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: A hospital-based case-control study of ovarian cancer was conducted in London and Oxford between October 1978 and February 1983 .  Menstrual characteristics , reproductive and contraceptive history and history of exposure to various environmental factors were compared between 235 women with histologically diagnosed epithelial ovarian cancer and 451 controls . High gravidity , hysterectomy , female sterilisation and oral contraceptive use were associated with a reduced risk of ovarian cancer . Infertility and late age at menopause were associated with an increase in risk . While these factors were related , they were each found to be independently associated with ovarian cancer risk after adjusting for the effect of the other factors BACKGROUND Ovarian germ cell tumors ( OGCT ) are highly curable when treated with cytoreductive surgery and platinum-based chemotherapy . We evaluated the safety and activity of a 3-day modified bleomycin , etoposide , and cisplatinum ( mBEP ) regimen in patients with OGCT . PATIENTS AND METHODS Patients with FIGO stages I-IV OGCT were treated with three ( stages I-III complete resection ) or four cycles ( incomplete resection or stage IV ) of bleomycin 15 mg iv , etoposide 120 mg/m(2 ) iv , and cisplatin 40 mg/m(2 ) iv for 3 days every 3 weeks . RESULTS Forty-eight patients ( 14 with dysgerminoma and 34 with non-dysgerminomatous tumors ) were included in our study . Most patients had stage I disease ( 65 % ) and complete resection of their tumor ( 67 % ) . Twenty percent of patients developed grade 3 or 4 neutropenia with 4 episodes of neutropenic fever . During follow-up ( median : 5 years ) , two patients developed progressive disease including one patient who died . All patients with stage I or II disease and all patients with dysgerminoma remain free of disease . However , 20 % of patients with non-dysgerminomatous tumors stage III or IV experienced progressive disease . CONCLUSION The modified 3-day BEP regimen was safe and effective in patients with OGCT . Further improvements are needed for patients with advanced , suboptimally debulked non-dysgerminomatous tumors OBJECTIVES The objectives were to describe the clinical characteristics and prognosis of surgically treated patients with stage II and III serous borderline tumors of the ovary with noninvasive implants .  MATERIAL S AND METHODS From 1990 to 2000 , 16 patients with stage II and III ovarian serous borderline tumors and noninvasive implants  were diagnosed and prospect ively followed at our center . All patients underwent surgical treatment including staging and their pathology was review ed . Fifteen patients had thorough surgical staging by laparotomy , while one patient was staged laparoscopically . No patient was treated with adjuvant therapy ( radiation or chemotherapy ) after surgical treatment and none were lost to follow-up . RESULTS The mean age at diagnosis was 42 years ( range 26 - 59 ) . Fourteen patients were treated by abdominal hysterectomy , bilateral salpingo-oophorectomy , omentectomy , and multiple peritoneal biopsies  , while 2 patients were treated conservatively for fertility preservation . Two patients underwent pelvic and para-aortic lymph node dissection . Fifteen of 16 patients had ovarian surface involvement with tumor . All patients but 2 had clinical evidence of extraovarian disease at the time of surgery . The mean duration of follow-up was 60.7 months ( range 2 - 134 months ) . Thirteen patients ( 81 % ) are alive without evidence of disease . Four patients ( 25 % ) required subsequent surgery for recurrent disease and all are still alive . Two patients have been treated with chemotherapy ( paclitaxel/carboplatin ) for progressive borderline disease , while an additional patient was treated after first relapse with chemotherapy for an invasive recurrence . CONCLUSIONS Carefully staged patients with advanced serous borderline tumors of the ovary and noninvasive implants have a good prognosis without adjuvant therapy PURPOSE This r and omized , multicenter , phase III noninferiority trial was design ed to test the efficacy and safety of the combination of pegylated liposomal doxorubicin ( PLD ) with carboplatin ( CD ) compared with st and ard carboplatin and paclitaxel ( CP ) in patients with platinum-sensitive relapsed/recurrent ovarian cancer ( ROC ) . PATIENTS AND METHODS Patients with histologically proven ovarian cancer with recurrence more than 6 months after first- or second-line platinum and taxane-based therapies were r and omly assigned by stratified blocks to CD ( carboplatin area under the curve [ AUC ] 5 plus PLD 30 mg/m(2 ) ) every 4 weeks or CP ( carboplatin AUC 5 plus paclitaxel 175 mg/m(2 ) ) every 3 weeks for at least 6 cycles . Primary end point was progression-free survival ( PFS ) ; secondary end points were toxicity , quality of life , and overall survival . RESULTS Overall 976 patients were recruited . With median follow-up of 22 months , PFS for the CD arm was statistically superior to the CP arm ( hazard ratio , 0.821 ; 95 % CI , 0.72 to 0.94 ; P = .005 ) ; median PFS was 11.3 versus 9.4 months , respectively . Although overall survival data are immature for final analysis , we report here a total of 334 deaths . Overall severe nonhematologic toxicity ( 36.8 % v 28.4 % ; P < .01 ) leading to early discontinuation ( 15 % v 6 % ; P < .001 ) occurred more frequently in the CP arm . More frequent grade 2 or greater alopecia ( 83.6 % v 7 % ) , hypersensitivity reactions ( 18.8 % v 5.6 % ) , and sensory neuropathy ( 26.9 % v 4.9 % ) were observed in the CP arm ; more h and -foot syndrome ( grade 2 to 3 , 12.0 % v 2.2 % ) , nausea ( 35.2 % v 24.2 % ) , and mucositis ( grade 2 - 3 , 13.9 % v 7 % ) in the CD arm . CONCLUSION To our knowledge , this trial is the largest in recurrent ovarian cancer and has demonstrated superiority in PFS and better therapeutic index of CD over st and ard CP OBJECTIVE To assess feasibility and safety of fertility-sparing laparoscopic staging in women affected by unexpected ovarian cancer desiring to preserve their fertility . DESIGN Prospect i ve study . SETTING University clinic . PATIENT(S ) Twenty-seven patients already operated on elsewhere for a presumably benign ovarian cyst . INTERVENTION(S ) Laparoscopic fertility-sparing staging operations . MAIN OUTCOME MEASURE(S ) Perioperative and survival data , reproductive outcome . RESULT ( S ) Histologic findings after first surgery : 12 low malignant potential neoplasms , 11 invasive epithelial ovarian carcinomas,1 sex-cord stromal , and 3 germ cell neoplasms . Fertility-sparing staging consisted of exploration of the peritoneal cavity , peritoneal washing cytology , multiple peritoneal biopsies , omolateral adnexectomy ( except in borderline tumors ) , omentectomy , omolateral or bilateral pelvic and aortic lymph node sampling ( except in borderline tumors , well differentiated , mucinous , and granulosa cell ( GC ) neoplasms ) , endometrial biopsy , appendectomy in mucinous type . Overall , seven patients ( 26 % ) were upstaged . Six patients received adjuvant platinum-based chemotherapy . Two term pregnancies occurred . After a median follow-up of 20 months all patients are alive ; one patient has FIGO stage Ic clear cell carcinoma , which recurred 8 months after surgery . CONCLUSION ( S ) Laparoscopic fertility-sparing staging in early ovarian malignancies is feasible and safe in selected and counseled patients and should be performed in experienced gynecological oncology centers trained in endoscopic procedures This study was undertaken to determine whether secondary surgical debulking is beneficial for patients with malignant ovarian germ cell tumors ( OGCT ) . Twenty patients with OGCT treated at our institution between 1975 and 1992 were retrospectively identified and analyzed . Survival was analyzed using the life-table methods of Kaplan and Meier and the statistical significance of various perioperative factors was tested by both the log-rank and the Wilcoxon tests . Histologic tumor type included 8 immature teratomas , 6 mixed tumors , 5 endodermal sinus tumors , and 1 dysgerminoma . After primary surgery , all patients received chemotherapy -- non-platinum-based in 12 patients , platinum-based in 5 , and both types in 3 patients . Treatment failure was classified as progression in 14 patients , persistence in 3 , and recurrence in 3 . Salvage surgery consisted of exploratory laparotomy and tumor debulking in 18 patients , inguinal lymphadenectomy in 1 , and thoracotomy and wedge resection in 1 . Sixteen patients subsequently received salvage chemotherapy . At the time of analysis , 11 patients were alive disease-free , 1 was alive with tumor , 6 had died of tumor progression , and 2 had died of treatment-related complications . Survival of patients with immature teratoma who underwent salvage surgery was significantly better than survival of those with other tumor cell types ( P = 0.006 ) . In conclusion , although the role of secondary debulking in chemorefractory OGCT remains undetermined , it may have some benefit for a select group of patients , particularly those with immature teratoma PURPOSE To determine the side effects and feasibility of cisplatin and carboplatin each in combination with paclitaxel as front-line therapy in advanced epithelial ovarian cancer . PATIENTS AND METHODS Patients were r and omly allocated to receive paclitaxel 175 mg/m(2 ) intravenously as a 3-hour infusion followed by either cisplatin 75 mg/m(2 ) or carboplatin ( area under the plasma concentration-time curve of 5 ) , both on day 1 . The schedule was repeated every 3 weeks for at least six cycles . Women allocated to paclitaxel-cisplatin were admitted to the hospital , whereas the carboplatin regimen was administered to out patients . RESULTS A total of 208 eligible patients were r and omized . Both regimens could be delivered in an optimal dose and without significant delay . Paclitaxel-carboplatin produced significantly less nausea and vomiting ( P : < .01 ) and less peripheral neurotoxicity ( P : = .04 ) but more granulocytopenia and thrombocytopenia ( P : < .01 ) . The overall response rate in 132 patients with measurable disease was 64 % ( 84 of 132 patients ) , and in patients with elevated CA 125 levels at start , it was 74 % ( 132 of 178 patients ) . With a median follow-up time of 37 months , the median progression-free survival time of all patients was 16 months and the median overall survival time was 31 months . The small number of patients entered onto the study caused wide confidence intervals ( CIs ) around the hazards ratio for progression-free survival of paclitaxel-carboplatin compared with paclitaxel-cisplatin ( hazards ratio , 1.07 ; 95 % CI , 0.78 to 1.48 ) and did not allow conclusions about efficacy . CONCLUSION Paclitaxel-carboplatin is a feasible regimen for out patients with ovarian cancer and has a better toxicity profile than paclitaxel-cisplatin PURPOSE Vascular endothelial growth factor ( VEGF ) plays an important role in the biology of ovarian cancer ( OC ) . Inhibitors of VEGF suppress tumor growth in OC models . Metronomic chemotherapy , defined as frequent administration of low doses of cytotoxic chemotherapy , suppresses tumor growth , possibly by inhibiting angiogenesis . A phase II trial was conducted to evaluate the antitumor activity and adverse effects of bevacizumab and metronomic oral cyclophosphamide in women with recurrent OC . PATIENTS AND METHODS Patients with measurable disease and prior treatment with a platinum-containing regimen were eligible . Up to two different regimens for recurrent disease were allowed . Treatment consisted of bevacizumab 10 mg/kg intravenously every 2 weeks and oral cyclophosphamide 50 mg/d . The primary end point was progression-free survival at 6 months . Plasma levels of VEGF , E-selectin , and thrombospondin-1 were obtained serially . RESULTS Seventy patients were enrolled . The probability of being alive and progression free at 6 months was 56 % ( + /- 6 % SE ) . A partial response was achieved in 17 patients ( 24 % ) . Median time to progression and survival were 7.2 and 16.9 months , 
    Output:
    
agent
In regards to surgery it is recommended to perform total omentectomy since subclinic metastasis have been documented in 10 - 30 % of all cases , and systematic limphadenectomy , necessary to be able to obtain an adequate surgical staging .
Minimal invasion surgery is not a recommended procedure for the treatment of advanced ovarian cancer .
Radiotherapy can be used to palliate symptoms .
In the present , there is not a st and ardized screening method .
Diagnosis in early stages means a better survival .
Radiotherapy can be indicated to palliate symptoms
***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: A hospital-based case-control study of ovarian cancer was conducted in London and Oxford between October 1978 and February 1983 .  Menstrual characteristics , reproductive and contraceptive history and history of exposure to various environmental factors were compared between 235 women with histologically diagnosed epithelial ovarian cancer and 451 controls . High gravidity , hysterectomy , female sterilisation and oral contraceptive use were associated with a reduced risk of ovarian cancer . Infertility and late age at menopause were associated with an increase in risk . While these factors were related , they were each found to be independently associated with ovarian cancer risk after adjusting for the effect of the other factors BACKGROUND Ovarian germ cell tumors ( OGCT ) are highly curable when treated with cytoreductive surgery and platinum-based chemotherapy . We evaluated the safety and activity of a 3-day modified bleomycin , etoposide , and cisplatinum ( mBEP ) regimen in patients with OGCT . PATIENTS AND METHODS Patients with FIGO stages I-IV OGCT were treated with three ( stages I-III complete resection ) or four cycles ( incomplete resection or stage IV ) of bleomycin 15 mg iv , etoposide 120 mg/m(2 ) iv , and cisplatin 40 mg/m(2 ) iv for 3 days every 3 weeks . RESULTS Forty-eight patients ( 14 with dysgerminoma and 34 with non-dysgerminomatous tumors ) were included in our study . Most patients had stage I disease ( 65 % ) and complete resection of their tumor ( 67 % ) . Twenty percent of patients developed grade 3 or 4 neutropenia with 4 episodes of neutropenic fever . During follow-up ( median : 5 years ) , two patients developed progressive disease including one patient who died . All patients with stage I or II disease and all patients with dysgerminoma remain free of disease . However , 20 % of patients with non-dysgerminomatous tumors stage III or IV experienced progressive disease . CONCLUSION The modified 3-day BEP regimen was safe and effective in patients with OGCT . Further improvements are needed for patients with advanced , suboptimally debulked non-dysgerminomatous tumors OBJECTIVES The objectives were to describe the clinical characteristics and prognosis of surgically treated patients with stage II and III serous borderline tumors of the ovary with noninvasive implants .  MATERIAL S AND METHODS From 1990 to 2000 , 16 patients with stage II and III ovarian serous borderline tumors and noninvasive implants  were diagnosed and prospect ively followed at our center . All patients underwent surgical treatment including staging and their pathology was review ed . Fifteen patients had thorough surgical staging by laparotomy , while one patient was staged laparoscopically . No patient was treated with adjuvant therapy ( radiation or chemotherapy ) after surgical treatment and none were lost to follow-up . RESULTS The mean age at diagnosis was 42 years ( range 26 - 59 ) . Fourteen patients were treated by abdominal hysterectomy , bilateral salpingo-oophorectomy , omentectomy , and multiple peritoneal biopsies  , while 2 patients were treated conservatively for fertility preservation . Two patients underwent pelvic and para-aortic lymph node dissection . Fifteen of 16 patients had ovarian surface involvement with tumor . All patients but 2 had clinical evidence of extraovarian disease at the time of surgery . The mean duration of follow-up was 60.7 months ( range 2 - 134 months ) . Thirteen patients ( 81 % ) are alive without evidence of disease . Four patients ( 25 % ) required subsequent surgery for recurrent disease and all are still alive . Two patients have been treated with chemotherapy ( paclitaxel/carboplatin ) for progressive borderline disease , while an additional patient was treated after first relapse with chemotherapy for an invasive recurrence . CONCLUSIONS Carefully staged patients with advanced serous borderline tumors of the ovary and noninvasive implants have a good prognosis without adjuvant therapy PURPOSE This r and omized , multicenter , phase III noninferiority trial was design ed to test the efficacy and safety of the combination of pegylated liposomal doxorubicin ( PLD ) with carboplatin ( CD ) compared with st and ard carboplatin and paclitaxel ( CP ) in patients with platinum-sensitive relapsed/recurrent ovarian cancer ( ROC ) . PATIENTS AND METHODS Patients with histologically proven ovarian cancer with recurrence more than 6 months after first- or second-line platinum and taxane-based therapies were r and omly assigned by stratified blocks to CD ( carboplatin area under the curve [ AUC ] 5 plus PLD 30 mg/m(2 ) ) every 4 weeks or CP ( carboplatin AUC 5 plus paclitaxel 175 mg/m(2 ) ) every 3 weeks for at least 6 cycles . Primary end point was progression-free survival ( PFS ) ; secondary end points were toxicity , quality of life , and overall survival . RESULTS Overall 976 patients were recruited . With median follow-up of 22 months , PFS for the CD arm was statistically superior to the CP arm ( hazard ratio , 0.821 ; 95 % CI , 0.72 to 0.94 ; P = .005 ) ; median PFS was 11.3 versus 9.4 months , respectively . Although overall survival data are immature for final analysis , we report here a total of 334 deaths . Overall severe nonhematologic toxicity ( 36.8 % v 28.4 % ; P < .01 ) leading to early discontinuation ( 15 % v 6 % ; P < .001 ) occurred more frequently in the CP arm . More frequent grade 2 or greater alopecia ( 83.6 % v 7 % ) , hypersensitivity reactions ( 18.8 % v 5.6 % ) , and sensory neuropathy ( 26.9 % v 4.9 % ) were observed in the CP arm ; more h and -foot syndrome ( grade 2 to 3 , 12.0 % v 2.2 % ) , nausea ( 35.2 % v 24.2 % ) , and mucositis ( grade 2 - 3 , 13.9 % v 7 % ) in the CD arm . CONCLUSION To our knowledge , this trial is the largest in recurrent ovarian cancer and has demonstrated superiority in PFS and better therapeutic index of CD over st and ard CP OBJECTIVE To assess feasibility and safety of fertility-sparing laparoscopic staging in women affected by unexpected ovarian cancer desiring to preserve their fertility . DESIGN Prospect i ve study . SETTING University clinic . PATIENT(S ) Twenty-seven patients already operated on elsewhere for a presumably benign ovarian cyst . INTERVENTION(S ) Laparoscopic fertility-sparing staging operations . MAIN OUTCOME MEASURE(S ) Perioperative and survival data , reproductive outcome . RESULT ( S ) Histologic findings after first surgery : 12 low malignant potential neoplasms , 11 invasive epithelial ovarian carcinomas,1 sex-cord stromal , and 3 germ cell neoplasms . Fertility-sparing staging consisted of exploration of the peritoneal cavity , peritoneal washing cytology , multiple peritoneal biopsies , omolateral adnexectomy ( except in borderline tumors ) , omentectomy , omolateral or bilateral pelvic and aortic lymph node sampling ( except in borderline tumors , well differentiated , mucinous , and granulosa cell ( GC ) neoplasms ) , endometrial biopsy , appendectomy in mucinous type . Overall , seven patients ( 26 % ) were upstaged . Six patients received adjuvant platinum-based chemotherapy . Two term pregnancies occurred . After a median follow-up of 20 months all patients are alive ; one patient has FIGO stage Ic clear cell carcinoma , which recurred 8 months after surgery . CONCLUSION ( S ) Laparoscopic fertility-sparing staging in early ovarian malignancies is feasible and safe in selected and counseled patients and should be performed in experienced gynecological oncology centers trained in endoscopic procedures This study was undertaken to determine whether secondary surgical debulking is beneficial for patients with malignant ovarian germ cell tumors ( OGCT ) . Twenty patients with OGCT treated at our institution between 1975 and 1992 were retrospectively identified and analyzed . Survival was analyzed using the life-table methods of Kaplan and Meier and the statistical significance of various perioperative factors was tested by both the log-rank and the Wilcoxon tests . Histologic tumor type included 8 immature teratomas , 6 mixed tumors , 5 endodermal sinus tumors , and 1 dysgerminoma . After primary surgery , all patients received chemotherapy -- non-platinum-based in 12 patients , platinum-based in 5 , and both types in 3 patients . Treatment failure was classified as progression in 14 patients , persistence in 3 , and recurrence in 3 . Salvage surgery consisted of exploratory laparotomy and tumor debulking in 18 patients , inguinal lymphadenectomy in 1 , and thoracotomy and wedge resection in 1 . Sixteen patients subsequently received salvage chemotherapy . At the time of analysis , 11 patients were alive disease-free , 1 was alive with tumor , 6 had died of tumor progression , and 2 had died of treatment-related complications . Survival of patients with immature teratoma who underwent salvage surgery was significantly better than survival of those with other tumor cell types ( P = 0.006 ) . In conclusion , although the role of secondary debulking in chemorefractory OGCT remains undetermined , it may have some benefit for a select group of patients , particularly those with immature teratoma PURPOSE To determine the side effects and feasibility of cisplatin and carboplatin each in combination with paclitaxel as front-line therapy in advanced epithelial ovarian cancer . PATIENTS AND METHODS Patients were r and omly allocated to receive paclitaxel 175 mg/m(2 ) intravenously as a 3-hour infusion followed by either cisplatin 75 mg/m(2 ) or carboplatin ( area under the plasma concentration-time curve of 5 ) , both on day 1 . The schedule was repeated every 3 weeks for at least six cycles . Women allocated to paclitaxel-cisplatin were admitted to the hospital , whereas the carboplatin regimen was administered to out patients . RESULTS A total of 208 eligible patients were r and omized . Both regimens could be delivered in an optimal dose and without significant delay . Paclitaxel-carboplatin produced significantly less nausea and vomiting ( P : < .01 ) and less peripheral neurotoxicity ( P : = .04 ) but more granulocytopenia and thrombocytopenia ( P : < .01 ) . The overall response rate in 132 patients with measurable disease was 64 % ( 84 of 132 patients ) , and in patients with elevated CA 125 levels at start , it was 74 % ( 132 of 178 patients ) . With a median follow-up time of 37 months , the median progression-free survival time of all patients was 16 months and the median overall survival time was 31 months . The small number of patients entered onto the study caused wide confidence intervals ( CIs ) around the hazards ratio for progression-free survival of paclitaxel-carboplatin compared with paclitaxel-cisplatin ( hazards ratio , 1.07 ; 95 % CI , 0.78 to 1.48 ) and did not allow conclusions about efficacy . CONCLUSION Paclitaxel-carboplatin is a feasible regimen for out patients with ovarian cancer and has a better toxicity profile than paclitaxel-cisplatin PURPOSE Vascular endothelial growth factor ( VEGF ) plays an important role in the biology of ovarian cancer ( OC ) . Inhibitors of VEGF suppress tumor growth in OC models . Metronomic chemotherapy , defined as frequent administration of low doses of cytotoxic chemotherapy , suppresses tumor growth , possibly by inhibiting angiogenesis . A phase II trial was conducted to evaluate the antitumor activity and adverse effects of bevacizumab and metronomic oral cyclophosphamide in women with recurrent OC . PATIENTS AND METHODS Patients with measurable disease and prior treatment with a platinum-containing regimen were eligible . Up to two different regimens for recurrent disease were allowed . Treatment consisted of bevacizumab 10 mg/kg intravenously every 2 weeks and oral cyclophosphamide 50 mg/d . The primary end point was progression-free survival at 6 months . Plasma levels of VEGF , E-selectin , and thrombospondin-1 were obtained serially . RESULTS Seventy patients were enrolled . The probability of being alive and progression free at 6 months was 56 % ( + /- 6 % SE ) . A partial response was achieved in 17 patients ( 24 % ) . Median time to progression and survival were 7.2 and 16.9 months , 
    Output:
    