***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: Treatment of chronic myeloid leukaemia ( CML ) with IFN-alpha ( IFN ) is known to confer significant survival benefit , but the drug 's impact on quality of life ( QoL ) in CML is unclear . We describe a cross-sectional comparison of QoL in patients r and omised to long-term treatment with IFN versus no IFN  within the UK MRC CML 3 trial , assessing the long-term consequences and psychosocial side effects of IFN therapy . Patients completed the EORTC QoL QLQ-C30 , an in-house leukaemia/IFN question naire , a brief assessment of sexual functioning and demographic details . In total , 163 eligible patients completed question naires ( 85 % response ) . Patients receiving IFN reported significantly worse QoL for emotional , cognitive and social functioning , pain and dyspnoea ( P<0.01 ) , and marginally worse fatigue , nausea and vomiting ( P<0.05 ) . As expected from other IFN use , those on IFN experienced more flu-like and febrile symptoms and skin problems than those not on IFN . In all , 35 % of patients stopped IFN before question naire completion . This made no material difference to the results , except that those continuing on IFN had slightly better self-assessed Global health/QoL than those who had stopped ( P<0.03 ) . IFN treatment adversely affected sexual health after allowing for age and gender . In conclusion , IFN treatment has a significant adverse impact on QoL. Patient awareness of the survival benefits and these QoL effects should enable better-informed decision-making . The impact on QoL of IFN dose , and of imatinib therapy versus IFN in early CP CML , are being investigated . QoL will need evaluating in future studies of combination treatment ( IFN+imatinib ) PURPOSE We conducted a phase III trial to determine whether first-line treatment with raltitrexed , a thymidine synthase inhibitor , and cisplatin results in superior outcome compared with cisplatin alone in patients with malignant pleural mesothelioma ( MPM ) . PATIENTS AND METHODS Eligible patients with histologically proven advanced MPM , not pretreated with chemotherapy , WHO performance status ( PS ) 0 to 2 , and adequate hematological , renal , and hepatic function were r and omly assigned to receive cisplatin 80 mg/m2 IV on day 1 , alone ( arm A ) or combined with raltitrexed 3 mg/m2 ( arm B ) . In patients with measurable disease , response was monitored using the Response Evaluation Criteria in Solid Tumors criteria . Health related quality of life ( HRQOL ) was measured using the European Organisation for Research and Treatment of Cancer QLQ-C30 and Lung Module ( QLQ-LC13 ) . RESULTS Two hundred fifty patients were r and omized : 80 % male ; median age , 58 years ; and WHO PS , 0 , 1 , 2 in 25 , 62 , and 13 % of cases , respectively . There were no toxic deaths . The main grade 3 or 4 toxicities observed were neutropenia and emesis , reported twice as often in the combination arm . Among 213 patients with measurable disease , response rate was 13.6 % ( arm A ) versus 23.6 % ( arm B ; P = .056 ) . No difference in HRQOL was observed on any of the scales . Median overall and 1-year survival in arms A and B were 8.8 ( 95 % CI , 7.8 to 10.8 ) v 11.4 months ( 95 % CI , 10.1 to 15 ) , respectively , and 40 % v 46 % , respectively ( P = .048 ) . CONCLUSION A combination of raltitrexed and cisplatin improves overall survival compared with cisplatin alone . This study confirms that a combination of cisplatin and an antifolate is superior to cisplatin alone in patients with MPM , without harmful effect on HRQOL CONTEXT The Consoli date d St and ards for Reporting of Trials ( CONSORT ) statement was developed to help improve the quality of reports of r and omized controlled trials ( RCTs ) . To date , a paucity of data exists regarding whether it has achieved this goal . OBJECTIVE To determine whether use of the CONSORT statement is associated with improvement in the quality of reports of RCTs . DESIGN AND SETTING Comparative before- and -after evaluation in which reports of RCTs published in 1994 ( pre-CONSORT ) were compared with RCT reports from the same journals published in 1998 ( post-CONSORT ) . We included 211 reports from BMJ , JAMA , and The Lancet ( journals that adopted CONSORT ) as well as The New Engl and Journal of Medicine ( a journal that did not adopt CONSORT and was used as a comparator ) . MAIN OUTCOME MEASURES Number of CONSORT items included in a report , frequency of unclear reporting of allocation concealment , and overall trial quality score based on the Jadad scale , a 5-point quality assessment instrument . RESULTS Compared with 1994 , the number of CONSORT checklist items in reports of RCTs increased in all 4 journals in 1998 , and this increase was statistically significant for the 3 adopter journals ( pre-CONSORT , 23.4 ; mean change , 3.7 ; 95 % confidence interval [ CI ] , 2.1 - 5.3 ) . The frequency of unclear reporting of allocation concealment decreased for each of the 4 journals , and this change was statistically significant for adopters ( pre-CONSORT , 61 % ; mean change , -22 % ; 95 % CI , -38 % to -6 % ) . Similarly , 3 of the 4 journals showed an improvement in the quality score for reports of RCTs , and this increase was statistically significant for adopter journals overall ( pre-CONSORT , 2.7 ; mean change , 0.4 ; 95 % CI , 0.1 - 0.8 ) . CONCLUSION Use of the CONSORT statement is associated with improvements in the quality of reports of RCTs The increasing success of intensive consolidation chemotherapy ( CCT ) as an alternative to bone marrow transplant ( BMT ) in acute myeloid leukaemia ( AML ) necessitates comparison of the impact on quality of life ( QoL ) of these two treatment modalities . Most QoL studies following BMT involve small patient numbers and provide ambivalent results . The present study examines  QoL in a large number of patients 1 year from the end of treatment within the United Kingdom Medical Research Council ( UK MRC ) AML10 trial of BMT versus CCT . Allogeneic-BMT ( Allo-BMT ) was observed to have an adverse impact on most QoL dimensions compared with Autologous-BMT ( A-BMT ) and CCT . More patients receiving BMT  had mouth dryness problems and worse sexual and social relationships , professional and leisure activities than CCT patients . QoL in A-BMT patients was less impacted than Allo-BMT . Intention-to-treat analysis showed similar results . These results indicate that a reconsideration of treatment strategies is warranted , and that further , good prospect i ve studies are needed to evaluate more clearly the effects of these treatments in long-term survivors The objective of this study was to obtain age- and sex-specific reference values for the European Organization for Research and Treatment of Cancer ( EORTC ) Quality of Life Question naire QLQ-C30 . A r and omly selected sample of the German adult population ( 3015 subjects ) was used , 2081 subjects agreed to take part in the investigation . Most of the scales and symptom items of the question naire proved to be dependent on age and sex . Men reported fewer symptoms than women . Age differences were even more pronounced . Younger people reported better functioning and fewer symptoms . Compared with the results of a similar Norwegian study ( Hjermstad MJ , Fayers PM , Bjordal K , Kaasa S. Health related quality of life in the general Norwegian population assessed by the European Organization for research and treatment of cancer core quality -of-life question naire : The QLQ-C30(+3 ) . J Clin Oncol 1998 , 16 , 1188 - 1196 ) the prevalence of some symptoms was markedly less . Norm values for age and sex groups are given and regression analyses are performed which help to calculate expected mean scores . The results show that age and sex differences must be taken into consideration when different groups of cancer patients are compared . The norm values help to interpret quality of life data for clinicians PURPOSE To date , only a few studies have evaluated the health-related quality of life ( HRQOL ) of patients with chronic lymphocytic leukemia ( CLL ) receiving chemotherapy . Therefore , the German CLL Study Group assessed HRQOL in younger patients with advanced CLL receiving first-line chemotherapy with fludarabine or fludarabine plus cyclophosphamide ( FC ) .  PATIENTS AND METHODS Three hundred seventy-five patients younger than 66 years with advanced CLL were r and omly assigned to receive either fludarabine alone ( fludarabine 25 mg/m2/d for 5 days intravenously [ IV ] , repeated every 28 days ) or FC ( fludarabine 30 mg/m2/d for 3 days IV plus cyclophosphamide 250 mg/m2/d for 3 days , repeated every 28 days ) . Six courses of treatment were planned to be administered . The European Organisation for Research and Treatment of Cancer Quality of Life Question naire C30 was sent to all patients at baseline and after 6 , 12 , and 24 months . RESULTS Eighty-nine percent of 362 included patients completed at least one question naire ( 163 fludarabine- and 158 FC-treated patients ) . Comparing the baseline levels of 249 CLL patients with the general German population , significant differences in nearly all HRQOL scales were assessed between the two groups . A multivariate analysis showed no significant differences in all HRQOL scales between both arms . In both treatment arms , symptoms such as fatigue , insomnia , and appetite loss improved to lower levels after the end chemotherapy . Except for lower physical status , no significant difference in HRQOL between male and female patients was evaluated . CONCLUSION Fludarabine-based treatment seems to improve HRQOL little to moderately in younger patients with advanced CLL . No significant difference between fludarabine- and FC-treated patients was observed A cross-sectional study of quality of life ( QOL ) was performed in 98 patients in continued first complete remission ( CR ) for 1–7.4 years , after inclusion in the AML 8A trial which prospect ively compared allogeneic bone marrow transplantation ( AlloBMT ) , autologous BMT ( ABMT ) and intensive consolidation chemotherapy . Several significant differences between the three treatment groups were observed , on the basis of patient self-reports , with regard to somatic symptoms ( mouth sores , cough , hair loss , headache ) , repeated acute medical problems , physical functioning , role functioning , leisure activities and , above all , sexual functioning . There were also significant differences for overall physical condition , and overall quality of life . For all these parameters , the ranking was uniformly AlloBMT lower than ABMT lower than chemotherapy . These differences remain significant after adjustment for time interval between CR and QOL evaluation , sex or age . These results , confirming a higher risk of permanent impairment of QOL after BMT , may have an impact on medical decisions and warrant further studies BACKGROUND Previous work highlighted a number of method ological constraints when reporting health-related quality of life ( HRQOL ) outcomes from r and omized controlled trials ( RCTs ) . Given this , the objective of this study was to investigate whether the quality of such HRQOL reports has improved over time . MATERIAL S AND METHODS On the basis of a predefined set of criteria , 159 RCTs with a HRQOL end point , published between 1990 and 2004 were identified and analyzed . Each study was evaluated by a number of issues ( e.g. sample size and industry sponsorship ) and by the " minimum st and ard checklist for evaluating HRQOL outcomes in cancer clinical trials " . RESULTS The quality of HRQOL reports , as measured by the overall checklist score , was independently related to more recently published studies ( P < 0.0001 ) . This relationship was independent of industry funded , HRQOL end point ( primary versus secondary ) , cancer disease site , size of the study and HRQOL difference between treatment arms . While only 39.3 % of studies published between 1990 and 2000 ( 89/159 RCTs ) were identified as being probably robust , thus likely to support clinical decision making , this percentage was 64.3 % for studies published after 2000 ( 70/159 RCTs ) . CONCLUSION Since we found a significant learning curve in HRQOL trial reporting since 1990 , it can be expected that HRQOL data will increasingly impact on clinical decision making and treatment policies in the near future Federal regulations provide 2 pathways for approval of new agents for the treatment of acute leukemia , regular and accelerated approval . Regular approval requires evidence of clinical benefit , which is generally defined as either prolongation of life or improved quality of life , or an effect on an end point established as a surrogate for clinical benefit . Accelerated approval can be obtained based on demonstration of an effect on a surrogate measure " reasonably likely " to predict clinical benefit , but requires demonstration of clinical benefit after approval as well . The acute leukemias are a heterogeneous and relatively uncommon group of diseases . The design and execution of prospect i ve r and omized clinical trials demonstrating prolongation of life or improved quality of life for patients with these disorders can be difficult and costly and require lengthy follow-up . Thus , the development of novel trial design and inclusion of vali date d surrogate markers for clinical benefit are needed 
    Output:
    
Imatinib greatly improved HRQOL compared to interferon based treatments in CML patients and fludarabine plus cyclophosphamide does not seem to have a deleterious impact on patient 's HRQOL when compared to fludarabine alone or chlorambucil in CLL patients .
This study revealed the paucity of HRQOL research in leukaemia patients .
Nonetheless , HRQOL assessment is feasible in RCTs and has the great potential of providing valuable outcomes to further support clinical decision making