human
***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 At present , treatment results for patients with advanced-stage Hodgkin 's disease remain unsatisfactory . St and ard chemotherapy M(C)OPP ( nitrogen mustard ( cyclophosphamide ) . vincristine , procabazine , and prednisone ) . ABVD ( adriamycine , bleomycine , vinblastine , and dacarbacine ) or M(C)OPP/ABVD + /- radiotherapy fail to achieve long-term complete remission in 35 % to 50 % of these patients . The BEACOPP ( bleomycin , etoposide , adriamycine , cyclophosphamide , vincristine , procarbazine , and prednisone ) regimen was developed to improve treatment results by dose intensification achieved by reduced duration of treatment ( time intensification ) and addition of etoposide . PATIENTS AND METHODS Thirty untreated patients with advanced Hodgkin 's disease stage IIB IV according to the Ann Arbor classification were treated with the time intensified BEACOPP regimen . Each patient was scheduled to receive eight cycles of chemotherapy with consolidating radiotherapy to sites of initial bulk disease and to residual tumor remaining after chemotherapy . RESULTS All patients were evaluable for assessment of toxicity , treatment response , freedom from treatment failure ( FFTF ) and survival ( SV ) . Of 30 treated patients , 29 patients received the intended eight cycles of BEACOPP . One patient in clinical CR , terminated the chemotherapy at his own request after six cycles and is at this time , 48 months after the end of treatment , in complete remission . Toxicity was tolerable with WHO grade 3/4 leucopenia in 28 % of chemotherapy cycles and one severe ( WHO grade 3 ) infection . No treatment-related death occurred . Cycles could generally be given on schedule . Complete remission ( CR ) was achieved in all but two patients ( 93 % ) . At present , only one patient has relapsed . At a median follow-up of 40 months , FFTF-rate is 89 % ( lower confidence limit : 80 % ) . One patient died due to progressive disease . CONCLUSION The BEACOPP regimen is feasible at moderate hematopoeitic toxicity . With a FFTF-rate of 89 % at a median follow-up of 40 months , the treatment results are very encouraging . A prospect i ve r and omised trial has been initiated to compare the BEACOPP regimen with the st and ard COPP/ABVD regimen in advanced-stage Hodgkin 's disease PURPOSE Current st and ard therapy for children and adolescents with Hodgkin 's disease includes combination chemotherapy and low-dose involved-field radiation ( LD-IFRT ) . Because radiation may be associated with adverse late effects , the Children 's Cancer Group ( CCG ) investigated whether radiation could be omitted in patients achieving a complete response to initial chemotherapy without jeopardizing the excellent outcome obtained with combined-modality therapy . PATIENTS AND METHODS Between January 1995 and December 1998 , 829 eligible patients were enrolled onto CCG 5942 . A total of 501 patients who achieved an initial complete response after risk-adapted combination chemotherapy were r and omized to receive LD-IFRT or no further treatment .  Event-free survival ( EFS ) and overall survival were assessed from the date of study entry or the date of r and omization , as appropriate . RESULTS The projected 3-year EFS from study entry for the entire cohort was 87 % + /- 1.2 % . Among patients who achieved a complete response to initial chemotherapy , 92 % + /- 1.9 % of those r and omized to receive LD-IFRT were alive and disease free 3 years after r and omization , versus 87 % + /- 2.2 % for patients r and omized to receive no further therapy ( stratified log-rank test ; P = .057 ) . With an " as-treated " analysis , 3-year EFS after r and omization for the radiation cohort was 93 % + /- 1.7 % versus 85 % + /- 2.3 % for patients receiving no further therapy ( stratified log-rank test ; P = .0024 ) . Three-year survival estimates for patients treated with and without LD-IFRT were 98 % + /- 1.1 % for patients who received radiation and 99 % + /- 0.5 % for patients who did not receive radiation . CONCLUSION LD-IFRT after an initial complete response to risk-adapted chemotherapy improved EFS . At this time , there is no survival advantage for LD-IFRT , but follow-up remains short BACKGROUND It is unclear whether patients with early-stage Hodgkin 's lymphoma and negative findings on positron-emission tomography ( PET ) after three cycles of chemotherapy with doxorubicin , bleomycin , vinblastine , and dacarbazine ( ABVD ) require radiotherapy . METHODS Patients with newly diagnosed stage IA or stage IIA Hodgkin 's lymphoma received three cycles of ABVD and then underwent PET scanning . Patients with negative PET findings were r and omly assigned to receive involved-field radiotherapy or no further treatment ; patients with positive PET findings received a fourth cycle of ABVD and radiotherapy . This trial assessing the noninferiority of no further treatment was design ed to exclude a difference in the 3-year progression-free survival rate of 7 or more percentage points from the assumed 95 % progression-free survival rate in the radiotherapy group . RESULTS A total of 602 patients ( 53.3 % male ; median age , 34 years ) were recruited , and 571 patients underwent PET scanning .  The PET findings were negative in 426 of these patients ( 74.6 % ) , 420 of whom were r and omly assigned to a study group ( 209 to the radiotherapy group and 211 to no further therapy ) . At a median of 60 months of follow-up , there had been 8 instances of disease progression in the radiotherapy group , and 8 patients had died ( 3 with disease progression , 1 of whom died from Hodgkin 's lymphoma ) ; there had been 20 instances of disease progression in the group with no further therapy , and 4 patients had died ( 2 with disease progression and none from Hodgkin 's lymphoma ) . In the radiotherapy group , 5 of the deaths occurred in patients who received no radiotherapy . The 3-year progression-free survival rate was 94.6 % ( 95 % confidence interval [ CI ] , 91.5 to 97.7 ) in the radiotherapy group and 90.8 % ( 95 % CI , 86.9 to 94.8 ) in the group that received no further therapy , with an absolute risk difference of -3.8 percentage points ( 95 % CI , -8.8 to 1.3 ) . CONCLUSIONS The results of this study did not show the noninferiority of the strategy of no further treatment after chemotherapy with regard to progression-free survival . Nevertheless , patients in this study with early-stage Hodgkin 's lymphoma and negative PET findings after three cycles of ABVD had a very good prognosis either with or without consolidation radiotherapy . ( Funded by Leukaemia and Lymphoma Research and others ; RAPID Clinical Trials.gov number , NCT00943423 . ) The Medical Research Council has for some years encouraged collaborative clinical trials in leukaemia and other cancers , reporting the results in the medical literature . One unreported result which deserves such publication is the development of the expertise to design and analyse such trials . This report was prepared by a group of British and American statisticians , but it is intended for people without any statistical expertise . Part I , which appears in this issue , discusses the design of such trials ; Part II , which will appear separately in the January 1977 issue of the Journal , gives full instructions for the statistical analysis of such trials by means of life tables and the logrank test , including a worked example , and discusses the interpretation of trial results , including brief reports of 2 particular trials . Both parts of this report are relevant to all clinical trials which study time to death , and wound be equally relevant to clinical trials which study time to other particular classes of untoward event : first stroke , perhaps , or first relapse , metastasis , disease recurrence , thrombosis , transplant rejection , or death from a particular cause . Part I , in this issue , collects together ideas that have mostly already appeared in the medical literature , but Part II , next month , is the first simple account yet published for non-statistical physicians of how to analyse efficiently data from clinical trials of survival duration . Such trials include the majority of all clinical trials of cancer therapy ; in cancer trials , however , it may be preferable to use these statistical methods to study time to local recurrence of tumour , or to study time to detectable metastatic spread , in addition to study ing total survival . Solid tumours can be staged at diagnosis ; if this , or any other available information in some other disease is an important determinant of outcome , it can be used to make the overall logrank test for the whole heterogeneous trial population more sensitive , and more intuitively satisfactory , for it will then only be necessary to compare like with like , and not , by chance , Stage I with Stage III PURPOSE Although survival rates have improved for patients with bulky and advanced-stage Hodgkin 's disease ( HD ) , current treatments entail substantial acute morbidity and risks for late effects such as infertility , second malignancies , and cardiopulmonary toxicities . A novel , brief chemotherapy regimen ( doxorubicin , vinblastine , mechlorethamine , vincristine , bleomycin , etoposide , and prednisone [ Stanford V ] ) was design ed to shorten the duration of treatment , significantly reduce cumulative doses of alkylating agents , doxorubicin , and bleomycin , and maintain dose-intensity ( DI ) . This brief chemotherapy was combined with radiation therapy ( RT ) to bulky disease sites . METHODS Since May 1989 , 65 previously untreated patients were treated for stage II HD with bulky mediastinal involvement ( n = 21 ) or for stage III or IV HD ( n = 44 ) . Patients received weekly chemotherapy for 12 weeks . Consolidative RT was given to the first 25 patients to sites of initial bulky disease or radiographic abnormalities that persisted after chemotherapy ; in the remaining 40 patients , RT was limited to bulky disease ( adenopathy > or = 5 cm and /or macroscopic splenic nodules defined by computed tomography [ CT ] ) . RESULTS With a median follow-up period of 2 years , actuarial 3-year survival rate is 96 % and failure-free survival ( FFS ) rate is 87 % . The 3-year FFS rate is 100 % for stage II patients with bulky mediastinal disease and 82 % for patients with stage III to IV disease . There were no treatment-related deaths . In a preliminary analysis on a subset of patients , female and male fertility appears to be preserved . CONCLUSION These preliminary results indicate that the Stanford V chemotherapy regimen with or without RT is well-tolerated and effective therapy for bulky , limited-stage , and advanced-stage HD . Less cumulative exposure to alkylating agents , doxorubicin , and bleomycin and limited use of radiation is expected to decrease risks for second neoplasms and late cardiopulmonary toxicity . Based on these results , the Stanford V chemotherapy with or without RT regimen deserves further study in the context of a r and omized clinical trial BACKGROUND BEACOPP , an intensified regimen consisting of bleomycin , etoposide , doxorubicin , cyclophosphamide , vincristine , procarbazine , and prednisone , has been advocated as the new st and ard of treatment for advanced Hodgkin 's lymphoma , in place of the combination of doxorubicin , bleomycin , vinblastine , and dacarbazine ( ABVD ) . METHODS We r and omly assigned 331 patients with previously untreated and unfavorable Hodgkin 's lymphoma ( stage IIB , III , or IV , or an international prognostic score of ≥3 on a scale of 0 to 7 , with higher scores indicating increased risk ) , to receive either BEACOPP or ABVD  , each followed by local radiotherapy  when indicated . Patients with residual or progressive disease after the initial therapy were to be treated according to a state-of-the-art high-dose salvage program . The median follow-up period was 61 months . RESULTS The 7-year rate of freedom from first progression was 85 % among patients who had received initial treatment with BEACOPP and 73 % among those who had received initial treatment with ABVD ( P=0.004 ) , and the 7-year rate of event-free survival was 78 % and 71 % , respectively ( P=0.15 ) . A total of 65 patients ( 20 in the BEACOPP group , and 45 in the ABVD group ) went on to receive the intended high-dose salvage regimen . As of the cutoff date , 3 of the 20 patients in the BEACOPP group and 15 of the 45 in the ABVD group who had had progressive disease or relapse after the initial therapy were alive and free of disease . After completion of the overall planned treatment , including salvage therapy , the 7-year rate of freedom from a second progression was 88 % in the BEACOPP group and 82 % in the ABVD group ( P=0.12 ) , and the 7-year rate of overall survival was 89 % and 84 % , respectively ( P=0.39 ) . Severe adverse events occurred more frequently in the BEACOPP 
    Output:
    
agent
***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 At present , treatment results for patients with advanced-stage Hodgkin 's disease remain unsatisfactory . St and ard chemotherapy M(C)OPP ( nitrogen mustard ( cyclophosphamide ) . vincristine , procabazine , and prednisone ) . ABVD ( adriamycine , bleomycine , vinblastine , and dacarbacine ) or M(C)OPP/ABVD + /- radiotherapy fail to achieve long-term complete remission in 35 % to 50 % of these patients . The BEACOPP ( bleomycin , etoposide , adriamycine , cyclophosphamide , vincristine , procarbazine , and prednisone ) regimen was developed to improve treatment results by dose intensification achieved by reduced duration of treatment ( time intensification ) and addition of etoposide . PATIENTS AND METHODS Thirty untreated patients with advanced Hodgkin 's disease stage IIB IV according to the Ann Arbor classification were treated with the time intensified BEACOPP regimen . Each patient was scheduled to receive eight cycles of chemotherapy with consolidating radiotherapy to sites of initial bulk disease and to residual tumor remaining after chemotherapy . RESULTS All patients were evaluable for assessment of toxicity , treatment response , freedom from treatment failure ( FFTF ) and survival ( SV ) . Of 30 treated patients , 29 patients received the intended eight cycles of BEACOPP . One patient in clinical CR , terminated the chemotherapy at his own request after six cycles and is at this time , 48 months after the end of treatment , in complete remission . Toxicity was tolerable with WHO grade 3/4 leucopenia in 28 % of chemotherapy cycles and one severe ( WHO grade 3 ) infection . No treatment-related death occurred . Cycles could generally be given on schedule . Complete remission ( CR ) was achieved in all but two patients ( 93 % ) . At present , only one patient has relapsed . At a median follow-up of 40 months , FFTF-rate is 89 % ( lower confidence limit : 80 % ) . One patient died due to progressive disease . CONCLUSION The BEACOPP regimen is feasible at moderate hematopoeitic toxicity . With a FFTF-rate of 89 % at a median follow-up of 40 months , the treatment results are very encouraging . A prospect i ve r and omised trial has been initiated to compare the BEACOPP regimen with the st and ard COPP/ABVD regimen in advanced-stage Hodgkin 's disease PURPOSE Current st and ard therapy for children and adolescents with Hodgkin 's disease includes combination chemotherapy and low-dose involved-field radiation ( LD-IFRT ) . Because radiation may be associated with adverse late effects , the Children 's Cancer Group ( CCG ) investigated whether radiation could be omitted in patients achieving a complete response to initial chemotherapy without jeopardizing the excellent outcome obtained with combined-modality therapy . PATIENTS AND METHODS Between January 1995 and December 1998 , 829 eligible patients were enrolled onto CCG 5942 . A total of 501 patients who achieved an initial complete response after risk-adapted combination chemotherapy were r and omized to receive LD-IFRT or no further treatment .  Event-free survival ( EFS ) and overall survival were assessed from the date of study entry or the date of r and omization , as appropriate . RESULTS The projected 3-year EFS from study entry for the entire cohort was 87 % + /- 1.2 % . Among patients who achieved a complete response to initial chemotherapy , 92 % + /- 1.9 % of those r and omized to receive LD-IFRT were alive and disease free 3 years after r and omization , versus 87 % + /- 2.2 % for patients r and omized to receive no further therapy ( stratified log-rank test ; P = .057 ) . With an " as-treated " analysis , 3-year EFS after r and omization for the radiation cohort was 93 % + /- 1.7 % versus 85 % + /- 2.3 % for patients receiving no further therapy ( stratified log-rank test ; P = .0024 ) . Three-year survival estimates for patients treated with and without LD-IFRT were 98 % + /- 1.1 % for patients who received radiation and 99 % + /- 0.5 % for patients who did not receive radiation . CONCLUSION LD-IFRT after an initial complete response to risk-adapted chemotherapy improved EFS . At this time , there is no survival advantage for LD-IFRT , but follow-up remains short BACKGROUND It is unclear whether patients with early-stage Hodgkin 's lymphoma and negative findings on positron-emission tomography ( PET ) after three cycles of chemotherapy with doxorubicin , bleomycin , vinblastine , and dacarbazine ( ABVD ) require radiotherapy . METHODS Patients with newly diagnosed stage IA or stage IIA Hodgkin 's lymphoma received three cycles of ABVD and then underwent PET scanning . Patients with negative PET findings were r and omly assigned to receive involved-field radiotherapy or no further treatment ; patients with positive PET findings received a fourth cycle of ABVD and radiotherapy . This trial assessing the noninferiority of no further treatment was design ed to exclude a difference in the 3-year progression-free survival rate of 7 or more percentage points from the assumed 95 % progression-free survival rate in the radiotherapy group . RESULTS A total of 602 patients ( 53.3 % male ; median age , 34 years ) were recruited , and 571 patients underwent PET scanning .  The PET findings were negative in 426 of these patients ( 74.6 % ) , 420 of whom were r and omly assigned to a study group ( 209 to the radiotherapy group and 211 to no further therapy ) . At a median of 60 months of follow-up , there had been 8 instances of disease progression in the radiotherapy group , and 8 patients had died ( 3 with disease progression , 1 of whom died from Hodgkin 's lymphoma ) ; there had been 20 instances of disease progression in the group with no further therapy , and 4 patients had died ( 2 with disease progression and none from Hodgkin 's lymphoma ) . In the radiotherapy group , 5 of the deaths occurred in patients who received no radiotherapy . The 3-year progression-free survival rate was 94.6 % ( 95 % confidence interval [ CI ] , 91.5 to 97.7 ) in the radiotherapy group and 90.8 % ( 95 % CI , 86.9 to 94.8 ) in the group that received no further therapy , with an absolute risk difference of -3.8 percentage points ( 95 % CI , -8.8 to 1.3 ) . CONCLUSIONS The results of this study did not show the noninferiority of the strategy of no further treatment after chemotherapy with regard to progression-free survival . Nevertheless , patients in this study with early-stage Hodgkin 's lymphoma and negative PET findings after three cycles of ABVD had a very good prognosis either with or without consolidation radiotherapy . ( Funded by Leukaemia and Lymphoma Research and others ; RAPID Clinical Trials.gov number , NCT00943423 . ) The Medical Research Council has for some years encouraged collaborative clinical trials in leukaemia and other cancers , reporting the results in the medical literature . One unreported result which deserves such publication is the development of the expertise to design and analyse such trials . This report was prepared by a group of British and American statisticians , but it is intended for people without any statistical expertise . Part I , which appears in this issue , discusses the design of such trials ; Part II , which will appear separately in the January 1977 issue of the Journal , gives full instructions for the statistical analysis of such trials by means of life tables and the logrank test , including a worked example , and discusses the interpretation of trial results , including brief reports of 2 particular trials . Both parts of this report are relevant to all clinical trials which study time to death , and wound be equally relevant to clinical trials which study time to other particular classes of untoward event : first stroke , perhaps , or first relapse , metastasis , disease recurrence , thrombosis , transplant rejection , or death from a particular cause . Part I , in this issue , collects together ideas that have mostly already appeared in the medical literature , but Part II , next month , is the first simple account yet published for non-statistical physicians of how to analyse efficiently data from clinical trials of survival duration . Such trials include the majority of all clinical trials of cancer therapy ; in cancer trials , however , it may be preferable to use these statistical methods to study time to local recurrence of tumour , or to study time to detectable metastatic spread , in addition to study ing total survival . Solid tumours can be staged at diagnosis ; if this , or any other available information in some other disease is an important determinant of outcome , it can be used to make the overall logrank test for the whole heterogeneous trial population more sensitive , and more intuitively satisfactory , for it will then only be necessary to compare like with like , and not , by chance , Stage I with Stage III PURPOSE Although survival rates have improved for patients with bulky and advanced-stage Hodgkin 's disease ( HD ) , current treatments entail substantial acute morbidity and risks for late effects such as infertility , second malignancies , and cardiopulmonary toxicities . A novel , brief chemotherapy regimen ( doxorubicin , vinblastine , mechlorethamine , vincristine , bleomycin , etoposide , and prednisone [ Stanford V ] ) was design ed to shorten the duration of treatment , significantly reduce cumulative doses of alkylating agents , doxorubicin , and bleomycin , and maintain dose-intensity ( DI ) . This brief chemotherapy was combined with radiation therapy ( RT ) to bulky disease sites . METHODS Since May 1989 , 65 previously untreated patients were treated for stage II HD with bulky mediastinal involvement ( n = 21 ) or for stage III or IV HD ( n = 44 ) . Patients received weekly chemotherapy for 12 weeks . Consolidative RT was given to the first 25 patients to sites of initial bulky disease or radiographic abnormalities that persisted after chemotherapy ; in the remaining 40 patients , RT was limited to bulky disease ( adenopathy > or = 5 cm and /or macroscopic splenic nodules defined by computed tomography [ CT ] ) . RESULTS With a median follow-up period of 2 years , actuarial 3-year survival rate is 96 % and failure-free survival ( FFS ) rate is 87 % . The 3-year FFS rate is 100 % for stage II patients with bulky mediastinal disease and 82 % for patients with stage III to IV disease . There were no treatment-related deaths . In a preliminary analysis on a subset of patients , female and male fertility appears to be preserved . CONCLUSION These preliminary results indicate that the Stanford V chemotherapy regimen with or without RT is well-tolerated and effective therapy for bulky , limited-stage , and advanced-stage HD . Less cumulative exposure to alkylating agents , doxorubicin , and bleomycin and limited use of radiation is expected to decrease risks for second neoplasms and late cardiopulmonary toxicity . Based on these results , the Stanford V chemotherapy with or without RT regimen deserves further study in the context of a r and omized clinical trial BACKGROUND BEACOPP , an intensified regimen consisting of bleomycin , etoposide , doxorubicin , cyclophosphamide , vincristine , procarbazine , and prednisone , has been advocated as the new st and ard of treatment for advanced Hodgkin 's lymphoma , in place of the combination of doxorubicin , bleomycin , vinblastine , and dacarbazine ( ABVD ) . METHODS We r and omly assigned 331 patients with previously untreated and unfavorable Hodgkin 's lymphoma ( stage IIB , III , or IV , or an international prognostic score of ≥3 on a scale of 0 to 7 , with higher scores indicating increased risk ) , to receive either BEACOPP or ABVD  , each followed by local radiotherapy  when indicated . Patients with residual or progressive disease after the initial therapy were to be treated according to a state-of-the-art high-dose salvage program . The median follow-up period was 61 months . RESULTS The 7-year rate of freedom from first progression was 85 % among patients who had received initial treatment with BEACOPP and 73 % among those who had received initial treatment with ABVD ( P=0.004 ) , and the 7-year rate of event-free survival was 78 % and 71 % , respectively ( P=0.15 ) . A total of 65 patients ( 20 in the BEACOPP group , and 45 in the ABVD group ) went on to receive the intended high-dose salvage regimen . As of the cutoff date , 3 of the 20 patients in the BEACOPP group and 15 of the 45 in the ABVD group who had had progressive disease or relapse after the initial therapy were alive and free of disease . After completion of the overall planned treatment , including salvage therapy , the 7-year rate of freedom from a second progression was 88 % in the BEACOPP group and 82 % in the ABVD group ( P=0.12 ) , and the 7-year rate of overall survival was 89 % and 84 % , respectively ( P=0.39 ) . Severe adverse events occurred more frequently in the BEACOPP 
    Output:
    