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 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 This study presents the analysis of results obtained in 237 Hodgkin 's disease patients , stages I and II , treated with combined modality therapy .  The overall and disease-free survival rates at 5 years were 96.6 and 85.2 % , respectively . The study has demonstrated the superiority of the following treatment program : one cycle of combination chemotherapy + radiation therapy + 5 cycles of combination chemotherapy . It has been found possible to reduce the number of radiation fields in combined modality therapy : for patients with stage IA-IIA lymphocyte predominant or nodular sclerosing Hodgkin 's disease it was sufficient only to treat clinical ly involved sites . Short- and long-term consequences of combined modality therapy have been analysed One hundred and fourteen untreated patients with pathological stage ( PS ) IA-IIB supradiaphragmatic Hodgkin 's Disease were r and omised to mantle radiotherapy alone ( 55 ) or mantle radiotherapy followed by 6 courses of adjuvant chemotherapy with mustine , vinblastine , prednisolone and procarbazine- MVPP ( 59 ) . Patients excluded were those outside the age range 16 - 65 years and those with massive mediastinal disease precluding laparotomy . Bulk disease was defined as a mass of lymph nodes measuring five centimetres or more in any axis . Mediastinal bulk was present if the ratio of the maximum width of mediastinal disease to the maximal chest diameter was more than one third . All patients achieved a complete remission . Median duration of follow-up was 62 months ( range 16 - 97 ) . The relapse free survival ( RFS ) was 81 % ; 69 % for radiotherapy alone and 93 % for adjuvant chemotherapy ( P = 0.002 ) . RFS was also shown to be adversely affected by B symptoms ( P = 0.0003 ) , bulk disease ( P = 0.018 ) , abnormal CXR ( P = 0.037 ) , and increasing stage ( P = 0.039 ) . Age , sex , histology , and number of sites involved had no significant effect upon RFS . A Cox multivariate analysis showed that only three variables had a significant adverse effect on RFS - radiotherapy alone , the presence of bulk disease , and B symptoms . The overall 5 year survival was 93 % with no statistically significant difference between the two treatment groups ( P = 0.54 ) . Survival was adversely affected by three variables - B symptoms ( P = 0.02 ) , the presence of bulk disease ( P = 0.002 ) , and pathological stage ( P = 0.05 ) . High risk groups for relapse are those with bulk and B symptoms . This analysis has shown that RFS was significantly improved by adjuvant chemotherapy , but that overall survival was not From April 1972 to May 1980 , 72 children and adolescents ( aged 5 to 19 years old , median 16 ) with Hodgkin 's disease , clinical stages IA-IIB ( IA , 18 ; II2A , two areas involved on the same side of the diaphragm , 23 ; II3+A , three areas or more , 16 ; IIB , 15 ) were prospect ively treated in two successive clinical trials ( H 72 and H 77 ) . Clinical stages IA and II2A received three courses of mechlorethamine , Oncovin , procarbazine , and prednisone ( MOPP ) and supradiaphragmatic radiotherapy ( 40 Gy ) , and no laparotomy was performed . Clinical stages II3+A and IIB received either six cycles of MOPP ( H 72 ) , three cycles of MOPP , or three cycles of CCNU , vinblastine , procarbazine , and prednisone ( CVPP ) ( H 77 ) and subsequently had a laparotomy followed by supradiaphragmatic radiotherapy and a lumboaortic field if results of laparotomy were positive . Patients without evidence of mediastinal involvement did not have mediastinal radiotherapy . At the completion of therapy , the disease in 70 of 72 patients was in complete remission ( one failure , one death during treatment ) . Eight patients relapsed ( in situ , 1 ; marginal , 1 ; nonirradiated subdiaphragmatic area , 6 ) after three to 57 months of complete remission ( median 20 months ) ; one patient died after relapse . There were three deaths after complete remission of the disease ( infection , two ; acute nonlymphocytic leukemia [ ANLL ] , one ) . As of June 1984 the median follow-up was 82 months ( range , 49 to 145 months ) , the actuarial probabilities for survival and freedom from relapse for all patients being 91.6 % and 87.6 % , respectively . There was no statistical difference according to clinical stage , age ( greater than 15 or less than 15 years ) , sex , or number of cycles of chemotherapy ( six or three ) . Bone growth defects related to radiotherapy were reduced particularly in the 29 patients who did not receive mediastinal radiotherapy . None of these patients had a mediastinal relapse . Azoospermia was the rule for the male patients studied , but young girls and young women retained reproductive integrity Seventy-nine patients with clinical stages IA , or II2A of Hodgkin 's disease were treated from January 1977 to April 1980 by a multiple therapy schedule , H 7701 . Three courses of MOPP chemotherapy were first given to all patients . They were then r and omly allocated to two groups : group 7701 S ( 38 patients ) was treated by mantle irradiation , excluding the mediastinum when this was not initially involved , or inverted Y radiotherapy ;  group 7701 F ( 41 patients ) was treated by focal irradiation only . After follow-up for 9 - 48 months ( median : 26 months ) , overall survival was 98,6 p. cent and relapse-free duration 94,9 p cent . No statistical difference exists between the two r and omized groups . Four patients relapsed ; three are now free of disease after further treatment , while one patient has since died . With this chemotherapy-radiotherapy selective of focal sequence , staging laparotomy is not indicated . Results and side effects of this treatment schedule are compared with those of other treatment strategies Since 1969 , 184 previously untreated and evaluable adult patients with Hodgkin 's disease , staged as I ( 43 ) or II ( 141 ) , have been treated . Eighty patients were part of the National Hodgkin 's Disease Study , r and omly assigned to receive  radiotherapy  to either an involved ( 39 ) or extended field ( 41 ) . In a subsequent single-arm study , 104 patients were treated with involved-field radiotherapy preceded and followed by three cycles of MOPP chemotherapy . Median duration s of follow-up have been 172 , 172 , and 92 months , for the involved-field radiotherapy , extended-field radiotherapy , and MOPP plus involved-field radiotherapy treatment groups , respectively . Although significant differences among the three treatment groups were observed with respect to disease-free survival ( p less than 0.001 ) , only the group of patients treated with involved-field radiotherapy had a statistically significant decline in overall survival as compared with the two other treatment groups ( p less than 0.001 ) . Moreover , patients who underwent clinical staging and were treated with MOPP plus involved-field radiotherapy had significantly prolonged disease-free survival compared with those who underwent surgical staging and were treated with extended-field radiotherapy ( p less than 0.001 ) . One of the patients who received MOPP plus involved-field radiotherapy had subsequent development of acute monocytic leukemia , and another had refractory anemia with excess blasts . One instance of diffuse poorly differentiated lymphocytic lymphoma was also observed . Acute monocytic leukemia developed in another patient treated with involved-field radiotherapy . The rates of amenorrhea in the group treated with MOPP plus involved-field radio-therapy were 9.6 percent and 78.5 percent for female patients younger and older than 30 years of age , respectively . Despite the universal azoospermia ensuing after MOPP plus involved-field radiotherapy , in three patients whose sperm counts were checked sequentially for 26 to 53 months after treatment , evidence of spermatogenesis was observed . Three patients with remission of Hodgkin 's disease after involved-field ( two ) and extended-field ( one ) radiotherapy died from cardiovascular disease that could only be attributed to the prior radiotherapy . Although further follow-up evaluation will be required to determine the impact of the three different treatment modalities on survival and long-term toxicity , MOPP plus involved-field radiotherapy appears to be superior to involved-field or extended-field radiotherapy alone in achieving prolonged disease-free survival without significant leukemogenic potential An analysis and progress report is presented of the r and omized clinical trials testing the value of adjuvant MOPP chemotherapy with irradiation in the management of Hodgkin 's disease . The 213 patients with Stages IA through IIIB have been followed for periods of up to 64 months . The chemotherapy controls the occult disease , result ing in significant improvement in disease‐free survival ( p = .002 ) . Over‐all survival is not yet affected , however , with combined 5‐year survival results of 92 % and 88 % in the two groups . The treatment program is difficult but feasible . No increased incidence of second malignancies has been observed in this study group . It is premature to conclude that adjuvant MOPP chemotherapy is indicated in the radiation management of Hodgkin 's disease The purpose of this study was to compare four methods of treatment for stage III-IV Hodgkin 's disease . Between January 1972 and September 1976 , 266 patients with stage IIIB , IVA , and IVB Hodgkin 's disease from 21 cancer treatment centers across Canada were registered as eligible ; 40 were found to be ineligible . Of the 226 remaining patients , only seven were followed for less than 10 years . All patients received three courses of mechlorethamine , vincristine , procarbazine , and prednisone ( MOPP ) chemotherapy , which induced a complete response ( CR ) in 36 % ; an additional 42 % obtained adequate disease control . Patients were r and omly assigned to ( 1 ) treatment with radiation to the abdomen and mantle ( group AX3 , 62 patients ) or ( 2 ) continue their treatment with an additional three courses of MOPP ( group A , 105 patients ) . For the A group , a second r and omization took place 3 months later ( regardless of status at that time ) to ( 1 ) no further treatment ( AC6 , 23 patients ) , ( 2 ) radiotherapy to the abdomen and mantle ( AX6 , 48 patients ) , or ( 3 ) maintenance chemotherapy at 3-month intervals for 1 year ( AC10 , 26 patients ) . The survival of AX3 patients was somewhat better than for the A group , but the difference was not significant ( P = .0565 ) . However , there was a significant interaction ( P = .0029 ) between age and treatment , so that among patients less than 30 years of age , the survival of the A group was better , whereas for older patients , treatment with AX3 result ed in improved survival . Age itself remained a significant prognostic factor for survival after controlling for the amount of radiotherapy delivered to the abdomen and the dose intensity of vincristine for the first three courses of chemotherapy . The addition of radiation therapy to MOPP significantly reduced the frequency of nodal relapses 
    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 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 This study presents the analysis of results obtained in 237 Hodgkin 's disease patients , stages I and II , treated with combined modality therapy .  The overall and disease-free survival rates at 5 years were 96.6 and 85.2 % , respectively . The study has demonstrated the superiority of the following treatment program : one cycle of combination chemotherapy + radiation therapy + 5 cycles of combination chemotherapy . It has been found possible to reduce the number of radiation fields in combined modality therapy : for patients with stage IA-IIA lymphocyte predominant or nodular sclerosing Hodgkin 's disease it was sufficient only to treat clinical ly involved sites . Short- and long-term consequences of combined modality therapy have been analysed One hundred and fourteen untreated patients with pathological stage ( PS ) IA-IIB supradiaphragmatic Hodgkin 's Disease were r and omised to mantle radiotherapy alone ( 55 ) or mantle radiotherapy followed by 6 courses of adjuvant chemotherapy with mustine , vinblastine , prednisolone and procarbazine- MVPP ( 59 ) . Patients excluded were those outside the age range 16 - 65 years and those with massive mediastinal disease precluding laparotomy . Bulk disease was defined as a mass of lymph nodes measuring five centimetres or more in any axis . Mediastinal bulk was present if the ratio of the maximum width of mediastinal disease to the maximal chest diameter was more than one third . All patients achieved a complete remission . Median duration of follow-up was 62 months ( range 16 - 97 ) . The relapse free survival ( RFS ) was 81 % ; 69 % for radiotherapy alone and 93 % for adjuvant chemotherapy ( P = 0.002 ) . RFS was also shown to be adversely affected by B symptoms ( P = 0.0003 ) , bulk disease ( P = 0.018 ) , abnormal CXR ( P = 0.037 ) , and increasing stage ( P = 0.039 ) . Age , sex , histology , and number of sites involved had no significant effect upon RFS . A Cox multivariate analysis showed that only three variables had a significant adverse effect on RFS - radiotherapy alone , the presence of bulk disease , and B symptoms . The overall 5 year survival was 93 % with no statistically significant difference between the two treatment groups ( P = 0.54 ) . Survival was adversely affected by three variables - B symptoms ( P = 0.02 ) , the presence of bulk disease ( P = 0.002 ) , and pathological stage ( P = 0.05 ) . High risk groups for relapse are those with bulk and B symptoms . This analysis has shown that RFS was significantly improved by adjuvant chemotherapy , but that overall survival was not From April 1972 to May 1980 , 72 children and adolescents ( aged 5 to 19 years old , median 16 ) with Hodgkin 's disease , clinical stages IA-IIB ( IA , 18 ; II2A , two areas involved on the same side of the diaphragm , 23 ; II3+A , three areas or more , 16 ; IIB , 15 ) were prospect ively treated in two successive clinical trials ( H 72 and H 77 ) . Clinical stages IA and II2A received three courses of mechlorethamine , Oncovin , procarbazine , and prednisone ( MOPP ) and supradiaphragmatic radiotherapy ( 40 Gy ) , and no laparotomy was performed . Clinical stages II3+A and IIB received either six cycles of MOPP ( H 72 ) , three cycles of MOPP , or three cycles of CCNU , vinblastine , procarbazine , and prednisone ( CVPP ) ( H 77 ) and subsequently had a laparotomy followed by supradiaphragmatic radiotherapy and a lumboaortic field if results of laparotomy were positive . Patients without evidence of mediastinal involvement did not have mediastinal radiotherapy . At the completion of therapy , the disease in 70 of 72 patients was in complete remission ( one failure , one death during treatment ) . Eight patients relapsed ( in situ , 1 ; marginal , 1 ; nonirradiated subdiaphragmatic area , 6 ) after three to 57 months of complete remission ( median 20 months ) ; one patient died after relapse . There were three deaths after complete remission of the disease ( infection , two ; acute nonlymphocytic leukemia [ ANLL ] , one ) . As of June 1984 the median follow-up was 82 months ( range , 49 to 145 months ) , the actuarial probabilities for survival and freedom from relapse for all patients being 91.6 % and 87.6 % , respectively . There was no statistical difference according to clinical stage , age ( greater than 15 or less than 15 years ) , sex , or number of cycles of chemotherapy ( six or three ) . Bone growth defects related to radiotherapy were reduced particularly in the 29 patients who did not receive mediastinal radiotherapy . None of these patients had a mediastinal relapse . Azoospermia was the rule for the male patients studied , but young girls and young women retained reproductive integrity Seventy-nine patients with clinical stages IA , or II2A of Hodgkin 's disease were treated from January 1977 to April 1980 by a multiple therapy schedule , H 7701 . Three courses of MOPP chemotherapy were first given to all patients . They were then r and omly allocated to two groups : group 7701 S ( 38 patients ) was treated by mantle irradiation , excluding the mediastinum when this was not initially involved , or inverted Y radiotherapy ;  group 7701 F ( 41 patients ) was treated by focal irradiation only . After follow-up for 9 - 48 months ( median : 26 months ) , overall survival was 98,6 p. cent and relapse-free duration 94,9 p cent . No statistical difference exists between the two r and omized groups . Four patients relapsed ; three are now free of disease after further treatment , while one patient has since died . With this chemotherapy-radiotherapy selective of focal sequence , staging laparotomy is not indicated . Results and side effects of this treatment schedule are compared with those of other treatment strategies Since 1969 , 184 previously untreated and evaluable adult patients with Hodgkin 's disease , staged as I ( 43 ) or II ( 141 ) , have been treated . Eighty patients were part of the National Hodgkin 's Disease Study , r and omly assigned to receive  radiotherapy  to either an involved ( 39 ) or extended field ( 41 ) . In a subsequent single-arm study , 104 patients were treated with involved-field radiotherapy preceded and followed by three cycles of MOPP chemotherapy . Median duration s of follow-up have been 172 , 172 , and 92 months , for the involved-field radiotherapy , extended-field radiotherapy , and MOPP plus involved-field radiotherapy treatment groups , respectively . Although significant differences among the three treatment groups were observed with respect to disease-free survival ( p less than 0.001 ) , only the group of patients treated with involved-field radiotherapy had a statistically significant decline in overall survival as compared with the two other treatment groups ( p less than 0.001 ) . Moreover , patients who underwent clinical staging and were treated with MOPP plus involved-field radiotherapy had significantly prolonged disease-free survival compared with those who underwent surgical staging and were treated with extended-field radiotherapy ( p less than 0.001 ) . One of the patients who received MOPP plus involved-field radiotherapy had subsequent development of acute monocytic leukemia , and another had refractory anemia with excess blasts . One instance of diffuse poorly differentiated lymphocytic lymphoma was also observed . Acute monocytic leukemia developed in another patient treated with involved-field radiotherapy . The rates of amenorrhea in the group treated with MOPP plus involved-field radio-therapy were 9.6 percent and 78.5 percent for female patients younger and older than 30 years of age , respectively . Despite the universal azoospermia ensuing after MOPP plus involved-field radiotherapy , in three patients whose sperm counts were checked sequentially for 26 to 53 months after treatment , evidence of spermatogenesis was observed . Three patients with remission of Hodgkin 's disease after involved-field ( two ) and extended-field ( one ) radiotherapy died from cardiovascular disease that could only be attributed to the prior radiotherapy . Although further follow-up evaluation will be required to determine the impact of the three different treatment modalities on survival and long-term toxicity , MOPP plus involved-field radiotherapy appears to be superior to involved-field or extended-field radiotherapy alone in achieving prolonged disease-free survival without significant leukemogenic potential An analysis and progress report is presented of the r and omized clinical trials testing the value of adjuvant MOPP chemotherapy with irradiation in the management of Hodgkin 's disease . The 213 patients with Stages IA through IIIB have been followed for periods of up to 64 months . The chemotherapy controls the occult disease , result ing in significant improvement in disease‐free survival ( p = .002 ) . Over‐all survival is not yet affected , however , with combined 5‐year survival results of 92 % and 88 % in the two groups . The treatment program is difficult but feasible . No increased incidence of second malignancies has been observed in this study group . It is premature to conclude that adjuvant MOPP chemotherapy is indicated in the radiation management of Hodgkin 's disease The purpose of this study was to compare four methods of treatment for stage III-IV Hodgkin 's disease . Between January 1972 and September 1976 , 266 patients with stage IIIB , IVA , and IVB Hodgkin 's disease from 21 cancer treatment centers across Canada were registered as eligible ; 40 were found to be ineligible . Of the 226 remaining patients , only seven were followed for less than 10 years . All patients received three courses of mechlorethamine , vincristine , procarbazine , and prednisone ( MOPP ) chemotherapy , which induced a complete response ( CR ) in 36 % ; an additional 42 % obtained adequate disease control . Patients were r and omly assigned to ( 1 ) treatment with radiation to the abdomen and mantle ( group AX3 , 62 patients ) or ( 2 ) continue their treatment with an additional three courses of MOPP ( group A , 105 patients ) . For the A group , a second r and omization took place 3 months later ( regardless of status at that time ) to ( 1 ) no further treatment ( AC6 , 23 patients ) , ( 2 ) radiotherapy to the abdomen and mantle ( AX6 , 48 patients ) , or ( 3 ) maintenance chemotherapy at 3-month intervals for 1 year ( AC10 , 26 patients ) . The survival of AX3 patients was somewhat better than for the A group , but the difference was not significant ( P = .0565 ) . However , there was a significant interaction ( P = .0029 ) between age and treatment , so that among patients less than 30 years of age , the survival of the A group was better , whereas for older patients , treatment with AX3 result ed in improved survival . Age itself remained a significant prognostic factor for survival after controlling for the amount of radiotherapy delivered to the abdomen and the dose intensity of vincristine for the first three courses of chemotherapy . The addition of radiation therapy to MOPP significantly reduced the frequency of nodal relapses 
    Output:
    