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 To evaluate the value of adjuvant external beam pelvic radiotherapy as adjunct to vaginal brachytherapy ( VBT ) in medium-risk endometrial carcinoma , with regard to locoregional tumor control , recurrences , survival , and toxicity . METHODS AND MATERIAL S Consecutive series of 527 evaluable patients were included in this r and omized trial . Median follow-up for patients alive was 62 months . The primary study endpoints were locoregional recurrences and overall survival . Secondary endpoints were recurrence-free survival , recurrence-free interval , cancer-specific survival , and toxicity . RESULTS Five-year locoregional relapse rates were 1.5 % after external beam radiotherapy ( EBRT ) plus VBT and 5 % after vaginal irradiation alone ( p = 0.013 ) , and 5-year overall survival rates were 89 % and 90 % , respectively ( p = 0.548 ) . Endometrial cancer-related death rates were 3.8 % after EBRT plus VBT and 6.8 % after VBT ( p = 0.118 ) . Pelvic recurrences ( exclusively vaginal recurrence ) were reduced by 93 % by the addition of EBRT to VBT .  Deep myometrial infiltration was a significant prognostic factor in this medium-risk group of endometrioid carcinomas but not International Federation of Gynecology and Obstetrics grade or DNA ploidy . Combined radiotherapy was well tolerated , with serious ( Grade 3 ) late side effects of less than 2 % . However , there was a significant difference in favor of VBT alone . CONCLUSIONS Despite a significant locoregional control benefit with combined radiotherapy , no survival improvement was recorded , but increased late toxicity was noted in the intestine , bladder , and vagina . Combined RT should probably be reserved for high-risk cases with two or more high-risk factors . VBT alone should be the adjuvant treatment option for purely medium-risk cases BACKGROUND Hysterectomy and bilateral salpingo-oophorectomy ( BSO ) is the st and ard surgery for stage I endometrial cancer . Systematic pelvic lymphadenectomy has been used to establish whether there is extra-uterine disease and as a therapeutic procedure ; however , r and omised trials need to be done to assess therapeutic efficacy . The ASTEC surgical trial investigated whether pelvic lymphadenectomy could improve survival of women with endometrial cancer . METHODS From 85 centres in four countries , 1408 women with histologically proven endometrial carcinoma thought preoperatively to be confined to the corpus were r and omly allocated by a minimisation method to st and ard surgery ( hysterectomy and BSO , peritoneal washings , and palpation of para-aortic nodes ; n=704 ) or st and ard surgery plus lymphadenectomy ( n=704 ) . The primary outcome measure was overall survival . To control for postsurgical treatment , women with early-stage disease at intermediate or high risk of recurrence were r and omised ( independent of lymph-node status ) into the ASTEC radiotherapy trial . Analysis was by intention to treat . This study is registered , number IS RCT N 16571884 . FINDINGS After a median follow-up of 37 months ( IQR 24 - 58 ) , 191 women ( 88 st and ard surgery group , 103 lymphadenectomy group ) had died , with a hazard ratio ( HR ) of 1.16 ( 95 % CI 0.87 - 1.54 ; p=0.31 ) in favour of st and ard surgery and an absolute difference in 5-year overall survival of 1 % ( 95 % CI -4 to 6 ) . 251 women died or had recurrent disease ( 107 st and ard surgery group , 144 lymphadenectomy group ) , with an HR of 1.35 ( 1.06 - 1.73 ; p=0.017 ) in favour of st and ard surgery and an absolute difference in 5-year recurrence-free survival of 6 % ( 1 - 12 ) . With adjustment for baseline characteristics and pathology details , the HR for overall survival was 1.04 ( 0.74 - 1.45 ; p=0.83 ) and for recurrence-free survival was 1.25 ( 0.93 - 1.66 ; p=0.14 ) . INTERPRETATION Our results show no evidence of benefit in terms of overall or recurrence-free survival for pelvic lymphadenectomy in women with early endometrial cancer . Pelvic lymphadenectomy can not be recommended as routine procedure for therapeutic purpose s outside of clinical trials BACKGROUND Despite their low risk for recurrence , many women with endometrial adenocarcinoma receive postoperative radiation therapy ( RT ) . This study was developed to determine if adjunctive external beam irradiation lowers the risk of recurrence and death in women with endometrial cancer International Federation of Gynaecology and Obstetrics ( FIGO ) stages IB , IC , and II ( occult disease ) . METHODS Four hundred forty-eight consenting patients with " intermediate risk " endometrial adenocarcinoma were r and omized after surgery to either no additional therapy ( NAT ) or whole pelvic radiation therapy ( RT ) .  They were followed to determine toxicity , date and location of recurrence , and overall survival . A high intermediate risk ( HIR ) subgroup of patients was defined as those with ( 1 ) moderate to poorly differentiated tumor , presence of lymphovascular invasion , and outer third myometrial invasion ; ( 2 ) age 50 or greater with any two risk factors listed above ; or ( 3 ) age of at least 70 with any risk factor listed above . All other eligible participants were considered to be in a low intermediate risk ( LIR ) subgroup . RESULTS Three hundred ninety-two women met all eligibility requirements ( 202 NAT , 190 RT ) . Median follow-up was 69 months . In the entire study population , there were 44 recurrences and 66 deaths ( 32 disease or treatment-related deaths ) , and the estimated 2-year cumulative incidence of recurrence ( CIR ) was 12 % in the NAT arm and 3 % in the RT arm ( relative hazard ( RH ) : 0.42 ; P=0.007 ) . The treatment difference was particularly evident among the HIR subgroup ( 2-year CIR in NAT versus RT : 26 % versus 6 % ; RH=0.42 ) . Overall , radiation had a substantial impact on pelvic and vaginal recurrences ( 18 in NAT and 3 in RT ) . The estimated 4-year survival was 86 % in the NAT arm and 92 % for the RT arm , not significantly different ( RH : 0.86 ; P=0.557 ) . CONCLUSIONS Adjunctive RT in early stage intermediate risk endometrial carcinoma decreases the risk of recurrence , but should be limited to patients whose risk factors fit a high intermediate risk definition BACKGROUND Pelvic lymph nodes are the most common site of extrauterine tumor spread in early-stage endometrial cancer , but the clinical impact of lymphadenectomy has not been addressed in r and omized studies . We conducted a r and omized clinical trial to determine whether the addition of pelvic systematic lymphadenectomy to st and ard hysterectomy with bilateral salpingo-oophorectomy improves overall and disease-free survival . METHODS From October 1 , 1996 , through March 31 , 2006 , 514 eligible patients with preoperative International Federation of Gynecology and Obstetrics stage I endometrial carcinoma were r and omly assigned to undergo pelvic systematic lymphadenectomy ( n = 264 ) or no lymphadenectomy ( n = 250 ) . Patients ' clinical data , pathological tumor characteristics , and operative and early postoperative data were recorded at discharge from hospital . Late postoperative complications , adjuvant therapy , and follow-up data were collected 6 months after surgery . Survival was analyzed by use of the log-rank test and a Cox multivariable regression analysis . All statistical tests were two-sided . RESULTS The median number of lymph nodes removed was 30 ( interquartile range = 22 - 42 ) in the pelvic systematic lymphadenectomy arm and 0 ( interquartile range = 0 - 0 ) in the no-lymphadenectomy arm ( P < .001 ) . Both early and late postoperative complications occurred statistically significantly more frequently in patients who had received pelvic systematic lymphadenectomy ( 81 patients in the lymphadenectomy arm and 34 patients in the no-lymphadenectomy arm , P = .001 ) . Pelvic systematic lymphadenectomy improved surgical staging as statistically significantly more patients with lymph node metastases were found in the lymphadenectomy arm than in the no-lymphadenectomy arm ( 13.3 % vs 3.2 % , difference = 10.1 % , 95 % confidence interval [ CI ] = 5.3 % to 14.9 % , P < .001 ) . At a median follow-up of 49 months , 78 events ( ie , recurrence or death ) had been observed and 53 patients had died . The unadjusted risks for first event and death were similar between the two arms ( hazard ratio [ HR ] for first event = 1.10 , 95 % CI = 0.70 to 1.71 , P = .68 , and HR for death = 1.20 , 95 % CI = 0.70 to 2.07 , P = .50 ) . The 5-year disease-free and overall survival rates in an intention-to-treat analysis were similar between arms ( 81.0 % and 85.9 % in the lymphadenectomy arm and 81.7 % and 90.0 % in the no-lymphadenectomy arm , respectively ) . CONCLUSION Although systematic pelvic lymphadenectomy statistically significantly improved surgical staging , it did not improve disease-free or overall survival From 1968 to 1974 , 540 patients with stage I adenocarcinoma of the corpus uteri entered a prospect i ve clinical trial to evaluate the effect of postoperative external pelvic irradiation . After primary surgery all patients received intravaginal radium irradiation ; 6000 rads was delivered to the surface of the vaginal mucosa . At the time vaginal radium was given , r and omization was performed : Group A received no further treatment ( controls ) ; group B received additional high-voltage irradiation to the pelvic field with a dose of 4000 rads to the pelvic lymph nodes . During the follow-up period of 3 to 10 years a significant reduction in vaginal and pelvic recurrences was found in group B as compared with group A ( 1.9 versus 6.9 % , P<.01 ) . On the other h and , more patients in group B developed distant metastases than those in group A ( 9.9 versus 5.4 % ) . Thus , the 5-year survival rate was not improved by external irradiation . A more detailed analysis of the series led to the conclusion that only patients with poorly differentiated tumors ( grade 3 ) , which infiltrate more than half the myometrial thickness , might benefit from additional external radiotherapy . In almost 20 % of 151 consecutive patients , tumor cells were found in endothelial lined spaces . Significantly more deaths and recurrences were found among these patients compared to those without vessel invasion ( 26.7 versus 9.1 % , P<.01 ) . ( Obstet Gynecol 56:419 , 1980 The purpose of the study was to compare postoperative vaginal irradiation with surgery alone in low-risk International Federation of Gynecology and Obstetrics ( FIGO ) stage IA-IB endometrial carcinoma . The study was a prospect i ve , r and omized trial of 645 evaluable low-risk endometrial carcinoma patients from 6 European gynecologic cancer centers . All tumors were in FIGO stage IA-IB , of endometrioid histological type , and FIGO grade 1 - 2 .  High-dose-rate afterloading equipments ( iridium [ Ir ] 192 or cobalt [ co ] 60 ) were used at 5 centers , and low-dose-rate ( LDR ) afterloading equipment ( cesium [ Cs ] 137 ) at 1 center . Perspex vaginal applicators or ovoids were normally used , and the dose was specified at 5 mm from the surface of the applicator . Three to 6 fractions ( 3.0 - 8.0 Gy ) were given , and the overall treatment time was 4 to 15 days . A total of 319 patients were treated with surgery plus vaginal irradiation ( treatment group ) , and 326 patients with surgery alone ( control group ) . Twenty-six recurrences ( 4.0 % ) were recorded in the complete series . The locoregional recurrence rate was 2.6 % , whereas distant metastases occurred in 1.4 % . The rate of vaginal recurrences was 1.2 % in the treatment group versus 3.1 % in the control group . The difference was not statistically significant ( P = 0.114 ) . Side effects were few and mild ( grade 1 - 2 ) . Dysuria , frequency , and incontinence were slightly more common after vaginal irradiation ( 2.8 % vs 0 
    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 To evaluate the value of adjuvant external beam pelvic radiotherapy as adjunct to vaginal brachytherapy ( VBT ) in medium-risk endometrial carcinoma , with regard to locoregional tumor control , recurrences , survival , and toxicity . METHODS AND MATERIAL S Consecutive series of 527 evaluable patients were included in this r and omized trial . Median follow-up for patients alive was 62 months . The primary study endpoints were locoregional recurrences and overall survival . Secondary endpoints were recurrence-free survival , recurrence-free interval , cancer-specific survival , and toxicity . RESULTS Five-year locoregional relapse rates were 1.5 % after external beam radiotherapy ( EBRT ) plus VBT and 5 % after vaginal irradiation alone ( p = 0.013 ) , and 5-year overall survival rates were 89 % and 90 % , respectively ( p = 0.548 ) . Endometrial cancer-related death rates were 3.8 % after EBRT plus VBT and 6.8 % after VBT ( p = 0.118 ) . Pelvic recurrences ( exclusively vaginal recurrence ) were reduced by 93 % by the addition of EBRT to VBT .  Deep myometrial infiltration was a significant prognostic factor in this medium-risk group of endometrioid carcinomas but not International Federation of Gynecology and Obstetrics grade or DNA ploidy . Combined radiotherapy was well tolerated , with serious ( Grade 3 ) late side effects of less than 2 % . However , there was a significant difference in favor of VBT alone . CONCLUSIONS Despite a significant locoregional control benefit with combined radiotherapy , no survival improvement was recorded , but increased late toxicity was noted in the intestine , bladder , and vagina . Combined RT should probably be reserved for high-risk cases with two or more high-risk factors . VBT alone should be the adjuvant treatment option for purely medium-risk cases BACKGROUND Hysterectomy and bilateral salpingo-oophorectomy ( BSO ) is the st and ard surgery for stage I endometrial cancer . Systematic pelvic lymphadenectomy has been used to establish whether there is extra-uterine disease and as a therapeutic procedure ; however , r and omised trials need to be done to assess therapeutic efficacy . The ASTEC surgical trial investigated whether pelvic lymphadenectomy could improve survival of women with endometrial cancer . METHODS From 85 centres in four countries , 1408 women with histologically proven endometrial carcinoma thought preoperatively to be confined to the corpus were r and omly allocated by a minimisation method to st and ard surgery ( hysterectomy and BSO , peritoneal washings , and palpation of para-aortic nodes ; n=704 ) or st and ard surgery plus lymphadenectomy ( n=704 ) . The primary outcome measure was overall survival . To control for postsurgical treatment , women with early-stage disease at intermediate or high risk of recurrence were r and omised ( independent of lymph-node status ) into the ASTEC radiotherapy trial . Analysis was by intention to treat . This study is registered , number IS RCT N 16571884 . FINDINGS After a median follow-up of 37 months ( IQR 24 - 58 ) , 191 women ( 88 st and ard surgery group , 103 lymphadenectomy group ) had died , with a hazard ratio ( HR ) of 1.16 ( 95 % CI 0.87 - 1.54 ; p=0.31 ) in favour of st and ard surgery and an absolute difference in 5-year overall survival of 1 % ( 95 % CI -4 to 6 ) . 251 women died or had recurrent disease ( 107 st and ard surgery group , 144 lymphadenectomy group ) , with an HR of 1.35 ( 1.06 - 1.73 ; p=0.017 ) in favour of st and ard surgery and an absolute difference in 5-year recurrence-free survival of 6 % ( 1 - 12 ) . With adjustment for baseline characteristics and pathology details , the HR for overall survival was 1.04 ( 0.74 - 1.45 ; p=0.83 ) and for recurrence-free survival was 1.25 ( 0.93 - 1.66 ; p=0.14 ) . INTERPRETATION Our results show no evidence of benefit in terms of overall or recurrence-free survival for pelvic lymphadenectomy in women with early endometrial cancer . Pelvic lymphadenectomy can not be recommended as routine procedure for therapeutic purpose s outside of clinical trials BACKGROUND Despite their low risk for recurrence , many women with endometrial adenocarcinoma receive postoperative radiation therapy ( RT ) . This study was developed to determine if adjunctive external beam irradiation lowers the risk of recurrence and death in women with endometrial cancer International Federation of Gynaecology and Obstetrics ( FIGO ) stages IB , IC , and II ( occult disease ) . METHODS Four hundred forty-eight consenting patients with " intermediate risk " endometrial adenocarcinoma were r and omized after surgery to either no additional therapy ( NAT ) or whole pelvic radiation therapy ( RT ) .  They were followed to determine toxicity , date and location of recurrence , and overall survival . A high intermediate risk ( HIR ) subgroup of patients was defined as those with ( 1 ) moderate to poorly differentiated tumor , presence of lymphovascular invasion , and outer third myometrial invasion ; ( 2 ) age 50 or greater with any two risk factors listed above ; or ( 3 ) age of at least 70 with any risk factor listed above . All other eligible participants were considered to be in a low intermediate risk ( LIR ) subgroup . RESULTS Three hundred ninety-two women met all eligibility requirements ( 202 NAT , 190 RT ) . Median follow-up was 69 months . In the entire study population , there were 44 recurrences and 66 deaths ( 32 disease or treatment-related deaths ) , and the estimated 2-year cumulative incidence of recurrence ( CIR ) was 12 % in the NAT arm and 3 % in the RT arm ( relative hazard ( RH ) : 0.42 ; P=0.007 ) . The treatment difference was particularly evident among the HIR subgroup ( 2-year CIR in NAT versus RT : 26 % versus 6 % ; RH=0.42 ) . Overall , radiation had a substantial impact on pelvic and vaginal recurrences ( 18 in NAT and 3 in RT ) . The estimated 4-year survival was 86 % in the NAT arm and 92 % for the RT arm , not significantly different ( RH : 0.86 ; P=0.557 ) . CONCLUSIONS Adjunctive RT in early stage intermediate risk endometrial carcinoma decreases the risk of recurrence , but should be limited to patients whose risk factors fit a high intermediate risk definition BACKGROUND Pelvic lymph nodes are the most common site of extrauterine tumor spread in early-stage endometrial cancer , but the clinical impact of lymphadenectomy has not been addressed in r and omized studies . We conducted a r and omized clinical trial to determine whether the addition of pelvic systematic lymphadenectomy to st and ard hysterectomy with bilateral salpingo-oophorectomy improves overall and disease-free survival . METHODS From October 1 , 1996 , through March 31 , 2006 , 514 eligible patients with preoperative International Federation of Gynecology and Obstetrics stage I endometrial carcinoma were r and omly assigned to undergo pelvic systematic lymphadenectomy ( n = 264 ) or no lymphadenectomy ( n = 250 ) . Patients ' clinical data , pathological tumor characteristics , and operative and early postoperative data were recorded at discharge from hospital . Late postoperative complications , adjuvant therapy , and follow-up data were collected 6 months after surgery . Survival was analyzed by use of the log-rank test and a Cox multivariable regression analysis . All statistical tests were two-sided . RESULTS The median number of lymph nodes removed was 30 ( interquartile range = 22 - 42 ) in the pelvic systematic lymphadenectomy arm and 0 ( interquartile range = 0 - 0 ) in the no-lymphadenectomy arm ( P < .001 ) . Both early and late postoperative complications occurred statistically significantly more frequently in patients who had received pelvic systematic lymphadenectomy ( 81 patients in the lymphadenectomy arm and 34 patients in the no-lymphadenectomy arm , P = .001 ) . Pelvic systematic lymphadenectomy improved surgical staging as statistically significantly more patients with lymph node metastases were found in the lymphadenectomy arm than in the no-lymphadenectomy arm ( 13.3 % vs 3.2 % , difference = 10.1 % , 95 % confidence interval [ CI ] = 5.3 % to 14.9 % , P < .001 ) . At a median follow-up of 49 months , 78 events ( ie , recurrence or death ) had been observed and 53 patients had died . The unadjusted risks for first event and death were similar between the two arms ( hazard ratio [ HR ] for first event = 1.10 , 95 % CI = 0.70 to 1.71 , P = .68 , and HR for death = 1.20 , 95 % CI = 0.70 to 2.07 , P = .50 ) . The 5-year disease-free and overall survival rates in an intention-to-treat analysis were similar between arms ( 81.0 % and 85.9 % in the lymphadenectomy arm and 81.7 % and 90.0 % in the no-lymphadenectomy arm , respectively ) . CONCLUSION Although systematic pelvic lymphadenectomy statistically significantly improved surgical staging , it did not improve disease-free or overall survival From 1968 to 1974 , 540 patients with stage I adenocarcinoma of the corpus uteri entered a prospect i ve clinical trial to evaluate the effect of postoperative external pelvic irradiation . After primary surgery all patients received intravaginal radium irradiation ; 6000 rads was delivered to the surface of the vaginal mucosa . At the time vaginal radium was given , r and omization was performed : Group A received no further treatment ( controls ) ; group B received additional high-voltage irradiation to the pelvic field with a dose of 4000 rads to the pelvic lymph nodes . During the follow-up period of 3 to 10 years a significant reduction in vaginal and pelvic recurrences was found in group B as compared with group A ( 1.9 versus 6.9 % , P<.01 ) . On the other h and , more patients in group B developed distant metastases than those in group A ( 9.9 versus 5.4 % ) . Thus , the 5-year survival rate was not improved by external irradiation . A more detailed analysis of the series led to the conclusion that only patients with poorly differentiated tumors ( grade 3 ) , which infiltrate more than half the myometrial thickness , might benefit from additional external radiotherapy . In almost 20 % of 151 consecutive patients , tumor cells were found in endothelial lined spaces . Significantly more deaths and recurrences were found among these patients compared to those without vessel invasion ( 26.7 versus 9.1 % , P<.01 ) . ( Obstet Gynecol 56:419 , 1980 The purpose of the study was to compare postoperative vaginal irradiation with surgery alone in low-risk International Federation of Gynecology and Obstetrics ( FIGO ) stage IA-IB endometrial carcinoma . The study was a prospect i ve , r and omized trial of 645 evaluable low-risk endometrial carcinoma patients from 6 European gynecologic cancer centers . All tumors were in FIGO stage IA-IB , of endometrioid histological type , and FIGO grade 1 - 2 .  High-dose-rate afterloading equipments ( iridium [ Ir ] 192 or cobalt [ co ] 60 ) were used at 5 centers , and low-dose-rate ( LDR ) afterloading equipment ( cesium [ Cs ] 137 ) at 1 center . Perspex vaginal applicators or ovoids were normally used , and the dose was specified at 5 mm from the surface of the applicator . Three to 6 fractions ( 3.0 - 8.0 Gy ) were given , and the overall treatment time was 4 to 15 days . A total of 319 patients were treated with surgery plus vaginal irradiation ( treatment group ) , and 326 patients with surgery alone ( control group ) . Twenty-six recurrences ( 4.0 % ) were recorded in the complete series . The locoregional recurrence rate was 2.6 % , whereas distant metastases occurred in 1.4 % . The rate of vaginal recurrences was 1.2 % in the treatment group versus 3.1 % in the control group . The difference was not statistically significant ( P = 0.114 ) . Side effects were few and mild ( grade 1 - 2 ) . Dysuria , frequency , and incontinence were slightly more common after vaginal irradiation ( 2.8 % vs 0 
    Output:
    