Trends in estimated PARP inhibitor eligibility and benefit among US epithelial ovarian cancer patients.

OBJECTIVE: To estimate the annual percentage of patients with epithelial ovarian cancer (EOC) who could be eligible for and benefit from PARP inhibitor therapy amidst changing US Food and Drug Administration (FDA)-approved indications. METHODS: This is a simulated retrospective observational study using publicly available data on patients with advanced-stage EOC. PARPi eligibility is based on FDA approvals and withdrawals from 2014 through 2023, along with published demographic and genomic data. Clinical trial data is used to estimate treatment benefit. PARPi including olaparib, niraparib, and rucaparib are analyzed in aggregate with sub-analyses by molecular classification and treatment timing. Results are reported as the percentage of EOC patients appropriate for any cancer-directed therapy. RESULTS: PARPi were approved for 9 different indications in EOC between 2014 and 2021; reduced to 6 indications by 2023. Eligibility increased from 2.0% (95% CI,1.3%-1.6%) in 2014 to a maximum of 93.4% (95% CI,90.1%-94.6%) in 2021. The maximum percentage of patients with 2-year PFS benefit was 22.0% (95% CI, 17.2%-26.8%) in 2021, projected to decrease to 13.0% (95% CI, 9.9%-15.9%) in 2024. Most of this decrease was seen in the homologous recombination deficient, BRCA wild-type population (8.4% to 4.0%). CONCLUSIONS: PARPi eligibility increased at a greater rate than benefit resulting in a low population-level benefit-to-eligibility ratio until 2021. Recent FDA withdrawals improved this ratio with an accompanied decrease in the absolute number of patients benefiting. To further optimize population-level benefit-to-eligibility ratio of targeted therapies in ovarian cancer, we need to identify better biomarkers, treatment combinations, and novel therapeutic targets.

Unmet financial needs among patients crowdfunding to support gynecologic cancer care.

BACKGROUND: Patients may use crowdfunding to solicit donations, typically from multiple small donors using internet-based means, to offset the financial toxicity of cancer care. OBJECTIVE: To describe crowdfunding campaigns by gynecologic cancer patients and to compare campaign characteristics and needs expressed between patients with cervical, uterine, and ovarian cancer. STUDY DESIGN: We queried the public crowdfunding forum GoFundMe.com for "cervical cancer," "uterine cancer," and "ovarian cancer." The first 200 consecutive posts for each cancer type fundraising within the United States were analyzed. Data on campaign goals and needs expressed were manually extracted. Descriptive statistics and bivariate analyses were performed. RESULTS: Among the 600 fundraising pages, the median campaign goal was $10,000 [IQR $5000-$23,000]. Campaigns raised a median of 28.6% of their goal with only 8.7% of campaigns reaching their goal after a median of 54 days online. On average, ovarian cancer campaigns had higher monetary goals, more donors, and larger donation amounts than cervical cancer campaigns and raised more money than both cervical and uterine cancer campaigns. Campaigns were fundraising to support medical costs (80-85%) followed by lost wages (36-56%) or living expenses (27-41%). Cervical cancer campaigns reported need for non-medical costs more frequently than uterine or ovarian cancer campaigns. States without Medicaid expansions (31% of the national population) were over-represented among cervical cancer and uterine cancer, but not ovarian cancer campaigns. CONCLUSIONS: Crowdfunding pages reveal patients fundraising for out-of-pocket costs in the thousands of dollars and a wide range of unmet financial needs based on cancer type.

Association between adherence to posttreatment National Comprehensive Cancer Network (NCCN) surveillance guidelines and detection of recurrent uterine cancer.

OBJECTIVE: To identify correlations between disease recurrence and adherence to NCCN posttreatment surveillance guidelines in patients who develop recurrent uterine cancer. METHODS: Retrospective analysis identified patients (n = 60) with recurrent uterine cancer and at least one surveillance visit with a gynecologic oncologist between 2011 and 2020. Adherence to NCCN guidelines and details of recurrence were recorded. RESULTS: Recurrent uterine cancer was identified in 60 patients with an average time to recurrence (TTR) of 25 months. Of those, 39 (65%) were adherent to NCCN surveillance guidelines and 36 (60%) were symptomatic at the time of recurrence diagnosis. Asymptomatic recurrence was diagnosed by imaging in 11 (46%), physical exam in 7 (29%), and blood work in 6 (25%) patients. Patients who were adherent to NCCN guidelines were diagnosed with recurrence on average 11 months earlier (p = 0.0336). Adherence was an independent predictor of TTR for all patients regardless of symptoms. There was no significant effect of age, race, primary language, or stage of disease on adherence. CONCLUSION: Adherence to NCCN posttreatment surveillance guidelines for uterine cancer is independently associated with an earlier diagnosis of recurrence.

The association of black race with receipt of hysterectomy and survival in low-risk endometrial cancer.

OBJECTIVE: To determine whether Black race is associated with treatment and survival among women with low-risk endometrial cancer. METHODS: Black and White women with Stage IA grade 1-2 endometrioid endometrial carcinoma diagnosed from 2010 to 2016 in the SEER 18 dataset were identified (n = 23,431), and clinical and socioeconomic attributes obtained. Five-year cancer-specific survival (CSS) and relative survival (RS) were calculated using SEER*Stat 8.3.9. Cox proportional hazards model was used to determine predictors of overall survival (OS) and CSS. RESULTS: There was a significantly higher proportion of Black women who did not have surgery compared to White women (3% vs 1%, respectively; p < 0.0001). Residing in the South, being insured with Medicaid, and residing in a county with low median income were also associated with non-receipt of surgery. Black women remained less likely to undergo hysterectomy on multivariable analysis (OR 0.44, 95% CI 0.32-0.60). Non-receipt of hysterectomy was predictive of decreased CSS (HR 0.14, 95% CI 0.09-0.21) and OS (HR 0.18, 95% 0.14-0.23) on adjusted analysis. Black race was also an independent predictor of increased cancer-specific death (HR 2.07, 95% CI 1.50-2.86) as well as death from any cause (HR 1.74, 95% CI 1.44-2.09) on adjusted analysis. CONCLUSIONS: Black women with low-risk endometrial cancer were less likely to undergo hysterectomy and experienced decreased survival relative to White women. Further investigation is warranted to better understand the socioeconomic, geographic, and biologic factors that influence this disparity.

Evaluation of patterns of progression on poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance in ovarian cancer: a cross-sectional study.

INTRODUCTION: Despite 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. METHODS: From 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. RESULTS: The 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. CONCLUSIONS: One-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.

The financial burden of PARP inhibitors on patients, payors, and financial assistance programs: Who bears the cost?

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 $9914-14,709). Financial assistance programs contributed average $358 and median $0 per month (IQR $0-150). Patients with public (p<0.01) or Medicare insurance (p<0.01) had higher OOP costs than without. CONCLUSIONS: OOP costs were generally low with 75% of patients paying <$5 per month. While limited by small sample size at a single institution, financial assistance programs appear to play a critical role to ensure access to PARP inhibitors as nearly 50% of patients utilized these programs.

Fluorescence Imaging of the Ureter in Minimally Invasive Pelvic Surgery.

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.

The Society of Gynecologic Oncology wellness curriculum pilot: A groundbreaking initiative for fellowship training.

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.

Comparative outcomes between robotic and abdominal radical hysterectomy for IB1 cervical cancer: Results from a single high volume institution.

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.

Timing of robotic hysterectomy after cervical excisional procedure.

INTRODUCTION: While 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. METHODS: A 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 (<6 weeks from excisional procedure), delayed surgical intervention (≥6 weeks from excisional procedure), and no excisional procedure. Secondary analysis was performed by hysterectomy type (simple vs radical). Peri-operative outcomes and complications were compared. Statistical analysis included Chi-square, Fisher's exact test, and Wilcoxon rank sum test. RESULTS: A 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. DISCUSSION: Waiting 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.

A Ketogenic Diet Reduces Central Obesity and Serum Insulin in Women with Ovarian or Endometrial Cancer.

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 ß-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 < 0.05) and android (3.0 compared with 3.3 kg, P < 0.05) fat mass. Percentage of change in visceral fat was greater in the KD group (compared with the ACS group; -21.2% compared with -4.6%, P < 0.05). Adjusted total lean mass did not differ between the groups. The KD (compared with ACS) group had lower adjusted fasting serum insulin (7.6 compared with 11.2 µU/mL, P < 0.01). There was a significant inverse association between the changes in serum ß-hydroxybutyrate and IGF-I concentrations (r = -0.57; P < 0.0001). Conclusions: In women with ovarian or endometrial cancer, a KD results in selective loss of fat mass and retention of lean mass. Visceral fat mass and fasting serum insulin also are reduced by the KD, perhaps owing to enhanced insulin sensitivity. Elevated serum ß-hydroxybutyrate may reflect a metabolic environment inhospitable to cancer proliferation. This trial was registered at www.clinicaltrials.gov as NCT03171506.

Cost effectiveness of neoadjuvant chemotherapy followed by interval cytoreductive surgery versus primary cytoreductive surgery for patients with advanced stage ovarian cancer during the initial treatment phase.

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.

The Impact of Racial, Geographic, and Socioeconomic Risk Factors on the Development of Advanced-Stage Cervical Cancer.

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Association between timing of cervical excision procedure to minimally invasive hysterectomy and surgical complications.

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/m2 (range 16-50kg/m2). 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 complications.

Adding bevacizumab to single agent chemotherapy for the treatment of platinum-resistant recurrent ovarian cancer: A cost effectiveness analysis of the AURELIA trial.

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.

Prior breast cancer and tamoxifen exposure does not influence outcomes in women with uterine papillary serous carcinoma.

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.

Robotic Radical Parametrectomy With Upper Vaginectomy and Pelvic Lymphadenectomy in Patients With Occult Cervical Carcinoma After Extrafascial Hysterectomy.

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.

Extremes in body mass index affect overall survival in women with cervical cancer.

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 25.0months, p=0.01 and 20.3 v 25.0months, p=0.03). Underweight patients also had worse OS (10.4 v 28.4months, p=0.031) and DSS (13.8 v 28.4months, p=0.04) compared to normal weight patients. Overweight/obese patients had worse OS than normal weight patients (22.2 v 28.4months, p=0.03) and a trend toward worse DSS (21.9 v 28.4months, 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.

Phase 1b safety study of farletuzumab, carboplatin and pegylated liposomal doxorubicin in patients with platinum-sensitive epithelial ovarian cancer.

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 2.5mg/kg plus carboplatin AUC5-6 and pegylated liposomal doxorubicin 30mg/m(2) every 4weeks for 6cycles. Subsequently, maintenance with single-agent farletuzumab 2.5mg/kg once weekly or farletuzumab 7.5mg/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 12.0cycles (range, 3-26) of farletuzumab as combination therapy or maintenance, for a median of 45.0weeks (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.

The effect of distance traveled on disease outcomes in gestational trophoblastic neoplasia.

BACKGROUND: Gestational trophoblastic neoplasia is a rare gynecological malignancy often treated at tertiary referral centers. Patients frequently travel long distances to obtain care for gestational trophoblastic neoplasia, which may affect cancer outcomes in these patients. OBJECTIVE: We examined the association between distance traveled to obtain care and disease burden at time of presentation as well as recurrence. STUDY DESIGN: We performed a retrospective cohort analysis of all patients diagnosed with gestational trophoblastic neoplasia from January 1995 to June 2015 at a high-volume tertiary referral center. Patients were included if they met International Federation of Gynecology and Obstetrics 2000 criteria for postmolar gestational trophoblastic neoplasia or had choriocarcinoma, placental-site trophoblastic tumor, or epithelioid trophoblastic tumor. Sixty patients were identified. Disease burden at presentation was examined using both the World Health Organization prognostic score and International Federation of Gynecology and Obstetrics. Patients who traveled more than 50 miles were considered long-distance travelers based on previous literature on the effect of distance traveled on cancer outcomes. Demographic, clinical, and pathological data were obtained by chart review. Bivariable comparisons were performed using the χ(2) test or Fisher exact test for categorical variables. The t test or Wilcoxon rank-sum test was used to compare continuous variables when normally or not normally distributed. RESULTS: Most patients presented at stage I (61%) with low-risk gestational trophoblastic neoplasia (70%). Median distance to care was 40 miles (range, 4-384). Eighteen patients (30%) had no insurance and 42 (70%) had either private or public insurance. Patients traveling more than 50 miles for care were more likely to have high-risk gestational trophoblastic neoplasia (46% vs 19%, P = .03), but there was no difference in recurrence (13% vs 11%, P = .89). Patients with high-risk gestational trophoblastic neoplasia lived 63 miles farther (92 vs 28 miles, P < .001) than patients with low-risk gestational trophoblastic neoplasia. Long-distance travelers had a longer period between antecedent pregnancy and gestational trophoblastic neoplasia diagnosis (10 weeks vs 4.5 weeks, P = .009) and were more likely to receive multiagent chemotherapy (86% vs 61%, P = .03). CONCLUSION: In this cohort, long distance traveled to obtain care for gestational trophoblastic neoplasia was associated with an increased risk of presenting with high-risk disease and requiring multiagent chemotherapy for treatment. Patients with high-risk gestational trophoblastic neoplasia traveled nearly 100 miles to obtain care. There may be a delay in diagnosis in women traveling more than 50 miles to obtain care; however, we found no difference in recurrence risk for long-distance travelers.