***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
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    Input: BACKGROUND To evaluate long-term survival of the first cohort of stage-4 neuroblastoma patients treated with the N7 induction chemotherapy , surgery of the primary tumor and  high-dose chemotherapy ( HDC ) containing Busulfan-Melphalan ( Bu-Mel ) followed by autologous stem cell transplantation ( ASCT ) . PROCEDURE From 1998 to 1999 , 47 children were included in the NB97 trial and treated with induction chemotherapy according to the N7  protocol  , followed by surgery of the primary tumor . HDC ( Busulfan , 600 mg/m(2 ) Melphalan , 140 mg/m(2 ) ) was administered in patients with partial response of metastases with no more than 3 mIBG spots . Radiotherapy was delivered to the primary tumor site when tumors displayed MYCN amplification . RESULTS Thirty-nine patients received Bu-Mel ( 83 % ) : 23 who had achieved complete response ( CR ) of metastases , 20 after induction treatment and 3 after second-line chemotherapy , and 16 in partial response ( PR ) . The toxicity of the whole treatment was manageable . The main HDC related-toxicity was hepatic veno-occlusive disease grade > 2 occurring in 15 % of the patients . The 8-year EFS of the whole cohort was 34 % ( 95 % CI , 22 - 48 % ) . The 8-year EFS of the 39 patients who received Bu-Mel and ASCT was 41 % ( 95 % CI , 27 - 57 % ) . Patients who achieved a CR of metastases at the end of induction chemotherapy had a significantly better outcome than the others ( 8-year EFS , 52 % vs. 20 % ; P = 0.02 ) . CONCLUSIONS The long-term results of this first prospect i ve cohort of patients with metastatic disease treated with the N7 induction chemotherapy and HDC ( Bu-Mel ) confirm published data with stable survival curves but with a longer follow-up BACKGROUND Myeloablative megatherapy is commonly used to improve the poor outlook of children with high-risk neuroblastoma , yet its role is poorly defined . We aim ed to assess whether megatherapy with autologous stem-cell transplantation could increase event-free survival and overall survival compared with maintenance chemotherapy . METHODS 295 patients with high-risk neuroblastoma ( ie , patients with stage 4 disease aged older than 1 year or those with MYCN-amplified tumours and stage 1 , 2 , 3 , or 4S disease or stage 4 disease and < 1 year old ) were r and omly assigned to myeloablative megatherapy ( melphalan , etoposide , and carboplatin ) with autologous stem-cell transplantation ( n=149 ) or to oral maintenance chemotherapy with cyclophosphamide ( n=146 ) . The primary endpoint was event-free survival . Secondary endpoints were overall survival and the number of treatment-related deaths . Analyses were done by intent to treat , as treated , and treated as r and omised . FINDINGS Intention-to-treat analysis showed that patients allocated megatherapy had increased 3-year event-free survival compared with those allocated maintenance therapy ( 47 % [ 95 % CI 38 - 55 ] vs 31 % [ 95 % CI 23 - 39 ] ; hazard ratio 1.404 [ 95 % CI 1.048 - 1.881 ] , p=0.0221 ) , but did not have significantly increased 3-year overall survival ( 62 % [ 95 % CI 54 - 70 ] vs 53 % [ 95 % CI 45 - 62 ] ; 1.329 [ 0.958 - 1.843 ] , p=0.0875 ) . Improved 3-year event-free survival and 3-year overall survival were also recorded for patients given megatherapy in the as-treated group ( n=212 ) and in the treated-as-r and omised group ( n=145 ) . Two patients died from therapy-related complications during induction treatment . No patients given maintenance therapy  died from acute treatment-related toxic effects . Five patients given megatherapy  died from acute complications related to megatherapy . INTERPRETATION Myeloablative chemotherapy with autologous stem-cell transplantation improves the outcome for children with high-risk neuroblastoma despite the raised risk of treatment-associated death BACKGROUND The current st and ard treatment for patients with high-risk neuroblastoma includes initial induction chemotherapy with a 21-day interval between induction treatments . We aim ed to assess whether an intensive chemotherapy protocol that had a 10-day interval between treatments would improve event-free survival ( EFS ) in patients aged 1 year or over with high-risk neuroblastoma . METHODS Between Oct 30 , 1990 , and March 18 , 1999 , patients with stage 4 neuroblastoma who had not received previous chemotherapy were enrolled from 29 centres in Europe . Patients were r and omly assigned to rapid treatment ( cisplatin [ C ] , vincristine [ O ] , carboplatin [ J ] , etoposide [ E ] , and cyclophosphamide [ C ] , known as COJEC ) or st and ard treatment ( vincristine [ O ] , cisplatin [ P ] , etoposide [ E ] , and cyclophosphamide [ C ] , ie , OPEC , alternated with vincristine [ O ] , carboplatin [ J ] , etoposide [ E ] , and cyclophosphamide [ C ] , ie , OJEC ) . Both regimens used the same total cumulative doses of each drug ( except vincristine ) , but the dose intensity of the rapid regimen was 1.8-times higher than that of the st and ard regimen . The st and ard regimen was given every 21 days if patients showed haematological recovery , whereas the rapid regimen was given every 10 days irrespective of haematological recovery . Response to chemotherapy was assessed according to the conventional International Neuroblastoma Response Criteria ( INRC ) . In responders , surgical excision of the primary tumour was attempted , followed by myeloablation ( with 200 mg/m2 of melphalan ) and haemopoietic stem-cell rescue . Primary endpoints were 3-year , 5-year , and 10-year EFS . Data were analysed by intention to treat . This trial is registered on the clinical trials site of the US National Cancer Institute website , number NCT00365755 , and also as EU-20592 and CCLG-NB-1990 - 11 . FINDINGS 262 patients , of median age 2.95 years ( range 1.03 - 20.97 ) , were r and omly assigned-132 patients to st and ard and 130 patients to rapid treatment . 111 patients in the st and ard group and 109 patients in the rapid group completed chemotherapy . Chemotherapy doses were recorded for 123 patients in the st and ard group and 126 patients in the rapid group . 97 of 123 ( 79 % ) patients in the st and ard group and 84 of 126 ( 67 % ) patients in the rapid group received at least 90 % of the scheduled chemotherapy , and the relative dose intensity was 1.94 compared with the st and ard regimen . 3-year EFS was 24.2 % for patients in the st and ard group and 31.0 % for those in the rapid group ( hazard ratio [ HR ] 0.86 [ 95 % CI 0.66 - 1.14 ] , p=0.30 . 5-year EFS was 18.2 % in the st and ard group and 30.2 % in the rapid group , representing a difference of 12.0 % ( 1.8 to 22.3 ) , p=0.022 . 10-year EFS was 18.2 % in the st and ard group and 27.1 % in the rapid group , representing a difference of 8.9 % ( -1.2 to 19.0 ) , p=0.085 . Myeloablation was given a median of 55 days earlier in patients assigned rapid treatment than those assigned st and ard treatment . Infective complications ( numbers of patients with febrile neutropenia and septicaemia , and if given , time on antibiotic and antifungal treatment ) and time in hospital were greater with rapid treatment . Occurrence of fungal infection was the same in both regimens . INTERPRETATION Dose intensity can be increased with a rapid induction regimen in patients with high-risk neuroblastoma . There was no significant difference in OS between the rapid and st and ard regimens at 5 years and 10 years . However , an increasing difference in EFS after 3 years suggests that the efficacy of the rapid regimen is better than the st and ard regimen . A rapid induction regimen enables myeloablation to be given much earlier , which might contribute to a better outcome UNLABELLED PURPOSE We assessed the long-term outcome of patients enrolled on CCG-3891 , a high-risk neuroblastoma study in which patients were r and omly assigned to undergo  autologous purged bone marrow transplantation ( ABMT ) or to receive chemotherapy , and subsequent treatment with 13-cis-retinoic acid ( cis-RA ) . PATIENTS AND METHODS Patients received the same induction chemotherapy , with r and om assignment ( N = 379 ) to consolidation with myeloablative chemotherapy , total-body irradiation , and ABMT versus three cycles of intensive chemotherapy .  Patients who completed consolidation without disease progression were r and omly assigned to receive no further therapy or cis-RA for 6 months . Results The event-free survival ( EFS ) for patients r and omly assigned to ABMT was significantly higher than those r and omly assigned to chemotherapy ; the 5-year EFS ( mean + /- SE ) was 30 % + /- 4 % versus 19 % + /- 3 % , respectively ( P = .04 ) . The 5-year EFS ( 42 % + /- 5 % v 31 % + /- 5 % ) from the time of second r and om assignment was higher for cis-RA than for no further therapy , though it was not significant . Overall survival ( OS ) was significantly higher for each r and om assignment by a test of the log(-log ( . ) ) transformation of the survival estimates at 5 years ( P < .01 ) . The 5-year OS from the second r and om assignment of patients who underwent both r and om assignments and who were assigned to ABMT/cis-RA was 59 % + /- 8 % ; for ABMT/no cis-RA , it was 41 % + /- 8 % [ corrected ] ; for continuing chemotherapy/cis-RA , it was 38 % + /- 7 % ; and for chemotherapy/no cis-RA , it was 36 % + /- 7 % . CONCLUSION Myeloablative therapy and autologous hematopoietic cell rescue result in significantly better 5-year EFS than nonmyeloablative chemo therapy ; neither myeloablative therapy with [ corrected ] autologous hematopoietic cell rescue nor cis-RA given after consolidation therapy significantly improved OS BACKGROUND The N7 protocol for poor-risk neuroblastoma uses dose-intensive chemotherapy ( as in N6 protocol [ Kushner et al. : J Clin Oncol 12:2607 - 2613 , 1994 ] but with lower dosing of vincristine ) for induction , surgical resection and 2100 cGy hyperfractionated radiotherapy for local control , and for consolidation , targeted radioimmunotherapy with 131I-labeled anti-GD2 3F8 monoclonal antibody and immunotherapy with unlabeled/unmodified 3F8 ( 400 mg/m2 ) . PROCEDURE The chemotherapy consists of : cyclophosphamide 70 mg/kg/d x 2 and a 72-hr infusion of doxorubicin 75 mg/m2 plus vincristine 2 mg/m2 , for courses 1 , 2 , 4 , and 6 ; and cisplatin 50 mg/m2/d x 4 and etoposide 200 mg/m2/d x 3 , for courses 3 , 5 , and 7 . 131I-3F8 is dosed at 20 mCi/kg , which is myeloablative and therefore necessitates stem-cell support . RESULTS Of the first 24 consecutive previously untreated patients more than 1 year old at diagnosis , 22 were stage 4 and two were unresectable stage 3 with MYCN amplification . Chemotherapy achieved CR/VGPR in 21 of 24 patients . Twenty patients to date have completed treatment with 131I-3F8  , and 15 patients have completed all treatment . With a median follow-up of 19 months , 18 of 24 patients remain progression-free . CONCLUSIONS Major toxicities were grade 4 myelosuppression and mucositis during chemotherapy , and self-limited pain and urticaria during antibody treatment . Late effects include hearing deficits and hypothyroidism BACKGROUND Myeloablative chemoradiotherapy and immunomagnetically purged autologous bone marrow transplantation has been shown to improve outcome for patients with high-risk neuroblastoma . Currently , peripheral blood stem cells ( PBSC ) are infused 
    Output:
    
For febrile neutropenia , septicemia , and renal toxicity , a statistically significant difference in favor of the st and ard treatment arm was identified ; for all other early toxicities no clear evidence of a difference between treatment groups was identified .
For endocrine complications and neurocognitive complications , a statistically significant difference in favor of the rapid COJEC arm was found ; for all other late non-hematological toxicities no clear evidence of a difference between treatment groups was identified .
Therefore , based on the currently available evidence , we are uncertain about the effects of rapid COJEC and st and ard induction therapy in patients with high-risk neuroblastoma .