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 The r and omized controlled trial ( RCT ) is the least biased measure of the effectiveness of interventions , including surgical interventions . The aim was to review the available evidence base in gynaecologic surgery , to assess what progress has been made and to determine gaps in the evidence for clinical decision-making . METHODS Systematic review s involving gynaecological surgery interventions were extracted from the Cochrane Data base of Systematic Review s ( Issue 2 , 2007 ) and data were extracted for key primary outcomes from each of the r and omized trials in the review s. The review s were categorized as to whether they had provided evidence of effectiveness for pre-defined outcomes of most relevance to patients . RESULTS Of 371 review s or protocol s published on the Cochrane Data base of Systematic Review s ( Issue 2 , 2007 ) , only 30 were completed review s assessing surgical interventions . Seven review s concluded there was evidence of a significant effect ( whether beneficial or harmful ) of the interventions studied for pre-defined primary outcomes ; 11 review s concluded there was some evidence of significant effects for primary outcomes along with some gaps for primary outcomes ; 12 review s concluded insufficient evidence of effectiveness . Common themes of unique method ological challenges and pitfalls with trials of surgical interventions were apparent . CONCLUSIONS Cochrane review s have gone a long way to establishing a sound evidence base in gynaecologic surgery : some gaps in the evidence have been eliminated and others highlighted . In general , gynaecology has been a specialty where surgical interventions have been well exposed to the scrutiny of RCTs compared with other surgical specialties Background The role of cytoreductive surgery in relapsed ovarian cancer is not clearly defined . Therefore , patient selection remains arbitrary and depends on the center ’s preference rather than on established selection criteria . The Descriptive Evaluation of preoperative Selection KriTeria for OPerability in recurrent OVARian cancer ( DESKTOP OVAR ) trial was undertaken to form a hypothesis for a panel of criteria for selecting patients who might benefit from surgery in relapsed ovarian cancer . Methods The DESKTOP trial was an exploratory study based on data from a retrospective analysis of hospital records . Twenty-five member institutions of the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Committee ( AGO OC ) and AGO-OVAR boards collected data on their patients with cytoreductive surgery for relapsed invasive epithelial ovarian cancer performed in 2000–2003 . Results Two hundred and sixty-seven patients were included .  Complete resection was associated with significantly longer survival compared with surgery leaving any postoperative residuals [ median 45.2 vs. 19.7 months ; hazard ratio ( HR ) 3.71 ; 95 % confidence interval ( CI ) 2.27–6.05 ; P < .0001 ] . Variables associated with complete resection were performance status ( PS ) [ Eastern Cooperative Oncology Group ( ECOG ) 0 vs. > 0 ; P < .001 ] , International Federation of Gynecology and Obstetrics ( FIGO ) stage at initial diagnosis ( FIGO I/II vs. III/IV , P = .036 ) , residual tumor after primary surgery ( none vs. present , P < .001 ) , and absence of ascites > 500 ml ( P < .001 ) . A combination of PS , early FIGO stage initially or no residual tumor after first surgery , and absence of ascites could predict complete resection in 79 % of patients . Conclusions Only complete resection was associated with prolonged survival in recurrent ovarian cancer . The identified criteria panel will be verified in a prospect i ve trial ( AGO-DESKTOP II ) evaluating whether it will render a useful tool for selecting the right patients for cytoreductive surgery in recurrent ovarian cancer BACKGROUND The GINECO group previously demonstrated that pegylated liposomal doxorubicin (PLD)-carboplatin combination was an effective and well-tolerated treatment for advanced ovarian cancer ( AOC ) patients in late relapse . The purpose of the present analysis was to confirm these results in a prospect i ve cohort of late-relapsing AOC patients . PATIENTS AND METHODS Eighty-one consecutive patients received PLD 30 mg/m(2 ) , followed by carboplatin ( area under the curve ) 5 mg min/ml , every 28 days for 6 courses or until progression . RESULTS The objective response ( OR ) rate was 65.4 % . The median progression-free survival ( PFS ) and overall survival ( OS ) were 13.6 months and 38.9 months , respectively . Haematological toxicities were more common than non-haematological toxicities . Non-hematologic adverse reactions were moderate and grade 3 palmar-plantar erythrodysesthesia was limited to one patient . No cardiotoxicity was observed and no toxic death occurred . CONCLUSION These data support the clinical efficacy and tolerability of PLD in combination with carboplatin as second-line therapy for AOC patients in late relapse Background : This phase 2 trial was design ed to evaluate the efficacy and toxicity of a combination of docetaxel , gemcitabine , and oxaliplatin for platinum- and paclitaxel-pretreated epithelial ovarian cancer . Patients and Methods : Heavily pretreated patients ( N = 30 ; median age , 61 years ) received docetaxel , 55 mg/m2 ; gemcitabine , 500 mg/m2 ( day 1 ) ; and oxaliplatin , 70 mg/m2 ( day 2 ) biweekly . Twelve patients had platinum-sensitive disease , and 18 patients had platinum-resistant disease . Results : Median follow-up was 18.6 months . No differences in patient characteristics were observed between patients with carboplatinum-sensitive and carboplatinum-resistant disease . In patients with carboplatin-sensitive disease , an overall response ( OR ) of 83.3 % , a progression-free survival of 10.6 months , and an overall survival of 18.9 months were observed . In patients with carboplatinum-resistant disease , an OR was seen in 38.9 % with a progression-free survival of 5.3 months and an overall survival of 16.3 months . Patients with platinum-refractory disease ( progression under previous carboplatinum therapy , n = 13 ) had an OR of 23 % , whereas patients with objective response but relapse less than 6 months after carboplatinum therapy had an OR of 80.0 % . Grade 3 and 4 toxicities were only observed for anemia ( 6.7 % ) , neutropenia ( 20.0 % ) , thrombopenia , peripheral neuropathy , and diarrhea ( 16.7 % ) . No neutropenic fever or treatment-related death occurred . Conclusions : In comparison with current st and ard protocol s , a combination of docetaxel , gemcitabine , and oxaliplatin showed considerably higher efficacy without remarkable increased toxicity ; particularly for patients with early relapse after a platinum-containing therapy OBJECTIVE The aim of this prospect i ve study was to evaluate the influence of secondary cytoreductive surgery on survival of patients with recurrent epithelial ovarian cancer . METHODS Between June 1993 and June 1999 , 149 patients after primary treatment underwent secondary cytoreductive surgery : 69 ( 46.3 % ) had recurrence-free interval ( RFI ) 7 - 12 months , 59 ( 39.6 % ) RFI 13 - 24 months , and 21 ( 14.1 % ) RFI > 24 months . Exclusion criteria included secondary cytoreduction during second-look laparotomy , interval cytoreduction , and palliative surgery in patients with intestinal obstruction or progressive disease . RESULTS The median follow-up was 27 months . According to multivariate analysis , RFI groups , prior chemotherapy combination , and residual tumor after secondary surgery were associated independently with overall survival . Residual tumor after secondary surgery was by far the most strongly predictive factor for patient 's survival ( hazard ratio ( HR ) 2.65 ; 95 % confidence interval ( CI ) 1.43 - 4.92 ) . The 2-year survival rates were 22.3 , 62.9 , and 22.7 % , respectively , for patients with RFI 7 - 12 , 13 - 24 , and > 24 months . The 5-year survival was 29 % for patients with RFI 13 - 24 months . No patients with RFI 7 - 12 and > 24 months outlived the 4-year estimate . Unexpectedly , RFI > 24 months was not correlated significantly with overall survival . However , 17 patients ( 81 % ) with RFI > 24 months were heavily treated with  chemotherapy  before secondary surgery . CONCLUSIONS Patients who have documented gross disease preoperatively should be selected for a secondary debulking operation ; the entity of surgical effort would be modulated in relation to previous treatment PURPOSE Topotecan , a topoisomerase I inhibitor , was evaluated in a multicenter , phase II study of women with epithelial ovarian carcinoma who relapsed after one or two prior regimens that included platinum and paclitaxel .  PATIENTS AND METHODS Topotecan 1.5 mg/m2 daily was administered as a 30-minute infusion for 5 consecutive days on a 21-day cycle . Eligibility criteria included bidimensionally measurable disease , Eastern Cooperative Oncology Group performance status of 2 or less , and adequate bone marrow , liver , and renal function .  Efficacy was assessed by independent radiologic review . RESULTS One hundred thirty-nine patients were treated ; 81 % were platinum resistant . Sixty-two patients had received one prior regimen and 77 patients had received two prior regimens . Nine patients were not assessable for response ; however , all patients were included in the response analysis . The overall response rate was 13.7 % ; 12.4 % in platinum-resistant and 19.2 % in platinum-sensitive patients . Stable disease lasted at least 8 weeks in 27.3 % of the patients . The median duration of response and time to progression were 18.1 and 12.1 weeks , respectively . The median survival was 47.0 weeks . Grade 4 neutropenia occurred in 82 % of the patients ( 34 % of the courses ) and thrombocytopenia in 30 % of the patients ( 9 % of the courses ) . Infectious complications occurred in 6 % of the courses . Nonhematologic toxicities were mild . There were no drug-related toxic deaths . CONCLUSION As a single agent , topotecan has modest activity in women with advanced epithelial ovarian carcinoma who have progressed or not responded after one or two prior regimens with platinum and paclitaxel . Further investigation of combination regimens is indicated in the primary therapy for ovarian cancer based on the mechanism of action and tolerability OBJECTIVE The Gynecologic Oncology Group has divided patients with advanced epithelial ovarian cancer into those with optimal residual cancer , in which the maximum diameter of residual is < or = 1 cm , and suboptimal residual cancer , in which the residual disease is > 1 cm . Within the optimal group of patients there is a survival difference between patients with microscopic residual disease and those with any macroscopic disease < or = 1 cm . No analysis of the effect of various residual disease diameters in patients with residual disease > or = 1 cm has been performed . This study evaluates the effect of residual disease diameter in patients with suboptimal disease entered on a r and omized trial of intense versus st and ard chemotherapy .  STUDY DESIGN Gynecologic Oncology Group protocol 97 compared cisplatin 50 mg/m2 and cyclophosphamide 500 mg/m2 for eight courses with the same drugs at 100 mg/m2 and 1000 mg/m2 for four courses , respectively . There was no difference in progression-free interval or survival between the two arms . Of the 458 stage III ( with residual disease > 1 cm ) and stage IV patients entered in this study , 294 stage III patients comprise the current analysis . Surgical reporting forms , operation reports , and pathology reports were review ed to determine initial greatest tumor diameter and residual tumor diameter . Patients were grouped by residual diameter . Multivariate analysis considered residual diameter of disease , age , histologic characteristics , performance status , and ascites . An adjusted relative hazard of dying of ovarian cancer was calculated for each residual disease group . RESULTS Patients ranged in age from 20 to 80 years , with a median of 60 years . All patients were Gynecologic Oncology Group performance status 0 to 2 . Fifty-two percent had grade 3 tumors , and 39 % and 9 % , respectively , had grade 2 or 1 tumors . All patients had stage III disease . Ninety percent had serous , endometrioid , or mixed epithelial cell type tumors . Multivariate analysis revealed a relative risk of dying as follows : residual disease < 2 cm , relative risk 1.00 ; 2 to 2.9 cm , relative risk 1.90 ; 3 to 3.9 cm , relative risk 1.91 ; 4 to 5.9 cm , relative risk 1.74 ; 6 to 7.9 cm , relative risk 1.85 ; 8 to 9.9 cm , relative risk 2.16 ; > or = 10 cm , relative risk 1.82 
    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 The r and omized controlled trial ( RCT ) is the least biased measure of the effectiveness of interventions , including surgical interventions . The aim was to review the available evidence base in gynaecologic surgery , to assess what progress has been made and to determine gaps in the evidence for clinical decision-making . METHODS Systematic review s involving gynaecological surgery interventions were extracted from the Cochrane Data base of Systematic Review s ( Issue 2 , 2007 ) and data were extracted for key primary outcomes from each of the r and omized trials in the review s. The review s were categorized as to whether they had provided evidence of effectiveness for pre-defined outcomes of most relevance to patients . RESULTS Of 371 review s or protocol s published on the Cochrane Data base of Systematic Review s ( Issue 2 , 2007 ) , only 30 were completed review s assessing surgical interventions . Seven review s concluded there was evidence of a significant effect ( whether beneficial or harmful ) of the interventions studied for pre-defined primary outcomes ; 11 review s concluded there was some evidence of significant effects for primary outcomes along with some gaps for primary outcomes ; 12 review s concluded insufficient evidence of effectiveness . Common themes of unique method ological challenges and pitfalls with trials of surgical interventions were apparent . CONCLUSIONS Cochrane review s have gone a long way to establishing a sound evidence base in gynaecologic surgery : some gaps in the evidence have been eliminated and others highlighted . In general , gynaecology has been a specialty where surgical interventions have been well exposed to the scrutiny of RCTs compared with other surgical specialties Background The role of cytoreductive surgery in relapsed ovarian cancer is not clearly defined . Therefore , patient selection remains arbitrary and depends on the center ’s preference rather than on established selection criteria . The Descriptive Evaluation of preoperative Selection KriTeria for OPerability in recurrent OVARian cancer ( DESKTOP OVAR ) trial was undertaken to form a hypothesis for a panel of criteria for selecting patients who might benefit from surgery in relapsed ovarian cancer . Methods The DESKTOP trial was an exploratory study based on data from a retrospective analysis of hospital records . Twenty-five member institutions of the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Committee ( AGO OC ) and AGO-OVAR boards collected data on their patients with cytoreductive surgery for relapsed invasive epithelial ovarian cancer performed in 2000–2003 . Results Two hundred and sixty-seven patients were included .  Complete resection was associated with significantly longer survival compared with surgery leaving any postoperative residuals [ median 45.2 vs. 19.7 months ; hazard ratio ( HR ) 3.71 ; 95 % confidence interval ( CI ) 2.27–6.05 ; P < .0001 ] . Variables associated with complete resection were performance status ( PS ) [ Eastern Cooperative Oncology Group ( ECOG ) 0 vs. > 0 ; P < .001 ] , International Federation of Gynecology and Obstetrics ( FIGO ) stage at initial diagnosis ( FIGO I/II vs. III/IV , P = .036 ) , residual tumor after primary surgery ( none vs. present , P < .001 ) , and absence of ascites > 500 ml ( P < .001 ) . A combination of PS , early FIGO stage initially or no residual tumor after first surgery , and absence of ascites could predict complete resection in 79 % of patients . Conclusions Only complete resection was associated with prolonged survival in recurrent ovarian cancer . The identified criteria panel will be verified in a prospect i ve trial ( AGO-DESKTOP II ) evaluating whether it will render a useful tool for selecting the right patients for cytoreductive surgery in recurrent ovarian cancer BACKGROUND The GINECO group previously demonstrated that pegylated liposomal doxorubicin (PLD)-carboplatin combination was an effective and well-tolerated treatment for advanced ovarian cancer ( AOC ) patients in late relapse . The purpose of the present analysis was to confirm these results in a prospect i ve cohort of late-relapsing AOC patients . PATIENTS AND METHODS Eighty-one consecutive patients received PLD 30 mg/m(2 ) , followed by carboplatin ( area under the curve ) 5 mg min/ml , every 28 days for 6 courses or until progression . RESULTS The objective response ( OR ) rate was 65.4 % . The median progression-free survival ( PFS ) and overall survival ( OS ) were 13.6 months and 38.9 months , respectively . Haematological toxicities were more common than non-haematological toxicities . Non-hematologic adverse reactions were moderate and grade 3 palmar-plantar erythrodysesthesia was limited to one patient . No cardiotoxicity was observed and no toxic death occurred . CONCLUSION These data support the clinical efficacy and tolerability of PLD in combination with carboplatin as second-line therapy for AOC patients in late relapse Background : This phase 2 trial was design ed to evaluate the efficacy and toxicity of a combination of docetaxel , gemcitabine , and oxaliplatin for platinum- and paclitaxel-pretreated epithelial ovarian cancer . Patients and Methods : Heavily pretreated patients ( N = 30 ; median age , 61 years ) received docetaxel , 55 mg/m2 ; gemcitabine , 500 mg/m2 ( day 1 ) ; and oxaliplatin , 70 mg/m2 ( day 2 ) biweekly . Twelve patients had platinum-sensitive disease , and 18 patients had platinum-resistant disease . Results : Median follow-up was 18.6 months . No differences in patient characteristics were observed between patients with carboplatinum-sensitive and carboplatinum-resistant disease . In patients with carboplatin-sensitive disease , an overall response ( OR ) of 83.3 % , a progression-free survival of 10.6 months , and an overall survival of 18.9 months were observed . In patients with carboplatinum-resistant disease , an OR was seen in 38.9 % with a progression-free survival of 5.3 months and an overall survival of 16.3 months . Patients with platinum-refractory disease ( progression under previous carboplatinum therapy , n = 13 ) had an OR of 23 % , whereas patients with objective response but relapse less than 6 months after carboplatinum therapy had an OR of 80.0 % . Grade 3 and 4 toxicities were only observed for anemia ( 6.7 % ) , neutropenia ( 20.0 % ) , thrombopenia , peripheral neuropathy , and diarrhea ( 16.7 % ) . No neutropenic fever or treatment-related death occurred . Conclusions : In comparison with current st and ard protocol s , a combination of docetaxel , gemcitabine , and oxaliplatin showed considerably higher efficacy without remarkable increased toxicity ; particularly for patients with early relapse after a platinum-containing therapy OBJECTIVE The aim of this prospect i ve study was to evaluate the influence of secondary cytoreductive surgery on survival of patients with recurrent epithelial ovarian cancer . METHODS Between June 1993 and June 1999 , 149 patients after primary treatment underwent secondary cytoreductive surgery : 69 ( 46.3 % ) had recurrence-free interval ( RFI ) 7 - 12 months , 59 ( 39.6 % ) RFI 13 - 24 months , and 21 ( 14.1 % ) RFI > 24 months . Exclusion criteria included secondary cytoreduction during second-look laparotomy , interval cytoreduction , and palliative surgery in patients with intestinal obstruction or progressive disease . RESULTS The median follow-up was 27 months . According to multivariate analysis , RFI groups , prior chemotherapy combination , and residual tumor after secondary surgery were associated independently with overall survival . Residual tumor after secondary surgery was by far the most strongly predictive factor for patient 's survival ( hazard ratio ( HR ) 2.65 ; 95 % confidence interval ( CI ) 1.43 - 4.92 ) . The 2-year survival rates were 22.3 , 62.9 , and 22.7 % , respectively , for patients with RFI 7 - 12 , 13 - 24 , and > 24 months . The 5-year survival was 29 % for patients with RFI 13 - 24 months . No patients with RFI 7 - 12 and > 24 months outlived the 4-year estimate . Unexpectedly , RFI > 24 months was not correlated significantly with overall survival . However , 17 patients ( 81 % ) with RFI > 24 months were heavily treated with  chemotherapy  before secondary surgery . CONCLUSIONS Patients who have documented gross disease preoperatively should be selected for a secondary debulking operation ; the entity of surgical effort would be modulated in relation to previous treatment PURPOSE Topotecan , a topoisomerase I inhibitor , was evaluated in a multicenter , phase II study of women with epithelial ovarian carcinoma who relapsed after one or two prior regimens that included platinum and paclitaxel .  PATIENTS AND METHODS Topotecan 1.5 mg/m2 daily was administered as a 30-minute infusion for 5 consecutive days on a 21-day cycle . Eligibility criteria included bidimensionally measurable disease , Eastern Cooperative Oncology Group performance status of 2 or less , and adequate bone marrow , liver , and renal function .  Efficacy was assessed by independent radiologic review . RESULTS One hundred thirty-nine patients were treated ; 81 % were platinum resistant . Sixty-two patients had received one prior regimen and 77 patients had received two prior regimens . Nine patients were not assessable for response ; however , all patients were included in the response analysis . The overall response rate was 13.7 % ; 12.4 % in platinum-resistant and 19.2 % in platinum-sensitive patients . Stable disease lasted at least 8 weeks in 27.3 % of the patients . The median duration of response and time to progression were 18.1 and 12.1 weeks , respectively . The median survival was 47.0 weeks . Grade 4 neutropenia occurred in 82 % of the patients ( 34 % of the courses ) and thrombocytopenia in 30 % of the patients ( 9 % of the courses ) . Infectious complications occurred in 6 % of the courses . Nonhematologic toxicities were mild . There were no drug-related toxic deaths . CONCLUSION As a single agent , topotecan has modest activity in women with advanced epithelial ovarian carcinoma who have progressed or not responded after one or two prior regimens with platinum and paclitaxel . Further investigation of combination regimens is indicated in the primary therapy for ovarian cancer based on the mechanism of action and tolerability OBJECTIVE The Gynecologic Oncology Group has divided patients with advanced epithelial ovarian cancer into those with optimal residual cancer , in which the maximum diameter of residual is < or = 1 cm , and suboptimal residual cancer , in which the residual disease is > 1 cm . Within the optimal group of patients there is a survival difference between patients with microscopic residual disease and those with any macroscopic disease < or = 1 cm . No analysis of the effect of various residual disease diameters in patients with residual disease > or = 1 cm has been performed . This study evaluates the effect of residual disease diameter in patients with suboptimal disease entered on a r and omized trial of intense versus st and ard chemotherapy .  STUDY DESIGN Gynecologic Oncology Group protocol 97 compared cisplatin 50 mg/m2 and cyclophosphamide 500 mg/m2 for eight courses with the same drugs at 100 mg/m2 and 1000 mg/m2 for four courses , respectively . There was no difference in progression-free interval or survival between the two arms . Of the 458 stage III ( with residual disease > 1 cm ) and stage IV patients entered in this study , 294 stage III patients comprise the current analysis . Surgical reporting forms , operation reports , and pathology reports were review ed to determine initial greatest tumor diameter and residual tumor diameter . Patients were grouped by residual diameter . Multivariate analysis considered residual diameter of disease , age , histologic characteristics , performance status , and ascites . An adjusted relative hazard of dying of ovarian cancer was calculated for each residual disease group . RESULTS Patients ranged in age from 20 to 80 years , with a median of 60 years . All patients were Gynecologic Oncology Group performance status 0 to 2 . Fifty-two percent had grade 3 tumors , and 39 % and 9 % , respectively , had grade 2 or 1 tumors . All patients had stage III disease . Ninety percent had serous , endometrioid , or mixed epithelial cell type tumors . Multivariate analysis revealed a relative risk of dying as follows : residual disease < 2 cm , relative risk 1.00 ; 2 to 2.9 cm , relative risk 1.90 ; 3 to 3.9 cm , relative risk 1.91 ; 4 to 5.9 cm , relative risk 1.74 ; 6 to 7.9 cm , relative risk 1.85 ; 8 to 9.9 cm , relative risk 2.16 ; > or = 10 cm , relative risk 1.82 
    Output:
    