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PDF file - 81K, Supplementary Table 2 Primers and probe sets utilized in this study were designed by the Primer Express 1.5 software and synthesized by Sigma-Aldrich. These primers and probes were utilized for quantitative PCR in ancillary biologic studies, and the data

PDF file - 106K, Patients were then assigned into one of three Ad5.SSTR/TK.RGD dose cohorts ranging from 1 x 109 vp/d to 1 x 1012 vp/d (6 x 107 pfu/d to 6 x 1010 pfu/d). This dose administration strategy has been validated in our preclinical studies; assigned Ad5.SSTR/TK

Purpose: Ad5.SSTR/TK.RGD is an infectivity-enhanced adenovirus expressing a therapeutic thymidine kinase suicide gene and a somatostatin receptor (SSTR) that allows for noninvasive gene transfer imaging. The purpose of this study was to identify the maximum tolerated dose (MTD), toxicities, clinical efficacy, and biologic effects of Ad5.SSTR/TK.RGD in patients with recurrent gynecologic cancer.Experimental Design: Eligible patients were treated intraperitoneally for 3 days with 1 × 109 to 1 × 1012 vp/dose of Ad5.SSTR/TK.RGD followed by intravenous ganciclovir for 14 days. Toxicity and clinical efficacy were assessed using Common Toxicity Criteria (CTC) Adverse Events grading and Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Imaging using In-111 pentetreotide was obtained before and after treatment. Tissue samples were obtained to evaluate for gene transfer, generation of wild-type virus, viral shedding, and antibody response.Results: Twelve patients were treated in three cohorts. The most common vector-related clinical toxicities were grade I/II constitutional or pain symptoms, experienced most often in patients treated at the highest dose. MTD was not identified. Five patients showed stable disease; all others experienced progressive disease. One patient with stable disease experienced complete resolution of disease and normalization of CA125 on further follow-up. Imaging detected increased In-111 pentetreotide retention in patients treated at the highest dose. Ancillary studies showed presence of Ad5.SSTR/TK.RGD virus and HSV1-tk expression in ascites samples collected at various time points in most patients treated within the higher dose cohorts.Conclusions: This study shows the safety, potential efficacy, and possible gene transfer imaging capacity of Ad5.SSTR/TK.RGD in patients with recurrent gynecologic cancer. Further development of this novel gene therapeutic appears to be warranted. Clin Cancer Res; 18(12); 3440–51. ©2012 AACR.

PDF file - 51K, Patients were then assigned into one of three Ad5.SSTR/TK.RGD dose cohorts ranging from 1 x 109 vp/d to 1 x 1012 vp/d (6 x 107 pfu/d to 6 x 1010 pfu/d). This dose administration strategy has been validated in our preclinical studies; assigned Ad5.SSTR/TK

IntroductionDespite improvement in progression-free survival with poly (ADP-ribose) polymerase inhibitors (PARPi) as maintenance therapy for ovarian cancer, many patients will eventually progress on therapy. Oligoprogression is uniquely suited to considerations of local consolidation therapy in this setting, but not commonly used in ovarian cancer. In this study we evaluated the proportion of patients on PARPi maintenance who developed limited sites of disease, the location of progression, and their natural history.MethodsFrom January 2006 to December 2020, natural language processing software (DEEP6AI) was used to identify 58 patients with ovarian cancer treated with PARPi maintenance after complete or partial response after surgery and platinum-based chemotherapy at our institution. Patients were assessed for presence and location of recurrence based on radiologic findings.ResultsThe median patient age was 65 (IQR 57–71) years. Patients had a median of two lines of chemotherapy prior to starting PARPi. With a median follow-up of 48 (range 12–149) months, 32 (55%) patients had a recurrence on maintenance olaparib and 11 (34%) patients developed oligoprogression (≤3 sites). For the 11 patients with oligoprogression, three patients developed recurrence in one site, five in two sites, and three in three sites. The sites of oligoprogression were pelvic/periaortic nodal (27%), peritoneal (27%), liver (27%), lung/mediastinal (14%), and brain (5%). The median progression-free survival for the entire cohort was 6.0 months (95% CI 4.2 to 7.8); median overall survival was not met. There were no significant differences in overall survival (p=0.81) or progression-free survival (p=0.95) between patients with and without oligoprogression.ConclusionsOne-third of patients on PARPi maintenance experienced oligoprogression defined as limited to ≤3 sites. These patients may benefit from local consolidation therapy. A larger dataset is needed to validate these findings to assess if trials investigating local therapy for these patients is of value.

OBJECTIVES: Poly(ADP-ribose) polymerase (PARP) inhibitors are expensive and their use is expanding. We aimed to evaluate cost sharing patterns between patients, payors, and financial assistance programs. METHODS: We identified ovarian cancer patients prescribed a PARP inhibitor from 5/2015–9/2019 using our pharmacy database. Cost information was collected for patients who filled their prescription at our specialty pharmacy. We calculated descriptive statistics for monthly PARP inhibitor costs for patients, payors, and financial assistance programs. We used Wilcoxon rank sum tests to evaluate monthly costs based on insurance characteristics. RESULTS: Seventy-six patients filled 94 different PARP inhibitor prescriptions with 42 (45%) prescriptions obtained using any type of financial assistance program. We analyzed 232 prescription months for the 41 prescriptions with available cost data. This included 18 (44%) prescriptions for rucaparib, 18 (44%) for niraparib, and 5 (12%) for olaparib. The total monthly drug cost was average $12,422 and median $13,700. The monthly out-of-pocket (OOP) cost for patients was average $46 and median $0 (IQR $0–4). Payors had the highest monthly costs with average $12,019 and median $13,662 (IQR $9,914–14,709). Financial assistance programs contributed average $358 and median $0 per month (IQR $0–150). Patients with public (p

Objectives Trainee well-being is a core component of ACGME program requirements and the SGO has recognized the high incidence of burnout among gynecologic oncologists and its negative impact. To foster a culture of wellness throughout the SGO community we sought to engage current fellows along with fellowship directors in a structured didactic program designed to teach wellness. We evaluated the feasibility of and preliminary responses to a pilot curriculum designed to teach skills that promote wellness and prevent burnout. Methods The SGO Wellness Taskforce developed a curriculum with topics based on established evidence as well as specialty specific stressors such as end of life discussions. Faculty leaders from 15 pilot-sites attended a full-day training course and then taught four modules over four months. Interactive modules engaged fellows through reflective writing, guided discussion, and multimedia presentations. Fellows completed the Perceived Stress Scale pre- and post-implementation and provided feedback regarding attitudes toward wellness and the individual modules. Faculty curriculum leaders completed surveys regarding their attitudes toward the curriculum as well as their trainees' reactions. Results Among 73 participating gynecologic oncology fellows, 95% (69/73) and 52/73 (71%) completed the pre-and post-surveys, respectively. Only 34/73 (49%) respondents reported that there was wellness programming at their institution prior to the initiation of the SGO curriculum. At institutions where such programming was available, 35% (12/34) reported not utilizing them. Fifty-five (80%) fellows had PSS scores greater than 12 compared to 39 (75%) post-intervention. After the curriculum, the percentage of fellows comfortable discussing wellness topics increased from 63 to 74%. Prior to the curriculum, 75% felt they could identify symptoms of burnout or psychosocial distress. This increased to 90% post-intervention. The modules were well received by fellows, and the time spent addressing wellness was widely appreciated. Conclusions A structured curriculum to promote wellness among gynecologic oncology fellows is feasible and was associated with observed decreased reported stress among fellows at participating programs. This curriculum addresses ACGME requirements regarding trainee well-being, and showed potential for more programmatic, nationwide implementation. Fellowship culture change was not directly measured, but may have been one of the most significant positive outcomes of the wellness program. Further longitudinal studies will be necessary to understand the natural course of fellow burnout and the impact of structured wellness programming.

e17526 Background: Adenocarcinoma and adenosquamous carcinoma of the cervix are subtypes of HPV related cervical cancer. As virally mediated tumors, they have become an obvious choice for immunotherapy treatment approach. Currently, there is little information about the presence of immunological tumor markers among patients with endocervical adenocarcinomas. We hypothesized cervical adenocarcinomas highly express immunotherapy markers. Here we characterize the protein status of immunotherapy markers in a large single institution dataset. Methods: An IRB approved retrospective review of cervical adenocarcinoma and adenosquamous carcinoma was performed. We gathered original slides for each patient and performed immunohistochemistry (IHC) for tumor markers CD8, PDL1, TIM3 and LAG3. Demographic and pathologic data was captured. Patients were categorized by positivity percentage for each marker. Descriptive statistics and univariate analysis were used. Results: A total of 97 patients met criteria for the study and slides were available for staining in 68 patients. Demographic data showed a median age of 42 years old with majority of patients identifying as White at 66%, followed by Hispanic (13%), Asian (10%), other (7%) and Black (1%). Of the entire cohort, 75% were adenocarcinoma, 25% were adenosquamous carcinoma. Among those with recorded status, 82% were HPV positive, 14% had metastasis, and 13% had recurrence. On univariate analysis, adenocarcinoma was significantly more common in patients who were LAG3 < 1% or PDL < 1% (p = 0.002, p = 0.007). Patients who were LAG3 < 1% or PDL < 1% were also less likely to have Grade 1 tumors (p = 0.006, 0.03). When analyzing by respective immune marker percentage group there were no statistically significant differences in LVSI, depth of invasion, stage, or recurrence rate. By IHC, 68% were PDL1 > 1% positive, 63% were LAG3 > 1% positive, 100% were TIM3 > 1% positive, 100% were CD8 > 1% positive. Seven of the 68 patients had a recurrence. Of those patients with recurrence, one was treated with immunotherapy. Conclusions: A large proportion of cervical adenocarcinomas displayed immunotherapy targets by IHC suggesting that combined immunotherapy agents may be useful in this population. Further study is needed to assess whether IHC is predictive of outcome or response.[Table: see text]

Objective To evaluate the utility of a society-based robotic surgery training program for fellows in gynecologic oncology. Methods All participants underwent a 2-day robotic surgery training course between 2015-2017. The course included interactive didactic sessions with video, dry labs, and robotic cadaver labs. The labs encompassed a wide range of subject matter including troubleshooting, instrument variation, radical hysterectomies, and lymph node dissections. Participants completed a pre- and post-course survey using a 5-point Likert scale ranging from "not confident" to "extremely confident" on various measures. Statistical analysis was performed using SPSS Statistics v. 24. Results The response rate was high with 86% of the 70 participants completing the survey. Sixteen (26.7%) of these individuals were attending physicians and 44 (73.3%) were fellows. In general, there was a significant increase in confidence in more complex procedures and concepts such as radical hysterectomy (p=0.01), lymph node dissection (p=0.01), troubleshooting (p=0.001), and managing complications (p=0.004). Faculty comfort and practice patterns were cited as the primary reason (58.9%) for limitations during robotic procedures followed secondarily by surgical resources (34.0%). Conclusion In both gynecologic oncology fellows and attendings, this educational theory-based curriculum significantly improved confidence in the majority of procedures and concepts taught, emphasizing the value of hands-on skill labs.

Objective Common robotic training curricula in the US entail completion of an online module followed by lab training with standardized exercises, such as manipulating needles with robotic needle drivers. Assessments are generally limited to elapsed time and subjective proficiency. We sought to test the feasibility of a simulation-based robotic hysterectomy curriculum to collect objective measurements of trainee progress, map the trainee learning curve and provide a system for trainee-specific evaluation. Methods An observational cohort study of a single institutions' residency members participating in a procedural hysterectomy simulation performed every 4 months. Each simulation episode had one-on-one teaching. The robotic platform was used to measure all movements within cartesian coordinates, the number of clutches, instrument collisions, time to complete the simulated hysterectomy, and unintended injuries during the procedure. Results Voluntary participation was high. Objective metrics were successfully recorded at each session and improved nearly universally. More senior residents demonstrated superior capabilities compared to junior residents as expected. The majority of residents (29/31) were able to complete an entire simulated hysterectomy in the allotted 30-minute training session period by the end of the year. Conclusions This program establishes learning curves based on objective data points using a risk-free simulation platform. The curves can then be used to evaluate trainee skill level and tailor teaching to specific objective competencies. The pilot curriculum can be tailored to the unique needs of each surgical discipline's residency training.

Study Objective Determine near-optimal dose, safety, and efficacy of nerindocianine in pelvic ureter detection with near-infrared fluorescence imaging in women undergoing minimally invasive pelvic surgery with 3 Food and Drug Administration–cleared imaging systems. Design Open label, phase 1/2a study. Setting University of Alabama at Birmingham. Patients Forty-one female subjects undergoing minimally invasive gynecologic surgery. Interventions Subjects received a single dose of nerindocianine sodium, starting at 0.06-mg/kg body weight and increased/decreased until the near-optimal dose was determined (part A). Examine the degree of concordance between endoscopic and robotic devices (part B). Measurements and Main Results In part A, composite scores were collected every 10 minutes for 30 minutes and then every 15 minutes through 90 minutes using a scale measuring the anatomy/laterality of ureter visualization. In part B (paired imaging system efficacy), 2 cohorts of 8 subjects each received the near-optimal dose. Composite scores for visualization of the ureter were collected at 10 and 30 minutes postinfusion with the Firefly Imaging System and either the PINPOINT or 1588 AIM endoscope. Composite scores were compared to examine the degree of concordance between devices. Part A comprised 25 total subjects enrolled in dosing groups 1, 2, and 3 (0.06-, 0.12-, and 0.045-mg/kg, respectively). Median time to first ureter visualization was 10 minutes (all groups). The nerindocianine 0.06-mg/kg and 0.12-mg/kg groups had longer length of time of visualization than the 0.045-mg/kg group, resulting in the selection of 0.06 mg/kg as the near-optimal dose. Part B enrolled 16 total subjects in 2 groups dosed at 0.06 mg/kg. Efficacy analysis showed no statistically significant difference in composite scores with Firefly versus PINPOINT or 1588 AIM. Conclusion Nerindocianine was well tolerated with visualization of the ureter demonstrated in 88.9% of the subjects through 90 minutes postdosing. No meaningful visualization differences were observed among the Food and Drug Administration–cleared surgical imaging systems used.

Background The glycolytic nature of cancer cells presents a potential treatment target that may be addressed by a ketogenic diet (KD). Objective We hypothesized that a KD would improve body composition and lower serum insulin and insulin-like growth factor-I (IGF-I) in women with ovarian or endometrial cancer. Methods In this randomized controlled trial, women with ovarian or endometrial cancer [age: ≥19 y; body mass index (kg/m2): ≥18.5] were randomly assigned to a KD (70:25:5 energy from fat, protein, and carbohydrate) or the American Cancer Society diet (ACS; high-fiber, low-fat). Body composition (DXA) and fasting serum insulin, IGF-I, and β-hydroxybutyrate were obtained at baseline and at 12 wk; urinary ketones were also measured throughout the intervention. We assessed differences between the diets with ANCOVA and independent t tests. We used correlation analyses to estimate associations between changes in serum analytes and body composition. Results After 12 wk, the KD (compared with ACS) group had lower adjusted total (35.3 compared with 38.0 kg, P

Study Objective To confirm the safety and feasibility outcomes of robotic radical parametrectomy and pelvic lymphadenectomy and compare the clinicopathological features of women requiring adjuvant treatment with the historical literature. Design Retrospective cohort study and review of literature (Canadian Task Force classification II-2). Setting Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill. Patients All patients who underwent robotic radical parametrectomy with upper vaginectomy (RRPV), and pelvic lymphadenectomy for occult cervical cancer discovered after an extrafascial hysterectomy at our institution between January 2007 and December 2015. Interventions RRPV and pelvic lymphadenectomy for occult cervical cancer discovered after an extrafascial hysterectomy. We also performed a literature review of the literature on radical parametrectomy after occult cervical carcinoma. Measurements and Main Results Seventeen patients with invasive carcinoma of the cervix discovered after extrafascial hysterectomy underwent RRPV with bilateral pelvic lymphadenectomy. There were 2 intraoperative complications, including 1 bowel injury and 1 bladder injury. One patient required a blood transfusion of 2 units. Three patients underwent adjuvant treatment with chemoradiation with radiation-sensitizing cisplatin. One of these patients had residual carcinoma on the upper vagina, 1 patient had positive parametria and pelvic nodes, and 1 patient had positive pelvic lymph nodes. No patients experienced recurrence, and 1 patient died from unknown causes at 59.4 months after surgery. We analyzed 15 studies reported in the literature and found 238 women who underwent radical parametrectomy; however, no specific preoperative pathological features predicted outcomes, the need for adjuvant treatment, or parametrial involvement. Conclusion RRPV is a feasible and safe treatment option. As reflected in the literature, RRPV can help avoid empiric adjuvant chemoradiation; however, no pathological features predict the need for adjuvant treatment after surgery.

Objectives To evaluate progression-free survival (PFS) and overall survival (OS) outcomes in women diagnosed with uterine papillary serous carcinoma (UPSC) who have had (UPSCBR+) or have not had (UPSCBR−) an antecedent history of breast cancer and to correlate their outcomes to prior tamoxifen exposure. Methods Data were collected for women diagnosed with UPSC at two academic institutions between January 1997 and July 2012. Patient demographics, tumor histology, stage, and treatments were recorded. Patients were divided into two groups: those with and without a personal history of breast cancer. Within the UPSCBR+ cohort, we identified those with a history of tamoxifen use. Cox regression modeling was used to explore associations between selected covariates of interest and the time-to-event outcomes of PFS and OS. Results Of 323 patients with UPSC, 46 (14%) were UPSCBR+. Of these, 15 (33%) had a history of tamoxifen use. UPSCBR+ patients were older than UPSCBR− (median years, 72 vs. 68, p=0.004). UPSCBR+ women showed no significant difference in PFS or OS compared to UPSCBR− (p=0.64 and p=0.73 respectively), even after controlling for age (p=0.15 and p=0.48 respectively). Within the UPSCBR+ cohort, there was no difference in PFS or OS with or without tamoxifen exposure (p=0.98 and p=0.94 respectively). Conclusions There was no difference in PFS or OS between the UPSCBR+ and UPSCBR− cohorts. We did not demonstrate significant OS or PFS differences in women who took tamoxifen prior to their endometrial cancer diagnosis. These findings have implications for counseling, and should be encouraging to women who are facing their second cancer diagnosis.

IntroductionWhile traditional teaching has been to wait 6 weeks between cervical excisional procedure and hysterectomy, studies have produced conflicting evidence, with data supporting a delay of anywhere between 48 hours to 6 weeks depending on surgical approach. Our study sought to evaluate if the time between cervical excisional procedure and robotic hysterectomy impacts peri-operative complication rates.MethodsA retrospective cohort of patients who underwent robotic hysterectomy from August 2006 to December 2013 for cervical dysplasia or International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA1–B1 cervical cancer at a single tertiary care center was performed. Patients were categorized into three groups: early surgical intervention (ResultsA total of 160 patients were identified. Of these, 32 (20.0%) had early surgical intervention, 52 (32.5%) had delayed surgical intervention, and 76 (47.5%) had no excisional procedure. There was no difference between groups in complication rates, including average estimated blood loss (82 vs 55 vs 71 mL; p=0.07), urologic injury (0% in all groups; p=1.0), anemia (3% vs 0% vs 1%; p=0.47), infection (0% vs 2% vs 3%; p=1.0), vaginal cuff separation (0% in all groups; p=1.0), or venous thromboembolism (0% vs 0% vs 1%; p=1.0). Additionally, there were no differences in length of stay (p=0.18) or 30-day readmission rates (p=1.0). Finally, there were no significant differences in peri-operative outcomes when stratified by radical versus simple hysterectomy.DiscussionWaiting 6 weeks between cervical excisional procedure and robotic hysterectomy does not impact peri-operative complication rates. This suggests that the time from excisional procedure should not factor into surgical planning for those who undergo robotic hysterectomy.

Objective To examine the effect of BMI on pathologic findings, cancer recurrence and survival in cervical cancer patients. Methods A retrospective cohort study of cervical cancer patients treated from July 2000 to March 2013 was performed. BMI was calculated, and patients were classified by BMI. The primary outcome was overall survival (OS). Secondary outcomes included stage, histopathology, disease-specific survival (DSS) and recurrence free survival (RFS). Kaplan–Meier survival curves were generated and compared using Cox proportional hazard ratios. Results Of 632 eligible patients, 24 (4%) were underweight, 191 (30%) were normal weight, 417 (66%) were overweight/obese. There was no difference in age (p = 0.91), stage at presentation (p = 0.91), grade (p = 0.46), or histology (p = 0.76) between weight categories. There were fewer White patients in the underweight (54%) and overweight/obese (58%) groups compared to the normal weight (71%) group (p = 0.04). After controlling for prognostic factors, underweight and overweight/obese patients had worse median RFS than normal weight patients (7.6 v 25.0 months, p = 0.01 and 20.3 v 25.0 months, p = 0.03). Underweight patients also had worse OS (10.4 v 28.4 months, p = 0.031) and DSS (13.8 v 28.4 months, p = 0.04) compared to normal weight patients. Overweight/obese patients had worse OS than normal weight patients (22.2 v 28.4 months, p = 0.03) and a trend toward worse DSS (21.9 v 28.4 months, p = 0.09). Conclusion Both extremes of weight (underweight and overweight/obesity) were associated with worse survival in patients with cervical cancer. Optimizing weight in cervical cancer patients may improve outcomes in these patients.

The Asian Society of Gynecologic Oncology International Workshop 2018 on gynecologic oncology was held in the Ajou University Hospital, Suwon, Korea on the 24th to 25th August 2018. The workshop was an opportunity for Asian doctors to discuss the latest findings of gynecologic cancer, including cervical, ovarian, and endometrial cancers, as well as the future of fertility-sparing treatments, minimally invasive/radical/debulking surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. Clinical guidelines and position statement of Asian countries were presented by experts. Asian clinical trials for gynecologic cancers were reviewed and experts emphasized the point that original Asian study is beneficial for Asian patients. In Junior session, young gynecologic oncologists presented their latest research on gynecologic cancers.

OBJECTIVE. To compare the perioperative morbidity and survival between abdominal radical hysterectomy (ARH) and robotic radical hysterectomy (RRH). METHODS. A retrospective cohort of patients undergoing radical hysterectomy for cervical cancer from 2010 to 2016 was identified. Patients with stage IB1 cervical cancer were included and were grouped by ARH vs. RRH. Tumor characteristics, perioperative complications, recurrence rate, progression-free survival (PFS), and overall survival (OS) were compared between groups. RESULTS. 105 patients were identified; 56 underwent ARH and 49 underwent RRH. Those who had ARH were more likely to have lesions that were ≥2 cm (62% vs. 39%, p = 0.02) and that were higher grade (p = 0.048). Other tumor characteristics were similar between groups. There was no difference in perioperative complication rates between groups. Additionally, there were no differences in recurrence risk (RR) (14% vs. 24%, p = 0.22), progression-free survival (PFS) (p = 0.28), or overall survival (OS) (p = 0.16). However, in those with tumors ≥2 cm there was a higher risk of recurrence in the overall cohort (30% vs. 8%, p = 0.006), and a shorter PFS in the RRH group (HR 0.31, p = 0.04). On multivariate analysis patients that underwent ARH or had tumors < 2 cm had a lower likelihood of recurrence (HR 0.38, p = 0.04; HR 0.175, p = 0.002) and death (HR 0.21, p = 0.029; HR 0.15, p = 0.02). CONCLUSION. Perioperative morbidity was similar between those undergoing ARH vs. RRH for IB1 cervical cancer. Patients with tumors ≥ 2 cm undergoing RRH had a shorter PFS compared to ARH. On multivariate analysis, RRH and tumor size ≥ 2 cm were independently associated with recurrence and death in this population.

Despite screening, disparities exist in cervical cancer incidence and outcomes. Demographic factors are associated with diagnosis at advanced stage (AS), but less is known about geographic factors. We sought to investigate risk factors for developing AS cervical cancer in Alabama.We identified women treated for cervical cancer from 2005 to 2015 at our institution. Stages II-IV were considered AS. ZIP codes were categorized by federal Rural-Urban Commuting Area Codes, and 16 historically underserved counties were categorized as Black Belt rural. Using data from the American College of Obstetricians and Gynecologists, we identified women's health provider locations. We explored associations between stage and multiple factors using logistic regression.Of 934 patients, 29.2% were black, 52.7% had AS cancer, and 63.4% lived in urban areas. Average distance to nearest American College of Obstetricians and Gynecologists Fellow in urban, rural, and Black Belt rural areas was 5.0, 10.6, and 13.7 miles, respectively. Black race, public insurance and age of older than 65 years were associated with increased risk of AS cancer. Living in a rural area trended toward higher risk but was not significant. When stratified by race, insurance status and age were associated with AS cancer in white women only.Living further from a women's health provider or in a rural area was not associated with a higher risk of AS cervical cancer. Black women had a higher risk of AS than white women regardless of age, insurance status, and geography. Disparities in cervical cancer are multifactorial and necessitate further research into socioeconomic, biologic, and systems causes.

Objective Farletuzumab is a humanized monoclonal antibody that binds to folate receptor alpha, over-expressed in epithelial ovarian cancer (EOC) but largely absent in normal tissue. Previously, carboplatin plus pegylated liposomal doxorubicin showed superior progression-free survival and an improved therapeutic index compared with carboplatin/paclitaxel in relapsed platinum-sensitive EOC. This study assessed safety of farletuzumab/carboplatin/pegylated liposomal doxorubicin in women with platinum-sensitive recurrent EOC. Methods This multicenter, single-arm study enrolled patients with platinum-sensitive EOC in first or second relapse for treatment with weekly farletuzumab 2.5 mg/kg plus carboplatin AUC5–6 and pegylated liposomal doxorubicin 30 mg/m2 every 4 weeks for 6 cycles. Subsequently, maintenance with single-agent farletuzumab 2.5 mg/kg once weekly or farletuzumab 7.5 mg/kg once every three weeks continued until progression. The primary objective was to assess the safety of farletuzumab/carboplatin/pegylated liposomal doxorubicin. Results Fifteen patients received a median of 12.0 cycles (range, 3–26) of farletuzumab as combination therapy or maintenance, for a median of 45.0 weeks (range 9–95). Farletuzumab/carboplatin/pegylated liposomal doxorubicin was generally well tolerated, with no farletuzumab-related grades 3–4 adverse events. The most commonly reported adverse events were associated with combination chemotherapy: fatigue (73.3%), nausea (46.7%), and neutropenia (40%). Ten patients had grade ≥3 adverse events, most frequently neutropenia and fatigue. No cardiac toxicity was seen. Best overall responses (RECIST) were a complete response for one patient, partial responses for 10 patients, and stable disease for four patients. Conclusions Farletuzumab plus carboplatin/pegylated liposomal doxorubicin in women with platinum-sensitive EOC demonstrated a safety profile consistent with that of carboplatin plus pegylated liposomal doxorubicin.

OBJECTIVE To examine whether preoperative thrombocytosis or leukocytosis is associated with increased postoperative morbidity or mortality. METHODS Patients with ovarian cancer undergoing primary surgery from 2005 to 2012 were identified from the American College of Surgeons National Surgical Quality Improvement Project. Thrombocytosis was defined as platelets greater than 450,000/mm and leukocytosis as white blood cells greater than 10,000/mm. We examined 30-day postoperative complications and mortality. Descriptive statistics and adjusted multivariable logistic regression were used for analysis. RESULTS We identified 1,072 patients. The incidence of thrombocytosis was 9.6%, leukocytosis was 18.7%, and 4.9% had both. Leukocytosis was associated with major complication (16.5% compared with 10.3%, P=.01) but not postoperative death (3.0% compared with 1.3%, P=.08). Thrombocytosis was also associated with major complication (19.4% compared with 10.7%, P

Tobacco use remains a significant cause of morbidity and mortality worldwide. Tobacco contains many carcinogens as well as nicotine, which contributes to the development of multiple malignancies. In addition to malignancies of the head and neck, several gynecologic malignancies have been associated with tobacco use including cervical, vulvar, and vaginal cancers. Additionally, tobacco is associated with worse prognosis and increased rate of complications in gynecologic cancer patients of all disease sites. Recent literature in the area of tobacco use and gynecologic malignancy is highlighted in this review including tobacco’s association with treatment complications, secondary malignancy, and surgical complications. A focus is placed on tobacco cessation as a means to improve these outcomes. The use of automated referrals to reduce provider burden and targeting of the preoperative window are valuable strategies. Smoking cessation should be encouraged by oncologists and survivorship programs as a means to improve the health of women with gynecologic malignancy and reduce healthcare costs.

Objective Advanced stage epithelial ovarian cancer (AEOC) can be treated with either neoadjuvant chemotherapy (NACT) or primary cytoreductive surgery (PCS). Although randomized controlled trials show that NACT is non-inferior in overall survival compared to PCS, there may be improvement in short-term morbidity. We sought to investigate the cost-effectiveness of NACT relative to PCS for AEOC from the US Medicare perspective. Methods A cost-effectiveness analysis using a Markov model with a 7-month time horizon comparing (1) 3cycles of NACT with carboplatin and paclitaxel (CT), followed by interval cytoreductive surgery, then 3 additional cycles of CT, or (2) PCS followed by 6cycles of CT. Input parameters included probability of chemotherapy complications, surgical complications, treatment completion, treatment costs, and utilities. Model outcomes included costs, life-years gained, quality-adjusted life-years (QALYs) gained, and incremental cost-effectiveness ratios (ICER), in terms of cost per life-year gained and cost per QALY gained. We accounted for differences in surgical complexity by incorporating the cost of additional procedures and the probability of undergoing those procedures. Probabilistic sensitivity analysis (PSA) was performed via Monte Carlo simulations. Results NACT resulted in a savings of $7034 per patient with a 0.035 QALY increase compared to PCS; therefore, NACT dominated PCS in the base case analysis. With PSA, NACT was the dominant strategy more than 99% of the time. Conclusions In the short-term, NACT is a cost-effective alternative compared to PCS in women with AEOC. These results may translate to longer term cost-effectiveness; however, data from randomized control trials continues to mature.

BACKGROUND The objective of the current study was to evaluate the effect of obesity on pretreatment quality of life (QoL) in gynecologic oncology patients. METHODS The authors analyzed collected data from an institution-wide cohort study of women with gynecologic cancers enrolled from August 2012 to June 2013. The Functional Assessment of Cancer Therapy-General, site-specific symptom scales, and the National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) global mental and physical health tools were administered. Survey results were linked to clinical data abstracted from medical records (demographics and comorbid conditions). Bivariate tests and multivariate linear regression models were used to evaluate factors associated with QoL scores. RESULTS A total of 182 women with ovarian, uterine, cervical, and vulvar/vaginal cancers were identified; of these, 152 (84%) were assessed before surgery. Mean body mass index was 33.5 kg/m2 and race included white (120 patients [79%]), black (22 patients [15%]), and other (10 patients [6.5%]). A total of 98 patients (64.5%) were obese (body mass index ≥30). On multivariate analysis, subscales for functional (17 vs 19; P = .04), emotional (16 vs 19; P = .008), and social (22 vs 24; P = .02) well-being as well as overall Functional Assessment of Cancer Therapy-General scores (77 vs 86; P = .002) and Patient-Reported Outcomes Measurement Information System global physical health scores (45 vs 49; P = .003) were found to be significantly lower in obese versus nonobese patients. CONCLUSIONS Before cancer treatment, obese patients with gynecologic malignancies appear to have worse baseline QoL than their normal-weight counterparts. Emerging models of QoL-based cancer outcome measures may disproportionately affect populations with a high obesity burden. The potential disparate impact of cancer therapy on longitudinal QoL in the obese versus nonobese patients needs to be evaluated. Cancer 2015;121:395–402. © 2014 American Cancer Society.

Minimally invasive surgery (MIS) is increasingly being used to treat uterine fibroids because of the significant patient and societal benefits of these techniques over traditional laparotomy. Morcellation affords the removal of large fibroids in MIS but carries the risk of disseminating occult malignant tissue. The benefits of MIS for treating fibroids must be carefully weighed against its risks of morcellation.

Blood products are scarce but essential medical resources. Initially transfusions showed increased perioperative complications, prolonged hospitalizations, and higher mortality. Recently developed restrictive transfusion policies have not shown those adverse affects in critically ill patients. Hospitals adopted these policies to guide blood product administration. The objective of this study is to determine compliance with a restrictive transfusion policy in gynecologic oncology patients.A retrospective chart review of gynecologic oncology patients undergoing transfusion with packed red blood cells (pRBCs) from 12/2008 to 9/2011 was performed. Cancer type and stage, surgical procedure, hemoglobin values, pRBC transfusions, intraoperative blood loss, and postoperative complications were collected. Each transfusion was classified as compliant or noncompliant.A total of 582 patients requiring 2,276 blood transfusions were identified. The mean age was 55.9 years. Ovarian and endometrial cancers were the most common malignancies. Gynecologic oncologists were 81.1% compliant with the restrictive transfusion policy; 59.0% of transfusions were secondary to exceptions. Noncompliant transfusions were commonly given on the day of surgery when intraoperative blood loss was1500 cc and for asymptomatic anemia. Only 64.7% of the transfusions were ordered in single unit increments. There was no significant difference in postoperative infections, thrombotic events, and mortality between compliant and noncompliant transfusions.The majority of gynecologic oncology patients receive transfusions compliant with the restrictive transfusion policy. Morbidity and mortality are not increased with a restrictive transfusion policy. Efforts to improve compliance should focus on limiting transfusions when the hemoglobin is ≥ 7 g/dL and transfusing in single pRBCs unit increments.

Objective The conditionally replicative adenovirus Ad5/3-Δ24 has a type-3 knob incorporated into the type-5 fiber that facilitates enhanced ovarian cancer infectivity. Preclinical studies have shown that Ad5/3-Δ24 achieves significant oncolysis and anti-tumor activity in ovarian cancer models. The purpose of this study was to evaluate in a phase I trial the feasibility and safety of intraperitoneal (IP) Ad5/3-Δ24 in recurrent ovarian cancer patients. Methods Eligible patients were treated with IP Ad5/3-Δ24 for 3 consecutive days in one of three dose cohorts ranging 1×10 10 –1×10 12 vp. Toxicity was assessed utilizing CTC grading and efficacy with RECIST. Ascites, serum, and other samples were obtained to evaluate gene transfer, generation of wildtype virus, viral shedding, and antibody response. Results Nine of 10 patients completed treatment per protocol. A total of 15 vector-related adverse events were experienced in 5 patients. These events included fever or chills, nausea, fatigue, and myalgia. All were grades 1–2 in nature, transient, and medically managed. Of the 8 treated patients evaluable for response, six patients had stable disease and 2 patients had progressive disease. Three patients had decreased CA-125 from pretreatment levels one month after treatment. Ancillary biologic studies indicated Ad5/3-Δ24 replication in patients in the higher dose cohorts. All patients experienced an anti-adenoviral neutralizing antibody effect. Conclusions This study suggests the feasibility and safety of a serotype chimeric infectivity-enhanced CRAd, Ad5/3-Δ24, as a potential therapeutic option for recurrent ovarian cancer patients.

Objective To determine if the time interval between excision procedure and definitive minimally invasive surgery (MIS) for cervical cancer impacts 30-day postoperative complications. Methods A retrospective cohort of patients diagnosed with cervical cancer from January 2000 to July 2015 was evaluated. Patients who underwent a cervical excision procedure followed by definitive MIS within 90days were included. Early definitive surgery was defined as ≤6 weeks following excision procedure, while delayed was defined as 6weeks to 3months. The primary outcome was 30-day complications. Statistical analysis included descriptive statistics and modified Poission regression. Results Overall, 138 patients met inclusion criteria. Of these, 33% ( n =46) had early definitive surgery and 67% ( n =92) had delayed definitive surgery. Median age was 42years (range 23–72years) and median BMI was 28kg/m 2 (range 16–50kg/m 2 ). Within demographic and surgical factors collected, only smoking status differed between groups with those in the delayed surgery group more likely to be non-smokers than those in the early surgery group ( p =0.04). When adjusting for relevant demographic and surgical factors, patients in the early group were twice as likely to have 30-day complication (aRR 2.6, 95%CI 1.14–5.76, p =0.02). Evaluating only women who underwent a radical procedure, 30-day complications remained higher in the early surgery group (RR 2.56; 95%CI 1.22–5.38, p =0.01). Conclusions Performing definitive MIS for cervical cancer within 6weeks after cervical excision is associated with increased risk for 30-day complications. Providers should consider delaying definitive surgical procedures for at least 6weeks following excision to reduce surgical com p lications.

Objective AURELIA, a randomized phase III trial of adding bevacizumab (B) to single agent chemotherapy (CT) for the treatment of platinum-resistant recurrent ovarian cancer, demonstrated improved progression free survival (PFS) in the B+CT arm compared to CT alone. We aimed to evaluate the cost effectiveness of adding B to CT in the treatment of platinum-resistant recurrent ovarian cancer. Methods A decision tree model was constructed to evaluate the cost effectiveness of adding bevacizumab (B) to single agent chemotherapy (CT) based on the arms of the AURELIA trial. Costs, quality-adjusted life years (QALYs), and progression free survival (PFS) were modeled over fifteen months. Model inputs were extracted from published literature and public sources. Incremental cost effectiveness ratios (ICERs) per QALY gained and ICERs per progression free life year saved (PF-LYS) were calculated. One-way sensitivity analyses were performed to evaluate the robustness of results. Results The ICER associated with B+CT is $410,455 per QALY gained and $217,080 per PF-LYS. At a willingness to pay (WTP) threshold of $50,000/QALY, adding B to single agent CT is not cost effective for this patient population. Even at a WTP threshold of $100,000/QALY, B+CT is not cost effective. These findings are robust to sensitivity analyses. Conclusions Despite gains in QALY and PFS, the addition of B to single agent CT for treatment of platinum-resistant recurrent ovarian cancer is not cost effective. Benefits, risks, and costs associated with treatment should be taken into consideration when prescribing chemotherapy for this patient population.

ObjectiveOpen radical hysterectomy followed by adjuvant radiation for cervical cancer has been associated with significant rates of morbidity. Radical hysterectomy is now often performed robotically. We sought to examine if the robotic platform decreased the morbidity associated with radical hysterectomy followed by adjuvant radiation.Materials/MethodsA retrospective cohort of patients with cervical cancer undergoing radical hysterectomy from 1995 to 2013 was evaluated. Complications were assessed using electronic record review and graded. χ2 tests and Student t tests were used for analysis.ResultsOverall, 243 patients underwent radical hysterectomy for cervical cancer. Surgical approach was 43% open and 57% robotic. Eighty-three patients (34.2%) required adjuvant radiation. Overall, radical hysterectomy plus adjuvant radiation was associated with increased risk of complication (29%) compared to radical hysterectomy alone (7%) (P < 0.001). Complications included lymphedema (n = 18), bowel-associated complications (n = 10), and urinary complications (n = 7). There was no difference in time to initiation of radiation between open and robotic surgery (43 vs 47 days; P = 0.33). There was no difference in grade 2/3 complications in patients receiving adjuvant radiation between open and robotic surgery (27.5% vs 27.9%; P = 0.97). Patients undergoing open surgery followed by radiation experienced a trend toward increased adhesion-related complications, such as bowel obstruction and ureteral stricture (10% vs 2.3%; P = 0.19); whereas patients undergoing robotic surgery followed by radiation experienced a trend toward increased lymphedema (19% vs 8%; P = 0.20).ConclusionsWe found no difference in long-term complications between patients who underwent robotic surgery compared to open radical hysterectomy with adjuvant radiation. There may be fewer adhesion-related complications with robotic surgery. However, as many radiation-related complications occur at later time points, continued follow-up to evaluate for potential differences between the 2 groups is necessary.

Objective Debate continues about optimal management of patients with node-positive stage I cervical cancer. Our objective was to determine if patient outcomes are affected by radical hysterectomy in the modern era of adjuvant chemoradiation. Methods Cervical cancer patients diagnosed from 2000 to 2008 were identified. Demographics, therapy, clinicopathologic data, progression free survival (PFS), overall survival (OS), total radiation exposure, and grade 3–4 complications were analyzed by student t, Mann–Whitney, Fisher's exact, Kaplan–Meier, and log rank tests. Results This single-institution review evaluated forty-one of 334 (13.4%) patients scheduled to undergo radical hysterectomy that had gross nodal disease diagnosed intraoperatively. 15 underwent aborted radical hysterectomy following lymphadenectomy; the remaining 26 underwent radical hysterectomy and lymphadenectomy. Eleven patients undergoing radical hysterectomy underwent whole pelvic radiation therapy (WPRT) while 8 (30.7%) patients underwent WPRT and postoperative vaginal brachytherapy (BT) for local treatment secondary to close margins. All patients undergoing aborted radical hysterectomy underwent WPRT and BT. With mean follow-up of 42.3months, there were no significant differences in urinary, gastrointestinal, or hematologic complications between groups. When comparing those undergoing radical hysterectomy to aborted radical hysterectomy, there were no significant differences in local recurrence (11.5% vs 26.7%, p=0.39) or distant recurrence (19.2% vs. 33.3%, p=0.45), PFS (74.9months vs 46.8months, p=0.106), or OS (91.8months vs 69.4months, p=0.886). Conclusions Treatment of patients with early stage cervical cancer and nodal metastasis may be tailored intraoperatively. Completion of radical hysterectomy and lymphadenectomy decreases radiation exposure without apparently compromising safety or outcome in the era of adjuvant chemoradiation.

Objective The purpose of this study was to investigate the incidence of mechanical complications associated with low-profile subcutaneous implantable venous access devices in gynecologic oncology patients. Methods Gynecologic oncology patients with low-profile Port-a-Caths implanted between March 2005 and July 2006 were identified into a computerized database. Patient demographics, operative complications, number of chemotherapy cycles, duration of implantation, and mechanical complications were collected. Primary outcomes included port leakage, catheter fracture, and catheter embolization. Results 112 patients underwent 115 Port-a-Cath placements with low profile single-lumen plastic ports with Groshong-valved catheters. Mean Port-a-Cath indwelling duration was 197days (range: 4–395) with a mean number of 12 chemotherapy cycles (range 0–64). The cumulative complication rate necessitating removal or replacement was 15%. Of the 14 Port-a-Caths removed, ten (8.7%) were secondary to mechanical malfunction: one for leakage at the port site, two for catheter fracture, and seven for fracture with catheter embolization to the heart or pulmonary vasculature—most commonly the right ventricle. Patients with embolization were asymptomatic and all embolized catheters were successfully retrieved by interventional radiology without complications. Conclusions The rates of catheter fracture and embolization have previously been reported to be low in patients with subcutaneous Port-a-Caths, and have not been studied in patients receiving low-profile subcutaneous Port-a-Caths. This study suggests that catheter fracture may be more common (8.7%) and must be considered in patients with malfunctioning low-profile Port-a-Caths. Embolized catheters can be removed by interventional radiology without significant adverse affects.

Objective Minimally invasive surgery offers advantages for management of obese patients, but technical difficulty often deters its utilization. Compared to laparotomy, robotic surgery should allow comparable staging and improved surgical outcomes. Therefore, we evaluated outcomes in robotic and laparotomy cohorts of obese women with endometrial cancer at our institution. Methods Retrospective robotic and laparotomy cohorts of obese women (BMI≥30kg/m 2 ) undergoing surgical management of primary endometrial cancer from March 2006 to March 2009 were formulated utilizing a computerized database. Patient demographics, operative statistics, peri-operative complications, and pathologic details were collected in an intent to treat analysis. Chi-square or Fisher's exact test and t -test were used for statistical analysis. Results 73 women underwent robotic surgical management, 11% converted to laparotomy. Mean BMI (39.8 vs. 41.9, p =0.152), number of co-morbidities (2.49 vs. 2.62, p =0.690), number of previous surgeries (0.97 vs. 0.94, p =0.841), and lymphadenectomies performed (65.8% vs. 56.7%, p =0.227) were similar between cohorts. Total lymph nodes obtained were not statistically different between cohorts (8.01 vs. 7.24, p =0.505). Total operative time and room time was significantly longer for robotic surgery; however, estimated blood loss, the percentage of patients receiving transfusion, hospital length of stay, wound complications (4.1% vs. 20.2%, p =0.002) and other complications (9.6% vs. 29.8%, p =0.001) were improved for the robotic cohort. Conclusions Robotic management of obese women with endometrial cancer yields acceptable staging results and improved surgical outcomes. Although operating time is longer, hospital time is shorter. Robotic surgery may be an ideal approach for these patients.

Conditionally replicative adenoviral (CRAd) virotherapy represents a promising therapeutic approach for cancer. We have demonstrated that a serotype chimeric adenoviral 5/3 fiber-knob modification achieves enhanced ovarian cancer infectivity, conditional replication, and oncolytic activity. This study evaluated the safety of intraperitoneal (IP) Ad5/3-Δ24 in advance of a phase I clinical trial in gynecologic cancers. Syrian hamster cohorts were treated with IP Ad5/3-Δ24 or control buffer for 3 consecutive days and euthanized on study days 8, 17, 57, and 89. Blood and tissue samples were harvested from each animal. For biodistribution studies, presence and quantitation of viral levels within samples were determined via quantitative polymerase chain reaction. For safety studies, animals were assessed for adverse vector-related tissue or laboratory effects. In the biodistribution study, low levels of Ad5/3-Δ24 DNA were noted outside of the abdominal cavity. Viral DNA levels in tissues obtained from the peritoneal cavity peaked at day 8 and declined thereafter. In the safety study, no specific histopathologic changes were attributable to virus administration. Hematologic findings noted in the 1 × 10(11) viral particles (vp)/dose group on Days 4 and/or 8 were indicative of an Ad5/3-Δ24-specific generalized inflammatory response; these findings resolved by day 56. The no observable adverse effect level was determined to be 1 × 10(10) vp/dose. This study elucidates the safety profile of IP administration of the serotype chimeric infectivity-enhanced CRAd, Ad5/3-Δ24, and provides guidance for a planned phase I trial for patients with recurrent gynecologic cancers.