***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: We present preliminary treatment results of a nation-wide cooperative clinical study for advanced neuroblastoma supported by a grant-in-aid for cancer research from the Japanese Ministry of Health and Welfare . This study involves 28 major pediatric oncology institutions in Japan and started in May , 1985 . Until 1987 we treated 84 patients with stage III and IV neuroblastoma whose prognosis was considered to be extremely poor . Every patient who entered this study received 6 cycles of A1 protocol consisted of high dose cyclophosphamide , vincristine , cis-platinum and THP-adriamycin , a newly introduced low-cardiotoxic anthracycline derivative . Having received 6 cycles of A1 protocol , patients were divided into 3 groups , i.e. , ACNU course , DTIC course and bone marrow transplantation course preconditioned by high dose melphalan . Of 77 patients who received more than 3 cycles of A1 protocol , tumor extirpation was performed in 69 patients . Total or subtotal resection of the original tumor and the regional lymph-nodes was possible in 57 cases . The high resectability of the tumor indicates marked effectiveness of this protocol . Of the 57 patients who followed this treatment protocol from the beginning ( virgin case ) , 31 ( 54.4 % ) showed complete response and 26 still remains in complete remission . 93.0 % of response rate ( CR + PR ) was obtained by the treatment protocol s , which was considerably high as compared with the results of other treatment protocol reported . This protocol also worked well in the patients who had failed with other treatment protocol . ( ABSTRACT TRUNCATED AT 250 WORDS Abstract : Neuroblastoma , a neoplasm of the sympathetic nervous system , is the most common extracranial tumor of childhood . Approximately 60 % of all patients have only a 10 % probability of long-term , disease-free survival if given conventional therapy that includes chemotherapy , local irradiation , and surgery . Recent pilot studies of intensive chemotherapy and total body irradiation ( TBI ) followed by allogeneic bone marrow transplantation ( BMT ) or autologous bone marrow transplantation ( ABMT ) have produced encouraging results . In this report , we up date our original study in which 20 patients with advanced neuroblastoma underwent intensive  four-drug chemotherapy , TBI , and ABMT or allogeneic BMT ; in addition , we provide data from our current study regarding the clinical use of sedimentation , filtration , and magnetic immunobeads for the ex vivo removal of neuroblastoma cells from autologous marrow . Reprints Current results suggest that purged autologous bone marrow transplant may improve outcome for some subsets of high risk neuroblastoma , but the risk of relapse is still high BACKGROUND High dose myeloablative chemotherapy ( " megatherapy " ) , with haematopoietic stem cell support , is now widely used to consoli date response to induction chemotherapy in patients with advanced neuroblastoma . PROCEDURE In this study ( European Neuroblastoma Study Group , ENSG1 ) , the value of melphalan myeloablative " megatherapy " was evaluated in a r and omised , multi-centre trial . Between 1982 and 1985 , 167 children with stages IV and III neuroblastoma ( 123 stage IV > 1 year old at diagnosis and 44 stage III and stage IV from 6 to 12 months old at diagnosis ) were treated with oncovin , cisplatin , epipodophyllotoxin , and cyclophosphamide ( OPEC ) induction chemotherapy every 3 weeks . After surgical excision of primary tumour , the 90 patients ( 69 % of the total ) who achieved complete response ( CR ) or good partial response ( GPR )  were eligible for r and omisation either to high dose melphalan ( 180 mg per square meter ) with autologous bone marrow support or to no further treatment . RESULTS Sixty-five ( 72 % ) of eligible children were actually r and omised and 21 of these patients were surviving at time of this analysis , with median follow-up from r and omisation of 14.3 years . Five year event-free survival ( EFS ) was 38 % ( 95 % confidence interval ( CI ) 21 - 54 % ) in the melphalan-treated group and 27 % ( 95 % CI 12 - 42 % ) in the " no-melphalan " group . This difference was not statistically significant ( P = 0.08 , log rank test ) but for the 48 r and omised stage IV patients aged > 1 year at diagnosis outcome was significantly better in the melphalan-treated group-5 year EFS 33 % versus 17 % ( P = 0.01 , log rank test ) . CONCLUSIONS In this trial , high dose melphalan improved the length of EFS and overall survival of children with stage IV neuroblastoma > 1 year of age who achieved CR or GPR after OPEC induction therapy and surgery . Multi-agent myeloablative regimens are now widely used as consolidation therapy for children with stage IV disease and in those with other disease stages when the MYCN gene copy number in tumour cells is amplified . Because they are more toxic , complex , and costly these combination megatherapy regimens should be compared with single agent melphalan in r and omised clinical trials BACKGROUND Pre clinical and preliminary clinical data indicate that ch14.18 , a monoclonal antibody against the tumor-associated disialoganglioside GD2 , has activity against neuroblastoma and that such activity is enhanced when ch14.18 is combined with granulocyte-macrophage colony-stimulating factor ( GM-CSF ) or interleukin-2 . We conducted a study to determine whether adding ch14.18 , GM-CSF , and interleukin-2 to st and ard isotretinoin therapy after intensive multimodal therapy would improve outcomes in high-risk neuroblastoma . METHODS Patients with high-risk neuroblastoma who had a response to induction therapy and stem-cell transplantation were r and omly assigned , in a 1:1 ratio , to receive st and ard therapy ( six cycles of isotretinoin ) or immunotherapy ( six cycles of isotretinoin and five concomitant cycles of ch14.18 in combination with alternating GM-CSF and interleukin-2 ) . Event-free survival and overall survival were compared between the immunotherapy group and the st and ard-therapy group , on an intention-to-treat basis . RESULTS A total of 226 eligible patients were r and omly assigned to a treatment group . In the immunotherapy group , a total of 52 % of patients had pain of grade 3 , 4 , or 5 , and 23 % and 25 % of patients had capillary leak syndrome and hypersensitivity reactions , respectively . With 61 % of the number of expected events observed , the study met the criteria for early stopping owing to efficacy . The median duration of follow-up was 2.1 years . Immunotherapy was superior to st and ard therapy with regard to rates of event-free survival ( 66±5 % vs. 46±5 % at 2 years , P=0.01 ) and overall survival ( 86±4 % vs. 75±5 % at 2 years , P=0.02 without adjustment for interim analyses ) . CONCLUSIONS Immunotherapy with ch14.18 , GM-CSF , and interleukin-2 was associated with a significantly improved outcome as compared with st and ard therapy in patients with high-risk neuroblastoma . ( Funded by the National Institutes of Health and the Food and Drug Administration ; Clinical Trials.gov number , NCT00026312 . This paper describes some of the statistical considerations in the intent-to-treat design and analysis of clinical trials . The pivotal property of a clinical trial is the assignment of treatments to patients at r and om . R and omization alone , however , is not sufficient to provide an unbiased comparison of therapies . An additional requirement is that the set of patients contributing to an analysis provides an unbiased assessment of treatment effects , or that any missing data are ignorable . A sufficient condition to provide an unbiased comparison is to obtain complete data on all r and omized subjects . This can be achieved by an intent-to-treat design wherein all patients are followed until death or the end of the trial , or until the outcome event is reached in a time-to-event trial , irrespective of whether the patient is still receiving or complying with the assigned treatment . The properties of this strategy are contrasted with those of an efficacy subset analysis in which patients and observable patient data are excluded from the analysis on the basis of information obtained postr and omization . I describe the potential bias that can be introduced by such postr and omization exclusions and the pursuant effects on type I error probabilities . Especially in a large study , the inflation in type I error probability can be severe , 0.50 or higher , even when the null hypothesis is true . St and ard statistical methods for the analysis of censored or incomplete observations all require the assumption of missing at r and om to some degree , and none of these methods adjust for the potential bias introduced by post hoc subset selection . Nor is such adjustment possible unless one posits a model that relates the missing observations to other observed information for each subject-models that are inherently untestable . Further , the subset selection bias is confounded with the subset-specific treatment effect , and the two components are not identifiable without additional untestable assumptions . Methods for sensitivity analysis to assess the impact of bias in the efficacy subset analysis are described . It is generally believed that the efficacy subset analysis has greater power than the intent-to-treat analysis . However , even when the efficacy subset analysis is assumed to be unbiased , or have a true type I error probability equal to the desired level alpha , situations are described where the intent-to-treat analysis in fact has greater power than the efficacy subset analysis . The intent-to-treat design , wherein all possible patients continue to be followed , is especially powerful when an effective treatment arrests progression of disease during its administration . Thus , a patient benefits long after the patient becomes noncompliant or the treatment is terminated . In such cases , a l and mark analysis using the observations from the last patient evaluation is likely to prove more powerful than life-table or longitudinal analyses . Examples are described Background The preliminary results of a study are usually presented as an abstract in conference meetings . The reporting quality of those abstract s and the relationship between their study design s and full paper publication rate is unknown . We hypothesized that r and omized controlled trials are more likely to be published as full papers than observational studies . Methods 154 oral abstract s presented at the World Congress of Sports Injury Prevention 2005 Oslo and the corresponding full paper publication were identified and analysed . The main outcome measures were frequency of publication , time to publication , impact factor , CONSORT ( for Consoli date d St and ards of Reporting Trials ) score , STROBE ( for Strengthening the Reporting of Observational Studies in Epidemiology ) score , and minor and major inconsistencies between the abstract and the full paper publication . Results Overall , 76 of the 154 ( 49 % ) presented abstract s were published as full papers in a peer- review ed journal with an impact factor of 1.946 ± 0.812 . No significant difference existed between the impact factor for r and omized controlled trials ( 2.122 ± 1.015 ) and observational studies ( 1.913 ± 0.765 , p = 0.469 ) . The full papers for the r and omized controlled trials were published after an average ( SD ) of 17 months ( ± 13 months ) ; for observational studies , the average ( SD ) was 12 months ( ± 14 months ) ( p = 0.323 ) . A trend was observed in this study that a higher percentage of r and omized controlled trial abstract s were published as full papers ( 71 % vs. 47 % , p = 0.078 ) than observational trials . The reporting quality of abstract s , published as full papers , significantly increased compared to conference abstract s both in r and omized control studies ( CONSORT : 5.7 ± 0.7 to 7.2 ± 1.3 ; p = 0.018 , CI -2.7 to -0.32 ) and in observational studies ( STROBE : 8.2 ± 1.3 to 8.6 ± 1.4 ; p = 0.007 , CI -0.63 to -0.10 ) . All of the published abstract s had at least one minor inconsistency ( title , authors , research center , outcome presentation , conclusion ) , while 65 % had at least major inconsistencies ( study objective , hypothesis , study design , primary outcome measures , sample size , statistical analysis , results , SD/CI ) . Comparing the results of conference and full paper ; results changed in 90 % vs. 68 % ( r and omized , controlled studies versus observational studies ) ; data were added ( full paper reported more result data ) in 60 % vs. 30 % , and deleted ( full paper reported fewer result data ) in 40 % vs. 30 % . Conclusions No significant differences with respect to type of study ( r and omized controlled versus observational ) , impact factor , and time to publication existed for the likelihood that a World Congress of Sports Injury conference abstract could be published as a full paper PURPOSE To assess the effect of local radiation administered to primary disease sites in children with high-risk neuroblastoma . MATERIAL S AND METHODS A total of 539 eligible patients were entered on protocol CCG-3891 , consisting of chemotherapy , primary surgery , and 10 Gy of external beam radiation therapy ( EBRT ) to gross residual disease , followed by r and omized assignment to continuation chemotherapy ( CC ) or autologous bone marrow transplantation ( ABMT ) . ABMT patients received total body irradiation ( TBI ) . RESULTS Estimated event-free survival and overall survival at 5 years were 
    Output:
    
The meta- analysis of secondary malignant disease and treatment-related death did not show any significant statistical differences between the treatment groups .
Based on the currently available evidence , myeloablative therapy seems to work in terms of event-free survival .
For overall survival there is currently no evidence of effect when additional follow-up data are included .
No definitive conclusions can be made regarding adverse effects and quality of life , although possible higher levels of adverse effects should be kept in mind .
This systematic review only allows a conclusion on the concept of myeloablative therapy ; no conclusions can be made regarding the best treatment strategy .
Survival rates may be overestimated due to the inclusion of patients with intermediate-risk disease