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: Japanese women with low-stage cervical cancer receiving radical hysterectomy and radiotherapy  have a good 5-year survival rate . However , women with risk factors such as nodal metastasis may benefit from adjuvant chemotherapy , which was studied in women having surgery alone or surgery plus radiotherapy .  Patients having surgery alone ( S ) ( n=623 ) or surgery and radiotherapy ( SR ) ( n=919 ) were r and omly assigned to receive or not receive oral 5-fluorouracil ( 5-FU ) for 1 year . The effect of various factors on survival was studied by multivariate analysis . Patients who received S obtained no benefit from 5-FU , whereas 5-FU-treated SR patients had significantly better 5-year survival than those not receiving chemotherapy ( P=0.043 ) . The SR patients without nodal metastases had a better survival rate if they received 5-FU ( P<0.001 ) , whereas those with nodal metastases did not . Oral 5-FU after radical hysterectomy with radiotherapy appears useful for patients with low-stage cervical cancer who have some risk factors but not for those with pelvic lymph node metastases Summary Adjuvant therapy may potentially improve prognosis in women with early-stage cervical cancer who are at high risk of relapse after primary therapy . Patients with lymph node involvement at surgery are at high risk of recurrence and may benefit from adjuvant therapy , but many patients are treated with radical radiotherapy . At present there is no method of accurately identifying patients at high risk of recurrence in the latter group . A retrospective analysis of 141 surgically managed cases with state I/IIa cervical cancer is presented . The study aims were to characterize patients at high risk of relapse , identify independent prognostic variables predicting for relapse and , using these variables , develop a model , that would accurately predict high-risk patients . Univariate analysis identified depht of invasion , substage , lymph node involvement , lymphatic and blood vessel invasion and tumour differentiation as significant prognostic variables . After stratification for depth of invasion , which did not conform to the proportional hazards assumption implicit in the Cox model , Cox regression analysis showed substage , lymphatic and vascular invasion and histological tumour type to be independent prognostic variables . Using these variables , classification models were constructed that would be applicable to patients treated with either surgery or radiotherapy . Applying the models to 110 cases with > 18 months follow-up , 11/18 ( 61 % ) and 11/19 cases ( 58 % ) predicted as being at high risk of relapse have developed recurrence . Highly active chemotherapy is now available for this disease . We have demonstrated that combined bleomycin , ifosfamide and cisplatin ( BIP ) is one of the most active regimens in this disease . BIP produces cytoreduction in around 70 % of patients with recurrent and primary advanced disease . Responses are achieved rapidly and acute radiotherapy toxicity is not enhanced by giving chemotherapy prior to radical local radiotherapy . A multicentre , prospect i ve r and omized trial testing the role of BIP as adjuvant therapy in patients with positive nodes at radical hysterectomy is now in progress . A complementary study testing the role of adjuvant chemotherapy in high-risk patients treated with radical radiotherapy  is in preparation BACKGROUND Adjuvant treatment modalities after radical hysterectomy have long been used in an attempt to eradicate microscopic tumor residuals in patients at high risk for recurrence . However , it has not been clearly demonstrated that adjuvant radiation , adjuvant chemotherapy , or both improve the outcome . To evaluate the effect of adjuvant treatment in patients with high-risk cervical cancer after radical hysterectomy , the Austrian Gynecologic Oncology Group conducted a prospect i ve , r and omized , multicenter clinical trial between 1989 and 1995 . MATERIAL AND METHODS Seventy-six patients with stage IB-IIB cervical cancer treated with radical hysterectomy with pelvic lymph node metastases and /or vascular invasion r and omly received adjuvant chemotherapy ( 400 mg/m2 carboplatin , and 30 mg bleomycin ) , st and ardized external pelvic radiation therapy , or no further treatment . RESULTS After a median follow-up of 4.1 years ( range , 2 - 7 ) there were no statistically significant differences ( P = 0.9530 ) in disease-free survival among the three treatment arms . CONCLUSION The data suggest that adjuvant chemotherapy or radiation do not improve survival or recurrence rates in high-risk cervical cancer patients after radical hysterectomy . The most important treatment for these patients seems to be radical abdominal hysterectomy with systematic pelvic lymphadenectomy INTRODUCTION Chemo-potentiation of radiation improves survival in women with cervical cancer . Our group has previously demonstrated the tolerability of weekly paclitaxel combined with cisplatin during radiation therapy . We sought to determine the efficacy of this regimen in patients with " high risk " cervical cancer , and to determine the short- and long-term toxicity of this approach . METHODS We prospect ively enrolled surgically staged patients with positive peritoneal cytology , resectable nodal metastases , or primary tumor > 6 cm . Patients were treated using external beam radiation with concomitant cisplatin ( 50 mg/m2 ) during weeks 1 , 4 , and 7 , and weekly paclitaxel ( 50 mg/m2 ) , followed by four courses of adjuvant cisplatin ( 50 mg/m2 ) and paclitaxel ( 135 mg/m2 ) . Toxicity , overall , and disease-free survival were evaluated . RESULTS Twenty-three patients were enrolled , and 21 were evaluable . Patient allotment by FIGO stage was : IB1 - seven , IB2 - five , IIA - two , IIB - four , IIIB - two , IV - three . Twenty patients ( 95 % ) completed radiation treatment ( median dose to point A was 8278 cGy ) . Seventeen patients ( 81 % ) completed all chemotherapy . At a median follow-up of 58 months the overall survival was 68 % . Overall survival for patients with clinical Stage I and II disease was 82 % at a median of 64 months . Hematologic toxicity was common but rarely result ed in treatment delays . Late complications requiring intervention ( obstruction , fistula , significant lymphocyst ) occurred in 11 patients ( 52 % ) . CONCLUSION The combination of paclitaxel and cisplatin appears efficacious in " high-risk " cervical cancer patients .  Hematologic toxicity was common but tolerable . Long-term survival was common in these patients , however late toxicity was significant . This regimen should be investigated in collaborative phase III trials PURPOSE To determine whether the addition of cisplatin-based chemotherapy ( CT ) to pelvic radiation therapy ( RT ) will improve the survival of early-stage , high-risk patients with cervical carcinoma . PATIENTS AND METHODS Patients with clinical stage IA(2 ) , IB , and IIA carcinoma of the cervix , initially treated with radical hysterectomy and pelvic lymphadenectomy , and who had positive pelvic lymph nodes and /or positive margins and /or microscopic involvement of the parametrium were eligible for this study . Patients were r and omized to receive RT or RT + CT . Patients in each group received 49.3 GY RT in 29 fractions to a st and ard pelvic field . Chemotherapy consisted of bolus cisplatin 70 mg/m(2 ) and a 96-hour infusion of fluorouracil 1,000 mg/m(2)/d every 3 weeks for four cycles , with the first and second cycles given concurrent to RT . RESULTS Between 1991 and 1996 , 268 patients were entered onto the study . Two hundred forty-three patients were assessable ( 127 RT + CT patients and 116 RT patients ) .  Progression-free and overall survival are significantly improved in the patients receiving CT . The hazard ratios for progression-free survival and overall survival in the RT only arm versus the RT + CT arm are 2.01 ( P = .003 ) and 1.96 ( P = . 007 ) , respectively . The projected progression-free survivals at 4 years is 63 % with RT and 80 % with RT + CT . The projected overall survival rate at 4 years is 71 % with RT and 81 % with RT + CT . Grade s 3 and 4 hematologic and gastrointestinal toxicity were more frequent in the RT + CT group . CONCLUSION The addition of concurrent cisplatin-based CT to RT significantly improves progression-free and overall survival for high-risk , early-stage patients who undergo radical hysterectomy and pelvic lymphadenectomy for carcinoma of the cervix PURPOSE To investigate , in a prospect i ve trial , the acute and chronic toxicity of patients with cervical cancer treated with surgery and postoperative intensity-modulated radiotherapy ( RT ) delivered using helical tomotherapy , with or without the administration of concurrent chemotherapy . PATIENTS AND METHODS A total of 24 evaluable patients entered the study between March 2006 and August 2009 . The indications for postoperative RT were tumor size , lymphovascular space invasion , and the depth of cervical stromal invasion in 15 patients ; 9 patients underwent postoperative RT because of surgically positive lymph nodes . All patients underwent pelvic RT delivered with helical tomotherapy and intracavitary high-dose-rate brachytherapy . Treatment consisted of concurrent weekly platinum in 17 , sequential carboplatin/Taxol in 1 , and RT alone in 6 . The patients were monitored for acute and chronic toxicity using the  Common Toxicity Criteria  , version 3.0 . RESULTS The median follow-up was 24 months ( range , 4 - 49 ) . At the last follow-up visit , 23 patients were alive and disease free . Of the 24 patients , 12 ( 50 % ) experienced acute Grade 3 gastrointestinal toxicity ( anorexia in 5 , diarrhea in 4 , and nausea in 3 ) . One patient developed acute Grade 4 genitourinary toxicity ( vesicovaginal fistula ) . For patients treated with concurrent chemotherapy , the incidence of acute Grade 3 and 4 hematologic toxicity was 71 % and 24 % , respectively . For patients treated without concurrent chemotherapy , the incidence of acute Grade 3 and 4 hematologic toxicity was 29 % and 14 % , respectively . Two long-term toxicities occurred ( vesicovaginal fistula at 25 months and small bowel obstruction at 30 months ) . The overall and progression-free survival rate at 3 years for all patients was 100 % and 89 % , respectively . CONCLUSION The results of our study have shown that postoperative external RT for cervical cancer delivered with helical tomotherapy and high-dose-rate brachytherapy and with or without chemotherapy is feasible , with acceptable acute and chronic toxicity Objective The mature results of the neoadjuvant and adjuvant chemotherapy arms of the nonr and omized , phase 2 Yale University  cisplatin , bleomycin , methotrexate , and 5-FU protocol are presented . Methods Sixty-seven patients were prospect ively accrued with a median follow-up of 5.4 years , and st and ard parameters of toxicity and efficacy were studied . Both univariate and multivariate analyses were applied . Results The 5-year disease-free survival of 78 % for the 25 patients in the adjuvant group , of which 80 % had high-risk features including positive margins , parametria , and lymph nodes and 28 % had adenocarcinomas , was comparable to recent relevant literature . Only 64 % of patients in this group received consolidation radiation therapy , which did not impact on survival . Only 12 % of patients recurred distantly . Notably , those who received 4 months or more of chemotherapy had prolonged survival ( P = 0.012 ) . In the neoadjuvant group , chemotherapy response rate among 42 patients ( with stages 1B-IIIB cancer ) was 79 % ( 50 % partial response , 29 % complete response ) , and no patient progressed . In the subgroup of 22 patients who underwent surgery after chemotherapy  , 59 % had nonsquamous histology . Forty-five percent of patients with stage IIB cancer were deemed operable after chemotherapy . Ninety-five percent received postoperative radiation therapy . There was a 9 % pathologic complete response rate , with positive lymph nodes found in 27 % . Notably , those who received 3 months or less of chemotherapy had improved overall survival ( P = 0.030 ) . Survival rates of these 22 patients at 3 and 5 years were 73 % and 63 % , respectively . Although not r and omized , these survival rates were similar to those achieved with chemoradiation . Conclusions Although there are several logistical/ design features of the cisplatin , bleomycin , methotrexate , and 5-FU regimen that are not in line with the current chemotherapy era , our experience with this well-tolerated regimen can serve as a proof of principle . Our data suggests that both neo 
    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: Japanese women with low-stage cervical cancer receiving radical hysterectomy and radiotherapy  have a good 5-year survival rate . However , women with risk factors such as nodal metastasis may benefit from adjuvant chemotherapy , which was studied in women having surgery alone or surgery plus radiotherapy .  Patients having surgery alone ( S ) ( n=623 ) or surgery and radiotherapy ( SR ) ( n=919 ) were r and omly assigned to receive or not receive oral 5-fluorouracil ( 5-FU ) for 1 year . The effect of various factors on survival was studied by multivariate analysis . Patients who received S obtained no benefit from 5-FU , whereas 5-FU-treated SR patients had significantly better 5-year survival than those not receiving chemotherapy ( P=0.043 ) . The SR patients without nodal metastases had a better survival rate if they received 5-FU ( P<0.001 ) , whereas those with nodal metastases did not . Oral 5-FU after radical hysterectomy with radiotherapy appears useful for patients with low-stage cervical cancer who have some risk factors but not for those with pelvic lymph node metastases Summary Adjuvant therapy may potentially improve prognosis in women with early-stage cervical cancer who are at high risk of relapse after primary therapy . Patients with lymph node involvement at surgery are at high risk of recurrence and may benefit from adjuvant therapy , but many patients are treated with radical radiotherapy . At present there is no method of accurately identifying patients at high risk of recurrence in the latter group . A retrospective analysis of 141 surgically managed cases with state I/IIa cervical cancer is presented . The study aims were to characterize patients at high risk of relapse , identify independent prognostic variables predicting for relapse and , using these variables , develop a model , that would accurately predict high-risk patients . Univariate analysis identified depht of invasion , substage , lymph node involvement , lymphatic and blood vessel invasion and tumour differentiation as significant prognostic variables . After stratification for depth of invasion , which did not conform to the proportional hazards assumption implicit in the Cox model , Cox regression analysis showed substage , lymphatic and vascular invasion and histological tumour type to be independent prognostic variables . Using these variables , classification models were constructed that would be applicable to patients treated with either surgery or radiotherapy . Applying the models to 110 cases with > 18 months follow-up , 11/18 ( 61 % ) and 11/19 cases ( 58 % ) predicted as being at high risk of relapse have developed recurrence . Highly active chemotherapy is now available for this disease . We have demonstrated that combined bleomycin , ifosfamide and cisplatin ( BIP ) is one of the most active regimens in this disease . BIP produces cytoreduction in around 70 % of patients with recurrent and primary advanced disease . Responses are achieved rapidly and acute radiotherapy toxicity is not enhanced by giving chemotherapy prior to radical local radiotherapy . A multicentre , prospect i ve r and omized trial testing the role of BIP as adjuvant therapy in patients with positive nodes at radical hysterectomy is now in progress . A complementary study testing the role of adjuvant chemotherapy in high-risk patients treated with radical radiotherapy  is in preparation BACKGROUND Adjuvant treatment modalities after radical hysterectomy have long been used in an attempt to eradicate microscopic tumor residuals in patients at high risk for recurrence . However , it has not been clearly demonstrated that adjuvant radiation , adjuvant chemotherapy , or both improve the outcome . To evaluate the effect of adjuvant treatment in patients with high-risk cervical cancer after radical hysterectomy , the Austrian Gynecologic Oncology Group conducted a prospect i ve , r and omized , multicenter clinical trial between 1989 and 1995 . MATERIAL AND METHODS Seventy-six patients with stage IB-IIB cervical cancer treated with radical hysterectomy with pelvic lymph node metastases and /or vascular invasion r and omly received adjuvant chemotherapy ( 400 mg/m2 carboplatin , and 30 mg bleomycin ) , st and ardized external pelvic radiation therapy , or no further treatment . RESULTS After a median follow-up of 4.1 years ( range , 2 - 7 ) there were no statistically significant differences ( P = 0.9530 ) in disease-free survival among the three treatment arms . CONCLUSION The data suggest that adjuvant chemotherapy or radiation do not improve survival or recurrence rates in high-risk cervical cancer patients after radical hysterectomy . The most important treatment for these patients seems to be radical abdominal hysterectomy with systematic pelvic lymphadenectomy INTRODUCTION Chemo-potentiation of radiation improves survival in women with cervical cancer . Our group has previously demonstrated the tolerability of weekly paclitaxel combined with cisplatin during radiation therapy . We sought to determine the efficacy of this regimen in patients with " high risk " cervical cancer , and to determine the short- and long-term toxicity of this approach . METHODS We prospect ively enrolled surgically staged patients with positive peritoneal cytology , resectable nodal metastases , or primary tumor > 6 cm . Patients were treated using external beam radiation with concomitant cisplatin ( 50 mg/m2 ) during weeks 1 , 4 , and 7 , and weekly paclitaxel ( 50 mg/m2 ) , followed by four courses of adjuvant cisplatin ( 50 mg/m2 ) and paclitaxel ( 135 mg/m2 ) . Toxicity , overall , and disease-free survival were evaluated . RESULTS Twenty-three patients were enrolled , and 21 were evaluable . Patient allotment by FIGO stage was : IB1 - seven , IB2 - five , IIA - two , IIB - four , IIIB - two , IV - three . Twenty patients ( 95 % ) completed radiation treatment ( median dose to point A was 8278 cGy ) . Seventeen patients ( 81 % ) completed all chemotherapy . At a median follow-up of 58 months the overall survival was 68 % . Overall survival for patients with clinical Stage I and II disease was 82 % at a median of 64 months . Hematologic toxicity was common but rarely result ed in treatment delays . Late complications requiring intervention ( obstruction , fistula , significant lymphocyst ) occurred in 11 patients ( 52 % ) . CONCLUSION The combination of paclitaxel and cisplatin appears efficacious in " high-risk " cervical cancer patients .  Hematologic toxicity was common but tolerable . Long-term survival was common in these patients , however late toxicity was significant . This regimen should be investigated in collaborative phase III trials PURPOSE To determine whether the addition of cisplatin-based chemotherapy ( CT ) to pelvic radiation therapy ( RT ) will improve the survival of early-stage , high-risk patients with cervical carcinoma . PATIENTS AND METHODS Patients with clinical stage IA(2 ) , IB , and IIA carcinoma of the cervix , initially treated with radical hysterectomy and pelvic lymphadenectomy , and who had positive pelvic lymph nodes and /or positive margins and /or microscopic involvement of the parametrium were eligible for this study . Patients were r and omized to receive RT or RT + CT . Patients in each group received 49.3 GY RT in 29 fractions to a st and ard pelvic field . Chemotherapy consisted of bolus cisplatin 70 mg/m(2 ) and a 96-hour infusion of fluorouracil 1,000 mg/m(2)/d every 3 weeks for four cycles , with the first and second cycles given concurrent to RT . RESULTS Between 1991 and 1996 , 268 patients were entered onto the study . Two hundred forty-three patients were assessable ( 127 RT + CT patients and 116 RT patients ) .  Progression-free and overall survival are significantly improved in the patients receiving CT . The hazard ratios for progression-free survival and overall survival in the RT only arm versus the RT + CT arm are 2.01 ( P = .003 ) and 1.96 ( P = . 007 ) , respectively . The projected progression-free survivals at 4 years is 63 % with RT and 80 % with RT + CT . The projected overall survival rate at 4 years is 71 % with RT and 81 % with RT + CT . Grade s 3 and 4 hematologic and gastrointestinal toxicity were more frequent in the RT + CT group . CONCLUSION The addition of concurrent cisplatin-based CT to RT significantly improves progression-free and overall survival for high-risk , early-stage patients who undergo radical hysterectomy and pelvic lymphadenectomy for carcinoma of the cervix PURPOSE To investigate , in a prospect i ve trial , the acute and chronic toxicity of patients with cervical cancer treated with surgery and postoperative intensity-modulated radiotherapy ( RT ) delivered using helical tomotherapy , with or without the administration of concurrent chemotherapy . PATIENTS AND METHODS A total of 24 evaluable patients entered the study between March 2006 and August 2009 . The indications for postoperative RT were tumor size , lymphovascular space invasion , and the depth of cervical stromal invasion in 15 patients ; 9 patients underwent postoperative RT because of surgically positive lymph nodes . All patients underwent pelvic RT delivered with helical tomotherapy and intracavitary high-dose-rate brachytherapy . Treatment consisted of concurrent weekly platinum in 17 , sequential carboplatin/Taxol in 1 , and RT alone in 6 . The patients were monitored for acute and chronic toxicity using the  Common Toxicity Criteria  , version 3.0 . RESULTS The median follow-up was 24 months ( range , 4 - 49 ) . At the last follow-up visit , 23 patients were alive and disease free . Of the 24 patients , 12 ( 50 % ) experienced acute Grade 3 gastrointestinal toxicity ( anorexia in 5 , diarrhea in 4 , and nausea in 3 ) . One patient developed acute Grade 4 genitourinary toxicity ( vesicovaginal fistula ) . For patients treated with concurrent chemotherapy , the incidence of acute Grade 3 and 4 hematologic toxicity was 71 % and 24 % , respectively . For patients treated without concurrent chemotherapy , the incidence of acute Grade 3 and 4 hematologic toxicity was 29 % and 14 % , respectively . Two long-term toxicities occurred ( vesicovaginal fistula at 25 months and small bowel obstruction at 30 months ) . The overall and progression-free survival rate at 3 years for all patients was 100 % and 89 % , respectively . CONCLUSION The results of our study have shown that postoperative external RT for cervical cancer delivered with helical tomotherapy and high-dose-rate brachytherapy and with or without chemotherapy is feasible , with acceptable acute and chronic toxicity Objective The mature results of the neoadjuvant and adjuvant chemotherapy arms of the nonr and omized , phase 2 Yale University  cisplatin , bleomycin , methotrexate , and 5-FU protocol are presented . Methods Sixty-seven patients were prospect ively accrued with a median follow-up of 5.4 years , and st and ard parameters of toxicity and efficacy were studied . Both univariate and multivariate analyses were applied . Results The 5-year disease-free survival of 78 % for the 25 patients in the adjuvant group , of which 80 % had high-risk features including positive margins , parametria , and lymph nodes and 28 % had adenocarcinomas , was comparable to recent relevant literature . Only 64 % of patients in this group received consolidation radiation therapy , which did not impact on survival . Only 12 % of patients recurred distantly . Notably , those who received 4 months or more of chemotherapy had prolonged survival ( P = 0.012 ) . In the neoadjuvant group , chemotherapy response rate among 42 patients ( with stages 1B-IIIB cancer ) was 79 % ( 50 % partial response , 29 % complete response ) , and no patient progressed . In the subgroup of 22 patients who underwent surgery after chemotherapy  , 59 % had nonsquamous histology . Forty-five percent of patients with stage IIB cancer were deemed operable after chemotherapy . Ninety-five percent received postoperative radiation therapy . There was a 9 % pathologic complete response rate , with positive lymph nodes found in 27 % . Notably , those who received 3 months or less of chemotherapy had improved overall survival ( P = 0.030 ) . Survival rates of these 22 patients at 3 and 5 years were 73 % and 63 % , respectively . Although not r and omized , these survival rates were similar to those achieved with chemoradiation . Conclusions Although there are several logistical/ design features of the cisplatin , bleomycin , methotrexate , and 5-FU regimen that are not in line with the current chemotherapy era , our experience with this well-tolerated regimen can serve as a proof of principle . Our data suggests that both neo 
    Output:
    