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: The objective of this study is to assess tumour response to neoadjuvant chemotherapy prior to radical hysterectomy in cervical cancer using magnetic resonance ( MR ) to monitor tumour volume and changes in molecular profile and to compare the survival to that of a control group . Eligibility included Stage Ib – IIb previously untreated cervical tumours > 10 cm3 .  Neoadjuvant chemotherapy in 22 patients ( methotrexate 300 mg m−2 ( with folinic acid rescue ) , bleomycin 30 mg m−2 , cisplatin 60 mg m−2 ) was repeated twice weekly for three courses and followed by radical hysterectomy . Post-operative radiotherapy was given in 14 cases . A total of 23 patients treated either with radical surgery or chemoradiotherapy over the same time period comprised the nonr and omised control group . MR scans before and after neoadjuvant chemotherapy and in the control group documented tumour volume on imaging and metabolites on in vivo spectroscopy . Changes were compared using a paired t-test . Survival was calculated using the Kaplan – Meier method . There were no significant differences between the neoadjuvant chemotherapy and control groups in age ( mean , s.d . 43.3±10 , 44.7±8.5 years , respectively , P=0.63 ) or tumour volume ( medians , quartiles 35.8 , 17.8 , 57.7 cm3 vs 23.0 , 15.0 , 37.0 cm3 , respectively , P=0.068 ) . The reduction in tumour volume post-chemotherapy ( median , quartiles 7.5 , 3.0 , 19.0 cm3 ) was significant ( P=0.002 ) . The reduction in –CH2 triglyceride approached significance ( P=0.05 ) , but other metabolites were unchanged . The 3-year survival in the chemotherapy group ( 49.1 % ) was not significantly different from the control group ( 46 % , P=0.94 ) . There is a significant reduction in tumour volume and –CH2 triglyceride levels  after neoadjuvant chemotherapy , but there is no survival advantage The purpose of this study was to investigate pretreatment variables related to prognosis and to evaluate long-term outcome in patients with bulky early-stage cervical carcinoma who were enrolled into a protocol treatment of neoadjuvant chemotherapy ( NAC ) followed by radical surgery . Between 1988 and 1999 , 162 women with previously untreated bulky ( ≥4 cm ) stage IB or IIA carcinoma of the uterine cervix registered to receive cisplatin , vincristine , and bleomycin for three cycles followed by radical hysterectomy and pelvic lymphadenectomy  , were enrolled into this study . The 5-year relapse-free ( RFS ) and overall survival ( OS ) rates of the whole series were 65 % and 69 % , respectively . In multivariate analyses , age ( < 35 vs. ≥ 35-year-old : relative risk [ RR ] , 2.06 ; 95 % confidence interval [ CI ] , 1.02–4.14 ; P = 0.043 ) and histologic type ( adeno-adenosquamous vs. squamous carcinoma : RR , 2.60 ; 95 % CI , 1.26–5.39 ; P = 0.010 ) were independent variables associated with RFS , and age ( < 35 vs. ≥ 35-year-old : RR , 2.53 ; 95 % CI , 1.24–5.14 ; P = 0.010 ) and pre-NAC tumor size ( > 5 vs. = 5 cm : RR , 2.06 ; 95 % CI , 1.09–3.90 ; P = 0.027 ) were significantly related to OS . Narrowing down patient selection to squamous carcinoma and age older than 35 years with stratification of tumor size ( break point of 5 cm ) is recommended in future trials involving cisplatin-based NAC plus radical surgery BACKGROUND Our aim was to evaluate the efficacy and safety of neoadjuvant chemotherapy followed by radical hysterectomy and adjuvant radiation concurrent with weekly cisplatin for locally advanced cervical carcinoma . PATIENTS AND METHODS Forty-three patients staged as IB2-IIIB were treated with three 21-day courses of carboplatin ( area under the time-concentration curve 6 mg.min/ml ) and paclitaxel at 175 mg/m(2 ) by 3-h infusion both on day 1 followed by radical type III hysterectomy and adjuvant radiation concurrent with 6-weekly doses of cisplatin at 40 mg/m(2 ) . Response rate , resectability , toxicity and survival were evaluated . RESULTS From December 2000 to June 2001 , 43 patients were recruited . All were evaluated for response and toxicity to neoadjuvant chemotherapy . A total of 129 courses were administered . Clinical responses were seen in 41 patients ( 95 % ) [ 95 % confidence interval ( CI ) 89.2 % to 100 % ] with four ( 9 % ) complete and 37 ( 86 % ) partial . Forty-one patients underwent surgery ( resectability 95 % ) ; pathologically complete or near-complete responses were seen in seven ( 17 % ) and eight ( 20 % ) , respectively , positive surgical margins in five ( 12 % ) , and positive pelvic lymph nodes in eight ( 20 % ) . Twenty-six patients were scheduled for adjuvant chemoradiation . External radiation was delivered for 42.8 days ( range 33 - 61 ) , with a mean dose of 49.3 Gy ( range 46 - 56 ) , and a median of five cisplatin courses ( two to six ) . The mean dose of brachytherapy was 32 Gy ( range 25.5 - 35.6 ) . Neoadjuvant therapy was well-tolerated with neutropenia grade 3 and 4 in 12 % and 3 % of the courses , respectively . Toxicity to adjuvant chemoradiation was mainly hematological and gastrointestinal , mostly grade s 1/2 . A total of 39 patients completed all scheduled treatment . At a median follow-up of 21 months ( range 3 - 26 ) , the projected overall survival in the intention-to-treat analysis was 79 % ( 95 % CI 62 % to 88 % ) . CONCLUSIONS The triple modality of neoadjuvant chemotherapy followed by radical hysterectomy and adjuvant radiation concurrent with cisplatin is a highly active treatment for locally advanced cervical carcinoma with acceptable toxicity Primary or neoadjuvant chemotherapy prior to definitive local therapy has potential advantages for locally advanced cervix cancer . It can downstage a cancer and allow definitive local therapy to be technically possible ( surgery ) , or potentially more effective ( radiotherapy ) . It can also eradicate sub clinical systemic metastases . This report review s a single institution 's experience of neoadjuvant chemotherapy prior to definitive local therapy for cervix cancer over a 13-year period . One hundred and six patients were treated with this intent . The patients were analysed for their response to chemotherapy , treatment received , survival , relapse and toxicity . The chemotherapy was feasible and the majority of patients had a complete or partial response ( 58.5 % ) . Eight patients did not proceed to local treatment . Forty-six patients had definitive surgery and 52 had definitive radiotherapy . The 5-year overall survival was 27 % and the majority of patients died with disease . The first site of relapse was usually in the pelvis ( 46.2 % ) . Late complications that required ongoing medical therapy ( n=6 ) or surgical intervention ( n=2 ) were recorded in eight patients ( 7.5 % ) . On univariate analysis stage ( P=0.04 ) , tumour size ( P=0.01 ) , lymph node status ( P=0.003 ) , response to chemotherapy ( P=0.045 ) and treatment ( P=0.003 ) were all significant predictors of survival . On multivariate analysis , tumour size ( P < 0.0001 ) and nodal status ( P=0.02 ) were significant predictors of survival . Despite the impressive responses to chemotherapy of advanced cervix cancer , there is evidence from r and omized trials that it does not improve or compromise survival prior to radiotherapy . As its role prior to surgery remains unclear , it should not be used in this setting outside a prospect i ve r and omized trial The efficacy and adverse events of neoadjuvant chemotherapy with irinotecan hydrochloride and nedaplatin were evaluated in patients with bulky stage Ib2 to IIb cervical squamous cell carcinoma . Eligibility included patients who received irinotecan ( 60 mg/m2 ) on days 1 and 8 and nedaplatin ( 80 mg/m2 ) on day 1 of a 21-day cycle . After 1 - 3 courses of chemotherapy , radical hysterectomy was performed . Sixty-eight patients were enrolled . Sixty-six were included in the full analysis set . Their median age was 47 years ( range 22 - 71 ) , the FIGO stage was Ib2 in 18 patients , IIa in 10 , and IIb in 38 .  Radical hysterectomy was performed after NAC in 63 patients ( 95.5 % ) . The number of administered courses of NAC was 1 in 13 patients , 2 in 43 , and 3 in 10 . The response rate , the primary endpoint of this study , was 75.8 % ( CR in 2 patients , PR in 48 , SD in 12 , PD in 0 , and NE in 4 ) . The mean number of treatment courses required for a response was 1.42 ( 1 course in 30 patients , 2 courses in 19 , and 3 courses in 1 ) . The incidences of grade 3 or 4 hematological toxicities were : neutropenia 72.2 % , leukopenia 16.7 % , anemia 13.6 % , thrombocytopenia 7.6 % , febrile neutropenia 1.5 % , and elevations of alanine aminotransferase and aspartate aminotransferase 1.5 % . Grade 3 or 4 non-hematologic toxicities were as follows : diarrhea 6.1 % , nausea 3 % , anorexia 1.5 % , vomiting 1.5 % , fever 1.5 % , allergic reactions 1.5 % , ileus 1.5 % and vesicovaginal fistula 1.5 % . Neoadjuvant chemotherapy with irinotecan and nedaplatin was an effective and well-tolerated treatment for patients with bulky stage Ib2 to IIb squamous cell carcinoma of the uterine cervix BACKGROUND R and omized studies comparing induction chemotherapy followed by surgical resection with radiation alone found that the neoadjuvant approach produces better results . So far , this latter modality has not been compared with st and ard concomitant chemoradiation . The objective of this report was to compare the results of two consecutive phase II studies : neoadjuvant chemotherapy followed by surgery or chemoradiation for the unresectable cases versus st and ard cisplatin-based chemoradiation . PATIENTS AND METHODS From February 1999 to July 1999 , 41 patients with cervical carcinoma , stages IB2-IIIB , were treated with neoadjuvant chemotherapy . Treatment consisted of three 21-day courses of cisplatin 100 mg/m(2 ) on day 1 and gemcitabine 1000 mg/m(2 ) on days 1 and 8 , followed by either surgery or concomitant chemoradiation for the non-operable cases . From August 1999 to December 1999 , an equal number of patients having comparable clinicopathological characteristics were treated with six weekly courses of cisplatin 40 mg/m(2 ) during st and ard pelvic radiation . RESULTS A total of 82 patients were analyzed . Both groups were similar with regard to age , histology , International Federation of Gynecology and Obstetrics ( FIGO ) stage , tumor size , pretreatment hemoglobin levels , parametrial infiltration and performance status . In the neoadjuvant arm the overall response rate to induction chemotherapy was 95 % ( 95 % confidence interval 88 % to 100 % ) . Twenty-three patients had surgery and 14 underwent chemoradiation . In the definitive chemoradiation study , 38 patients completed treatment , the median number of cisplatin courses was six for a dose intensity of 33 mg/m(2)/week . Doses to points A and B were 85 Gy ( range 68 - 95 ) and 55 Gy ( range 51 - 65 ) , respectively . Chemoradiation was delivered in 44.6 ( range 28 - 113 ) days . Complete response rates after all treatment were similar : 97 % and 87 % in the neoadjuvant and chemoradiation groups , respectively . At a median follow-up of 28 ( range 2 - 33 ) and 24 ( range 3 - 30 ) months , respectively , there were no differences in overall survival . To date , 15 and 13 patients in 
    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: The objective of this study is to assess tumour response to neoadjuvant chemotherapy prior to radical hysterectomy in cervical cancer using magnetic resonance ( MR ) to monitor tumour volume and changes in molecular profile and to compare the survival to that of a control group . Eligibility included Stage Ib – IIb previously untreated cervical tumours > 10 cm3 .  Neoadjuvant chemotherapy in 22 patients ( methotrexate 300 mg m−2 ( with folinic acid rescue ) , bleomycin 30 mg m−2 , cisplatin 60 mg m−2 ) was repeated twice weekly for three courses and followed by radical hysterectomy . Post-operative radiotherapy was given in 14 cases . A total of 23 patients treated either with radical surgery or chemoradiotherapy over the same time period comprised the nonr and omised control group . MR scans before and after neoadjuvant chemotherapy and in the control group documented tumour volume on imaging and metabolites on in vivo spectroscopy . Changes were compared using a paired t-test . Survival was calculated using the Kaplan – Meier method . There were no significant differences between the neoadjuvant chemotherapy and control groups in age ( mean , s.d . 43.3±10 , 44.7±8.5 years , respectively , P=0.63 ) or tumour volume ( medians , quartiles 35.8 , 17.8 , 57.7 cm3 vs 23.0 , 15.0 , 37.0 cm3 , respectively , P=0.068 ) . The reduction in tumour volume post-chemotherapy ( median , quartiles 7.5 , 3.0 , 19.0 cm3 ) was significant ( P=0.002 ) . The reduction in –CH2 triglyceride approached significance ( P=0.05 ) , but other metabolites were unchanged . The 3-year survival in the chemotherapy group ( 49.1 % ) was not significantly different from the control group ( 46 % , P=0.94 ) . There is a significant reduction in tumour volume and –CH2 triglyceride levels  after neoadjuvant chemotherapy , but there is no survival advantage The purpose of this study was to investigate pretreatment variables related to prognosis and to evaluate long-term outcome in patients with bulky early-stage cervical carcinoma who were enrolled into a protocol treatment of neoadjuvant chemotherapy ( NAC ) followed by radical surgery . Between 1988 and 1999 , 162 women with previously untreated bulky ( ≥4 cm ) stage IB or IIA carcinoma of the uterine cervix registered to receive cisplatin , vincristine , and bleomycin for three cycles followed by radical hysterectomy and pelvic lymphadenectomy  , were enrolled into this study . The 5-year relapse-free ( RFS ) and overall survival ( OS ) rates of the whole series were 65 % and 69 % , respectively . In multivariate analyses , age ( < 35 vs. ≥ 35-year-old : relative risk [ RR ] , 2.06 ; 95 % confidence interval [ CI ] , 1.02–4.14 ; P = 0.043 ) and histologic type ( adeno-adenosquamous vs. squamous carcinoma : RR , 2.60 ; 95 % CI , 1.26–5.39 ; P = 0.010 ) were independent variables associated with RFS , and age ( < 35 vs. ≥ 35-year-old : RR , 2.53 ; 95 % CI , 1.24–5.14 ; P = 0.010 ) and pre-NAC tumor size ( > 5 vs. = 5 cm : RR , 2.06 ; 95 % CI , 1.09–3.90 ; P = 0.027 ) were significantly related to OS . Narrowing down patient selection to squamous carcinoma and age older than 35 years with stratification of tumor size ( break point of 5 cm ) is recommended in future trials involving cisplatin-based NAC plus radical surgery BACKGROUND Our aim was to evaluate the efficacy and safety of neoadjuvant chemotherapy followed by radical hysterectomy and adjuvant radiation concurrent with weekly cisplatin for locally advanced cervical carcinoma . PATIENTS AND METHODS Forty-three patients staged as IB2-IIIB were treated with three 21-day courses of carboplatin ( area under the time-concentration curve 6 mg.min/ml ) and paclitaxel at 175 mg/m(2 ) by 3-h infusion both on day 1 followed by radical type III hysterectomy and adjuvant radiation concurrent with 6-weekly doses of cisplatin at 40 mg/m(2 ) . Response rate , resectability , toxicity and survival were evaluated . RESULTS From December 2000 to June 2001 , 43 patients were recruited . All were evaluated for response and toxicity to neoadjuvant chemotherapy . A total of 129 courses were administered . Clinical responses were seen in 41 patients ( 95 % ) [ 95 % confidence interval ( CI ) 89.2 % to 100 % ] with four ( 9 % ) complete and 37 ( 86 % ) partial . Forty-one patients underwent surgery ( resectability 95 % ) ; pathologically complete or near-complete responses were seen in seven ( 17 % ) and eight ( 20 % ) , respectively , positive surgical margins in five ( 12 % ) , and positive pelvic lymph nodes in eight ( 20 % ) . Twenty-six patients were scheduled for adjuvant chemoradiation . External radiation was delivered for 42.8 days ( range 33 - 61 ) , with a mean dose of 49.3 Gy ( range 46 - 56 ) , and a median of five cisplatin courses ( two to six ) . The mean dose of brachytherapy was 32 Gy ( range 25.5 - 35.6 ) . Neoadjuvant therapy was well-tolerated with neutropenia grade 3 and 4 in 12 % and 3 % of the courses , respectively . Toxicity to adjuvant chemoradiation was mainly hematological and gastrointestinal , mostly grade s 1/2 . A total of 39 patients completed all scheduled treatment . At a median follow-up of 21 months ( range 3 - 26 ) , the projected overall survival in the intention-to-treat analysis was 79 % ( 95 % CI 62 % to 88 % ) . CONCLUSIONS The triple modality of neoadjuvant chemotherapy followed by radical hysterectomy and adjuvant radiation concurrent with cisplatin is a highly active treatment for locally advanced cervical carcinoma with acceptable toxicity Primary or neoadjuvant chemotherapy prior to definitive local therapy has potential advantages for locally advanced cervix cancer . It can downstage a cancer and allow definitive local therapy to be technically possible ( surgery ) , or potentially more effective ( radiotherapy ) . It can also eradicate sub clinical systemic metastases . This report review s a single institution 's experience of neoadjuvant chemotherapy prior to definitive local therapy for cervix cancer over a 13-year period . One hundred and six patients were treated with this intent . The patients were analysed for their response to chemotherapy , treatment received , survival , relapse and toxicity . The chemotherapy was feasible and the majority of patients had a complete or partial response ( 58.5 % ) . Eight patients did not proceed to local treatment . Forty-six patients had definitive surgery and 52 had definitive radiotherapy . The 5-year overall survival was 27 % and the majority of patients died with disease . The first site of relapse was usually in the pelvis ( 46.2 % ) . Late complications that required ongoing medical therapy ( n=6 ) or surgical intervention ( n=2 ) were recorded in eight patients ( 7.5 % ) . On univariate analysis stage ( P=0.04 ) , tumour size ( P=0.01 ) , lymph node status ( P=0.003 ) , response to chemotherapy ( P=0.045 ) and treatment ( P=0.003 ) were all significant predictors of survival . On multivariate analysis , tumour size ( P < 0.0001 ) and nodal status ( P=0.02 ) were significant predictors of survival . Despite the impressive responses to chemotherapy of advanced cervix cancer , there is evidence from r and omized trials that it does not improve or compromise survival prior to radiotherapy . As its role prior to surgery remains unclear , it should not be used in this setting outside a prospect i ve r and omized trial The efficacy and adverse events of neoadjuvant chemotherapy with irinotecan hydrochloride and nedaplatin were evaluated in patients with bulky stage Ib2 to IIb cervical squamous cell carcinoma . Eligibility included patients who received irinotecan ( 60 mg/m2 ) on days 1 and 8 and nedaplatin ( 80 mg/m2 ) on day 1 of a 21-day cycle . After 1 - 3 courses of chemotherapy , radical hysterectomy was performed . Sixty-eight patients were enrolled . Sixty-six were included in the full analysis set . Their median age was 47 years ( range 22 - 71 ) , the FIGO stage was Ib2 in 18 patients , IIa in 10 , and IIb in 38 .  Radical hysterectomy was performed after NAC in 63 patients ( 95.5 % ) . The number of administered courses of NAC was 1 in 13 patients , 2 in 43 , and 3 in 10 . The response rate , the primary endpoint of this study , was 75.8 % ( CR in 2 patients , PR in 48 , SD in 12 , PD in 0 , and NE in 4 ) . The mean number of treatment courses required for a response was 1.42 ( 1 course in 30 patients , 2 courses in 19 , and 3 courses in 1 ) . The incidences of grade 3 or 4 hematological toxicities were : neutropenia 72.2 % , leukopenia 16.7 % , anemia 13.6 % , thrombocytopenia 7.6 % , febrile neutropenia 1.5 % , and elevations of alanine aminotransferase and aspartate aminotransferase 1.5 % . Grade 3 or 4 non-hematologic toxicities were as follows : diarrhea 6.1 % , nausea 3 % , anorexia 1.5 % , vomiting 1.5 % , fever 1.5 % , allergic reactions 1.5 % , ileus 1.5 % and vesicovaginal fistula 1.5 % . Neoadjuvant chemotherapy with irinotecan and nedaplatin was an effective and well-tolerated treatment for patients with bulky stage Ib2 to IIb squamous cell carcinoma of the uterine cervix BACKGROUND R and omized studies comparing induction chemotherapy followed by surgical resection with radiation alone found that the neoadjuvant approach produces better results . So far , this latter modality has not been compared with st and ard concomitant chemoradiation . The objective of this report was to compare the results of two consecutive phase II studies : neoadjuvant chemotherapy followed by surgery or chemoradiation for the unresectable cases versus st and ard cisplatin-based chemoradiation . PATIENTS AND METHODS From February 1999 to July 1999 , 41 patients with cervical carcinoma , stages IB2-IIIB , were treated with neoadjuvant chemotherapy . Treatment consisted of three 21-day courses of cisplatin 100 mg/m(2 ) on day 1 and gemcitabine 1000 mg/m(2 ) on days 1 and 8 , followed by either surgery or concomitant chemoradiation for the non-operable cases . From August 1999 to December 1999 , an equal number of patients having comparable clinicopathological characteristics were treated with six weekly courses of cisplatin 40 mg/m(2 ) during st and ard pelvic radiation . RESULTS A total of 82 patients were analyzed . Both groups were similar with regard to age , histology , International Federation of Gynecology and Obstetrics ( FIGO ) stage , tumor size , pretreatment hemoglobin levels , parametrial infiltration and performance status . In the neoadjuvant arm the overall response rate to induction chemotherapy was 95 % ( 95 % confidence interval 88 % to 100 % ) . Twenty-three patients had surgery and 14 underwent chemoradiation . In the definitive chemoradiation study , 38 patients completed treatment , the median number of cisplatin courses was six for a dose intensity of 33 mg/m(2)/week . Doses to points A and B were 85 Gy ( range 68 - 95 ) and 55 Gy ( range 51 - 65 ) , respectively . Chemoradiation was delivered in 44.6 ( range 28 - 113 ) days . Complete response rates after all treatment were similar : 97 % and 87 % in the neoadjuvant and chemoradiation groups , respectively . At a median follow-up of 28 ( range 2 - 33 ) and 24 ( range 3 - 30 ) months , respectively , there were no differences in overall survival . To date , 15 and 13 patients in 
    Output:
    