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: Background : We investigated the feasibility of dose-dense neoadjuvant chemotherapy ( NACT ) with paclitaxel and carboplatin before radical chemoradiation ( CRT ) and assessed the response rate to such a regimen . Methods : CxII is a single-arm phase II trial of 46 patients , with locally advanced cervical cancer ( stage Ib2-IVa ) . Patients received dose-dense carboplatin ( AUC2 ) and paclitaxel ( 80 mg m−2 ) weekly for six cycles followed by CRT ( 40 mg m−2 of weekly cisplatin , 50.4 Gy , 28 fractions plus brachytherapy ) . The primary end point was response rate 12 weeks post-CRT . Results : Baseline characteristics were : median age at diagnosis 43 years ; 72 % squamous , 22 % adenocarcinoma and 7 % adenosquamous histologies ; FIGO stage IB2 ( 11 % ) , II ( 50 % ) , III ( 33 % ) , IV ( 7 % ) . Complete or partial response rate was 70 % ( 95 % CI : 54–82 ) post-NACT and 85 % ( 95 % CI : 71–94 ) post-CRT . The median follow-up was 39.1 months . Overall and progression-free survivals at 3 years were 67 % ( 95 % CI : 51–79 ) and 68 % ( 95 % CI : 51–79 ) , respectively . Grade 3/4 toxicities were 20 % during NACT ( 11 % haematological , 9 % non-haematological ) and 52 % during CRT ( haematological : 41 % , non-haematological : 22 % ) . Conclusion : A good response rate is achieved by dose-dense weekly NACT with carboplatin and paclitaxel followed by radical CRT . This treatment regimen is feasible as evidence d by the acceptable toxicity of NACT and by the high compliance to radiotherapy ( 98 % ) Objective Patients with stage IB2 to IIA cervical cancer have a poor survival regardless of what primary treatment is performed . We conducted a study to demonstrate whether neoadjuvant treatment could offer survival benefits to those patients . Methods Between January 2006 and December 2009 , 123 patients with stage IB2 to IIA cervical cancer were enrolled and r and omly assigned to receive 1 of the following 4 treatments : radical surgery alone ( arm RS ) , brachytherapy with a total dose of 15Gy to point A followed by radical surgery ( arm BT ) , intravenous chemotherapy with cisplatin 50 mg/m2 plus 5-fluorouracil 750 mg/m2 at a 2-week interval for 2 courses followed by radical surgery ( arm IVCT ) , or intra-arterial chemotherapy with the same regimen as the IVCT arm followed by radical surgery ( arm IACT ) . Two weeks after neoadjuvant treatment , all patients underwent evaluation for response and operability . Those who were not amenable to surgery received concurrent chemoradiotherapy . Results With a mean follow-up of 34.8 months , 120 patients were evaluable . Baseline characteristics were similarly distributed in the 4 arms . Clinical overall response rates were 61.3 % , 42.9 % , and 79.3 % in the BT , IVCT , and IACT groups , respectively . Two patients achieved pathological complete response . Three-year progression-free survival rates were 70.7 % , 66.3 % , 81.5 % , and 79.7 % in the RS , BT , IVCT , and IACT arms , respectively ( P = 0.354 ) . Three-year overall survival was 73.3 % , 68.3 % , 82.9 % and 80.4 % , respectively ( P = 0.431 ) . Multivariate analysis showed that only lymph node status correlated with progression-free survival . Conclusions Neoadjuvant treatment had no significant impact on the outcomes of patients with stage IB2 to IIA cervical cancer BACKGROUND Stage Ib and IIa cervical carcinoma can be cured by radical surgery or radiotherapy . These two procedures are equally effective , but differ in associated morbidity and type of complications . In this prospect i ve r and omised trial of radiotherapy versus surgery , our aim was to assess the 5-year survival and the rate and pattern of complications and recurrences associated with each treatment . METHODS Between September , 1986 , and December , 1991 , 469 women with newly diagnosed stage Ib and IIa cervical carcinoma were referred to our institute . 343 eligible patients were r and omised : 172 to surgery and 171 to radical radiotherapy . Adjuvant radiotherapy was delivered after surgery for women with surgical stage pT2b or greater , less than 3 mm of safe cervical stroma , cut-through , or positive nodes . The primary outcome measures were 5-year survival and the rate of complications . The analysis of survival and recurrence was by intention to treat and analysis of complications was by treatment delivered . FINDINGS 170 patients in the surgery group and 167 in the radiotherapy group were included in the intention-to-treat analysis ; scheduled treatment was delivered to 169 and 158 women , respectively , 62 of 114 women with cervical diameters of 4 cm or smaller and 46 of 55 with diameters larger than 4 cm received adjuvant therapy . After a median follow-up of 87 ( range 57 - 120 ) months , 5-year overall and disease-free survival were identical in the surgery and radiotherapy groups ( 83 % and 74 % , respectively , for both groups ) , 86 women developed recurrent disease : 42 ( 25 % ) in the surgery group and 44 ( 26 % ) in the radiotherapy group . Significant factors for survival in univariate and multivariate analyses were : cervical diameter , positive lymphangiography , and adeno-carcinomatous histotype . 48 ( 28 % ) surgery-group patients had severe morbidity compared with 19 ( 12 % ) radiotherapy-group patients ( p = 0.0004 ) . INTERPRETATION There is no treatment of choice for early-stage cervical carcinoma in terms of overall or disease-free survival . The combination of surgery and radiotherapy has the worst morbidity , especially urological complications . The optimum therapy for each patient should take account of clinical factors such as menopausal status , age , medical illness , histological type , and cervical diameter to yield the best cure with minimum complications OBJECTIVE To determine if three courses consisting of 50 mg/m2 cis-platinum , 1 mg/m2 vincristine , and 25 mg/m2 bleomycin ( day 1 - 3 ) at 10-day intervals can improve survival before Wertheim-Meigs + radiotherapy . MATERIAL Two hundred five unselected stage Ib patients ( having tumors > 2 cm in diameter ) were divided into two groups at r and om : ( 1 ) The group control consisted of 103 patients ( 56 bulky , > 4 cm diameter ) treated with Wertheim-Meigs ( if the tumor was resectable with free surgical margins ) + adjuvant radiotherapy to whole pelvis ( extended field radiation was used only in patients with paraaortic lymph node metastases ) . When the tumor was unresectable , a surgical staging was performed and radiotherapy was the chosen treatment . ( 2 ) Neoadjuvant ( 102 patients , 61 bulky ) had neoadjuvant chemotherapy and then the same treatment as the control patients . RESULTS After 67 ( 31 - 102 ) months of follow-up , no difference was seen in tumors > 2 and < 4 cm in both groups ( C = 77 % vs N = 82 % ) , but statistically significant differences were seen in survival and disease-free survival , in bulky tumors , and between patients with neoadjuvant chemotherapy + Wertheim-Meigs + radiotherapy ( 80 % ) and the control ( 61 % ) . This was due to an increased operability that was substantially improved in bulky tumors in the neoadjuvant chemotherapy group ( 61/61 , 100 % ) vs control ( 48/56 , 85 % ; P < 0.01 ) . After 7 years of follow-up , the outcome of the unresectable bulky control group of patients is significantly worse ( 14 % ) than that of the resectable group ( 69 % ; P < 0.001 ) . With regard to recurrences , a significant decrease in pelvic failures in the neoadjuvant chemotherapy group was observed ( P < 0.001 ) . Survival was improved in bulky resectable cases ( N = 81 % vs C = 69 % , P < 0.05 ) . Pathological findings for the surgical specimens revealed differences between both groups because all the risk factors such as parametrial and lymph node metastases , tumor bulk , and vascular embolism had been decreased ( P < 0.001 ) . CONCLUSION Neoadjuvant chemotherapy can improve survival because of increased operability with free survival margins and a decrease in pathologic risk factors in unselected , bulky ( > 4 cm diameter ) stage Ib patients PURPOSE Neoadjuvant chemotherapy may represent an alternative to irradiation in locally advanced squamous cell cervical cancer . Aims of this study were to compare a three-drug ( paclitaxel , ifosfamide , and cisplatin [ TIP ] ) with a two-drug ( ifosfamide and cisplatin [ IP ] ) regimen and to assess the prognostic value of pathologic response on survival . PATIENTS AND METHODS Patients ( n = 219 ) were r and omly assigned to ifosfamide 5 g/m(2 ) during 24 hours plus cisplatin 75 mg/m(2 ) , or paclitaxel 175 mg/m(2 ) plus ifosfamide 5 g/m(2 ) during 24 hours and cisplatin 75 mg/m(2 ) every 3 weeks for three courses . RESULTS Grade s 3 to 4 neutropenia , anemia , and thrombocytopenia were more frequent with TIP . We recorded four deaths related to toxicity . The optimal pathologic response ( OPT ) rate ( residual disease < 3 mm stromal invasion ) was higher with TIP than with IP ( 48 % v 23 % ; odds ratio , 3.22 ; 95 % CI , 1.69 to 5.88 ; P = .0003 ) . At a median follow-up of 43.4 months , 79 women experienced disease progression or died ( 46 in the IP arm , 33 in the TIP arm ) . Patients receiving TIP experienced a treatment failure rate 25 % less than those receiving IP , but this difference was not statistically significant ( hazard ratio [ HR ] , 0.75 ; 95 % CI , 0.48 to 1.17 ; P = .20 ) . Sixty-one patients died ( 37 in the IP arm , 24 in the TIP arm ) , and the HR of death was in favor of TIP , although not significantly ( HR , 0.66 ; 95 % CI , 0.39 to 1.10 ; P = .11 ) . In patients assessable for response ( n = 189 ) , the average death rates were higher in the group that did not achieve OPT ( HR , 5.88 ; 95 % CI , 2.50 to 13.84 ; P < .0001 ) . CONCLUSION The TIP regimen is associated with a higher response rate than the IP regimen , without a statistically significant effect on overall survival . OPT was a prognostic factor for survival One hundred fifty-one patients ( 107 stage IIB and 44 stage IIIB ) who had completed 2 years of follow-up after treatment with neoadjuvant chemotherapy ( " Quick " VBP scheme ) , prior to st and ard therapy , are presented . Four groups of patients with different prognosis and operability status , according to tumor response , were identified . In the first group ( excellent responders ) 96 % of the patients had no evidence of disease ( NED ) , whereas in the fourth group ( no response ) , only 33 % had NED after 2 years of follow-up . In the first group , no pelvic failure was observed . On the other h and , of 21 patients in group 4 , 11 ( 52 % ) had pelvic recurrences . The response to neoadjuvant therapy is strongly associated with the initial tumor volume ecographically evaluated . The critical pretreatment volume for response was 84 cm3 ( 4.85 cm in diameter ) .  Surgery and radiotherapy  were equally effective in those patients with initial tumor volume of 84 cm3 or less . But surgery appears to have a better outcome in those patients with tumors larger than the critical pretreatment tumor volume . Radiotherapy in this controversial group was ineffective in avoiding pelvic recurrences , especially when the tumor volume was not sufficiently reduced . The advantage of neoadjuvant chemotherapy is evident in stage IIB , with 79 % ( 85/107 ) of patients showing no evidence of disease as compared with 47 % ( 24/51 ) in a nonr and omized control group ( P less than 0.01 ) . Statistically significant differences were also obtained in stage IIIB ( 50 % vs 26 % in the control group ) OBJECTIVE To assess the 
    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: Background : We investigated the feasibility of dose-dense neoadjuvant chemotherapy ( NACT ) with paclitaxel and carboplatin before radical chemoradiation ( CRT ) and assessed the response rate to such a regimen . Methods : CxII is a single-arm phase II trial of 46 patients , with locally advanced cervical cancer ( stage Ib2-IVa ) . Patients received dose-dense carboplatin ( AUC2 ) and paclitaxel ( 80 mg m−2 ) weekly for six cycles followed by CRT ( 40 mg m−2 of weekly cisplatin , 50.4 Gy , 28 fractions plus brachytherapy ) . The primary end point was response rate 12 weeks post-CRT . Results : Baseline characteristics were : median age at diagnosis 43 years ; 72 % squamous , 22 % adenocarcinoma and 7 % adenosquamous histologies ; FIGO stage IB2 ( 11 % ) , II ( 50 % ) , III ( 33 % ) , IV ( 7 % ) . Complete or partial response rate was 70 % ( 95 % CI : 54–82 ) post-NACT and 85 % ( 95 % CI : 71–94 ) post-CRT . The median follow-up was 39.1 months . Overall and progression-free survivals at 3 years were 67 % ( 95 % CI : 51–79 ) and 68 % ( 95 % CI : 51–79 ) , respectively . Grade 3/4 toxicities were 20 % during NACT ( 11 % haematological , 9 % non-haematological ) and 52 % during CRT ( haematological : 41 % , non-haematological : 22 % ) . Conclusion : A good response rate is achieved by dose-dense weekly NACT with carboplatin and paclitaxel followed by radical CRT . This treatment regimen is feasible as evidence d by the acceptable toxicity of NACT and by the high compliance to radiotherapy ( 98 % ) Objective Patients with stage IB2 to IIA cervical cancer have a poor survival regardless of what primary treatment is performed . We conducted a study to demonstrate whether neoadjuvant treatment could offer survival benefits to those patients . Methods Between January 2006 and December 2009 , 123 patients with stage IB2 to IIA cervical cancer were enrolled and r and omly assigned to receive 1 of the following 4 treatments : radical surgery alone ( arm RS ) , brachytherapy with a total dose of 15Gy to point A followed by radical surgery ( arm BT ) , intravenous chemotherapy with cisplatin 50 mg/m2 plus 5-fluorouracil 750 mg/m2 at a 2-week interval for 2 courses followed by radical surgery ( arm IVCT ) , or intra-arterial chemotherapy with the same regimen as the IVCT arm followed by radical surgery ( arm IACT ) . Two weeks after neoadjuvant treatment , all patients underwent evaluation for response and operability . Those who were not amenable to surgery received concurrent chemoradiotherapy . Results With a mean follow-up of 34.8 months , 120 patients were evaluable . Baseline characteristics were similarly distributed in the 4 arms . Clinical overall response rates were 61.3 % , 42.9 % , and 79.3 % in the BT , IVCT , and IACT groups , respectively . Two patients achieved pathological complete response . Three-year progression-free survival rates were 70.7 % , 66.3 % , 81.5 % , and 79.7 % in the RS , BT , IVCT , and IACT arms , respectively ( P = 0.354 ) . Three-year overall survival was 73.3 % , 68.3 % , 82.9 % and 80.4 % , respectively ( P = 0.431 ) . Multivariate analysis showed that only lymph node status correlated with progression-free survival . Conclusions Neoadjuvant treatment had no significant impact on the outcomes of patients with stage IB2 to IIA cervical cancer BACKGROUND Stage Ib and IIa cervical carcinoma can be cured by radical surgery or radiotherapy . These two procedures are equally effective , but differ in associated morbidity and type of complications . In this prospect i ve r and omised trial of radiotherapy versus surgery , our aim was to assess the 5-year survival and the rate and pattern of complications and recurrences associated with each treatment . METHODS Between September , 1986 , and December , 1991 , 469 women with newly diagnosed stage Ib and IIa cervical carcinoma were referred to our institute . 343 eligible patients were r and omised : 172 to surgery and 171 to radical radiotherapy . Adjuvant radiotherapy was delivered after surgery for women with surgical stage pT2b or greater , less than 3 mm of safe cervical stroma , cut-through , or positive nodes . The primary outcome measures were 5-year survival and the rate of complications . The analysis of survival and recurrence was by intention to treat and analysis of complications was by treatment delivered . FINDINGS 170 patients in the surgery group and 167 in the radiotherapy group were included in the intention-to-treat analysis ; scheduled treatment was delivered to 169 and 158 women , respectively , 62 of 114 women with cervical diameters of 4 cm or smaller and 46 of 55 with diameters larger than 4 cm received adjuvant therapy . After a median follow-up of 87 ( range 57 - 120 ) months , 5-year overall and disease-free survival were identical in the surgery and radiotherapy groups ( 83 % and 74 % , respectively , for both groups ) , 86 women developed recurrent disease : 42 ( 25 % ) in the surgery group and 44 ( 26 % ) in the radiotherapy group . Significant factors for survival in univariate and multivariate analyses were : cervical diameter , positive lymphangiography , and adeno-carcinomatous histotype . 48 ( 28 % ) surgery-group patients had severe morbidity compared with 19 ( 12 % ) radiotherapy-group patients ( p = 0.0004 ) . INTERPRETATION There is no treatment of choice for early-stage cervical carcinoma in terms of overall or disease-free survival . The combination of surgery and radiotherapy has the worst morbidity , especially urological complications . The optimum therapy for each patient should take account of clinical factors such as menopausal status , age , medical illness , histological type , and cervical diameter to yield the best cure with minimum complications OBJECTIVE To determine if three courses consisting of 50 mg/m2 cis-platinum , 1 mg/m2 vincristine , and 25 mg/m2 bleomycin ( day 1 - 3 ) at 10-day intervals can improve survival before Wertheim-Meigs + radiotherapy . MATERIAL Two hundred five unselected stage Ib patients ( having tumors > 2 cm in diameter ) were divided into two groups at r and om : ( 1 ) The group control consisted of 103 patients ( 56 bulky , > 4 cm diameter ) treated with Wertheim-Meigs ( if the tumor was resectable with free surgical margins ) + adjuvant radiotherapy to whole pelvis ( extended field radiation was used only in patients with paraaortic lymph node metastases ) . When the tumor was unresectable , a surgical staging was performed and radiotherapy was the chosen treatment . ( 2 ) Neoadjuvant ( 102 patients , 61 bulky ) had neoadjuvant chemotherapy and then the same treatment as the control patients . RESULTS After 67 ( 31 - 102 ) months of follow-up , no difference was seen in tumors > 2 and < 4 cm in both groups ( C = 77 % vs N = 82 % ) , but statistically significant differences were seen in survival and disease-free survival , in bulky tumors , and between patients with neoadjuvant chemotherapy + Wertheim-Meigs + radiotherapy ( 80 % ) and the control ( 61 % ) . This was due to an increased operability that was substantially improved in bulky tumors in the neoadjuvant chemotherapy group ( 61/61 , 100 % ) vs control ( 48/56 , 85 % ; P < 0.01 ) . After 7 years of follow-up , the outcome of the unresectable bulky control group of patients is significantly worse ( 14 % ) than that of the resectable group ( 69 % ; P < 0.001 ) . With regard to recurrences , a significant decrease in pelvic failures in the neoadjuvant chemotherapy group was observed ( P < 0.001 ) . Survival was improved in bulky resectable cases ( N = 81 % vs C = 69 % , P < 0.05 ) . Pathological findings for the surgical specimens revealed differences between both groups because all the risk factors such as parametrial and lymph node metastases , tumor bulk , and vascular embolism had been decreased ( P < 0.001 ) . CONCLUSION Neoadjuvant chemotherapy can improve survival because of increased operability with free survival margins and a decrease in pathologic risk factors in unselected , bulky ( > 4 cm diameter ) stage Ib patients PURPOSE Neoadjuvant chemotherapy may represent an alternative to irradiation in locally advanced squamous cell cervical cancer . Aims of this study were to compare a three-drug ( paclitaxel , ifosfamide , and cisplatin [ TIP ] ) with a two-drug ( ifosfamide and cisplatin [ IP ] ) regimen and to assess the prognostic value of pathologic response on survival . PATIENTS AND METHODS Patients ( n = 219 ) were r and omly assigned to ifosfamide 5 g/m(2 ) during 24 hours plus cisplatin 75 mg/m(2 ) , or paclitaxel 175 mg/m(2 ) plus ifosfamide 5 g/m(2 ) during 24 hours and cisplatin 75 mg/m(2 ) every 3 weeks for three courses . RESULTS Grade s 3 to 4 neutropenia , anemia , and thrombocytopenia were more frequent with TIP . We recorded four deaths related to toxicity . The optimal pathologic response ( OPT ) rate ( residual disease < 3 mm stromal invasion ) was higher with TIP than with IP ( 48 % v 23 % ; odds ratio , 3.22 ; 95 % CI , 1.69 to 5.88 ; P = .0003 ) . At a median follow-up of 43.4 months , 79 women experienced disease progression or died ( 46 in the IP arm , 33 in the TIP arm ) . Patients receiving TIP experienced a treatment failure rate 25 % less than those receiving IP , but this difference was not statistically significant ( hazard ratio [ HR ] , 0.75 ; 95 % CI , 0.48 to 1.17 ; P = .20 ) . Sixty-one patients died ( 37 in the IP arm , 24 in the TIP arm ) , and the HR of death was in favor of TIP , although not significantly ( HR , 0.66 ; 95 % CI , 0.39 to 1.10 ; P = .11 ) . In patients assessable for response ( n = 189 ) , the average death rates were higher in the group that did not achieve OPT ( HR , 5.88 ; 95 % CI , 2.50 to 13.84 ; P < .0001 ) . CONCLUSION The TIP regimen is associated with a higher response rate than the IP regimen , without a statistically significant effect on overall survival . OPT was a prognostic factor for survival One hundred fifty-one patients ( 107 stage IIB and 44 stage IIIB ) who had completed 2 years of follow-up after treatment with neoadjuvant chemotherapy ( " Quick " VBP scheme ) , prior to st and ard therapy , are presented . Four groups of patients with different prognosis and operability status , according to tumor response , were identified . In the first group ( excellent responders ) 96 % of the patients had no evidence of disease ( NED ) , whereas in the fourth group ( no response ) , only 33 % had NED after 2 years of follow-up . In the first group , no pelvic failure was observed . On the other h and , of 21 patients in group 4 , 11 ( 52 % ) had pelvic recurrences . The response to neoadjuvant therapy is strongly associated with the initial tumor volume ecographically evaluated . The critical pretreatment volume for response was 84 cm3 ( 4.85 cm in diameter ) .  Surgery and radiotherapy  were equally effective in those patients with initial tumor volume of 84 cm3 or less . But surgery appears to have a better outcome in those patients with tumors larger than the critical pretreatment tumor volume . Radiotherapy in this controversial group was ineffective in avoiding pelvic recurrences , especially when the tumor volume was not sufficiently reduced . The advantage of neoadjuvant chemotherapy is evident in stage IIB , with 79 % ( 85/107 ) of patients showing no evidence of disease as compared with 47 % ( 24/51 ) in a nonr and omized control group ( P less than 0.01 ) . Statistically significant differences were also obtained in stage IIIB ( 50 % vs 26 % in the control group ) OBJECTIVE To assess the 
    Output:
    