutes and in arm B ( prolonged infusion ) at 250 mg/m2 in 6 hours infusion . All patients received gemcitabine on days 1 and 8 and cisplatin at 75 mg/m2 on day 2 of a 3-week cycle for four cycles , followed by two cycles of gemcitabine as monotherapy . Results : A total of 249 patients ( 188 men and 61 women , median age 58 years ) were r and omized between arm A ( 125 patients ) and arm B ( 124 patients ) . Adenocarcinoma ( 53.9 % ) was the predominant histologic type ; 92 % of patients were in stage IV . The two groups were balanced for prognostic factors ; however , group A had fewer patients with significant weight loss and no patient with lung cancer as a second malignancy or after radiotherapy for brain metastases . Grade 3 or greater toxicity was rare : anemia in 0.8 and 3.2 % , neutropenia in 21.6 and 22.6 % , thrombocytopenia in 0 and 1.6 % , and nausea/vomiting in 4 and 8.1 % for arms A and B , respectively . Alopecia was seen in 54.5 % of patients in arm B , as compared with 9. 
    Output:
    
The quality of HRQOL reporting has improved ; both reporting of clinical ly significant differences and statistical testing of HRQOL have improved .
The number of NSCLC RCTs incorporating HRQOL assessment s has considerably increased .
HRQOL continues to demonstrate its importance in RCTs , especially in those studies in which no OS difference is found .