Surgery in Recurrent Ovarian Cancer: The Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) DESKTOP OVAR Trial Extensive cytoreductive surgery combined with intra-operative intraperitoneal perfusion with cisplatin under hyperthermic conditions (OVHIPEC) in patients with recurrent ovarian cancer: a feasibility pilot. Clinically occult recurrent ovarian cancer: patient selection for secondary cytoreductive surgery using combined PET/CT. The role of secondary cytoreduction in the treatment of ovarian cancer: Hacettepe University experience. Secondary cytoreductive surgery for localized intra-abdominal recurrences in epithelial ovarian cancer. Cytoreductive Surgery and Intraperitoneal Chemohyperthermia for Recurrent Peritoneal Carcinomatosis from Ovarian Cancer Secondary Cytoreductive Surgery in Patients with Platinum-Sensitive Recurrent Ovarian Cancer Secondary cytoreductive surgery for patients with recurrent epithelial ovarian carcinoma. Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label phase II study in patients treated after prior chemotherapy that contained cisplatin or carboplatin and paclitaxel. The effect of diameter of largest residual disease on survival after primary cytoreductive surgery in patients with suboptimal residual epithelial ovarian carcinoma. Secondary cytoreductive surgery for recurrent ovarian cancer. A prospective study Hyperthermic intraperitoneal chemotherapy in conjunction with surgery for the treatment of recurrent ovarian carcinoma.
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 AIMS The feasibility , morbidity and toxicity of an intensified surgical treatment strategy consisting of aggressive cytoreductive surgery , intra-operative intraperitoneal perfusion of cisplatin and hyperthermia were evaluated in women with recurrent ovarian cancer . METHODS Five heavily pre-treated patients with extensive abdominal tumour bulk entered this pilot study . In all cases aggressive cytoreduction leaving tumour remnants < 5 mm in diameter could be performed . This was followed intra-operatively by perfusion of the abdominal cavity with hyperthermic cisplatin 50 - 70 mg/m(2)for 90 min . During perfusion the intra-abdominal temperature was maintained at 40 degrees C. The median duration of surgery was 10 hours ( range 9 - 11 hours ) . RESULTS No major intra- or post-operative complications emerged . Median post-operative ileus ( resuming of soft diet ) was 11 days ( 9 - 13 days ) . The mean period of hospitalization was 25 days ( range 17 - 42 ) . Toxicity due to i.p . cisplatin was mainly metabolic and of grade 1 - 2 , while no nephrotoxicity was observed . The pharmacokinetics of cisplatin indicated that the maximum concentration of cisplatin measured in the perfusate was 15 times higher than in plasma . CONCLUSIONS We conclude that aggressive cytoreduction combined with hyperthermic intra-operative intraperitoneal cisplatin was feasible in a small group of heavily pre-treated ovarian cancer patients with extensive tumour bulk with acceptable morbidity and toxicity . Further studies are required in larger groups of patients to further establish the feasibility of this intensified treatment strategy . We stress that OVHIPEC is not a treatment modality on its own for advanced ovarian cancer . The effectiveness of OVHIPEC is likely to be dependent on the effectiveness of post-operative adjuvant chemotherapeutic regimens OBJECTIVE The aim of this study was to evaluate the utility of combined positron emission tomography/computed tomography ( PET/CT ) for identifying ovarian cancer tumor masses > or = 1 cm in patients with clinical ly occult recurrent disease by conventional CT imaging .  METHODS Twenty-two patients with epithelial ovarian cancer , rising serum CA125 levels , and negative or equivocal conventional CT imaging > or = 6 months after primary therapy underwent combined PET/CT imaging followed by surgical re assessment .  Fisher 's exact test was used to measure the ability of PET/CT to predict macroscopic disease > or = 1 cm . RESULTS The median patient age was 55 years , and 91 % of patients had FIGO Stage IIIC/IV disease . The median increase in serum CA125 was 24 U/ml ( range 10 to 330 U/ml ) . Conventional CT was reported as negative ( n = 15 ) or equivocal ( n = 7 ) in all cases . Eighteen patients were ultimately found to harbor recurrent ovarian cancer measuring > or = 1 cm at the time of surgery , with a median maximal tumor diameter of 2.3 cm ( range 1.5 to 3.2 cm ) . The overall patient-based accuracy of PET/CT  in detecting recurrent disease > or = 1 cm was 81.8 % , with a sensitivity of 83.3 % and positive predictive value of 93.8 % ( P = 0.046 ) . Of patients with recurrent ovarian cancer > or = 1 cm , complete cytoreduction to no gross residual tumor was accomplished in 72.2 % . CONCLUSION PET/CT imaging demonstrates high sensitivity and positive predictive value in identifying potentially resectable , macroscopic recurrent ovarian cancer among patients with biochemical evidence of recurrence and negative or equivocal conventional CT findings . In appropriately selected patients , early identification of macroscopic recurrent disease may facilitate complete surgical cytoreduction OBJECTIVE This study was undertaken to evaluate the role of secondary cytoreduction in patients with recurrent epithelial ovarian cancer . STUDY DESIGN Secondarily , cytoreduced patients were retrospectively analyzed with respect to the clinicopathologic variables . RESULTS A total of 64 patients were evaluated in this report . Multivariable analysis revealed 3 factors to be significant : optimal cytoreduction during primary ( P = .003 , odds ratio [ OR ] : 0.30 ; 95 % CI : 0.14 - 0.66 ) , secondary cytoreduction  ( P = .04 , OR : 0.47 ; 95 % CI : 0.22 - 0.99 ) , and the endometrioid histologic type ( P = .005 , OR : 0.09 ; 95 % CI : 0.02 - 0.48 ) . Intrinsic factors of the tumors ( grade , stage , age ) , size , and number of recurrent tumors were nonsignificant . CONCLUSION Secondary cytoreductive surgery should be offered in selected recurrent epithelial ovarian cancer patients . Further prospect i ve r and omized series are needed to determine specific recommendations OBJECTIVE The aim of this study was to evaluate the role of secondary cytoreductive surgery in patients with recurrent epithelial ovarian cancer with an apparent solitary intra-abdominal focus . METHODS We conducted a retrospective review of patients with epithelial ovarian cancer who underwent secondary cytoreduction for recurrence at the University of Texas M. D. And erson Cancer Center between 1985 and 1994 . Eligible patients included those who had a laparotomy to resect a tumor that was apparently solitary .  Cytoreductive surgery was defined as optimal if the diameter of the largest residual tumor was < or = 2 cm and suboptimal if > 2 cm . RESULTS Twenty-five patients met our eligibility criteria . Their mean age was 55 years ( range , 35 - 73 years ) . The median time from primary diagnosis to recurrence was 37.6 months . Tumor was found to be confined to a solitary site in 15 patients ( 60 % ) , to two sites in 6 ( 24 % ) , and to three or more sites in 4 ( 16 % ) . Surgical procedures included cytoreduction in 10 patients , intestinal resection in 8 , splenectomy in 3 , and limited biopsies in 4 . Secondary cytoreduction was optimal in 18 of 25 patients ( 72 % ) . The median post secondary cytoreduction survival was 25.1 months for patients who had suboptimal secondary cytoreduction compared with 56.9 months for those who had optimal cytoreduction ( P = 0.08 ) . CONCLUSIONS Secondary cytoreductive surgery for recurrent ovarian cancer at an apparently solitary intra-abdominal site result ed in optimal residual tumor in a high proportion of patients . Although there was no survival advantage for patients whose tumor was optimally debulked , there was a trend toward improved survival . A large prospect i ve r and omized trial of secondary cytoreduction for recurrence is recommended Aggressive surgical cytoreduction has been shown to have a positive impact on survival of patients with ovarian cancer . After first-line chemotherapy , 47 % of patients relapse within 5 years , and median survival after second line chemotherapy is 10—15 months . Adding intraperitoneal chemohyperthermia ( IPCH ) to surgical cytoreduction could further control ceolomic spread of disease . The aim of this study was to determine morbidity and mortality , regional relapse-free survival and , preliminarily , overall survival after combining cytoreductive surgery with IPCH for the treatment of peritoneal carcinomatosis from ovarian epithelial cancer relapsed after prior chemotherapy . Thirty women affected with such a relapse were included . Patients underwent extensive cytoreductive surgery including tumor resections and peritonectomy , followed by intraoperative IPCH with cisplatin . Complete surgical cytoreduction down to nodules less than 2.5 mm ( CC0—CC1 ) was obtained in 23 patients ( 77 % ) . One patient died postoperatively from a pulmonary embolism . Major postoperative morbidity was 5/30 ( 16.7 % ) . We registered one case of anastomotic leakage , a spontaneous ileum perforation , a postoperative cholecystitis , a hydrothorax , and one patient with bone marrow toxicity . Kaplan-Meier estimates of median locoregional relapse-free survival and median overall survival were 17.1 months and 28.1 months , respectively . Patients with CC0—CC1 had locoregional relapse-free and overall survival rates of 24.4 and 37.8 months , whereas the remainder had survival rates of 4.1 and 11.0 months . We concluded that cytoreductive surgery combined with IPCH is feasible with acceptable morbidity and mortality and seems to promise good results in selected patients affected with peritoneal carcinomatosis from ovarian cancer ABSTRACT Background Secondary surgical cytoreduction ( SCR ) represents a promising therapeutic strategy for patients affected by ovarian cancer disease recurrence . The aim of this prospect i ve observational trial was to analyze the role of SCR in patients with platinum-sensitive ovarian cancer . Methods Patients with platinum-sensitive ovarian cancer underwent SCR  by a single surgical team . Clinical and oncologic data were prospect ively recorded . A total of 47 patients underwent SCR from 1999 to 2003 . Results The mean operating time was 210 minutes , and mean blood loss was 500 mL. The most frequent surgical procedures carried out were splenectomy , lymphadenectomy , bowel resection , and extensive peritonectomy . Optimal cytoreduction was achieved in 41 patients . Thirty-seven patients had no visible tumor at the end of SCR . Overall median survival was 49 months . Patients who achieved optimal residual disease had a median survival of 61 months , whereas patients who had residual disease > 1 cm had a median survival of 19 months . Conclusions Positive CA-125 ( cancer antigen 125 ) was identified as a negative prognostic factor at multivariate analysis . After careful selection , optimal cytoreduction can be achieved in most patients who are subjected to SCR with acceptable morbidity . Residual tumor and CA-125 represent the most important prognostic factors 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 . The difference in survival between those with < 2 cm residual disease and those with > or = 2 cm residual disease was significant ( p < 0.01 ) . There is no significant difference in the risk of dying between groups with residual disease > or = 2 cm . CONCLUSIONS Among patients with suboptimal ( > 1 cm residual disease ) epithelial ovarian cancer , those who have small diameter residual disease ( < 2 cm ) tend to survive longer than those who have larger residual disease . Among those with larger residual disease , size does not affect prognosis appreciably Background . The prognosis for patients with recurrent epithelial ovarian cancer is poor . Most are treated with salvage chemotherapy . The role of secondary cytoreductive surgery is controversial . Hence , this prospect i ve study was undertaken to determine the feasibility and benefit of secondary cytoreductive surgery before the administration of salvage chemotherapy OBJECTIVES To review experience of secondary surgical cytoreduction ( SSC ) with hyperthermic intraperitoneal chemotherapy ( IPHC ) . METHODS Eligible patients with ovarian cancer in whom pre-operative evaluation indicated that there was a good possibility that disease could be resected to < or = 5 mm underwent surgery followed by intraperitoneal perfusion of cisplatin ( 100 mg/m2 ) or mitomycin C ( 30 - 40 mg total dose ) heated to 41 - 43 degrees C ( 105.8 - 109.4 degrees F ) for 90 min . Data for analysis were extracted from retrospective chart review . RESULTS Eighteen patients underwent surgery and IPHC between 9/02 and 3/05 . Characteristics were median age 64 ( 37 - 77 ) years , mean prior laparotomies 1.4 ( 0 - 3 ) , mean chemotherapy regimens 3.2 ( 0 - 7 ) , mean time from initial therapy to IPHC 30.6 ( 1 - 88 ) months . Original histology : papillary serous 12 , poorly differentiated adenocarcinoma 1 , serous low malignant potential 2 , mucinous 1 and mixed subtypes 2 . 13 had recurrent disease and 5 had persistent disease following front-line therapy . 15 received cisplatin and 3 mitomycin C. The mean duration of surgery was 9.8 ( 5 - 16 ) h. The maximum dimension of residual lesions at the end of surgery prior to IPHC was nil ( n=11 ) , < or = 2 mm ( n=4 ) , < or = 5 mm ( n=2 ) and < or = 10 mm ( n=1 ) . Mean time to return of bowel function was 7 ( 5 - 20 ) days and mean time to hospital discharge 11.5 ( 5 - 49 ) days . All patients developed CTEP grade 1 or 2 metabolic or hematologic toxicities . CTEP grade 3 or 4 metabolic toxicity occurred in 72 % and a hematologic toxicity in 28 % . There was one peri-operative death due to pulmonary embolus . Median progression-free interval was 10 months and median overall survival was 31 months . Improved outcome was significantly related to the size of residual disease prior to IPHC and postoperative chemotherapy . CONCLUSIONS IPHC is a relatively well-tolerated procedure with the majority of the morbidity being related to associated surgery . When combined with SSC it has the potential to extend quality life in some patients with recurrent ovarian cancer and warrants continued research . R and omized studies are needed earlier in the course of the disease
BACKGROUND The st and ard management of primary ovarian cancer is optimal cytoreductive surgery followed by platinum-based chemotherapy .
Most women with primary ovarian cancer achieve remission on this combination therapy .
For women achieving clinical remission after completion of initial treatment , most ( 60 % ) with advanced epithelial ovarian cancer will ultimately develop recurrent disease .
However , the st and ard treatment of women with recurrent ovarian cancer remains poorly defined .
Surgery for recurrent ovarian cancer has been suggested to be associated with increased overall survival .
OBJECTIVES To evaluate the effectiveness and safety of optimal secondary cytoreductive surgery for women with recurrent epithelial ovarian cancer .
To assess the impact of various residual tumour sizes , over a range between 0 cm and 2 cm , on overall survival .