Publications by authors named "Laura J Havrilesky"

190 Publications

Evaluation of pelvic washing specimens in patients with endometrial cancer: Cytomorphological features, diagnostic agreement, and pathologist experience.

Cancer Cytopathol 2021 Jan 22. Epub 2021 Jan 22.

Department of Pathology, Duke University, Durham, North Carolina.

Background: Pelvic washings for patients with endometrial cancer is recommended but not used for staging. The International System for Reporting Serous Fluid Cytology (TIS) has standardized diagnostic categories, but the criteria remain incomplete. The 3 primary goals of this study were to 1) investigate features that distinguish atypical/indeterminate from malignant specimens, 2) measure the level of agreement between chart and reviewer diagnoses, and 3) determine whether the number of years in practice had an effect on the diagnoses rendered.

Methods: Pelvic washings and surgical pathology specimens for 52 patients with a chart diagnosis of atypical/indeterminate, suspicious, or malignant cytology and 52 age-matched controls with a negative chart diagnosis were included, reviewed blindly by 2 cytopathologists, and assigned a study diagnosis. Morphologic features were assessed. Agreement between original chart diagnoses and reviewer diagnoses were assessed as well as effect of years in practice.

Results: The overall cellularity in cell block (CB) slides for the malignant category was significantly increased compared with the atypical/indeterminate category (P < .0001). In addition, the number of atypical groups in ThinPrep for malignant washings was significantly increased compared with the atypical category (P < .001) and the negative and suspicious categories (P < .0001) in the CB. Overall agreement between the original and adjudicated diagnoses was high (γ = 0.983). There was no significant difference between diagnoses rendered and years in practice.

Conclusion: The overall cellularity and number of atypical cells can be used to distinguish between malignant and atypical pelvic washing specimens. There is high reproducibility in the diagnostic categories and high agreement among pathologists, regardless of practice experience. These findings can help refine the criteria for TIS.
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http://dx.doi.org/10.1002/cncy.22406DOI Listing
January 2021

Results and Clinical Utilization of Foundation Medicine Molecular Tumor Profiling in Uterine and Ovarian Cancers.

Target Oncol 2021 Jan 5;16(1):109-118. Epub 2021 Jan 5.

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University, 201 Trent Drive, 203 Baker House, Durham, NC, 27710, USA.

Background: Recent advances in next-generation sequencing have allowed for an increase in molecular tumor profiling.

Objective: We sought to assess the actionability and clinical utilization of molecular tumor profiling results obtained via Foundation Medicine tumor sequencing tests in uterine and ovarian cancers.

Patients And Methods: We performed a single-institution retrospective chart review to obtain demographic and clinical information in patients with uterine and ovarian cancer whose tumors were submitted to Foundation Medicine for molecular tumor profiling over a 7-year period. Alterations identified on testing were stratified according to the OncoKB database actionability algorithm. Descriptive statistics were primarily used to analyze the data.

Results: Tumors from 185 women with gynecologic cancer were submitted for molecular tumor profiling between 2013 and 2019. The majority of tests (144/185; 78%) were ordered after a diagnosis of recurrence. In 60 (32%), no actionable molecular alteration was identified. Thirteen (7%) identified an alteration that directed to a US Food and Drug Administration-approved therapy in that tumor type, while 112 (61%) had alterations with investigational or hypothetical treatment implications. In patients with any actionable finding, treatment was initiated in 27 (15%) based on these results.

Conclusions: The majority of uterine and ovarian cancers (93%) did not have molecular alterations with corresponding Food and Drug Administration-approved treatments. Even in patients with a potentially actionable alteration, gynecologic oncologists were more likely to choose an alternative therapy. Further investigation is warranted to determine which patients with uterine and ovarian cancer are most likely to benefit from molecular tumor profiling and the ideal timing of testing. The potential to identify effective therapeutic options in a minority of patients needs to be balanced with the current limited clinical applicability of these results in most cases.
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http://dx.doi.org/10.1007/s11523-020-00785-zDOI Listing
January 2021

Universal screening for Lynch syndrome in uterine cancer patients: A quality improvement initiative.

Gynecol Oncol 2021 Jan 21;160(1):169-174. Epub 2020 Oct 21.

Division of Gynecologic Oncology, Duke Cancer Institute, Duke University Health System, Durham, North Carolina, United States of America.

Objective: To determine the feasibility and effectiveness of a quality improvement initiative (QI) to adopt universal screening for Lynch syndrome in uterine cancer patients at an institution that previously employed age-based screening.

Methods: Prior to the initiative, tumors of patients with uterine cancer diagnosed at age ≤ 60 years were screened for mismatch repair deficiency (MMR) and microsatellite instability (MSI). The QI process change model adopted universal testing of all uterine cancer specimens and implemented provider training, standardized documentation, and enhanced use of the electronic medical record (EMR). We compared screening rates, results of screening, follow up of abnormal results, and final diagnoses from the pre- and post-implementation periods.

Results: Pre- and post-implementation screening rates for women age ≤ 60 years at the time of diagnosis were 45/78 (57.7%) and 64/68 (94.5%), respectively. The screening rate for all patients with uterine cancer increased from 73/190 (38.4%) to 172/182 (94.5%). The rate of abnormal screening results increased from 15/190 (7.9%) to 44/182 (24.0%) cases. Genetics referral rates among screen positives increased from 3/15 (20.0%) to 16/44 (36.4%). Germline diagnoses increased from 2/190 (1.1%) with two Lynch syndrome diagnoses to 4/182 (2.2%) including three Lynch syndrome diagnoses and one BRCA1 germline diagnosis. The number of patients errantly not screened decreased from at least 32 patients to 3 patients after the intervention.

Conclusions: Adherence to screening guidelines significantly improved after interventions involving provider education, optimal use of the EMR, and simplification of screening indications. These interventions are feasible at other institutions and translatable to other screening indications.
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http://dx.doi.org/10.1016/j.ygyno.2020.10.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577655PMC
January 2021

Association of Medicaid expansion with mortality from gynecologic cancers.

Am J Obstet Gynecol 2021 Mar 20;224(3):323-325. Epub 2020 Nov 20.

Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC.

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http://dx.doi.org/10.1016/j.ajog.2020.11.024DOI Listing
March 2021

Adherence to Oral Anticancer Therapeutics in the Gynecologic Oncology Population.

Obstet Gynecol 2020 12;136(6):1145-1153

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, and Family Medicine and Community Health, Duke University, Duke University School of Medicine, and the Duke Cancer Institute, Durham, North Carolina.

Introduction: To gain a better understanding of gynecologic oncology patient adherence to oral anticancer agents through both a cross-sectional survey of adherence and qualitative interviews with patients and clinicians regarding their experience with these medications.

Methods: Eligible participants completed a survey for this cross-sectional study that included an assessment of adherence, distress, quality of life, and health literacy. Any woman taking an oral anticancer agent for a gynecologic malignancy at a tertiary academic medical center for 30 days or more was eligible. Semi-structured qualitative interviews (n=14) were then conducted to explore experiences with oral anticancer agents. We also conducted a qualitative group interview with physicians and nurse practitioners.

Results: One hundred women taking oral anticancer agents were enrolled. Fifty-four percent reported perfect adherence to their medication, 21% reported equivocal adherence (demonstrating at least one nonadherent behavior in the previous 7 days), and 25% reported nonadherence (demonstrating more than one nonadherent behavior in the previous 7 days). Qualitative analysis identified five major themes: ease of use compared with traditional therapy; the mental burden of self-administrated medication; perceived importance of the medication; management of side effects; and the desire for consistent physician communication. Common misperceptions expressed in the health care professional interviews included high adherence to oral medications and a belief that cost was the biggest barrier to adherence.

Conclusion: Almost half of the patients surveyed reported equivocal or nonadherence to their oral anticancer agent. The qualitative interviews identified several important themes, many of which were not recognized by physicians and nurse practitioners. These findings highlight the need for patient and health care professional interventions to improve patient adherence.
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http://dx.doi.org/10.1097/AOG.0000000000004170DOI Listing
December 2020

Cost-effectiveness analysis comparing "PARP inhibitors-for-all" to the biomarker-directed use of PARP inhibitor maintenance therapy for newly diagnosed advanced stage ovarian cancer.

Gynecol Oncol 2020 Nov 27;159(2):483-490. Epub 2020 Aug 27.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, United States of America; Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, United States of America.

Objectives: Clinical trials evaluating universal PARP inhibitor (PARPi) frontline maintenance therapy for advanced stage ovarian cancer have reported progression-free survival (PFS) benefit. It is unclear whether PARPi maintenance therapy will universally enhance value (clinical benefits relative to cost of delivery). We compared a "PARPi-for-all" to a biomarker-directed frontline maintenance therapy approach as a value-based care strategy.

Methods: The cost of two frontline PARPi maintenance strategies, PARPi-for-all and biomarker-directed maintenance, was compared using modified Markov decision models simulating the study designs of the PRIMA, VELIA, and, PAOLA-1 trials. Outcomes of interest included overall costs and incremental cost-effectiveness ratios (ICERs) reported in US dollars per quality adjusted progression-free life-year (QA-PFY) gained.

Results: PARPi-for-all was more costly and provided greater PFS benefit than a biomarker-directed strategy for each trial. The mean cost per patient for the PARPi-for-all strategy was $166,269, $286,715, and $366,506 for the PRIMA, VELIA, and PAOLA-1 models, respectively. For the biomarker-directed strategy, the mean cost per patient was $98,188, $167,334, and $260,671 for the PRIMA, VELIA, and PAOLA-1 models. ICERs of PARPi-for-all compared to biomarker-directed maintenance were: $593,250/QA-PFY (PRIMA), $1,512,495/QA-PFY (VELIA), and $3,347,915/QA-PFY (PAOLA-1). At current drug pricing, there is no PFS improvement in a biomarker negative cohort that would make PARPi-for-all cost-effective compared to biomarker-directed maintenance.

Conclusions: This study highlights the high costs of universal PARPi maintenance treatment, compared with a biomarker-directed PARPi strategy. Maintenance therapy in the front-line setting should be reserved for those with germline or somatic HRD mutations until the cost of therapy is significantly reduced.
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http://dx.doi.org/10.1016/j.ygyno.2020.08.003DOI Listing
November 2020

Management of high, moderate, and low penetrance ovarian cancer susceptibility mutations: an assessment of current risk reduction practices.

Int J Gynecol Cancer 2020 Oct 23;30(10):1583-1588. Epub 2020 Aug 23.

Northwell Health Cancer Institute, Lake Success, New York, USA.

Objective: Limited information exists regarding risk reduction strategies for women with moderate and low penetrance ovarian cancer susceptibility mutations. We sought to assess current risk reduction practice patterns for carriers of these mutations through a survey of members of the Society of Gynecologic Oncology.

Methods: Society of Gynecologic Oncology members were emailed a survey consisting of two vignettes: (1) a 35-year-old premenopausal woman; (2) a 55-year-old postmenopausal woman with comorbidities. Each vignette contained sub-scenarios in which the patient had either a (relative risk (RR)=30-60), (RR=5.0), or (RR=1.5-2.0) mutation. Respondents were queried about their preferred management approach. Summary statistics were performed to describe results of the survey. We used χ testing for statistical analyses, comparing results according to mutation type and demographic information.

Results: A total of 193 (15%) of 1284 Society of Gynecologic Oncology members responded. For the premenopausal woman, 99%, 80%, and 40% would perform a risk reducing salpingo-oophorectomy prior to menopause in the setting of a , and mutation, respectively. For the postmenopausal woman, 98%, 85%, and 42% would proceed with risk reducing salpingo-oophorectomy in the setting of a and mutation, respectively. Response distribution for carriers of and mutations were different from in both vignettes (p<0.001).

Conclusions: Respondents were more likely to perform risk reducing salpingo-oophorectomy, in the setting of a and mutation, earlier and more frequently in the setting of a mutation. However, there was a lack of consensus about management of the moderate and low penetrance mutations, suggesting that more data regarding age specific risks and appropriate risk reduction strategies for these alterations are needed.
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http://dx.doi.org/10.1136/ijgc-2020-001536DOI Listing
October 2020

The cost-effectiveness of prenatal congenital heart defect screening methods in IVF pregnancies.

Ultrasound Obstet Gynecol 2020 Apr 18. Epub 2020 Apr 18.

Duke University, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC.

Objectives: To determine if a policy of universal fetal echocardiography (echo) for IVF pregnancies is cost-effective as a screening strategy for congenital heart defects (CHDs) and to examine the cost-effectiveness of various CHD screening strategies in IVF pregnancies.

Study Design: A decision-analysis model was designed from a societal perspective with respect to the obstetric patient, to compare the cost-effectiveness of three screening strategies: (1) Anatomic-US: selective fetal echo following an abnormal detailed anatomic survey; (2) ICSI-Only: fetal echo for all pregnancies following IVF with ICSI; (3) All-IVF: fetal echo for all IVF pregnancies. The model initiated at conception and had a time horizon of 1 year post-delivery. Sensitivities and specificities for each strategy, probabilities of major and minor CHDs, and all other clinical estimates were derived from the literature. Costs, including imaging, consults, surgeries, caregiver productivity losses, were derived from the literature and Medicare databases. Effectiveness was quantified as quality-adjusted life years (QALYs) based on how the strategies would affect the quality of life of the obstetric patient. Secondary effectiveness was quantified as cases of CHD and, specifically, cases of major CHD detected.

Results: The average base case cost of each strategy was: Anatomic-US $8,119, ICSI-Only $8,408, and All-IVF $8,560. The effectiveness of each strategy was: Anatomic-US 1.74487 QALYs, ICSI-Only 1.74497 QALYs, and All-IVF 1.74499 QALYs. ICSI-Only had an incremental cost effectiveness ratio (ICER) of $2,840,494/QALY when compared to Anatomic-US; All-IVF had an ICER of $5,962,457/QALY when compared to ICSI-Only. Both ICERs considerably exceed the standard willingness-to-pay threshold of $50,000 to $100,000 per QALY. In a secondary analysis, ICSI-Only had an ICER of $527,562 per additional case of major CHD detected when compared to Anatomic-US. All-IVF had an ICER of $790,510 per case of major CHD detected when compared to ICSI-Only. It was determined that it costs society 5 times more to detect one additional major CHD through intensive screening of all IVF pregnancies than to pay for the neonate's first year of care.

Conclusion: The most cost-effective screening method for CHDs in pregnancies following IVF either with or without ICSI is to obtain a fetal echo only when abnormal cardiac findings are noted on detailed anatomy scans. Routine fetal echo for all IVF pregnancies is not cost-effective. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/uog.22048DOI Listing
April 2020

Are Videos or Text Better for Describing Attributes in Stated-Preference Surveys?

Patient 2020 08;13(4):401-408

Duke Clinical Research Institute, Duke University, 200 Morris Street, Durham, NC, 27701, USA.

Objective: In stated-preference research, the conventional approach to describing study attributes is through text, often with easy-to-understand graphics. More recently, researchers have begun to present attribute descriptions and content in videos. Some experts have expressed concern regarding internalization and retention of information conveyed via video.

Objective: Our study aimed to compare respondents' understanding of attribute information provided via text versus video.

Methods: Potential respondents were randomized to receive a text or video version of the survey. In the text version, all content was provided in text format along with still graphics. In the video version, text content was interspersed with four video clips, providing the same information as the text version. In both versions, 10 questions were embedded to assess respondents' understanding of the information presented relating to ovarian cancer treatments. Half of the questions were on treatment benefits and the other half were on treatment-related risks. Some questions asked about the decision context and definitions of treatment features, and others asked about the graphic presentation of treatment features. Preferences for ovarian cancer treatments were also compared between respondents receiving text versus video versions.

Results: Overall, 150 respondents were recruited. Of the 95 who were eligible and completed the survey, 54 respondents received the text version and 41 received the video version. Median times to completion were 24 and 30 min in the video and text arms, respectively (p < 0.01). Both groups spent an average of 35 min completing the survey. On the first comprehension question, 43% in the text arm and 61% in the video arm provided the correct response (p = 0.08). Although the mean number of correct responses was significantly higher in the video versus text arms (9.1 vs. 8.6, p = 0.02), there were no systematic differences in preferences between arms.

Conclusions: The quality of stated-preference data relies on respondents' understanding of study content. Information provided via video may better engage survey participants and improve their retention of content.
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http://dx.doi.org/10.1007/s40271-020-00416-9DOI Listing
August 2020

Patient preferences for maintenance PARP inhibitor therapy in ovarian cancer treatment.

Gynecol Oncol 2020 03 22;156(3):561-567. Epub 2020 Jan 22.

Duke Cancer Institute, Duke University Medical Center, Durham, NC, United States of America; Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, United States of America; Department of Population Health Sciences, Duke University School of Medicine, Durham, NC, United States of America.

Objective: To measure preferences of women with ovarian cancer regarding risks, side effects, costs and benefits afforded by maintenance therapy (MT) with a poly ADP ribose polymerase (PARP) inhibitor.

Methods: A discrete-choice experiment elicited preferences of women with ovarian cancer regarding 6 attributes (levels in parentheses) relevant to decisions for MT versus treatment break: (1) overall survival (OS; 36, 38, 42 months); (2) progression-free survival (PFS; 15, 17, 21 months); (3) nausea (none, mild, moderate); (4) fatigue (none, mild, moderate); (5) probability of death from myelodysplastic syndrome/acute myelogenous leukemia (MDS/AML; 0% to 10%); (6) monthly out-of-pocket cost ($0 to $1000). Participants chose between 2 variable MT scenarios and a static scenario representing treatment break, with multiple iterations. Random-parameters logit regression was applied to model choices as a function of attribute levels.

Results: 95 eligible participants completed the survey; mean age was 62, 48% had recurrence, and 17% were ever-PARP inhibitor users. Participants valued OS (average importance weight 24.5 out of 100) and monthly costs (24.6) most highly, followed by risk of death from MDS/AML (17.9), nausea (14.7), PFS (10.5) and fatigue (7.8). Participants would accept 5% risk of MDS/AML if treatment provided 2.2 months additional OS or 4.8 months PFS. Participants would require gains of 2.6 months PFS to accept mild treatment-related fatigue and 4.4 months to accept mild nausea.

Conclusions: When considering MT, women with ovarian cancer are most motivated by gains in OS. Women expect at least 3-4 months of PFS benefit to bear mild side effects of treatment.
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http://dx.doi.org/10.1016/j.ygyno.2020.01.026DOI Listing
March 2020

Lidocaine-Prilocaine Cream Compared With Injected Lidocaine for Vulvar Biopsy: A Randomized Controlled Trial.

Obstet Gynecol 2020 02;135(2):311-318

Department of Obstetrics and Gynecology, and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, and the Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina.

Objective: To compare pain control during vulvar biopsy after either application of 5% lidocaine-prilocaine cream or injection of 1% lidocaine.

Methods: In a single-site randomized trial, patients who needed vulvar biopsy on a non-hair-bearing surface were recruited from a gynecologic oncology clinic to compare lidocaine-prilocaine cream (placed at least 10 minutes before biopsy) with lidocaine injection (at least 1 minute prior). A sample size of 53 participants in each arm (N=106) was planned. Pain was recorded using a 100 mm visual analog scale at three time points: baseline, after application of anesthesia, and after biopsy. The primary outcome was highest pain score recorded. Secondary outcomes were pain score at biopsy, patient experience, and tolerability and acceptability. Linear regression was used to compare the primary outcome between arms while controlling for baseline vulvar pain. A convenience analysis was performed in March 2019.

Results: From October 2018 to March 2019, 38 patients completed informed consent and were randomized. Participants were women with median age of 60 years. Most characteristics between groups were similar. Nineteen were analyzed in the lidocaine-prilocaine group, and 18 were analyzed in the lidocaine injection group. The median highest pain score in the lidocaine-prilocaine group was 20.0 mm vs 56.5 mm in the lidocaine injection group. Controlling for baseline pain, the highest pain score in the lidocaine-prilocaine arm was 25.7 mm lower than in the lidocaine injection arm (95% CI [-45.1 to -6.3]; P<.01). Patients randomized to lidocaine-prilocaine had a significantly better experience than those receiving injected lidocaine (median experience score 2.0 mm vs 17.0 mm; P=.02).

Conclusion: Lidocaine-prilocaine cream before vulvar biopsy resulted in a lower maximum pain score and a significantly better patient rating of the biopsy experience when compared with lidocaine injection. Lidocaine-prilocaine cream, alone, is a reasonable option to use for vulvar biopsy.

Clinical Trial Registration: ClinicalTrials.gov, NCT03654417.
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http://dx.doi.org/10.1097/AOG.0000000000003660DOI Listing
February 2020

Cell-free DNA for Down syndrome screening in obese women: Is it a cost-effective strategy?

Prenat Diagn 2020 01 5;40(2):173-178. Epub 2019 Dec 5.

Division of Maternal and Fetal Medicine, Duke University Medical Center, Durham, NC.

Objective: Determine cost differences between cell-free DNA (cfDNA) and serum integrated screening (INT) in obese women given the limitations of aneuploidy screening in this population.

Methods: Using a decision-analytic model, we estimated the cost-effectiveness of trisomy 21 screening in class III obese women using cfDNA compared with INT. Primary outcomes of the model were cost, number of unnecessary invasive tests, procedure-related fetal losses, and missed cases of trisomy 21.

Results: In base case, the mean cost of cfDNA was $498 greater than INT ($1399 vs $901). cfDNA resulted in lower probabilities of unnecessary invasive testing (2.9% vs 3.5%), procedure-related loss (0.015% vs 0.019%), and missed cases of T21 (0.00013% vs 0.02%). cfDNA cost $87 485 per unnecessary invasive test avoided, $11 million per procedure-related fetal loss avoided, and $2.2 million per missed case of T21 avoided. In sensitivity analysis, when the probability of insufficient fetal fraction is assumed to be >25%, cfDNA is both costlier than INT and results in more unnecessary invasive testing (a dominated strategy).

Conclusion: When the probability of insufficient fetal fraction more than 25% (a maternal weight of ≥300 lbs), cfDNA is costlier and results in more unnecessary invasive testing than INT.
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http://dx.doi.org/10.1002/pd.5605DOI Listing
January 2020

Off-study utilization of experimental therapies: Analysis of GOG249-eligible cohorts using real world data.

Gynecol Oncol 2020 01 21;156(1):154-161. Epub 2019 Nov 21.

Department of Radiation Oncology, Duke University, Durham, NC, USA. Electronic address:

Objective: Adjuvant management of women with high-intermediate- and high-risk early-stage endometrial cancer remains controversial. Recently published results of GOG 249 revealed that vaginal brachytherapy plus chemotherapy (VBT + CT) was not superior to whole pelvic radiation therapy (WPRT) and was associated with more toxicities and higher nodal recurrences. This study examined off-study utilization of VBT + CT among women who met criteria for GOG 249 in the period prior to study publication.

Methods: Women diagnosed with FIGO IA-IIB endometrioid, serous, or clear cell uterine cancer between 2004-2015 and treated with hysterectomy and radiotherapy (RT) were identified in the National Cancer Database. Cochrane-Armitrage trend test was used to assess trends over time. Univariate and multivariate Cox analyses were performed to calculate odds ratio (OR) of VBT + CT receipt and hazard ratio (HR) of OS. Propensity-score matched analysis was conducted to account for baseline differences.

Results: 9956 women met inclusion criteria. 7548 women (75.8%) received WPRT while 2408 (24.2%) received VBT + CT in the study period. From 2004-2015, there was a significant increase in VBT + CT use (p < 0.001) with the largest overall increase occurring in 2009 to 22%. Factors significantly associated with VBT + CT receipt included higher socioeconomic status (p < 0.001), higher grade endometrioid cancer (p < 0.001), and aggressive histology (p < 0.001). After propensity-score matching, VBT + CT was associated with improved OS (HR 0.74, 95% CI 0.58-0.93); however, when stratified by FIGO stage, VBT + CT was only associated with improved OS for FIGO stage 1B (HR 0.62, 95% CI 0.44-0.87).

Conclusions: There was significant use of experimental arm off-study treatment in the United States prior to report of GOG 249 results. Providers should be cautious when offering off-study treatment utilizing an experimental regimen given uncertainty about efficacy and toxicity.
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http://dx.doi.org/10.1016/j.ygyno.2019.09.017DOI Listing
January 2020

Simulated Costs of the ASCO Patient-Centered Oncology Payment Model in Medicare Beneficiaries With Newly Diagnosed Advanced Ovarian Cancer.

J Oncol Pract 2019 12 15;15(12):e1018-e1027. Epub 2019 Oct 15.

Duke Cancer Institute, Durham, NC.

Purpose: Efforts to curb the rising costs of cancer care while improving quality include alternative payment models (APMs), which offer incentives to reduce avoidable spending and provide high-quality and cost-efficient care. The impact of proposed APMs has not been quantified in real-world practice. In this study, we evaluated ASCO's Patient-Centered Oncology Payment (PCOP) model in existing fee-for-service (FFS) Medicare beneficiaries to understand the magnitude of potential cost savings.

Materials And Methods: SEER-Medicare data were used to identify women with advanced ovarian cancer diagnosed between 2000 and 2012 who either (1) underwent primary debulking surgery followed by chemotherapy or (2) received neoadjuvant chemotherapy followed by surgery. Medicare payments in each cohort were used to compare FFS and PCOP and to estimate the potential for cost savings across health care services received, including outpatient emergency department visits, hospitalizations, and imaging.

Results: Three thousand seven hundred seventy-seven primary debulking surgery and 866 neoadjuvant chemotherapy patients were included in the study, with mean total costs of $75,433 and $95,138 in 2016 US$, respectively Most costs were related to chemotherapy or hospitalization. Additional PCOP-related payments would be offset if hospitalizations could be reduced by 11.6% or imaging claims by 88%.

Conclusion: APMs have the potential to reduce costs of current FFS reimbursement via either a large reduction in imaging or a modest reduction in hospitalizations during treatment of ovarian cancer. PCOP is a reasonable payment structure for oncologists if the additional payments can provide the necessary resources to invest in improved coordination of care.
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http://dx.doi.org/10.1200/JOP.19.00026DOI Listing
December 2019

Patient preferences for attributes of primary surgical debulking versus neoadjuvant chemotherapy for treatment of newly diagnosed ovarian cancer.

Cancer 2019 12 27;125(24):4399-4406. Epub 2019 Aug 27.

Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina.

Background: Randomized trials have reported conflicting findings on survival for advanced-stage ovarian cancer treated with primary debulking surgery (PDS) versus neoadjuvant chemotherapy with interval debulking; surgical complications and mortality are higher with PDS. We assessed women's preferences for tradeoffs related to this important clinical decision.

Methods: Ovarian cancer patients were recruited to complete a discrete-choice experiment (DCE) consisting of 8 choice tasks presenting experimentally designed treatment alternatives in terms of treatment order, extent of surgery including risk of ostomy, chance of death from surgical complications (1%-10%), readmission for surgical complications (5%-50%), progression-free survival (1-3 years), and overall survival (3-5 years). Random-parameters logit regression was applied to model participants' choices as a function of attribute levels.

Results: A total of 101 ovarian cancer survivors completed the DCE survey; of these participants, 30% were receiving chemotherapy at the time, and 33% had prior recurrence. Overall survival was of greatest importance to participants (36/100), followed by risk of readmission due to complications (23/100), progression-free survival (19/100), surgical mortality (16/100), extent of surgery (4/100), and order of surgery and chemotherapy (2/100). Overall, the participants would tolerate a 15-percentage point increase in risk of major complications (95% confidence interval [CI], 3%-29%) or a 4-percentage point increase in the risk of surgical mortality (95% CI, 2%-13%) in order to increase their expected overall survival from 3 to 3.5 years.

Conclusions: Patients would accept a moderately higher risk of perioperative complications and surgical mortality in exchange for substantial gains in survival. These quantitative findings provide clinicians with a framework to discuss preferences with patients and to incorporate preferences into clinical trial design.
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http://dx.doi.org/10.1002/cncr.32447DOI Listing
December 2019

Place of death by region and urbanization among gynecologic cancer patients: 2006-2016.

Gynecol Oncol 2019 10 1;155(1):98-104. Epub 2019 Aug 1.

Duke Cancer Institute, Department of Radiation Oncology, Durham, NC, United States of America; Duke University Medical Center, Department of Radiation Oncology, Durham, NC, United States of America.

Objective: To evaluate associations between US region of residence and urbanization and the place of death among women with gynecologic malignancies in the United States.

Methods: A retrospective cross-sectional study was performed using publicly available death certificate data from the National Center for Health Statistics. All gynecologic cancer deaths were included from 2006 to 2016. Comparisons among categories were performed with a two-tailed chi-square test, with p-values <0.05 considered significant.

Results: From 2006 to 2016, 328,026 women died from gynecologic malignancies in the US. Of these deaths, 40.1% (n = 134,333) occurred in the patient's home, 24.9%(n = 81,823) in the hospital, and 11.3% (37,188) in an inpatient hospice facility. Place of death varied by geographic region. The Northeast had the largest percentage of gynecologic cancer patients (31.3%) die as a hospital inpatient. The West had the highest percentage of deaths (49.3%) at home. Deaths in a hospice facility were the highest (14.1%) in the South. Place of death varied by urbanization; patients residing in large central metro or rural counties were the most likely to die during hospital admission (28.7% and 27.1%, respectively). Patients living in medium-sized metro areas were the least likely to die in hospitals (21.8%) and most likely to die in a hospice facility (14.3%). All comparisons were significant by study definition.

Conclusion: The place of death for patients with gynecologic malignancies varies by US region and urbanization. These disparities are multifactorial in nature, likely influenced by both sociodemographic factors and regional resource availability. In this study, however, rural and central metro areas are identified as regions that may benefit from further hospice development and advocacy.
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http://dx.doi.org/10.1016/j.ygyno.2019.07.013DOI Listing
October 2019

Gender variation in Medicare utilization and payments in gynecologic oncology.

Gynecol Oncol 2019 09 12;154(3):602-607. Epub 2019 Jul 12.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, United States of America. Electronic address:

Objectives: The Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File (POSPUF) and Medicare Physician and Other Supplier National Provider Identifier (POS NPI) Aggregate Report are publicly available files from the Center for Medicare and Medicaid Services that include payments to providers who care for fee-for-service Medicare recipients. The aim of this study was to analyze variability in gynecologic oncologists' Medicare reimbursements, with attention to differences in provider gender and time in practice.

Methods: The 2015 POSPUF and POS NPI were analyzed with respect to gynecologic oncologists. We searched external publicly available data sources to confirm subspecialty and to determine each provider's number of years in practice. Evaluation and management (E&M) and procedure/surgery codes were analyzed; drug delivery codes were excluded due to variability in billing by facility/hospital.

Results: The POS NPI file included 733 gynecologic oncologist providers receiving $55,626,739 in total payments. Female providers comprised 39% of gynecologic oncologists and received 31% of reimbursements (30% of E&M reimbursements and 24% of surgical reimbursements). During the first ten years in practice, female providers comprised 58% of providers and accounted for 52% of reimbursed services, compared to 38% of providers/26% of reimbursed services (11-20 years), and 18% of providers/19% of reimbursed services (>20 years).

Conclusion: Male gynecologic oncologists perform more Medicare services than their female counterparts. There is a comparable number of services performed between genders among both the most senior and the most junior providers, with a gender gap in services and reimbursements among mid-career providers.
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http://dx.doi.org/10.1016/j.ygyno.2019.06.007DOI Listing
September 2019

Associations between lymphovascular space invasion, nodal recurrence, and survival in patients with surgical stage I endometrioid endometrial adenocarcinoma.

World J Surg Oncol 2019 May 10;17(1):80. Epub 2019 May 10.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA.

Objective: To investigate the predictive value of lymphovascular space invasion (LVSI) for nodal recurrence and overall survival (OS) in patients with stage I endometrioid endometrial cancer (EC) following surgical staging that included adequate lymph node sampling.

Methods: Retrospective analyses of patients undergoing surgical staging for FIGO stage I endometrioid EC between 1998 and 2015 were performed using an institutional database and the National Cancer Database (NCDB). Using the institutional database, logistic regression modeling identified predictors of nodal recurrence; Cox proportional hazards modeling was used to predict progression-free survival (PFS). Utilizing NCDB, Cox proportional hazards modeling was used to predict OS. The Kaplan-Meier method was used to estimate hazard ratios (HR). Survival curves were compared using the log-rank test.

Results: Among 275 institutional cases, LVSI was present in 48 (17.5%). There were 11 nodal recurrences: 18.8% (9/48) of cases with LVSI had a nodal recurrence compared to 0.88% (2/227) of those without LVSI. In multivariate analysis of institutional data, LVSI was the only significant predictor of nodal recurrence (p = 0.002). Among 28,076 NCDB cases, LVSI was present in 3766 (13.5%). In multivariate analysis of NCDB, grade 3, LVSI, and depth of invasion (all p <  0.001) were prognostic for OS after adjusting for adjuvant radiation.

Conclusion: LVSI is an independent prognostic factor for nodal recurrence in stage I endometrial cancer with lymph node assessment. LVSI is associated with lower OS in NCDB. Given these findings, adjuvant therapy could be considered in these patients.
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http://dx.doi.org/10.1186/s12957-019-1620-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511118PMC
May 2019

Radiation Records in the National Cancer Database: Variations in Coding and/or Practice Can Significantly Alter Survival Results.

JCO Clin Cancer Inform 2019 05;3:1-9

Duke University Medical Center, Durham, NC.

Purpose: The aim of the current work was to quantify internally inconsistent and anomalous radiation therapy (RT) data in the National Cancer Database (NCDB) and determine their association with overall survival (OS) using node-positive uterine cancer as a test clinical scenario.

Materials And Methods: We identified all NCDB participants with International Federation of Gynecology and Obstetrics stage IIIC1 to IIIC2 uterine cancer treated with hysterectomy and adjuvant RT between 1998 and 2012. Variables that were reviewed to identify anomalous data included RT site, modality, dose, fractions, timing, duration, and stage. We used χ testing to associate anomalous data with reporting facility and demographic variables. OS was estimated using the Kaplan-Meier method and comparison between cohorts was performed using the log-rank test. Univariable and multivariable Cox proportional hazards regression analyses were performed.

Results: Of the 14,298 analyzed participants, 2,288 (16.0%) had one or more anomalous data entry, 538 (3.8%) likely because of an incomplete RT course. χ testing suggested differences in anomalous data prevalence by reporting facility type ( = .0007), geographic region ( < .001), distance from participants' homes ( < .001), diagnosis year ( < .001), and location of RT relative to reporting facility ( = .0038). Five-year OS in those with one or more anomalous data entry was 51.3% versus 58.0% for those without anomalous data ( < .001), and anomalous data remained significantly associated with OS on multivariable analysis. After excluding insufficient, excessive, or unknown total RT dose, anomalous data were no longer significant on multivariable analysis.

Conclusion: The overwhelming majority of RT data within the NCDB seem to be appropriate for the clinical scenario. Nevertheless, approximately one eighth of participants in this test clinical scenario had adjuvant RT data that were internally inconsistent or outside generously defined norms. The presence of anomalous RT data was significantly associated with compromised OS, an effect not observed after correcting for total RT dose.
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http://dx.doi.org/10.1200/CCI.18.00118DOI Listing
May 2019

Constitutively active ESR1 mutations in gynecologic malignancies and clinical response to estrogen-receptor directed therapies.

Gynecol Oncol 2019 07 13;154(1):199-206. Epub 2019 Apr 13.

Duke University Medical Center, Durham, NC, United States of America.

Objective: Endocrine therapy is often considered as a treatment for hormone-responsive gynecologic malignancies. In breast cancer, activating mutations in the estrogen receptor (mutESR1) contribute to therapeutic resistance to endocrine therapy, especially aromatase inhibitors (AIs). The purpose of this study was to evaluate the frequency and clinical relevance of ESR1 genomic alterations in gynecologic malignancies.

Methods: DNA from FFPE tumor tissue obtained during routine clinical care for 9645 gynecologic malignancies (ovary, fallopian tube, uterus, cervix, vagina, vulvar, and placenta) was analyzed for all classes of genomic alterations (base substitutions (muts), insertions, deletions, rearrangements, and amplifications) in ESR1 by hybrid capture next generation sequencing. A subset of alterations was characterized in laboratory-based transcription assays for response to endocrine therapies.

Results: A total of 295 ESR1 genomic alterations were identified in 285 (3.0%) cases. mutESR1 were present in 86 (0.9%) cases and were more common in uterine compared to other cancers (2.0% vs <1%, respectively p < 0.001). mutESR1 were enriched in carcinomas with endometrioid versus serous histology (4.4% vs 0.2% respectively, p < 0.0001 in uterine and 3.5% vs 0.3% respectively, p = 0.0004 in ovarian carcinomas). In three of four patients with serial sampling, mutESR1 emerged under the selective pressure of AI therapy. Despite decreased potency of estrogen receptor (ER) antagonists in transcriptional assays, clinical benefit was observed following treatment with selective ER-targeted therapy, in one case lasting >48 months.

Conclusions: While the prevalence of ESR1 mutations in gynecologic malignancies is low, there are significant clinical implications useful in guiding therapeutic approaches for these cancers.
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http://dx.doi.org/10.1016/j.ygyno.2019.04.010DOI Listing
July 2019

Phase II trial of nintedanib in patients with bevacizumab-resistant recurrent epithelial ovarian, tubal, and peritoneal cancer.

Gynecol Oncol 2019 06 28;153(3):555-561. Epub 2019 Mar 28.

Division of Gynecologic Oncology, University of Virginia, United States of America.

Background: Bevacizumab provides benefit in epithelial ovarian cancer (EOC), yet resistance to bevacizumab often occurs. We determined if nintedanib, a tyrosine kinase inhibitor of VEGF, FGF, and PDGF receptors has antitumor activity in bevacizumab-resistant recurrent EOC, tubal, and peritoneal cancer.

Methods: This phase II study evaluated nintedanib 200 mg/day until disease progression or unacceptable toxicity. The primary objective was 6-month progression free survival (PFS6m). Secondary objectives were response rate and toxicity. Simon two-stage optimal design was used. Baseline angiogenic plasma biomarkers were measured.

Results: 27 patients were enrolled evaluable for PFS; 26 were evaluable for PFS6m. The median age was 65 years (range 44-73); 89.9% had high-grade serous EOC; 70% received at least >2 prior chemotherapies; and 81% (22/27) had chemoresistant disease. With median follow up of 15.6 months (range 2-38) the PFS6m rate was 11.5% (3/26). Three participants had long duration of disease control (8-16 months). Median PFS and overall survival were 1.8 and 16 months, respectively. Response rate was 7.4% (2/27 PR). Thirty-seven percent (10/27) had stable disease, while 56% (15/27) had progressive disease. Adverse events included Grade 3 liver enzyme elevation (15%), Grade 3 diarrhea (7%), Grade 2 fatigue (7%), and Grade 2 nausea/vomiting (15%). PD patients exhibited higher levels of CD73, IL6, and VEGFD (p < 0.05) compared to PR/SD patients. IL6 was associated with worse PFS (p = 0.03).

Conclusions: Single-agent nintedanib has minimal activity in an unselected bevacizumab-resistant EOC population. Nintedanib was tolerable and toxicities were manageable. Plasma CD73, IL6, and VEGFD were identified as prognostic markers for progressive disease, and IL6 was associated with worse PFS confirming similar observations made in patients treated with other anti-angiogenic agents.
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http://dx.doi.org/10.1016/j.ygyno.2019.03.246DOI Listing
June 2019

The cost-effectiveness of ertapenem for the treatment of chorioamnionitis after cesarean delivery.

J Matern Fetal Neonatal Med 2020 Dec 28;33(24):4096-4101. Epub 2019 Mar 28.

Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Duke University, Duke University Medical Center, Durham, NC, USA.

Chorioamnionitis affects 1-4% of pregnancies, and patients who undergo cesarean delivery in the setting of chorioamnionitis have an increased risk of endometritis and surgical site infection (SSI). The standard treatment for chorioamnionitis after cesarean delivery is a combination regimen of intravenous ampicillin, gentamicin, and clindamycin with variable duration (single dose to 24 h). However, newer evidence suggests that ertapenem may decrease the risk of postoperative infectious morbidity with the added benefit of a single postpartum dose, compared to between 3 and 10 doses of AGC. Concerns regarding the cost of ertapenem have been cited as a deterrent for this regimen. The objective of this study was to investigate the cost-effectiveness of single-dose ertapenem compared to existing standard regimens. A decision analytic cost-effectiveness model was designed from a hospital perspective to compare four strategies for the postpartum management of chorioamnionitis after cesarean delivery: (i) no antibiotics; (ii) a one-time intravenous dose of ampicillin, gentamicin, and clindamycin (AGC-1); (iii) 24-h coverage with intravenous ampicillin, gentamicin, and clindamycin (AGC-24); and (iv) intravenous ertapenem, one dose. Medical costs, rates of SSI and endometritis following cesarean delivery, and costs of postcesarean infection (SSI or endometritis) were abstracted from the literature. Antibiotic drug costs were obtained from the pharmacy department at a private academic hospital. The cost of each regimen was calculated as costs to the hospital and included antibiotics (no antibiotics $0, AGC-1 $66, ertapenem $140, and AGC-24 $208), administration, and labor costs. Effectiveness was quantified as percentage of patients who avoided postcesarean infectious morbidity (endometritis or SSI). The base case cost of each strategy was: AGC-1 $704, ertapenem $733, AGC-24 $846, and no antibiotics $971. Ertapenem had an effectiveness of 88%, AGC-1 and AGC-24 were 87% each, and no antibiotics was 81%. No antibiotics and AGC-24 were more costly and equally or less effective than comparators (dominated strategies). Ertapenem was more costly, but more effective than AGC-1, with an incremental cost-effectiveness ratio of $3738 per infection avoided. In a sensitivity analysis comparing ertapenem to the most commonly used strategy of ACG-24, the ertapenem strategy remained less costly if the rate of endometritis with ertapenem was <11% (base case estimate 8%) or the rate of SSI with ertapenem was <7% (base case estimate 4%). Ertapenem is a cost-saving alternative to 24-h AGC treatment for chorioamnionitis in the setting of cesarean delivery, and may be considered a cost-effective treatment when compared to a one time dose of AGC depending on infection rates.
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http://dx.doi.org/10.1080/14767058.2019.1597042DOI Listing
December 2020

A pilot study of lower extremity lymphedema, lower extremity function, and quality of life in women after minimally invasive endometrial cancer staging surgery.

Gynecol Oncol 2019 05 15;153(2):399-404. Epub 2019 Mar 15.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University, Durham, NC, United States of America; Duke Cancer Institute, Durham, NC, United States of America.

Objective: The primary aim of this study was to pilot the use of an objective measurement technique to prospectively evaluate the incidence of lower extremity lymphedema (LEL) after minimally invasive staging surgery for endometrial cancer. Secondary objectives included observation of changes in lower extremity function and quality of life in this patient population.

Methods: A prospective evaluation of LEL was performed in 97 women who underwent minimally invasive staging surgery for endometrial cancer using comparative circumferential volume measurements. Postoperative changes in lower extremity function and global quality of life were also assessed using patient-reported outcome measures.

Results: Ninety-seven patients were included for lymphedema analysis. The rate of LEL was 25% at 4-6 weeks, 19% at 6-9 months, and 27% at 12-18 months postoperatively. The presence of LEL was associated with a significant worsening from baseline Lower Extremity Functional Scale (LEFS) scores at 4-6 weeks (-27.0% vs -3.7%, p = 0.02) and 6-9 months (-13.0% vs 0%, p = 0.01). LEL was not associated with a change in patient-reported global quality of life.

Conclusions: Up to one in four women experience lymphedema following surgical staging for endometrial cancer, and its presence is associated with diminished lower extremity function. Larger, prospective trials using the objective methodology piloted in this study should better clarify risk factors and long-term outcomes of this morbidity.
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http://dx.doi.org/10.1016/j.ygyno.2019.02.021DOI Listing
May 2019

Targeted composite value-based endpoints in platinum-sensitive recurrent ovarian cancer.

Gynecol Oncol 2019 03;152(3):445-451

Duke University Medical Center, Durham, NC, USA.

Objectives: FDA-approved treatments for platinum-sensitive recurrent ovarian cancer (PSROC) include bevacizumab and PARP inhibitors (PARPi); clinical decisions regarding therapy must be made prior to initiating chemotherapy. Using the American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) value frameworks, we assessed relative values of concurrent/maintenance biologic therapies in PSROC.

Methods: Value scores were calculated for key maintenance therapies based on randomized controlled trials: bevacizumab (OCEANS, GOG 213); olaparib (Study 19, SOLO2); niraparib (NOVA); rucaparib (ARIEL3). Personalized value scorecards were constructed for patients with germline/somatic-BRCA mutations, homologous recombination deficiency (HRD), and wild-type BRCA (wBRCA). ASCO value scores assess clinical benefit, toxicity, long-term survival, symptom palliation, treatment-free interval, and quality of life (QOL). ESMO value scores assess clinical benefit, toxicity, and QOL.

Results: ASCO scores were highest for maintenance PARPi in germline/somatic-BRCA mutation cohorts: olaparib (SOLO2) = 47, (Study 19) = 62; niraparib = 50; rucaparib = 54. HRD cohorts had slightly lower scores: niraparib = 46; rucaparib = 37. wBRCA cohorts had the lowest scores: niraparib = 26; rucaparib = 26; and olaparib (Study 19) = 32, as did patients receiving bevacizumab (OCEANS) = 35, (GOG 213) = 26. ESMO scores demonstrated high-value for maintenance PARPi in germline/somatic-BRCA mutation cohorts and low-value for bevacizumab and PARPi in wBRCA cohorts.

Conclusions: The value of maintenance PARPi therapy depends heavily on BRCA status, with the highest value scores in germline/somatic-BRCA mutation cohorts. Personalized value scorecards provide a visual aid to assess the harm-benefit balance of maintenance PARPi for PSROC.
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http://dx.doi.org/10.1016/j.ygyno.2018.11.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522787PMC
March 2019

U.S. Food and Drug Administration-Approved Poly (ADP-Ribose) Polymerase Inhibitor Maintenance Therapy for Recurrent Ovarian Cancer: A Cost-Effectiveness Analysis.

Obstet Gynecol 2019 04;133(4):795-802

Division of Surgery, Department of Gynecologic Oncology and Reproductive Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas; and the Division of Gynecologic Oncology, Duke University Medical Center, Durham, North Carolina.

Objective: We sought to determine whether use of a poly (ADP-ribose) polymerase inhibitor is cost effective for maintenance treatment of platinum-sensitive recurrent ovarian cancer.

Methods: A decision analysis model compared four maintenance strategies: 1) observation, 2) BRCA germline mutation testing and selective treatment of carriers (gBRCA only), 3) BRCA germline and tumor homologous recombination deficiency testing and selective treatment of either BRCA carriers or those with tumor HRD (gBRCA and HRD only), and 4) treat all with niraparib to progression (treat all). Costs were estimated in 2016 U.S. dollars. Incremental cost-effectiveness ratios were in dollars per progression-free quality-adjusted life-year (QALY). One-way sensitivity analyses tested multiple assumptions.

Results: Maintenance poly (ADP-ribose) polymerase inhibitor was costlier and more effective than observation. Mean costs and progression-free QALYs were $827 and 3.4 months for observation, $46,157 and 5.7 for a BRCA-only strategy, $109,368 and 8.5 for a gBRCA and homologous recombination deficiency-only strategy, and $169,127 and 8.8 for a treat-all strategy. gBRCA-only had an incremental cost-effectiveness ratio of $243,092/progression-free QALY compared with observation; other strategies did not approach cost effectiveness. Using the current U.S. Food and Drug Administration label for maintenance poly (ADP-ribose) polymerase inhibitor regardless of biomarker status, the third-party payer cost per month (28-day supply) would need to be reduced from approximately $14,700 to $3,600 to be considered cost effective compared with observation using a willingness to pay threshold of $100,000/progression-free QALY.

Conclusion: Maintenance poly (ADP-ribose) polymerase inhibitor therapy for platinum-sensitive recurrent ovarian cancer is not cost effective. Treatment of patients with BRCA mutation alone or with homologous recombination deficiency-positive tumors are preferred strategies compared with a treat-all strategy. Lowering the cost may make selective niraparib maintenance therapy cost effective compared with observation.
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http://dx.doi.org/10.1097/AOG.0000000000003171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181403PMC
April 2019

Impact of a documentation intervention on health-assessment metrics on an inpatient gynecologic oncology service.

Gynecol Oncol 2019 05 27;153(2):385-390. Epub 2019 Feb 27.

Department of Obstetrics and Gynecology, Duke University Medical Center, United States of America; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, United States of America.

Objective: Accurate documentation is critical for patient care and hospital reimbursement. We sought to improve the accuracy of severity of illness (SOI) and risk of mortality (ROM) scores through implementation of documentation initiatives.

Methods: We performed a pre- versus post-implementation analysis to assess the impact of a documentation intervention bundle on calculated admission/discharge SOI/ROM scores on an inpatient gynecologic oncology service. Introduced in January 2017, the bundle included educational in-service, introduction of problem-based progress notes, a documentation tip ID badge and video, and weekly chart audits. Admission/discharge SOI/ROM scores (range 1-4) were obtained from hospital performance services. Demographics and 30-day mortality were collected from electronic medical records for all inpatients in historic (calendar year 2015) and intervention (2017) cohorts. Primary outcomes (discharge SOI/ROM) were modelled using ordinal and multinomial logistic regressions, controlling for confounders. 30-day observed/expected mortality ratios were reported for each cohort.

Results: 629 patients were included: 378 (60%) in 2015, 251 (40%) in 2017. Increased odds of having higher SOI score were observed in the intervention cohort for medical (OR = 2.22; 95% CI 1.38, 3.58) and surgical admissions (OR = 2.63; 95% CI 1.47, 4.40). Surgical (OR = 5.54; 95% CI 1.29, 23.96), but not medical (OR = 1.45; 95% CI 0.46, 4.57), admissions in the intervention cohort had higher odds of having the worst ROM score. Observed/expected mortality was 0.24 in the intervention compared to 0.37 in historic cohort (p = 0.58, NS).

Conclusion: An intervention bundle to improve physician documentation accuracy resulted in higher discharge SOI scores for medical and surgical admissions.
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http://dx.doi.org/10.1016/j.ygyno.2019.02.009DOI Listing
May 2019

Cost-effectiveness of hyperthermic intraperitoneal chemotherapy (HIPEC) at interval debulking of epithelial ovarian cancer following neoadjuvant chemotherapy.

Gynecol Oncol 2019 05 1;153(2):376-380. Epub 2019 Feb 1.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, United States of America; Duke Cancer Institute, United States of America. Electronic address:

Objectives: A recent randomized controlled trial demonstrated an overall survival benefit to the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to neoadjuvant chemotherapy (NACT) for stage III epithelial ovarian cancer (EOC). The objective of the current study was to quantify the cost-effectiveness of HIPEC in this setting.

Methods: A decision analytic cost-effectiveness model was designed from a payer perspective to compare 2 surgical management strategies for EOC: (1) interval cytoreductive surgery (ICS); (2) ICS + HIPEC. Overall survival and ostomy rates with HIPEC were modeled from published studies. We assumed that 25% of each arm would later undergo secondary cytoreductive surgery, with the ICS arm eligible for HIPEC at that time. Costs were obtained from Medicare data, published studies, and the financial department of an academic hospital. Quality of life was not different between the arms; we assigned utilities based on a prior time-trade off study of ovarian cancer treatment. A Monte Carlo probabilistic sensitivity analysis was performed in the base case; primary outcome was the incremental cost-effectiveness ratio (ICER), expressed in 2017 US Dollars/quality-adjusted life years (QALYs).

Results: ICS was the least costly strategy at $78,849, compared to ICS + HIPEC at $79,954. ICS + HIPEC was more effective than ICS (2.9 QALYs versus 2.45 QALYs for ICS). ICS + HIPEC was highly cost-effective, with an ICER of $2436/QALY compared to ICS. In one-way sensitivity analyses, probability of ostomy reversal and use of HIPEC at secondary cytoreduction did not substantially impact the cost-effectiveness of ICS + HIPEC.

Conclusion: ICS + HIPEC constitutes cost-effective management of stage III EOC when NACT is performed.
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http://dx.doi.org/10.1016/j.ygyno.2019.01.025DOI Listing
May 2019

Preferences of women with epithelial ovarian cancer for aspects of genetic testing.

Gynecol Oncol Res Pract 2019 22;6. Epub 2019 Jan 22.

1Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Duke Cancer Institute, Box 3079, Durham, NC 27710 USA.

Background: Although genetic testing is recommended for women with epithelial ovarian cancer (EOC), little is known about patient preferences for various testing options. We measured relative preferences for attributes of testing in women with EOC referred for genetic counseling.

Methods: Subjects were recruited to participate in a discrete-choice-experiment survey to elicit preferences for attributes of genetic testing: out-of-pocket cost ($0, $100, $250, or $1000), probability of a deleterious mutation (60, 80%, or 88%), probability of a variant of uncertain significance (VUS) result (5, 20%, or 40%), sample requirements (blood or saliva), and turn-around time (1, 2 or 4 weeks). Subjects viewed educational videos followed by a series of choices between pairs of constructed genetic tests with varying attribute levels. Random-parameters logit was used to estimate preference weights for attribute levels. Relative importance weights and money-equivalent values were calculated.

Results: Ninety-four patients were enrolled; 68 (76.4%) presented for genetic counseling. Test cost was the most important attribute to subjects (importance weight = 41 out of 100) followed by probability to detect deleterious mutations (36) and probability of a VUS result (20). Sample requirements and turnaround time did not drive test choices. Subjects were willing to pay an additional $155 and $70 for incremental 5% improvements in the probability to detect deleterious mutations and probability of a VUS result. At genetics consultation, 55/68 (80.9%) subjects chose multigene testing.

Conclusions: Low out-of-pocket cost, high probability of detecting deleterious mutations and high probability of a VUS result are preferred by patients with EOC considering genetic testing.
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http://dx.doi.org/10.1186/s40661-019-0066-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341581PMC
January 2019

Changes in insurance coverage for cancer patients receiving brachytherapy before and after enactment of the Affordable Care Act.

Brachytherapy 2019 Jan - Feb;18(1):115-121. Epub 2018 Oct 21.

Department of Radiation Oncology, Duke University Medical Center, Durham, NC. Electronic address:

Purpose: The Patient Protection and Affordable Care Act called for expansion of Medicaid in 2014. As some states elected to expand Medicaid and others did not, the goal of this study was to determine the effect of Medicaid expansion on the insurance status at cancer diagnosis of brachytherapy patients.

Methods And Materials: Patients aged 19-64 years with breast, cervical, uterine, or prostate cancer treated with brachytherapy from 2011 to 2014 with known insurance status were identified within the Surveillance, Epidemiology, and End Results registry. Fisher's exact test was used to test for associations of insurance status with expanded versus nonexpanded states. For multivariate analysis, a binomial logistic regression was performed, dichotomized to uninsured versus any insurance.

Results: Fifteen thousand four hundred ninety-seven subjects met entry criteria. In the entire cohort, rates of uninsurance were higher in nonexpanded states at baseline (4.5% vs. 2.9%, p < 0.00001). With selective Medicaid expansion in 2014, expanded states had a reduction in uninsurance rates (2.9-1.8%, p = 0.026), whereas nonexpanded states had a nonsignificant increase in uninsurance (4.5-5.0%, p = 0.371). There was a reduction in uninsurance in expanded states in areas of highest poverty (2.9-1.1%, p = 0.0004) not seen in nonexpanded states. These associations remained significant on multivariate analysis (OR 2.2, 95% CI 1.8-2.8, p < 0.00001).

Conclusions: Patients who received brachytherapy were less likely to be uninsured in states where Medicaid was expanded, particularly evident in regions with highest poverty levels. These results should help inform policy decisions and efforts to ensure that all patients have access to high quality treatments, such as brachytherapy.
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http://dx.doi.org/10.1016/j.brachy.2018.08.017DOI Listing
April 2019