A phase II trial of bevacizumab and rucaparib in recurrent carcinoma of the cervix or endometrium.

OBJECTIVE: The aim of this study was to examine the tolerability and efficacy of combination bevacizumab rucaparib therapy in patients with recurrent cervical or endometrial cancer. PATIENTS & METHODS: Thirty-three patients with recurrent cervical or endometrial cancer were enrolled. Patients were required to have tumor progression after first line treatment for metastatic, or recurrent disease. Rucaparib was given at 600 mg BID twice daily for each 21-day cycle. Bevacizumab was given at 15 mg/kg on day 1 of each 21-day cycle. The primary endpoint was efficacy as determined by objective response rate or 6-month progression free survival. RESULTS: Of the 33 patients enrolled, 28 were evaluable. Patients with endometrial cancer had a response rate of 17% while patients with cervical cancer had a response rate of 14%. Median progression free survival was 3.8 months (95% C·I 2.5 to 5.7 months), and median overall survival was 10.1 months (95% C·I 7.0 to 15.1 months). Patients with ARID1A mutations displayed a better response rate (33%) and 6-month progression free survival (PFS6) rate (67%) than the entire study population. Observed toxicity was similar to that of previous studies with bevacizumab and rucaparib. CONCLUSIONS: The combination of bevacizumab with rucaparib did not show significantly increased anti-tumor activity in all patients with recurrent cervical or endometrial cancer. However, patients with ARID1A mutations had a higher response rate and PFS6 suggesting this subgroup may benefit from the combination of bevacizumab and rucaparib. Further study is needed to confirm this observation. No new safety signals were seen.

A phase Ib/II and pharmacokinetic study of EP0057 (formerly CRLX101) in combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer.

BACKGROUND: EP0057 (formerly CRLX101) is an investigational nanoparticle-drug conjugate (NDC) of a cyclodextrin-based polymer backbone plus camptothecin, a topoisomerase-1 inhibitor. Prior studies showed efficacy in recurrent or persistent, epithelial ovarian, fallopian tube or primary peritoneal cancer (EOC). METHODS: This phase Ib/2 trial assessed safety and efficacy of EP0057 Q2W plus weekly paclitaxel in patients with EOC. The recommended phase 2 dose (RP2D) was identified using a 3+3 design. The single-arm phase 2 assessed overall response (ORR) per RECIST 1.1 in patients previously treated with bevacizumab. Secondary objectives included progression free survival (PFS) and duration of response. RESULTS: The RP2D was established as 15 mg/m2 EP0057 Q2W plus 80 mg/m2 paclitaxel administered 3 weeks on/1 week off. Nine patients enrolled on phase 1b, with no DLTs; 21 additional patients enrolled on phase 2. All completed >1 cycle. Median age was 62 (44-76) years, 57% ≥3 prior therapies. For the primary analysis, 6/19 patients with prior bevacizumab had confirmed responses (ORR=31.6% (95% CI: 15.4% to 54.0%)) including one complete response (CR). Median PFS was 5.4 months. Most common grade 3/4 adverse events attributed to treatment were decreased neutrophil count (13, 43%) and anemia (3, 10%). CONCLUSIONS: Although the observed ORR was not statistically better than the historical control rate, EP0057 remains an interesting option for treatment of recurrent EOC. EP0057 exhibits high plasma drug retention, slow clearance, and controlled slow release of CPT from the polymer when administered alone and with paclitaxel. (NCT02389985) 242 words.

A randomized phase II evaluation of weekly gemcitabine plus pazopanib versus weekly gemcitabine alone in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma.

OBJECTIVE: Angiogenesis inhibition is a valuable strategy for ovarian cancer (EOC). Pazopanib (paz) is a potent small molecular inhibitor of VEGF-1, -2, -3, PDGFR, c-kit, and has activity as a single agent in ovarian cancer. We designed a trial to assess the benefit of adding paz to gemcitabine (gem) in patients with recurrent EOC. METHODS: An open-label, randomized, multi-site, phase 2 trial was conducted (NCT01610206) including patients with platinum resistant or sensitive disease, ≤ 3 prior lines of chemotherapy, and measurable/evaluable disease. Patients were randomly assigned to weekly gem 1000 mg/m2 on days 1 and 8 of a 21 day cycle, with or without paz 800 mg QD, stratified by platinum sensitivity and number of prior lines (1 vs 2 or 3). The primary endpoint was PFS. RESULTS: 148 patients were enrolled 2012-2017. Median age was 63 years (30-82); 60% were platinum resistant; median surveillance was 13 months (0.4-54 months). Median PFS was 5.3 (95% CI, 4.2-5.8) vs 2.9 months (95% CI, 2.1-4.1) in the gem arm. The PFS effect was most pronounced in the platinum resistant group (5.32 vs 2.33 months Tarone-Ware p < 0.001). There was no difference in OS. Overall RR (PR 20% vs 11%, Chi-squre p = 0.02) and DCR (80% vs 60%, Chi-square p < 0.001) were higher in the combination. High grade AEs in the combination arm included ≥ Grade 3: hypertension (15%), neutropenia (35%), and thrombocytopenia (12%). CONCLUSIONS: The addition of paz to gem enhanced anti-tumor activity; those with platinum-resistant disease derived the most benefit from combination therapy, even in the setting of receiving prior bevacizumab.

The new classifications of ovarian, fallopian tube, and primary peritoneal cancer and their clinical implications.

The roles of histologic characterization and staging are to provide reproducible metrics for cancer classification with which to direct the most appropriate clinical care and to yield the most stable reliable system to allow both prospective and retrospective data analysis. Both the histologic and staging classifications of malignant ovarian/tubal/peritoneal cancers have recently changed. The World Health Organization sponsored a review and reclassification of the pathology of cancers of the ovaries, fallopian tubes, and peritoneum, and published these updates in 2014. In so doing, they codified the two-tiered grading system that has been in use in serous ovarian cancers for nearly a decade. In parallel, FIGO reviewed and updated the surgical staging system, applied to all histotypes of ovarian, tubal, and peritoneal cancers, also published in 2014. In both cases, the changes made are meant to encompass a better understanding of disease, but both have important merits and drawbacks. Changes in staging complicate analysis of retrospective data against current data. Though in some aspects controversial, the changes overall are meant to represent a better biologic understanding of disease that we hope will lead to an improvement in patient care and directed therapy.

A multicenter, open-label, expanded phase 2 study to evaluate the safety and efficacy of etirinotecan pegol, a polymer conjugate of irinotecan, in women with recurrent platinum-resistant or refractory ovarian cancer.

OBJECTIVE: Etirinotecan pegol (EP) is a novel polyethylene glycol conjugated form of irinotecan with documented activity in platinum-resistant ovarian cancer (PROC). We report the results of the expanded portion of a phase II study of EP in patients with PROC who received prior pegylated liposomal doxorubicin (PLD) or who were unable to receive it. METHODS: This multicenter, open-label, phase II study evaluated EP q21d for PROC. The primary endpoint was objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors version 1.0. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Patient populations evaluated included a modified intent-to-treat (mITT) group consisting of all patients who received at least one dose and with measurable disease and a primary efficacy (pEFF) group (subset of the mITT population who received prior PLD). RESULTS: One hundred thirty-nine patients were enrolled. Of the 132 patients in the mITT group, 20 achieved an ORR (15.2%; 95% CI 9.5-22.4); median PFS and OS were 4.4 months and 10.2 months, respectively. In the pEFF group (n=104), 15 patients (14.4%; 95% CI 8.3-22.7) achieved an ORR; median PFS and OS were 4.4 months and 10.9 months, respectively. The most common grade 3/4 toxicities were diarrhea (20%), abdominal pain (17%), vomiting (14%), dehydration (13%), and nausea (13%). Severe diarrhea was reduced to 15% with strict adherence to screening and management guidelines. CONCLUSIONS: This study confirms the activity and safety of single-agent EP in patients with PROC, including patients who received prior PLD. Further evaluation earlier in the disease course and in combination is warranted.

Three sequential chemotherapy doublets for the treatment of newly diagnosed advanced müllerian malignancies: the modified triple doublet regimen.

OBJECTIVE: Previously, we reported the use of three sequential doublets (Triple Doublets) in the treatment of women with newly diagnosed and advanced stage müllerian malignancies. The surgically defined negative second look operation (SLO) rate to Triple Doublets was 38%. Modifications were made to this treatment regimen that were predicted to reduce toxicity and possibly increase efficacy. METHODS: Open label two-cohort study. Patients with a new diagnosis of Stages II-IV müllerian malignancy were eligible. After cytoreductive surgery, patients were treated with three sequential doublets including 3 cycles of carboplatin and gemcitabine, and 3 cycles of carboplatin and paclitaxel, and 3 cycles of doxorubicin and topotecan. After therapy, all women were clinically staged and evaluated at SLO if clinical staging was negative for residual disease. Primary endpoints were toxicity and negative SLO rate with rates of 60% and 40% defined a priori in optimally cytoreduced (cohort 1) and suboptimally cytoreduced or Stage IV (cohort 2), respectively. RESULTS: Eighty-five eligible patients were enrolled with a median age of 52 years. Forty-seven and thirty-eight women were in cohorts 1 and 2, respectively. 723 cycles of chemotherapy were delivered with no toxic deaths. Grades 3 and 4 toxicities included neutropenia in 75% of patients and thrombocytopenia in 65% of patients during at least one cycle of therapy. Fever and neutropenia were seen in 3.5% of patients. All Grades 3 and 4 non-hematologic toxicities were seen at a frequency of <10%. Seventy women underwent SLO with a negative SLO rate of 53% with an additional 9% having microscopically positive procedures. Negative SLO rate was 74% in cohort 1 and 36% in cohort 2. CONCLUSIONS: Treatment with the modified triple doublet regimen is tolerable with an encouraging pathologic CR rate.

Treatment of uterine papillary serous carcinoma with platinum-based chemotherapy and paclitaxel.

Uterine papillary serous carcinoma (UPSC) is more aggressive than endometrioid endometrial cancer, as it often presents with advanced disease and follows a pattern of spread that resembles the serous carcinoma of the ovary. There exists little data on evaluating the combination of carboplatin and paclitaxel in UPSC. Institutional Review Board permission was obtained for a retrospective review. Tumor registry search was used to identify all patients with UPSC from 1990 to 2003. Charts were retrospectively evaluated from patients who had received at least three cycles of carboplatin and paclitaxel as first-line chemotherapy. Only patients with histologically confirmed UPSC who were treated first line with carboplatin/paclitaxel chemotherapy were included. Nineteen patients with UPSC were identified, who were treated with carboplatin and paclitaxel in the first-line adjuvant setting after initial surgical cytoreduction. All patients received at least three cycles, with 12 of the 19 patients receiving six cycles. Five patients were treated with consolidation radiotherapy following first-line chemotherapy. Mean age was 69 years (range 55-88). The majority of patients had stage III disease (n= 11). Mean follow-up for the group was 29.5 months (7-76 months). A median progression-free interval of 12 months was seen across the entire cohort. Fourteen patients achieved a complete response following chemotherapy. The results of Gynecologic Oncology Group protocol 122 suggest that patients with advanced endometrial cancer have an improved progression-free survival when treated primarily with chemotherapy rather than radiation therapy. The results of our study show a high response rate to paclitaxel/carboplatin outpatient chemotherapy in a group of patients historically believed to have chemoresistant disease. Further prospective study of this regimen is planned.

Phase I/II dose finding study of combination cisplatin and gemcitabine in patients with recurrent cervix cancer.

OBJECTIVES: To evaluate the toxicity and efficacy of cisplatin and gemcitabine in women with recurrent cervical cancer. METHODS: A multi-institutional phase I/II dose finding study of cisplatin and gemcitabine delivered to women with recurrent previously radiated cervical carcinoma. RESULTS: Twenty eight patients were enrolled. The mean and median age of patients was 51 years (age range 35 to 70 years). Chemotherapy was given on a 28-day cycle; cisplatin was administered at a fixed dose of 50 mg/m(2), day 1 and gemcitabine, days 1, 8, and 15. Gemcitabine doses started at 600 mg/m(2) (dose level 1) and were escalated by 100 mg/m(2)/dose level until 1000 mg/m(2) (dose level 5). Twenty seven patients were evaluable for toxicity and disease response, and 75 cycles of chemotherapy were administered. Toxicities were predominantly hematological; 18% of patients experienced grade 3 anemia, 37% grade 3 and 11% grade 4 leukopenia, 41% grade 3 neutropenia, and 26% grade 3 thrombocytopenia. The maximally tolerated dose (MTD) was not reached. One patient experienced a dose-limiting toxicity on dose level 2 (febrile neutropenia). One patient had a CR and 3 patients had a PR to therapy (15% response rate), 41% of patients had SD, and 44% had progression of cancer. Median survival was 11.9 months. CONCLUSION: Although this 28-day gemcitabine and cisplatin regimen in recurrent cervix cancer has tolerable toxicity, 21-day regimens are recommended because of improved practicality, higher dose intensity, and higher response rates.

BAG-1 expression in normal and neoplastic endometrium.

OBJECTIVE: BAG-1 has anti-apoptotic actions and is known to bind BCL-2 and steroid receptors. High levels of BAG-1 have been implicated as a prognostic indicator in breast cancer. Whether this observation can be generalized to endometrial cancer remains unknown. METHODS: IRB permission was obtained for use of human discarded tissue. Immunohistochemical analyses were performed on: proliferative endometrium (PEM, 6), secretory endometrium (SEM, 28), "low-grade" neoplastic lesions (complex atypical hyperplasia and grade 1 endometrial adenocarcinomas) (19), and "high-grade" cancers (grade 2 and 3 endometrial adenocarcinomas) (13). The level of total BAG-1 and its isoforms was evaluated by Western blot in lysates from Ishikawa cells (grade 1), MFE 296 cells (grade 2), and SK-UT(2) cells (grade 3). RESULTS: The proportion of "high-grade" cancers with positive cytoplasmic staining for BAG-1 was higher than that of secretory endometrium (P = 0.006). Additionally, the proportion of specimens with positive staining for nuclear BAG-1 expression was significantly higher among high-grade carcinoma specimens compared to secretory specimens (P = 0.009). A high proportion (91%) of all specimens were positive for BCL-2, limiting the ability to subcategorize the other variables analyzed. There was no relationship between positive nuclear BAG-1 expression and either estrogen receptor (ER) or progesterone receptor (PR) expression. BAG-1 was expressed in the three cell lines evaluated and total BAG-1 level was not different among the different cell lines. CONCLUSION: BAG-1 is expressed in the endometrium. High-grade cancers stain more frequently than secretory endometrium for both cytoplasmic and nuclear BAG-1 expression, perhaps indicating an association between expression of BAG-1 and prognosis.

A phase II trial of three sequential doublets for the treatment of advanced müllerian malignancies.

OBJECTIVES: In an effort to improve the results of primary chemotherapy for müllerian malignancies a novel chemotherapy program was piloted that delivered three sequential chemotherapy doublets. The primary endpoints were surgically defined response rates and evaluation of toxicity. METHODS: After primary cytoreductive surgery patients were treated with three sequential doublets including three initial cycles of carboplatin and paclitaxel (doublet 1) and then two cycles of cisplatin (day 1) and gemcitabine (days 1 and 8; doublet 2), and finally two cycles of doxorubicin (day 1) and topotecan (days 3,4, and 5; doublet 3). Cycles 4 through 7 were given with G-CSF (Neupogen) support at a dose of 5 mcg/kg/day. After therapy, all women were clinically staged and evaluated by second-look laparoscopy/laparotomy (SLO) if clinical staging was negative for residual disease. RESULTS: A total of 49 eligible patients were enrolled with a median age of 52 (SD 9). Forty-four women had either ovarian cancer or primary peritoneal carcinoma with 3 women diagnosed with fallopian tube carcinoma and 2 with papillary serous carcinoma of the uterus. Eighty-four percent of patients had stage IIIc/IV tumors, with 29% having >1 cm residual disease after primary cytoreductive surgery. Thirty-nine of 49 (80%) patients completed therapy. A total of 283 cycles of chemotherapy were delivered with acceptable toxicities. There were no toxic deaths. Five women were withdrawn from trial (3 for Taxol hypersensitivity, 1 for gemcitabine pulmonary hypersensitivity, and 1 for serious line infection). Neutropenia, typically without fever, was relatively frequent in the first doublet. Nausea and thrombocytopenia were the predominant toxicities in doublet 2. Thirty-nine women completed all cycles of treatment. Thirty-six women had restaging results consistent with a clinical complete response (CR) and underwent SLO. The pathologic CR rate of the patients undergoing SLO was 38%. CONCLUSIONS: Treatment with this sequential doublet regimen is feasible with a 38% pathologic CR rate.

Endometrial cancer in women 40 years old or younger.

OBJECTIVE: The aim of this study was to characterize endometrial cancer in women 40 years of age and younger, with special attention toward body-mass index (BMI). METHODS: A retrospective review of women age 40 and under with endometrial cancer was performed. Patients were identified via tumor registry data as well as a search of pathology department diagnoses over the dates 1980-1998. Data were abstracted regarding tumor grade and histology, stage, treatment, smoking, use of oral contraceptives, BMI, medical and family history, parity, and survival. Data were also collected with regard to uterine conservation and pregnancies following endometrial cancer diagnoses. RESULTS: Ninety-five patients were identified. The age range was 24-40 years (median 37) with BMI ranging from 17.5 to 63.6 (median 28.4). Forty-eight patients (52%) were not obese, with BMI < 30. Seventy-six patients (80%) had stage I disease and 60 patients (63%) had grade 1 disease. All but 4 patients had endometrioid histology. Women with BMI < 25 were more likely to have advanced disease (P = 0.04) and more likely to have high-risk histology (P = 0.02). Of the 4 patients with high-risk histology (clear cell or serous papillary), all had BMI < 25. Twelve patients were treated medically rather than surgically, and 4 patients achieved pregnancy, with 5 live births. CONCLUSION: Women under 40 who are not obese are at higher risk of both advanced disease and high-risk histology. Further study at the molecular and genetic level is ongoing in our laboratory to determine whether the mechanism of disease is different in slender woman.

Multimodality therapy in early-stage neuroendocrine carcinoma of the uterine cervix.

OBJECTIVE: Patients with early-stage neuroendocrine cervical carcinoma (NECC) have a high mortality rate despite aggressive therapy. The rarity of this tumor precludes initiation of a randomized, prospective trial. We reviewed our experience in early stage disease and performed a meta-analysis of the literature to identify prognostic factors and determine optimal multimodality therapy. METHODS: Eleven women with International Federation of Gynecology and Obstetrics (FIGO) early stage (IB--IIA) NECC were treated with surgery and chemotherapy at our institutions between 1978 and 1998. Administration of radiation therapy was recorded, but not required for inclusion in this study. A gynecologic pathologist reviewed all histopathologic sections. Medical records were retrospectively reviewed and clinical data obtained. Twenty-three early-stage NECC patients who were similarly treated during the study interval were identified by a Medline search of the English literature and included in the analysis. The Kaplan--Meier method and log-rank test were used for survival analysis. RESULTS: The overall 2-year survival rate for the 34 patients was 38%. The median age was 37 years (range, 20--75 years). Median cervical tumor diameter was 3.2 cm (range 0.5--11.0 cm). Lymphovascular space invasion was present in 21 (78%) of 27 patients (7 unknown). Fifteen (52%) of twenty-nine had lymph node metastases (5 unknown). Fifteen patients received postoperative platinum/etoposide (PE), seven received vincristine/adriamycin/cyclophosphamide (VAC), two received alternating cycles of VAC and PE, and ten received other chemotherapy regimens. Twenty women were treated with radiation therapy. The presence of lymph node metastases was a poor prognostic factor (P < 0.001). PE and VAC chemotherapy was associated with increased survival (P < 0.01). CONCLUSION: NECC is a highly lethal variant of cervical cancer. The presence of lymph node metastases is the most important prognostic variable. Postoperative VAC or PE appears most likely to improve chances for survival.

The role of cytoreductive surgery in the management of stage IV uterine papillary serous carcinoma.

OBJECTIVE: The aim of this study was to evaluate the survival impact of cytoreductive surgery and other prognostic determinants in patients with Stage IV uterine papillary serous carcinoma (UPSC). METHODS: All patients with FIGO Stage IV UPSC diagnosed between January 1, 1989 and December 31, 1998 were identified from tumor registry databases. Individual patient data were collected retrospectively. Survival analysis and comparisons were performed using the method of Kaplan and Meier, the log-rank test, and the Cox proportional hazards regression model. Predictors of surgical outcome were evaluated using the log-rank test. RESULTS: Thirty-one patients underwent primary cytoreductive surgery for Stage IV UPSC (median age, 65 years). The median survival for all patients was 14.4 months. Optimal cytoreduction was defined as residual disease < or =1 cm in maximal diameter. The only significant predictor of a suboptimal surgical outcome was the presence of disease in three or more anatomic regions. Overall, 16 of 31 patients (51.6%) completed primary surgery with optimal disease status. Optimal cytoreduction was associated with a median survival of 26.2 months, compared with 9.6 months for patients left with suboptimal residual disease (P < 0.001). At 24 months, 57.1% of optimally cytoreduced patients were still alive, compared with just 6.7% of patients left with suboptimal disease. Furthermore, patients with only microscopic residual tumor had a significantly longer median survival (30.4 months) than both patients with 0.1- to 1.0-cm residual disease (20.5 months) and those left with suboptimal disease (P = 0.004). Postoperative platinum-based chemotherapy was associated with a median survival of 17.1 months, compared with 9.5 months without such therapy (P = 0.018). Patients receiving the combination of platinum + paclitaxel had a median survival rate of 29.1 months versus 14.4 months for patients receiving platinum + cyclophosphamide +/- doxorubicin (P = 0.054). On multivariate analysis, the only statistically significant predictor of survival was the cytoreductive surgical outcome. CONCLUSIONS: The strongest predictor of overall survival for patients with Stage IV UPSC was the amount of residual disease following surgery. Recommended management for this group of patients should consist of maximal surgical cytoreduction followed by platinum-based chemotherapy, preferably in combination with paclitaxel.

A model for predicting surgical outcome in patients with advanced ovarian carcinoma using computed tomography.

BACKGROUND: A reliable model for predicting the outcome of primary cytoreductive surgery may be a useful tool in the clinical management of patients with advanced epithelial ovarian carcinoma. METHODS: Forty-one women with a preoperative computed tomographic (CT) scan of the abdomen and pelvis and a histologic diagnosis of Stage III or IV epithelial ovarian carcinoma following primary surgery performed by one of nine gynecologic oncologists were identified from tumor registry databases. All CT scans were analyzed retrospectively using a panel of 25 radiographic features without knowledge of the operative findings. Patient demographics, surgical findings and outcome, Gynecologic Oncology Group performance status, and pre-operative serum CA125 values were collected from patient medical records. Residual disease measuring < or = 1 cm in maximal diameter was considered an optimal surgical result. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each radiographic feature and clinical characteristic. Based on statistical probability of each factor predicting cytoreductive outcome, 13 radiographic features, in addition to performance status, were selected for inclusion in the final model. Each parameter was assigned a numeric value based on the strength of statistical association, and a total Predictive Index score was tabulated for each patient. Receiver operating characteristic (ROC) curve analysis was used to assess the ability of the model to predict surgical outcome. Statistical significance was evaluated using the Fisher exact test. RESULTS: Twenty of 41 patients (48.8%) underwent optimal cytoreduction to /= 2 cm), bowel mesentery involvement (>/= 2 cm), suprarenal paraaortic lymph nodes (>/= 1 cm), omental extension (spleen, stomach, or lesser sac), and pelvic sidewall involvement and/or hydroureter were most strongly associated with surgical outcome. Using the Predictive Index scores, a receiver operating characteristic curve was generated with an area under the curve = 0. 969 +/- 0.023. In the final model, a Predictive Index score >/= 4 had the highest overall accuracy at 92.7% and identified patients undergoing suboptimal surgery with a sensitivity of 100% (21/21). The specificity, or ability to identify patients undergoing optimal surgery, was 85.0% (17/20). The PPV of a Predictive Index score >/= 4 was 87.5% (21/24), and the NPV was 100%. The ability of this model to correctly predict surgical outcome was statistically significant (P < 0.001). CONCLUSIONS: In this model, a Predictive Index score >/= 4 demonstrated high sensitivity, specificity, PPV, and NPV, and was highly accurate in identifying patients with advanced epithelial ovarian carcinoma unlikely to undergo optimal primary cytoreductive surgery. The Predictive Index model may have clinical utility in guiding the management of patients with ovarian carcinoma.