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Objectives Intraperitoneal (IP) chemotherapy following neoadjuvant chemotherapy (NACT) and interval tumor reductive surgery (TRS) for advanced ovarian cancer is feasible, however, the impact on disease outcomes remains unclear. We compare outcomes of patients treated with IP chemotherapy versus intravenous (IV) chemotherapy following NACT and interval TRS. Methods In this retrospective review, patients with advanced ovarian cancer were included if they received NACT followed by optimal interval TRS between 1/2004 and 4/2017. Patients were excluded if they had an ECOG PS >1, received >6 cycles of NACT or postoperative chemotherapy, and/or received bevacizumab during primary therapy. Primary outcomes were progression free survival (PFS) and overall survival (OS). Results There were 134 patients included in this study, 37 (28%) received IP and 97 (72%) received IV chemotherapy postoperatively. Patients in the IV group were older (median 66.3 vs 59.7 years, p = 0.0039) though there were no differences in BMI, race, BRCA status, stage, or histology. Median PFS was 3 months longer in the IP group (14.5 versus 11.5 months, p = 0.028) however there was no significant difference in OS. On univariate analysis, increasing number of NACT cycles (HR 1.914, 95% CI 1.024–3.497) and residual disease at completion of TRS (HR 1.541, 95% CI 1.042–2.248) were associated with decreased PFS; IP chemotherapy was associated with increased PFS (HR 0.633, 95% CI 0.414–0.944). These associations remained on multivariate analysis. Toxicity was comparable between the groups. Conclusions IP after NACT and optimal interval TRS was associated with in improved PFS compared to IV chemotherapy without significant differences in toxicity.

Oligonucleotide array and tissue microarray analysis (TMA) by our group has revealed that folate binding protein (FOLR1) is overexpressed in some types of uterine cancer, particularly tumors with serous histology. Since FOLR1 overexpression is a frequent event in some types of endometrial carcinoma, we examined the relationship between FOLR1 overexpression and clinical and pathologic features to determine its prognostic relevance.A tissue microarray (TMA) comprised of primary tumor specimens from 485 patients diagnosed with endometrial adenocarcinoma was used to identify cases characterized by FOLR1 overexpression. A proportional hazards model was used to evaluate the association of FOLR1 overexpression with progression-free survival while accounting for confounding influences.Overexpression of FOLR1 was observed in 50/292 (17%) cases and was seen more often in poorly differentiated cancers (22/90 [24%], p=0.051) and tumors with serous histology (16/32 [50%], p0.001). A shorter progression-free survival was noted in patients with FOLR1 overexpression (log-rank p=0.016) that persisted when the data were limited to patients with stage III/IV disease (log-rank p=0.021) or serous tumors (log-rank p=0.020). Multivariate Cox regression analysis revealed that patients with FOLR1 overexpression had a shorter progression-free survival (H.R. 2.14; 95% CI 1.07-4.28) even when controlling for stage, grade, myometrial invasion and adjuvant chemotherapy.Our data show that FOLR1 overexpression is not only a biomarker associated with endometrial cancer, but it also appears to be a prognostic factor associated with adverse outcome. These findings suggest that FOLR1 may be an appealing target for biological therapies in some types of endometrial carcinomas.

No consensus exists which patients with surgical stage 1 epithelial ovarian should receive postoperative chemotherapy. The purpose of this study was to evaluate the prognostic impact of preoperative CA-125 and to establish a prognostic index to identify patients in different risk categories.Data of 600 surgically staged patients with FIGO stage 1 EOC treated in eleven gynecological cancer centers in Australia, the USA and Europe were analyzed. Eligible patients include those with invasive EOC where a preoperative CA-125 was obtained and standard surgical staging performed. Overall survival (OS) was chosen as study endpoint. Preoperative CA-125 values were compared with other prognostic factors, and univariate and multivariate Cox models were calculated.Two hundred and one patients (33.5%) had preoperative CA-125or =30 U/ml and CA-125 levelsor =30 U/ml were associated with lower grade, sub-stage 1A and mucinous histologic cell type. Patients with elevated CA-125 levels were more likely to receive chemotherapy. OS probability was 95% and 85% for patients with pretreatment CA-125or =30 U/ml and30 U/ml, respectively (p 0.003). Multivariate analysis confirmed preoperative serum CA-12530 U/ml (OR 2.7) and age at diagnosis70 years (OR 2.6) as the only independent predictors for overall survival.Pretreatment of CA-125or =30 U/ml dominates over histologic cell type, sub-stage and grade to identify a subgroup of FIGO stage 1 patients with a genuinely good prognosis with extremely good survival and who could possibly be spared with adjuvant chemotherapy.

Carter J, Johnson P, Saltzman A, Chen D, Carney P, Hartenbach E, Cosin J, Fowler J, Carson L, Twiggs L. Lack of adverse effect on quality of life of up to six cycles of chemotherapy in gynecologic cancer patients. Int JGynecol Cancer 1997; 7: 439–444. The aim of this study was to determine whether the prescription of up to six cycles of chemotherapy adversely affected the quality of life (QOL) of patients with a variety of gynecologic cancers. Over a 29 month period, patients presenting to a single gynecologic oncology clinic and who were prescribed cytotoxic chemotherapy were asked to complete a modified FACT-G quality of life form. Scoring was performed according to the FACT-G scoring guide. Analysis of variance was used to compare the mean transformed scores for each cycle. Sixty patients received a total of 257 cycles of chemotherapy. All patients who were offered the test satisfactorily completed the test. Average age was 56.3 years (range: 16–84). Tumor sites included ovary (N = 29), cervix (N = 15), uterus(N = 12), and vulva (N = 4). The associated histologies included adenocarcinoma (N = 35), squamous (N = 18),sarcoma (N = 6), and germ cell tumor (N = 1). The original stage at diagnosis was stage I (N = 16), stage II (N = 9),stage III (N = 22) and stage IV (N = 13). QOL scores for patients with cervical cancers were significantly inferior to patients with ovarian cancers (P = 0.03), uterine cancers (P = 0.02), and vulvar tumors (P = 0.01). A significant improvement in the physical well-being (PWB) subscale QOL score from cycle 2 to cycle 5 was noted (P = 0.03). Two other subscale QOL scores, emotional well-being(EWB) and functional well-being (FWB), revealed an overall improvement from cycle 1 to cycle 6; however, these results did not reach statistical significance. A general downward trend was noted in the social well-being (SWB) and relationship with doctor (RWD) subscale scores. Moreover, overall quality of life, as represented by the summed individual scores, was not significantly affected over the treatment cycles. Again, while an improvement was noted with progressive cycles, these results did not reach statistical significance. This study confirms that the prescription of up to six cycles of cytotoxic chemotherapy to patients with gynecologic cancers results in an overall improvement in subscale and overall QOL; however, the changes noted did not reach statistical significance.

Patients with gynecologic malignancies may develop stenosis of the large pelvic veins as a result of their disease or its treatment. The percutaneous insertion of a stainless steel vascular stent is a novel approach to the management of an extrinsically compressed vein. The objective of this study was to review the results of treating lower extremity edema secondary to a pelvic venous stenosis through the percutaneous insertion of a stainless steel vascular stent. A retrospective review was performed on gynecologic oncology patients who presented with an edematous lower extremity and underwent an evaluation to diagnose proximal venous stenosis. The evaluation included sonography, venography, and balloon angioplasty prior to the percutaneous insertion of a stainless steel vascular stent. If a venous thrombosis was documented, thrombolysis with urokinase was performed prior to evaluation for venous stenosis. Records were reviewed for the etiology of the venous stenosis, the location and type of stent inserted, and the ability of the stent to maintain patency and provide symptomatic relief. Patency was evaluated at 1-week and then at 1-, 3-, and 6-month intervals. The probability of vascular stent patency was calculated using life table analysis. Ten patients with cervical (n = 4), corpus (n = 3), ovarian (n = 1), vulvar (n = 1), and vaginal (n = 1) cancer had one or more vascular stents inserted for the treatment of a stenosed pelvic vein. The etiologies of venous stenosis were radiation fibrosis and surgery (n = 5), postoperative fibrosis (n = 3), and metastatic tumor (n = 2). The stented vessels were the left common (n = 5) or left external (n = 4) iliac veins, the right common (n = 1) or right external (n = 3) iliac veins, and the right common femoral vein (n = 1). The median follow-up was 21 months. All patients had subjective resolution of their edematous extremity while the stents were patent. The interval probability of patency of stented veins was greater than 85% at each evaluation interval. Patency was 100% for patients beyond 6 months of follow-up. There were no major complications. The percutaneous intravascular insertion of a stainless steel stent was safe and subjectively effective in the management of venous stenosis associated with a gynecologic cancer. A prospective trial with objective endpoints may be warranted.

The purpose of this study was to review the clinical outcomes and cost of administration of a prophylactic antibiotic compared to G-CSF for the prevention of neutropenic morbidity associated with taxol. The study group was composed of 62 patients with ovarian cancer who received a 24-h infusion of a taxol-based regimen at doses less than or equal to 175 mg/m2 between June 1992 and April 1994. The records were retrospectively reviewed and the patients were grouped and analyzed according to the management of their myelosuppression. Group I patients (n = 29) were observed until their absolute neutrophil count (ANC) was less than 500/microliters and then were placed on ciprofloxacin 500 mg orally twice a day until their ANC was 1,000/microliters. Group II patients (n = 15) received G-CSF from Day 2 until the ANC was greater than 10,000/microliters beginning with their first cycle. Group III patients (n = 18) received their taxol regimen without either ciprofloxacin or G-CSF. Two hundred eighty-two taxol-based chemotherapy cycles were administered to these 62 patients. There was no statistically significant difference between the groups concerning disease status as measured by age, stage, performance status, dose intensity, or number of previous regimens. There were two episodes of febrile neutropenia in Group I and three episodes in Group II. Group III had 15 episodes of febrile neutropenia. The estimated cost of the different prophylactic regimens was $5,215.00 for Group I versus $104,000.00 for G-CSF in Group II. Within the three groups, there were 27 patients with an episode of febrile neutropenia (n = 20) or prolonged myelosuppression (n = 7) that were followed for an additional 104 taxol cycles. Twenty-four of these patients received G-CSF prophylaxis with intermittent ciprofloxacin and three received only ciprofloxacin. There were eight more episodes of febrile neutropenia in the patients receiving G-CSF. There were no additional febrile episodes on cycles prophylaxed with ciprofloxacin. There was no septic mortality. For patients receiving a 24 h infusion of taxol at doses less than 175 mg/m2, ciprofloxacin given through the ANC nadir may be effective in preventing febrile morbidity. A prospective randomized trial is underway to evaluate this approach.

The aim of this study was to evaluate the blood flow characteristics of the uterine artery and intratumoral vessels in patients with GTD. Twelve patients with GTD were evaluated with TVS, and 11 also had CFD sonography performed. Spectral analysis of both uterine artery and samples intratumoral and intramyometrial vessels revealed systolic frequencies and PI that were significantly higher in the uterine artery than in sampled intratumoral vessels (P < 0.05). Uterine artery PI correlated significantly with age (P = 0.043), uterine size (P = 0.003), and beta-HCG titer (P = 0.03). Intratumoral PI correlated significantly with uterine size (P = 0.05). Intratumoral PI did not correlate with patient age, the shape or orientation of the uterus, presence or absence of subendometrial halo, endometrial thickness or echogenicity, or impression of myometrial invasion. Regression analysis of beta-HCG titers on uterine artery and intratumoral PI revealed a linear association. TVS and color flow Doppler sonography are useful in the assessment of patients with GTD. The PI is strongly associated with prognosis and correlates with beta-HCG titers.

Patients with unresectable locally recurrent gynecologic malignancies pose a difficult therapeutic challenge. Conventional therapies are frequently unsuccessful and offer only marginal palliation. In this study, interstitial 192iridium-needle implants and concomitant infusional 5-fluorouracil (5FU) and cisplatin (CDDP) or carboplatin (CBDCA) chemotherapy were used to treat 14 women with recurrent pelvic tumors. Malignancies of the cervix, endometrium ovary, tube and vulva are represented; all patients were heavily pretreated. Twenty interstitial implants were performed in these 14 patients. Needle distributions and doses were individualized to accommodate the recurrent tumor volumes. Tumor responses were seen in 12 patients (six complete and six partial responses). Four women remain clinically free of disease and four are alive with disease at 18–34 months of follow-up. There were no severe acute toxicities, however, four patients have subsequently developed fistulae associated with tumor progression. Although longer follow-up is required, the high response rate, wide applicability and acceptable toxicity observed in this heavily pretreated patient population warrant further study of combined interstitial radiation and chemotherapy.

Background. Increased rates of bowel perforation in patients with recurrent epithelial ovarian cancer (EOC) treated with bevacizumab have been reported, but the risk factors for this association are uncertain. We sought to identify factors associated with bowel perforation and fistula formation in recurrent EOC patients treated with bevacizumab. Methods. A chart review of all patients treated with bevacizumab for recurrent EOC at a single institution was performed. Pertinent patient characteristics and treatment information were collected. Univariate logistic regression was performed to analyze multiple variables. Results. One hundred twelve patients who were treated with 160 different bevacizumab regimens were identified. The median age was 60 years (range, 29–78 years). Patients had received a median of 4 prior chemotherapy regimens (range, 1–10). The median number of cycles was 4 (range, 0.5–31). Ten patients (9%) were diagnosed with bowel perforations, and another 2 patients (1.8%) were diagnosed with fistulas. The 30-day mortality following perforation was 50%, with 30% of patients dying within 1 week. Patients with rectovaginal nodularity were more likely to develop a bowel perforation or fistula than those who did not have this finding, OR=3.64 (95% CI=1.1 to 12.1, p =0.04). None of the other variables were significantly associated with bowel perforations or fistula formation. Conclusions. Rectovaginal nodularity is associated with an increased risk of bowel perforation or fistula formation for patients with recurrent EOC treated with bevacizumab. Careful consideration should be given prior to initiating bevacizumab treatment in EOC patients with rectovaginal nodularity since the mortality rate with bevacizumab associated bowel perforations is 50%.

The objective is to determine the relationship between obesity and defects in DNA mismatch repair (MMR) in women with endometrial cancer and to establish whether our previous finding of a higher rate of previous malignancy in thinner women with endometrial cancer is related to these factors. Specimens from 109 patients with primary uterine cancer were used to create a tissue microarray, which was stained with antibodies against MMR genes MLH1, MSH2, MSH6, and PMS2. Genotyping of normal and tumor tissues for microsatellite instability (MSI) was performed. Patients were stratified by body mass index (BMI) and correlated with a history of previous malignancy and defects in MMR. The average BMI of the overall population was 33 kg/m(2). Defective MMR was seen in 22% of tumors. The mean BMI in patients with tumors with MSI was 30.5, compared with 33.8 in microsatellite stable (MSS) tumors (P= 0.06); MSS tumors were more commonly seen in patients with a BMI more than 40 (25% vs 5% in patients with tumors with MSI, P= 0.07). Prior to their diagnosis of endometrial cancer, 16/109 (15%) patients reported having a prior malignancy, 11 (69%) had breast cancer, and 1 had colorectal cancer. Patients with tumors with MSI had previous cancer in 17% of cases, compared with 14% of patients with MSS tumors (P= 0.75). Our previous finding of an increased rate of prior malignancy in thinner patients with endometrial cancer does not appear to be due to alterations in MMR, and hereditary nonpolyposis colorectal cancer-associated cancers are rarely the prior malignancy.

Objectives: To examine outcomes in stage III endometrial cancer with respect to treatment with chemotherapy +/− radiation and the difference between lowand high-risk histology. Methods: We conducted a single-institution retrospective cohort study. All patients with stage III epithelial endometrial cancer were reviewed for clinicopathologic characteristics, cancer treatment, and outcomes. Patients with endometrioid and mucinous histology were grouped as low-risk and patients with a serous or clear cell component as high-risk histology. Results: A total of 80 patients with stage III endometrial cancer were included (60 with endometrioid and 20 with serous/clear cell). The median age was 58 and 62 years and body mass index was 32 and 30, respectively, for endometrioid and serous/clear cell. Ninety-six percent of patients had complete surgical staging. Overall recurrence was 26% and was lower in the endometrioid compared to serous/clear cell histology (15% vs. 60%, P b 0.0001). Of the 53 patients with endometrioid adenocarcinomawho received adjuvant therapy, 17% of those with chemotherapy only, 12% of thosewith chemotherapy/PVRT, and 0/ 4with chemotherapy/brachytherapy recurred. However, of the patients with high-risk histology, 56% recurred after chemotherapy only compared with 78% after chemotherapy/PVRT (P= 0.63). Five-year progression-free survival (PFS) for endometrioid histology was 83% whereas the median PFS for serous/clear cell was 22 months (P b 0.001). Five-year PFS for endometrioid histology was 87% with chemotherapy/PVRT vs. 83% with chemotherapy only (P= 0.63); 5year overall survivalwas 86% vs. 83% (P= 0.44).Median PFS for serous/ clear cell was 32 months for chemotherapy only and 13 months with chemotherapy/PVRT (P= 0.47). Median overall survival was 33 and 37 months, respectively (P= 0.91). For endometrioid histology, 71% of recurrences were extrapelvic, with one vaginal recurrence in chemotherapy/PVRT and one pelvic in chemotherapy only. For serous/clear cell histology, 83% of recurrences were distant, with one vaginal recurrence in each treatment group. Conclusions: Outcomes for patients with stage III endometrioid endometrial cancer are very favorable (15% recurrence) and similar for patients treated with chemotherapy +/− radiation. As expected, outcomes for serous and clear cell uterine cancers are poor and not significantly different for patients treated with chemotherapy +/− radiation. This provides further evidence that rare tumors such as serous and clear cell uterine cancers should be studied separately and that there is a desperate need for novel therapies in this group.

number 1: The futility of transvaginal ultrasound in type II endometrial cancer C. Billingsley, K. Kenne, C. Cansino, D. O'Malley, D. Cohn, J. Fowler, E. Eisenhauer, L. Copeland, F. Backes, R. Salani, The Ohio State University, Columbus, OH, USA, University of California Davis, Sacramento, CA, USA, University of Cincinnati, UC Health Medical Arts Building, Cincinnati, OH, USA Objectives: To determine the utility of transvaginal ultrasound (TVUS) in women with type II endometrial cancer, including serous, clear cell, and high-grade carcinomas. Methods: A retrospective review was conducted in women with pathology proven type II endometrial cancer that underwent preoperative TVUS. The following data were obtained: endometrial stripe (EMS) measurement, presence of intracavitary fluid or lesion, myometrial and/or adnexal masses, uterine size and volume. Pathology reports were reviewed and clinicopathologic factors were abstracted. Descriptive analyses were performed to assess demographic and comparative data. Results: Sixty-three women comprised the study cohort and the median age was 65 years. The most commonly reported symptom was postmenopausal bleeding in 51 patients (80.9%). The EMS was reported as thin (b5 mm) or indistinct in 18 patients (28.6%). Approximately 60% of patients were noted to have one or more ultrasound abnormalities: intracavitary lesion (18, 28.6%), intracavitary fluid (8, 12.7%), myometrial lesion (19, 30.2%), and adnexal mass (8, 12.7%). Poorly differentiated endometrioid cancer (33; 52.4%) represented the predominant histology. Of the 28% of women with a thin/indistinct EMS, seven women did not have an ultrasound abnormality, representing 11% of women with type II endometrial cancer who had no abnormal ultrasound findings whatsoever. Conclusions: Women with type II endometrial cancer were found to have a thin/indistinct EMS on TVUS in approximately 25% of cases. Furthermore, lack of any ultrasound abnormality, including a thickened EMS, were noted in 11% of patients. The use of TVUS, which has been of diagnostic and triaging value for women with type I cancer, is of limited utility in type II endometrial cancer. Therefore, endometrial sampling should be included in the evaluation of all women with postmenopausal bleeding, regardless of EMS thickness. doi:10.1016/j.ygyno.2014.04.019 Abstract number 2: Durationof intra-chemotherapy anemia is associatedwith prognosis and survival in epithelial ovarian cancer R. Brightwell, K. Eng, S. Lele, K. Odunsi, Roswell Park Cancer Institute,number 2: Durationof intra-chemotherapy anemia is associatedwith prognosis and survival in epithelial ovarian cancer R. Brightwell, K. Eng, S. Lele, K. Odunsi, Roswell Park Cancer Institute

Objectives: The aim of this study was to determine the rate of burnout among gynecologic oncologists and evaluate factors associated with burnout in this population. Methods: This study used a cross-sectional design. Current members of the SGO were sent an anonymous email survey that included 76 items measuring burnout, psychosocial distress, career satisfaction, and quality of life (QOL). Results: Of the 1086 members invited, 436 (40.1%) responded, and 369 of those (84.6%) completed the survey. Median age was 48 years, 66% had been practicing N10 years, 58.8%worked an average of N60 h/week, the median number of operating room hours was 15/week, nights on call was 3/week, 77% managed chemotherapy, and 59% practiced in an academic setting. More than 32% of physicians scored above clinical cutoffs for emotional exhaustion (EE) and/or depersonalization (DP), suggesting high rates of burnout, with 30% and 10% scoring in the clinical range on EE and DP, respectively. In addition, 33% screened positive for depression (PRIME MD/PHQ2), 13% endorsed a history of suicidal ideation, 15% screened positive for alcohol abuse (CAGE), and 34% reported impaired QOL (MOS SF-12). Nonetheless, 70% reported high levels of personal accomplishment, and results suggested most were satisfied with their careers, with 89% indicating that they would enter medicine again and 61% stating they would encourage their child to pursue a career in medicine. Analyses indicated that those in the high burnout category were significantly less likely to report that they would becomephysicians again (P= 0.002) and less likely to encourage a child to enter medicine (P b .001). Burnout was also significantly associated with a positive screen for depression (P b 0.001) or alcohol abuse (P=0.02), history of suicidal ideation (P b 0.001), and impaired QOL (P b 0.001). Interestingly, personal accomplishment scores were not significantly correlatedwith career satisfaction (P= 0.225), depression (P N 0.99), alcohol abuse (P N 0.99), or suicidal ideation (P N 0.99). Conclusions: Burnout is a significant problem associated with psychosocial distress and lower levels of career satisfaction. Interventions targeted at improving QOL and treatment of depression or alcohol abusemay have an impact on burnout. However, significant barriers may exist because 44.5% of respondents reported they would be reluctant to seek medical care for depression, substance use, or other mental health concerns.