Publications by authors named "Paula S Lee"

41 Publications

Placental uterine artery embolization followed by delayed hysterectomy for placenta percreta: A case series.

Gynecol Oncol Rep 2021 Aug 16;37:100833. Epub 2021 Jul 16.

Division of Gynecologic Oncology, Duke Cancer Institute, Duke University Hospital, Durham, NC, USA.

We describe outcomes of patients with suspected placenta percreta treated with placental uterine artery embolization (P-UAE) followed by delayed hysterectomy. This is a prospective case series of subjects from 2005 to 2018 with suspected placenta percreta who underwent P-UAE at the time of cesarean delivery followed by delayed hysterectomy. Both scheduled and unscheduled surgical cases were included. Maternal characteristics, surgical approaches, intra- and postoperative outcomes were abstracted from medical records. In total, twenty-two subjects were included. Median (interquartile range, IQR) delivery gestational age was 34.6 (31.9, 35.7) weeks, occurring as scheduled in 17 (77.3%) subjects and unscheduled in 5 (22.7%). Delayed hysterectomy was performed as scheduled in 17 (77.3%) subjects at a median (IQR) 40.5 (38.0, 44.0) days after delivery, and 5 (22.7%) subjects had a hysterectomy prior to scheduled date, median (IQR) 27.0 (17.0, 35.0) days after delivery. Indications for the 5 unscheduled hysterectomies included bleeding (n = 3) and suspected endometritis (n = 2). Three subjects (13.6%) received a blood transfusion (1, 3, 3 units) during delivery, and 7 (31.8%) were transfused during delayed hysterectomy (median [IQR] 2 [1,3] units). Three (13.6%) subjects had bladder resection at the time of hysterectomy; 1 (4.5%) had an unintentional cystotomy and 1 (4.5%) had a ureteral injury. P-UAE followed by delayed hysterectomy appears to be a safe and feasible, although appropriate patient selection and close surveillance are imperative, as 22.7% of patients underwent unscheduled hysterectomy.
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http://dx.doi.org/10.1016/j.gore.2021.100833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326725PMC
August 2021

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

Int J Gynecol Cancer 2020 10 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

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

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

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

Hysterectomy with sentinel lymph node biopsy in the setting of pre-operative diagnosis of endometrial intraepithelial neoplasia: A cost-effectiveness analysis.

Gynecol Oncol 2018 12 23;151(3):506-512. Epub 2018 Sep 23.

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

Objectives: Sentinel lymph node biopsy (SLNB) may be considered in the setting of a pre-operative diagnosis of endometrial intraepithelial neoplasia (EIN) due to high rates of concurrent invasive cancer. The aim of this study is to compare the cost-effectiveness of different surgical management strategies for a pre-operative diagnosis of EIN.

Methods: A decision model was developed from a third party payer perspective to compare four surgical strategies for the management of EIN: (1) hysterectomy; (2) hysterectomy with frozen section (hysterectomy + frozen); (3) hysterectomy with SLNB (hysterectomy + SLNB); (4) hysterectomy with frozen section and SLNB (hysterectomy + frozen + SLNB). The probability that frozen section identifies high- or low-risk cancer, final pathology distribution, adjuvant treatments, and surgery/imaging costs were abstracted from the literature, Medicare reimbursement data, and the financial department of a private academic hospital. Adjuvant treatments were determined through NCCN guidelines and published studies. Effectiveness was quantified as percentage of patients who received the guideline-based treatment that aligned with their true stage.

Results: The base case cost and effectiveness of each strategy was: hysterectomy-$4383/89%, hysterectomy + frozen-$5220/99.2%, hysterectomy + SLNB-$5354/94.7% and hysterectomy + frozen + SLNB-$5938/99.6%. Hysterectomy + frozen had an incremental cost effectiveness ratio of $8111 per patient who received adjuvant treatment that aligned with true stage compared to hysterectomy. Hysterectomy + frozen + SLNB had an ICER of $168,171 per additional patient who received adjuvant treatment that aligned with their true stage compared to hysterectomy + frozen.

Conclusion: Hysterectomy + frozen + SLNB is a costly strategy for pre-operative EIN when compared to hysterectomy + frozen, with limited clinical benefit. Hysterectomy with frozen section and subsequent intraoperative staging decisions should continue to be standard of care.
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http://dx.doi.org/10.1016/j.ygyno.2018.09.020DOI Listing
December 2018

Near-infrared fluorescence for detection of sentinel lymph nodes in women with cervical and uterine cancers (FILM): a randomised, phase 3, multicentre, non-inferiority trial.

Lancet Oncol 2018 10 22;19(10):1394-1403. Epub 2018 Aug 22.

Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

Background: Accurate identification of sentinel lymph nodes in patients with cancer improves detection of metastatic disease and decreases surgical morbidity. We sought to establish whether indocyanine green fluorescent dye is non-inferior to isosulfan blue dye in detecting sentinel lymph nodes in women with cervical and uterine cancers.

Methods: In this non-inferiority, within-patient comparison study, patients aged 18 years or older with clinical stage I endometrial or cervical cancer undergoing curative surgery were randomly assigned 1:1 to lymphatic mapping with isosulfan blue dye (visualised by white light) followed by indocyanine green (visualised by near-infrared imaging), or indocyanine green followed by isosulfan blue dye. Permuted block randomisation with stratification by study site was done with a computerised random number generator. All participants were masked to their randomisation assignment until after the procedure; however, investigators were not masked to the procedure used. Laparoscopic surgery with the PINPOINT near-infrared fluorescence imaging system (Stryker, Kalamazoo, MI, USA) was used in all cases. The primary outcome was efficacy of intraoperative indocyanine green with near-infrared fluorescence imaging versus that of isosulfan blue dye in the identification of lymph nodes, defined as the number of lymph nodes identified by indocyanine green and isosulfan blue dye, respectively (and confirmed as lymphoid tissue by histology), divided by the number of lymph nodes identified intraoperatively and excised. The study had a 5% non-inferiority margin needed to show non-inferiority of the frequency of lymph node detection with indocyanine green to that with isosulfan blue dye with 80% power at a 5% two-sided significance level. Analyses were done in both per-protocol and modified intention-to-treat populations. The trial was registered with ClinicalTrials.gov, number NCT02209532, and is completed and closed.

Findings: Between Dec 21, 2015, and June 19, 2017, 180 patients were enrolled and randomly assigned to the two groups (90 to each group); 176 patients received the intervention and were evaluable (modified intention-to-treat population). 13 patients with major protocol violations were subsequently excluded from the per-protocol population. 517 sentinel nodes were identified in the per-protocol population (n=163), of which 478 (92%) were confirmed to be lymph nodes on pathological processing: 219 (92%) of 238 nodes that were both blue and green, all seven nodes that were blue only, and 252 (95%) of 265 nodes that were green only (p=0·33). Seven sentinel lymph nodes were neither blue nor green but were removed for appearing suspicious or enlarged on visual examination. In total, 471 (97%) of 485 lymph nodes were identified with the green dye and 226 (47%) with the blue dye (difference 50%, 95% CI 39-62; p<0·0001). In the modified intention-to-treat population (n=176), 545 nodes were identified, of which 513 (94%) were confirmed to be lymph nodes on pathological processing: 229 (92%) of 248 nodes that were both blue and green, all nine nodes that were blue only, and 266 (95%) of 279 nodes that were green only (p=0·30). Nine sentinal lymph nodes were neither blue nor green but were removed for appearing suspicious or enlarged on visual examination. 495 (96%) of 513 nodes were identified with the green dye and 238 (46%) with the blue dye (50%, 39-61; p<0·0001).

Interpretation: Indocyanine green dye with near-infrared fluorescence imaging identified more sentinel nodes than isosulfan blue dye in women with cervical and uterine cancers, with no difference in the pathological confirmation of nodal tissue between the two mapping substances.

Funding: Novadaq.
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http://dx.doi.org/10.1016/S1470-2045(18)30448-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580418PMC
October 2018

Predicting 6- and 12-Month Risk of Mortality in Patients With Platinum-Resistant Advanced-Stage Ovarian Cancer: Prognostic Model to Guide Palliative Care Referrals.

Int J Gynecol Cancer 2018 02;28(2):302-307

Objective: Predictive models are increasingly being used in clinical practice. The aim of the study was to develop a predictive model to identify patients with platinum-resistant ovarian cancer with a prognosis of less than 6 to 12 months who may benefit from immediate referral to hospice care.

Methods: A retrospective chart review identified patients with platinum-resistant epithelial ovarian cancer who were treated at our institution between 2000 and 2011. A predictive model for survival was constructed based on the time from development of platinum resistance to death. Multivariate logistic regression modeling was used to identify significant survival predictors and to develop a predictive model. The following variables were included: time from diagnosis to platinum resistance, initial stage, debulking status, number of relapses, comorbidity score, albumin, hemoglobin, CA-125 levels, liver/lung metastasis, and the presence of a significant clinical event (SCE). An SCE was defined as a malignant bowel obstruction, pleural effusion, or ascites occurring on or before the diagnosis of platinum resistance.

Results: One hundred sixty-four patients met inclusion criteria. In the regression analysis, only an SCE and the presence of liver or lung metastasis were associated with poorer short-term survival (P < 0.001). Nine percent of patients with an SCE or liver or lung metastasis survived 6 months or greater and 0% survived 12 months or greater, compared with 85% and 67% of patients without an SCE or liver or lung metastasis, respectively.

Conclusions: Patients with platinum-resistant ovarian cancer who have experienced an SCE or liver or lung metastasis have a high risk of death within 6 months and should be considered for immediate referral to hospice care.
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http://dx.doi.org/10.1097/IGC.0000000000001182DOI Listing
February 2018

Use of a novel sentinel lymph node mapping algorithm reduces the need for pelvic lymphadenectomy in low-grade endometrial cancer.

Gynecol Oncol 2017 12 19;147(3):535-540. Epub 2017 Oct 19.

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

Objectives: To evaluate the capability of a novel sentinel lymph node (SLN) mapping algorithm to reduce the need for pelvic lymphadenectomy (PLND) in patients with low-grade (G1-2) endometrial cancer (LGEC).

Methods: Patients with LGEC underwent evaluation according to a novel lymphatic assessment algorithm during hysterectomy with SLN biopsy at two academic gynecologic oncology programs. Side-specific PLND was only performed if ipsilateral SLN mapping failed and high-risk uterine features were identified on frozen section (FS). Side-specific and PLND rates were compared to theoretical PLND rates based on the NCCN EC SLN mapping algorithm.

Results: Since 11/2015, 113 LGEC patients have been managed according to the algorithm. SLN mapping was bilateral (81%), unilateral (12%), or neither (6%). Nine patients (8.0%) had LN metastases identified. Of the 21 patients requiring intraoperative FS due to failed SLN mapping, high-risk uterine features were identified in eight (38%). These patients underwent either bilateral (2) or unilateral (6) PLND. Side-specific and overall PLND rates were 5.3% and 7.1%, respectively. If all patients with failed mapping had undergone PLND according to the NCCN algorithm, side-specific and overall PLND rates would have been higher, 12.4% and 18.6%, respectively (P=0.01). All patients who failed to map and did not undergo side-specific PLND had low-risk uterine features on final pathology.

Conclusions: Lymphatic assessment using SLN mapping followed by selective FS to determine need for PLND is feasible. When compared to the NCCN algorithm, this novel "Reflex Frozen Section" strategy eliminates PLND in patients at lowest risk for metastasis without compromising identification of metastatic nodal disease.
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http://dx.doi.org/10.1016/j.ygyno.2017.10.020DOI Listing
December 2017

Multidisciplinary approach to manage antenatally suspected placenta percreta: updated algorithm and patient outcomes.

Gynecol Oncol Res Pract 2017 22;4:11. Epub 2017 Aug 22.

Department of Obstetrics and Gynecology, Duke University Hospital, Durham, North Carolina 27710 USA.

Background: Due to the significant morbidity and mortality associated with placenta percreta, alternative management options are needed. Beginning in 2005, our institution implemented a multidisciplinary strategy to patients with suspected placenta percreta. The purpose of this study is to present our current strategy, maternal morbidity and outcomes of patients treated by our approach.

Methods: From 2005 to 2014, a retrospective cohort study of patients with suspected placenta percreta at an academic tertiary care institution was performed. Treatment modalities included immediate hysterectomy at the time of cesarean section (CHYS), planned delayed hysterectomy (interval hysterectomy 6 weeks after delivery) (DH), and fertility sparing (uterine conservation) (FS). Prognostic factors of maternal morbidity were identified from medical records. Complications directly related to interventional procedures and DH was recorded. Descriptive statistics were utilized.

Results: Of the 21 patients with suspected placenta percreta, 7 underwent CHYS, 13 underwent DH, and 1 had FS with uterine preservation. Of the 20 cases that underwent hysterectomy, final pathology showed 11 increta, 7 percreta, and 2 inconclusive. 19/20 cases underwent interventional radiology (IR) procedures. Selective embolization was utilized in 14 cases (2/7 CHYS; 12/13 DH). The median time from cesarean section (CS) to DH was 41 [26-68] days. There were no cases of emergent hysterectomy, delayed hemorrhage, or sepsis in the DH group. Both estimated blood loss and number of packed red blood cell transfusions were significantly higher in the CHYS group. 3/21 cases required massive transfusion (2 CHYS, 1 FS) with median total blood product transfusion of 13 units [12-15]. The four IR-related complications occurred in the DH group. Incidence of postoperative complications was similar between both groups. Median hospital length of stay (LOS) after CHYS was 4 days [3-8] compared to DH cohort: 7 days [3-33] after CS and 4 days [1 -10] after DH. The DH cohort had a higher rate of hospital readmission of 54% (7/13) compared to 14% (1/7) CHYS, most commonly due to pain. There were no maternal deaths.

Conclusion: This multidisciplinary strategy may appear feasible; however, further investigation is warranted to evaluate the effectiveness of alternative approaches to cesarean hysterectomy in cases of morbidly adherent placenta.
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http://dx.doi.org/10.1186/s40661-017-0049-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5567476PMC
August 2017

Prospective Evaluation of Lymph Node Processing at Staging Surgery for High-grade Endometrial Cancer.

Int J Gynecol Pathol 2018 May;37(3):252-255

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Duke Cancer Institute (B.A.D., A.A.S., A.B., P.S.L., L.J.H.) Departments of Obstetrics and Gynecology, Division of Gynecologic Oncology (J.E., Z.H.) Pathology (S.A., A.H.S.H.) Biostatistics (X.L.), Duke University Medical Center, Durham, North Carolina Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Virginia Tech Carilion School of Medicine, Roanoke, Virgina (F.A.V.).

To determine whether the processing of additional adipose tissue collected during lymph node (LN) dissection results in the identification of additional LNs during endometrial cancer (EC) staging and to determine if the division of LNs into nodal basin-specific specimens has an effect on the number of LNs identified during EC staging. A prospective randomized controlled trial was performed on women with high-grade EC undergoing surgical staging. Subjects were randomized to collection of LNs into nodal basin-specific containers on the randomized side versus simple labeling on the nonrandomized side. The total number of LNs and total number of LNs with metastases on the randomized versus the nonrandomized side were compared. The remaining adipose tissue from each LN specimen was submitted for histologic examination. We analyzed the number of LNs with and without metastases identified from additional adipose tissue. Of 120 consented subjects, 56 had sufficient data for analysis. The additional adipose tissue contained 7.5 additional LNs per patient on average (range: 0-26). In 2/54 total cases (3.7%) and 2/5 cases with nodal metastases (40%), the additional adipose contained LNs with metastases. In both cases, metastases were also detected in grossly identified LN candidates. The mean number of LNs identified was not significantly different based on method of collection (P=0.22). The mean number of LNs containing metastases per side was not significantly different (P=0.58). Processing of adipose tissue does increase the total number of LNs identified, however, it does not influence EC stage. No difference in LN counts was noted with basin-specific collection.
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http://dx.doi.org/10.1097/PGP.0000000000000418DOI Listing
May 2018

Cost Comparison of Genetic Testing Strategies in Women With Epithelial Ovarian Cancer.

J Oncol Pract 2017 02 3;13(2):e120-e129. Epub 2017 Jan 3.

Duke University Medical Center, Durham, NC; and Ohio State University Medical Center, Columbus, OH.

Purpose: The advent of multigene panels has increased genetic testing options for women with epithelial ovarian cancer (EOC). We designed a decision model to compare costs and probabilities of identifying a deleterious mutation or variant of uncertain significance (VUS) using different genetic testing strategies.

Methods: A decision model was developed to compare costs and outcomes of two testing strategies for women with EOC: multigene testing (MGT) versus single-gene testing for BRCA1/2. Outcomes were mean cost and number of deleterious mutations and VUSs identified. Model inputs were obtained from published genetic testing data in EOC. One-way sensitivity analyses and Monte Carlo probabilistic sensitivity analyses were performed.

Results: No family history model: MGT cost $1,160 more on average than BRCA1/2 testing and identified an additional 3.8 deleterious mutations for every 100 women tested. For each additional deleterious mutation identified, MGT cost $30,812 and identified 5.4 additional VUSs. Family history model: MGT cost $654 more on average and identified an additional 7.0 deleterious mutations for every 100 women tested. For each additional deleterious mutation identified, MGT cost $9,909 and identified 2.6 additional VUSs.

Conclusion: MGT was associated with a higher additional cost per deleterious mutation identified and a higher ratio of VUS burden to actionable information in women with no family history as compared with women with a family history. Family history should be considered when determining an initial genetic testing platform in women with EOC.
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http://dx.doi.org/10.1200/JOP.2016.011866DOI Listing
February 2017

Performance of sentinel lymph node biopsy in high-risk endometrial cancer.

Gynecol Oncol Rep 2016 Aug 19;17:69-71. Epub 2016 Apr 19.

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

Objective: To determine the rate and performance of sentinel lymph node (SLN) mapping among women with high-risk endometrial cancers.

Methods: Patients diagnosed between 2012 and 2015 with uterine cancer of grade 3 endometrioid, clear cell, serous or carcinosarcoma histology and who underwent SLN mapping prior to full pelvic lymph node dissection were included. Subjects underwent methylene blue or ICG injection for laparoscopic (N = 16) or robotic-assisted laparoscopic (N = 20) staging. Outcomes included SLN mapping rates, SLN and non-SLN positive rates, false negative SLN algorithm rate, and the negative predictive value (NPV) of the SLN algorithm. Fisher's exact test was used to compare mapping and node positivity rates.

Results: 9/36 (25%) patients with high-risk uterine cancer had at least one metastatic lymph node identified. Successful mapping occurred in 30/36 (83%) patients. SLN mapped to pelvic nodes bilaterally in 20 (56%), unilaterally in 9 (25%), and aortic nodes only in 1 (3%). Malignancy was identified in 14/95 (15%) of all sentinel nodes and 12/775 (1.5%) of all non-sentinel nodes (p < 0.001). The false negative rate of SLN mapping alone was 2/26 (7.7%); the NPV was 92.3%. When the SLN algorithm was applied retrospectively the false negative rate was 0/31 (0%); the NPV was 100%.

Conclusion: SLN mapping rates for high-risk cancers are slightly lower than in prior reports of lower risk cancers. The NPV of the SLN mapping alone is 92% and rises to 100% when the SLN algorithm is applied. Such results are acceptable and consistent with larger subsets of lower risk endometrial cancers.
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http://dx.doi.org/10.1016/j.gore.2016.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941561PMC
August 2016

Second-line dovitinib (TKI258) in patients with FGFR2-mutated or FGFR2-non-mutated advanced or metastatic endometrial cancer: a non-randomised, open-label, two-group, two-stage, phase 2 study.

Lancet Oncol 2015 Jun 13;16(6):686-94. Epub 2015 May 13.

University College London Cancer Institute, London, UK.

Background: Activating FGFR2 mutations are found in 10-16% of primary endometrial cancers and provide an opportunity for targeted therapy. We assessed the safety and activity of dovitinib, a potent tyrosine-kinase inhibitor of fibroblast growth factor receptors, VEGF receptors, PDGFR-β, and c-KIT, as second-line therapy both in patients with FGFR2-mutated (FGFR2(mut)) endometrial cancer and in those with FGFR2-non-mutated (FGFR2(non-mut)) endometrial cancer.

Methods: In this phase 2, non-randomised, two-group, two-stage study, we enrolled adult women who had progressive disease after first-line chemotherapy for advanced or metastatic endometrial cancer from 46 clinical sites in seven countries. We grouped women according to FGFR2 mutation status and gave all women dovitinib (500 mg per day, orally, on a 5-days-on and 2-days-off schedule) until disease progression, unacceptable toxicity, death, or study discontinuation for any other reason. The primary endpoint was proportion of patients in each group who were progression-free at 18 weeks. For each group, the second stage of the trial (enrolment of 20 additional patients) could proceed if at least eight of the first 20 treated patients were progression free at 18 weeks. Activity was assessed in all enrolled patients and safety was assessed in all patients who received at least one dose of dovitinib. The completed study is registered with ClinicalTrials.gov, number NCT01379534.

Findings: Of 248 patients with FGFR2 prescreening results, 27 (11%) had FGFR2(mut) endometrial cancer. Between Feb 17, 2012, and Dec 13, 2013, we enrolled 22 patients in the FGFR2(mut) group and 31 patients in the FGFR2(non-mut) group. Seven (31·8%, 95% CI 13·9-54·9) patients in the FGFR2(mut) group and nine (29·0%, 14·2-48·0) in the FGFR2(non-mut) group were progression-free at 18 weeks. On the basis of predefined criteria, neither group continued to stage two: seven (35%) of the first 20 patients in the FGFR2(mut) group were progression free at 18 weeks, as were five (25%) of the first 20 in the FGFR2(mut) population. Rates of treatment-emergent adverse events were similar between groups and events were most frequently gastrointestinal. Overall, the most common grade 3 or 4 adverse events suspected to be related to the study drug were hypertension (nine patients; 17%) and diarrhoea (five; 9%). The most frequently reported serious adverse events suspected to be related to study drug were pulmonary embolism (four patients; 8%), vomiting (four; 8%), dehydration (three; 6%), and diarrhoea (three; 6%). Only one death was deemed to be treatment-related: one patient in the FGFR2(non-mut) group died from cardiac arrest with contributing reason of pulmonary embolism (grade 4, suspected to be study drug related) 4 days previously.

Interpretation: Second-line dovitinib in FGFR2(mut) and FGFR2(non-mut) advanced or metastatic endometrial cancer had single-agent activity, although it did not reach the prespecified study criteria. Observed treatment effects seemed independent of FGFR2 mutation status. These data should be considered exploratory and additional studies are needed.

Funding: Novartis Pharmaceuticals.
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http://dx.doi.org/10.1016/S1470-2045(15)70159-2DOI Listing
June 2015

Comprehensive care in gynecologic oncology: The importance of palliative care.

Gynecol Oncol 2015 May 4;137(2):193-202. Epub 2015 Mar 4.

University of Washington Medical Center, 1949 NE Pacific St., Seattle, WA 98195, USA.

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http://dx.doi.org/10.1016/j.ygyno.2015.02.026DOI Listing
May 2015

Improving quality and decreasing cost in gynecologic oncology care. Society of gynecologic oncology recommendations for clinical practice.

Gynecol Oncol 2015 May 28;137(2):280-4. Epub 2015 Feb 28.

University of Louisville, 2301 S 3rd St., Louisville, KY 40292, USA.

Objective: To identify potential cost savings in gynecologic oncology care without sacrificing quality.

Methods: Members of the Clinical Practice Committee of the Society of Gynecologic Oncology were asked to review current practice patterns in gynecologic oncology and assess the potential for cost savings founded on evidence-based medicine and current guidelines.

Results: Five clinical practices were identified including the following: vaginal cytology for endometrial cancer survivors; colposcopy for low grade cytologic abnormalities for cervical cancer survivors; routine imaging studies for gynecologic cancer survivors; screening for ovarian cancer with serum biomarkers and ultrasound; and improving palliative care for gynecologic cancer patients. Review of the published literature and guidelines were performed to make evidence-based recommendations for cost effective quality gynecologic oncology care.

Recommendations: • Do not perform Pap tests of the vaginal cuff in patients with a history of endometrial cancer. • Do not perform colposcopy for low grade Pap tests in women with a history of cervical cancer. • Avoid routine imaging for cancer surveillance in asymptomatic women with gynecologic cancer, specifically ovarian, endometrial, cervical, vulvar and vaginal cancer. • Do not screen women at low risk for ovarian cancer with ultrasound or CA-125 or other biomarkers. • Do not delay basic level palliative care for women with advanced or relapsed gynecologic cancer, do refer to a palliative care specialist when needed, and avoid unnecessary treatments at life's end.
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http://dx.doi.org/10.1016/j.ygyno.2015.02.021DOI Listing
May 2015

Vaginal cuff thermal injury by mode of colpotomy at total laparoscopic hysterectomy: a randomized clinical trial.

J Minim Invasive Gynecol 2015 Feb 8;22(2):227-33. Epub 2014 Oct 8.

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University, Durham, North Carolina.

Study Objective: To evaluate if the use of Valleylab mode ("V mode") (Covidien, Mansfield, MA) electrothermal energy for colpotomy during total laparoscopic hysterectomy (LH) results in a smaller margin of thermal injury to the upper vagina compared with traditional cut/coagulate (cut/coag) electrothermal energy.

Design: Prospective randomized clinical trial (Canadian Task Force classification I).

Setting: University medical center.

Patients: A total of 101 subjects who underwent LH between June 2010 and August 2012.

Interventions: Subjects were randomized to colpotomy by V mode electrothermal energy or cut/coag electrothermal energy.

Measurements And Main Results: The primary end point was the median depth of thermal injury measured in millimeters. The secondary end points included the proportion of subjects who developed granulation tissue, induration, infection, or dehiscence at the vaginal cuff at 4 weeks, 3 months, or 6 months postoperatively. There was no significant difference in the median depth of thermal injury in the cut/coag and V mode arms (anterior margin: 0.68 mm vs 0.63 mm [p = .94], posterior margin: 0.66 mm vs 0.70 mm [p = .87], respectively). Twenty-seven percent of subjects in each arm developed at least 1 of the clinical end points at 4 weeks, 3 months, or 6 months postoperatively (granulation tissue: 6%-18% vs 8%-21%, induration: 0%-2% vs 4%-5%, infection: 0%-4% vs 0%-10%, dehiscence: 2% vs 0% in the cut/coag and V mode arms, respectively), with no difference between arms (p = 1.0).

Conclusion: The V mode does not reduce the depth of thermal injury compared with cut/coag electrothermal energy when used for colpotomy incision during total laparoscopic hysterectomy (Clinical Trials.gov ID: NCT02080546).
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http://dx.doi.org/10.1016/j.jmig.2014.10.002DOI Listing
February 2015

Patient preferences in advanced or recurrent ovarian cancer.

Cancer 2014 Dec 4;120(23):3651-9. Epub 2014 Aug 4.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina; Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina.

Background: The objective of this study was to elucidate relative preferences of women with ovarian cancer for symptoms, treatment-related side effects, and progression-free survival (PFS) relevant to choosing a treatment regimen.

Methods: Women with advanced or recurrent ovarian cancer participated in a survey that included 3 methods to measure patient preferences (ratings, rankings, and a discrete-choice experiment) for 7 attributes: mode of administration, visit frequency, peripheral neuropathy, nausea and vomiting, fatigue, abdominal discomfort, and PFS. Participants were asked to choose between 2 unlabeled treatment scenarios that were characterized using the 7 attributes. Each participant completed 12 choice questions in which attribute levels were assigned according to an experimental design and a fixed-choice question representing 2 chemotherapy regimens for ovarian cancer.

Results: In total, 95 women completed the survey. Participants' ratings and rankings revealed greater concern and importance for PFS than for any other attribute (P < .0001 for all). The discrete-choice experiment revealed that the relative odds that a participant would choose a scenario with 18 months, 21 months, and 24 months of PFS versus 15 months of PFS were 1.5 (P = .01), 3.4 (P < .001), and 7.5 (P < .001), respectively. However, participants' choices indicated that they were willing to accept a shorter PFS to avoid severe side effects: 6.7 months to reduce nausea and vomiting from severe to mild, 5.0 months to reduce neuropathy from severe to mild, and 3.7 months to reduce abdominal symptoms from severe to moderate.

Conclusions: PFS is the predominant driver of patient preferences for chemotherapy regimens. However, women in the current study were willing to trade significant PFS time for reductions in treatment-related toxicity.
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http://dx.doi.org/10.1002/cncr.28940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429767PMC
December 2014

A phase II trial of brivanib in recurrent or persistent endometrial cancer: an NRG Oncology/Gynecologic Oncology Group Study.

Gynecol Oncol 2014 Oct 11;135(1):38-43. Epub 2014 Jul 11.

Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. Electronic address:

Purpose: Brivanib, an oral, multi-targeted tyrosine kinase inhibitor with activity against vascular endothelial growth factor (VEGF) and fibroblast growth factor receptor (FGFR) was investigated as a single agent in a phase II trial to assess the activity and tolerability in recurrent or persistent endometrial cancer (EMC).

Patients And Methods: Eligible patients had persistent or recurrent EMC after receiving one to two prior cytotoxic regimens, measurable disease, and performance status of ≤2. Treatment consisted of brivanib 800 mg orally every day until disease progression or prohibitive toxicity. Primary endpoints were progression-free survival (PFS) at six months and objective tumor response. Expression of multiple angiogenic proteins and FGFR2 mutation status was assessed.

Results: Forty-five patients were enrolled. Forty-three patients were eligible and evaluable. Median age was 64 years. Twenty-four patients (55.8%) received prior radiation. Median number of cycles was two (range 1-24). No GI perforations but one rectal fistula were seen. Nine patients had grade 3 hypertension, with one experiencing grade 4 confusion. Eight patients (18.6%; 90% CI 9.6%-31.7%) had responses (one CR and seven PRs), and 13 patients (30.2%; 90% CI 18.9%-43.9%) were PFS at six months. Median PFS and overall survival (OS) were 3.3 and 10.7 months, respectively. When modeled jointly, VEGF and angiopoietin-2 expression may diametrically predict PFS. Estrogen receptor-α (ER) expression was positively correlated with OS.

Conclusion: Brivanib is reasonably well tolerated and worthy of further investigation based on PFS at six months in recurrent or persistent EMC.
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http://dx.doi.org/10.1016/j.ygyno.2014.07.083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278402PMC
October 2014

A phase II evaluation of pazopanib in the treatment of recurrent or persistent carcinosarcoma of the uterus: a gynecologic oncology group study.

Gynecol Oncol 2014 Jun 1;133(3):537-41. Epub 2014 Mar 1.

Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.

Objective: Carcinosarcomas of the female genital tract, also called malignant mixed müllerian tumors, are aggressive biphasic tumors. Second-line treatment options in the recurrent/persistent setting have yielded marginal responses. Given the potential role of angiogenesis in the gynecological carcinomas, pazopanib, a VEGFR inhibitor, was investigated in the management of patients with recurrent carcinosarcoma of the uterus.

Methods: Eligible patients had histologically confirmed carcinosarcoma of the uterus, a maximum of two prior lines of therapy, adequate renal, hepatic and hematologic function and a performance status of 0-2. Pazopanib was administered orally at 800mg. Two dose reductions were allowed. The primary objective was to ascertain the activity of pazopanib as measured by the proportion of patients who survive progression-free for at least six months and the proportion of patients that have objective tumor responses. Secondary objectives included the frequency and severity of adverse events as assessed by CTCAE v4.0.

Results: Of the 22 enrolled patients, 19 were eligible and evaluable for toxicity and survival. No patients had a partial or complete response (90% confidence interval [CI]: 0%, 14.6%). Three patients (15.8%) had PFS ≥6months (90% CI: 4.4%, 35.9%). The median PFS was 2.0months (first and third quartiles were 1.6 and 4.0months, respectively). The median overall survival was 8.7months (first and third quartiles were 2.6 and 14.0months, respectively).

Conclusion: Pazopanib demonstrated minimal activity as a second or third line treatment for advanced uterine carcinosarcoma. Potential clinical trial participation should be discussed with the patients.
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http://dx.doi.org/10.1016/j.ygyno.2014.02.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4360988PMC
June 2014

Relationship between minimally invasive hysterectomy, pelvic cytology, and lymph vascular space invasion: a single institution study of 458 patients.

Gynecol Oncol 2014 May 28;133(2):211-5. Epub 2014 Feb 28.

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

Objective: The aim of this study is to determine whether a minimally invasive approach to hysterectomy is associated with an increased rate of lymph vascular space invasion (LVSI) and/or malignant pelvic peritoneal cytology in endometrial cancer.

Methods: We performed a single institution analysis of 458 women with endometrial cancer who underwent either total abdominal hysterectomy (TAH) or minimally invasive hysterectomy (MIH) with use of a disposable uterine manipulator. All patients had endometrial cancer diagnosed by endometrial biopsy at a single academic institution between 2002 and 2012. Exclusion criteria were pre-operative D&C and/or hysteroscopy, uterine perforation or morcellation, and conversion to laparotomy. Multivariate logistic regression models to determine if type of hysterectomy predicts either LVSI or presence of abnormal cytology were controlled for grade, stage, depth of invasion, tumor size, cervical and adnexal involvement.

Results: LVSI was identified in 39/214 (18%) MIH and 44/242 (18%) TAH (p=0.99). Pelvic washings were malignant in 14/203 (7%) MIH and 16/241 (7%) TAH (p=1.0). Washings were atypical or inconclusive in 16/203 (8%) MIH and 6/241 (2.5%) TAH (p=0.014). In multivariate analyses, type of hysterectomy was not a significant predictor of either LVSI (p=0.29) or presence of malignant washings (p=0.66), but was a predictor of atypical or inconclusive washings (p=0.03).

Conclusion: Minimally invasive hysterectomy with use of a uterine manipulator for endometrial cancer is not associated with LVSI or malignant cytology. Algorithms that better determine the etiology and implications of inconclusive or atypical pelvic cytology are needed to inform the possible additional risk associated with a minimally invasive approach to endometrial cancer.
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http://dx.doi.org/10.1016/j.ygyno.2014.02.025DOI Listing
May 2014

Metastatic adenocarcinoma after laparoscopic supracervical hysterectomy with morcellation: A case report.

Gynecol Oncol Case Rep 2013 16;5:19-21. Epub 2013 Mar 16.

Department of Obstetrics and Gynecology, Duke University Medical Center, USA ; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, USA ; Duke Cancer Institute, USA.

•Uterine morcellation is common in minimally invasive hysterectomy but should be performed with caution due to risk of unsuspected malignancy.•Intraoperative techniques should be considered to minimize dissemination of endometrial tissue during morcellation.•Strategies to ensure accurate pathologic evaluation of morcellated specimens and to improve preoperative risk stratification before morcellation procedures are necessary.
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http://dx.doi.org/10.1016/j.gynor.2013.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3862316PMC
December 2013

Targeting molecular pathways in endometrial cancer: a focus on the FGFR pathway.

Cancer Treat Rev 2014 May 22;40(4):507-12. Epub 2013 Nov 22.

Duke University Medical Center (DUMC) 3079, Durham, NC 27710, United States. Electronic address:

In the majority of cases, endometrial cancer is localized and highly curable through surgery and adjuvant radiotherapy. However, for patients with advanced or metastatic disease, prognosis is poor. Systemic treatments such as cytotoxic chemotherapy or hormonal therapy can cause significant toxicities including chemotherapy-related gastrointestinal, neurologic, and immunosuppressive toxicities and hormone-related hypertension, increased blood sugar, thrombosis, and pulmonary emboli. In addition, these therapies rarely lead to sustained disease control. Novel therapies with greater efficacy and reduced toxicity are needed. Recent progress in the identification of genetic abnormalities in cell signaling proteins has spurred the development of targeted agents for the treatment of patients with endometrial cancer. The fibroblast growth factor receptor (FGFR) pathway is one of several signaling pathways that have been implicated in the pathogenesis and progression of endometrial cancer. The activity of novel FGFR-targeted agents in preclinical endometrial cancer models and clinical trials will be reviewed.
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http://dx.doi.org/10.1016/j.ctrv.2013.11.004DOI Listing
May 2014

Palliative and hospice care in gynecologic cancer: a review.

Gynecol Oncol 2013 Oct 14;131(1):215-21. Epub 2013 Jun 14.

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

Despite the increasing availability of palliative care, oncology providers often misunderstand and underutilize these resources. The goals of palliative care are relief of suffering and provision of the best possible quality of life for both the patient and her family, regardless of where she is in the natural history of her disease. Lack of understanding and awareness of the services provided by palliative care physicians underlie barriers to referral. Oncologic providers spend a significant amount of time palliating the symptoms of cancer and its treatment; involvement of specialty palliative care providers can assist in managing the complex patient. Patients with gynecologic malignancies remain an ideal population for palliative care intervention. This review of the literature explores the current state of palliative care in the treatment of gynecologic cancers and its implications for the quality and cost of this treatment.
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http://dx.doi.org/10.1016/j.ygyno.2013.06.012DOI Listing
October 2013

Cost-effectiveness of early palliative care intervention in recurrent platinum-resistant ovarian cancer.

Gynecol Oncol 2013 Sep 14;130(3):426-30. Epub 2013 Jun 14.

Duke University Medical Center, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Durham, NC 27710, USA.

Objective: To determine if early palliative care intervention in patients with recurrent, platinum-resistant ovarian cancer is potentially cost saving or cost-effective.

Methods: A decision model with a 6 month time horizon evaluated routine care versus routine care plus early referral to a palliative medicine specialist (EPC) for recurrent platinum-resistant ovarian cancer. Model parameters included rates of inpatient admissions, emergency department (ED) visits, chemotherapy administration, and quality of life (QOL). From published ovarian cancer data, we assumed baseline rates over the final 6 months: hospitalization 70%, chemotherapy 60%, and ED visit 30%. Published data from a randomized trial evaluating EPC in metastatic lung cancer were used to model odds ratios (ORs) for potential reductions in hospitalization (OR 0.69), chemotherapy (OR 0.77), and emergency department care (OR 0.74) and improvement in QOL (OR 1.07). The costs of hospitalization, ED visit, chemotherapy, and EPC were based on published data. Ranges were used for sensitivity analysis. Effectiveness was quantified in quality adjusted life years (QALYs); survival was assumed equivalent between strategies.

Results: EPC was associated with a cost savings of $1285 per patient over routine care. In sensitivity analysis incorporating QOL, EPC was either dominant or cost-effective, with an incremental cost-effectiveness ratio (ICER) <$50,000/QALY, unless the cost of outpatient EPC exceeded $2400. Assuming no clinical benefit other than QOL (no change in chemotherapy administration, hospitalizations or ED visits), EPC remained highly cost-effective with ICER $37,440/QALY.

Conclusion: Early palliative care intervention has the potential to reduce costs associated with end of life care in patients with ovarian cancer.
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http://dx.doi.org/10.1016/j.ygyno.2013.06.011DOI Listing
September 2013

Timing of end-of-life care discussion with performance on end-of-life quality indicators in ovarian cancer.

Gynecol Oncol 2013 Jul 13;130(1):156-61. Epub 2013 Apr 13.

Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC 27710, USA.

Objectives: (1) To describe the prevalence, timing and setting of documented end-of-life (EOL) discussions in patients with advanced ovarian cancer; and (2) to assess the impact of timing and setting of documented end-of-life discussions on EOL quality care measures.

Methods: A retrospective study of women who died of ovarian cancer diagnosed between 1999 and 2008 was conducted. The following are the EOL quality measures assessed: chemotherapy in the last 14 days of life, >1 hospitalization in the last 30 days, >1 ER visit in the last 30 days, intensive care unit (ICU) admission in the last 30 days, dying in an acute care setting, admitted to hospice ≤3 days.

Results: One hundred seventy-seven (80%) patients had documented end-of-life discussions. Median interval from EOL discussion until death was 29 days. Seventy-eight patients (44%) had EOL discussions as outpatient and 99 (56%) as inpatient. Sixty-four out of 220 (29%) patients' care did not conform to at least one EOL quality measure. An EOL discussion at least 30 days before death was associated with a lower incidence of: chemotherapy in the last 14 days of life (p=0.003), >1 hospitalization in the last 30 days (p<0.001), ICU admission in the last 30 days (p=0.005), dying in acute care setting (p=0.01), admitted to hospice ≤3 days (p=0.02). EOL discussion as outpatient was associated with fewer patients hospitalized >1 in the last 30days of life (p<0.001).

Conclusions: End-of-life care discussions are occurring too late in the disease process. Conformance with EOL quality measures can be achieved with earlier end-of-life care discussions.
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http://dx.doi.org/10.1016/j.ygyno.2013.04.010DOI Listing
July 2013

A phase I trial of dasatinib, an SRC-family kinase inhibitor, in combination with paclitaxel and carboplatin in patients with advanced or recurrent ovarian cancer.

Clin Cancer Res 2012 Oct 26;18(19):5489-98. Epub 2012 Jul 26.

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

Purpose: We conducted a phase I study of dasatinib, an oral SRC-family tyrosine kinase inhibitor, in combination with paclitaxel and carboplatin in the treatment of advanced and recurrent epithelial ovarian cancer.

Experimental Design: The primary objective was to determine the maximum tolerated dose (MTD). Secondary objectives included defining toxicity, response rate (RR), pharmacokinetics, and pharmacodynamics. Using a "3+3" design, cohorts of three to six patients received paclitaxel (175 mg/m(2)) and carboplatin (AUC 6) every 3 weeks with escalating doses of dasatinib (100, 120, and 150 mg daily), followed by an eight-patient expansion cohort.

Results: Twenty patients were enrolled between June 2007 and December 2009. The median age was 61 years (range: 42-82) with a median of 2 prior regimens (range: 0-6), and 71% had platinum-sensitive disease. There were three to six patients in each cohort, and eight in the expansion cohort. Pharmacokinetics were observed over the first two cycles of therapy. One DLT was observed in the 100 mg dasatinib cohort (grade 3 myalgia). Other toxicities in all cycles included neutropenia (95% grade 3-4; 91% in the 150 mg dosing cohort), thrombocytopenia (35% grade 3-4), and fatigue (10% grade 3). The RR was 40% [three complete responses, (15%); five partial responses, (25%)],10 patients (50%) had stable disease, and two were not evaluable. The PFS(6-month) actuarial estimate was 86%. The median PFS and OS were 7.8 and 16.2 months, respectively.

Conclusions: Due to the high incidence of myelosuppression with subsequent cycles, the recommended phase II dose of dasatinib is 150 mg daily in combination with paclitaxel and carboplatin. The combination was safe with evidence of clinical activity.
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http://dx.doi.org/10.1158/1078-0432.CCR-12-0507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3463759PMC
October 2012

The regulation of MASPIN expression in epithelial ovarian cancer: association with p53 status, and MASPIN promoter methylation: a gynecologic oncology group study.

Gynecol Oncol 2011 Nov 8;123(2):314-9. Epub 2011 Sep 8.

Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC 27710, USA.

Objectives: To elucidate the regulation of MASPIN expression in epithelial ovarian cancer (EOC) and associations with p53 status and MASPIN promoter methylation.

Methods: Seven EOC cell lines and 110 advanced stage EOC specimens were analyzed for MASPIN promoter methylation. The cell lines were treated with 5-azacytidine (5-azaC) and evaluated for MASPIN promoter methylation, protein, and mRNA expression. Wild-type (wt) p53 was transiently transfected into the mutant p53 (m p53) SKOV3 cells which were treated with 5-azaC. Phosphor imager analysis quantified the percent methylation of the MASPIN promoter.

Results: Of the 3 MASPIN-low m p53 cell lines 2 had greater than 5% MASPIN methylation whereas only 1 of 4 MASPIN-high wt p53 cell lines had greater than 5% MASPIN methylation. Despite the presence of aberrant MASPIN promoter methylation in SKOV3 cells, wt p53-transfection alone resulted in a 3.3-fold increase in MASPIN mRNA. The combination of 5-azaC and wt p53-transfection produced a 36% reduction in MASPIN promoter methylation and 4.5-fold increase in MASPIN transcription. Among the 110 ovarian cancer specimens analyzed for methylation of the MASPIN promoter, 81.8% were weakly methylated, 14.5% were heavily methylated and 3.6% were fully methylated. There was no relationship between promoter methylation and p53 status or MASPIN protein expression. However, MASPIN protein was 6 times more likely to be detected in cancer specimens that harbor a p53 mutation relative to cancer specimens with a wt p53 gene.

Conclusion: The regulation of MASPIN is a complex multifactorial process that may be controlled by both p53-dependent and -independent epigenetic mechanisms.
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http://dx.doi.org/10.1016/j.ygyno.2011.08.003DOI Listing
November 2011

Cost comparison of strategies for the management of venous thromboembolic event risk following laparotomy for ovarian cancer.

Gynecol Oncol 2011 Sep 12;122(3):467-72. Epub 2011 Jul 12.

Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC 27710, USA.

Objective: To evaluate the costs and effectiveness of thromboprophylaxis strategies following laparotomy for ovarian cancer.

Methods: We constructed a decision model to evaluate six strategies for management of postoperative venous thromboembolism (VTE) risk: (1) no thromboprophylaxis; (2) inpatient sequential compression device (SCD); (3) inpatient unfractionated heparin (UFH) 5000 units TID; (4) inpatient low molecular weight heparin (LMWH) 40 mg daily; (5) UFH 5000 units TID×1 month; (6) LMWH 40 mg daily×1 month. Rates of VTE, heparin-induced thrombocytopenia, and significant bleeding for each strategy were obtained from published literature. Costs were based on institutional charges or obtained from the Agency for Healthcare Research and Quality Nationwide Inpatient Sample database for 2008 and average wholesale pricing. Sensitivity analyses were performed to account for uncertainty in estimates.

Results: In the base case, UFH×1 month was the least expensive (mean cost $1611) and most effective (VTE risk 1.9%) strategy. LMWH×1 month was equally effective but more expensive ($2197). Inpatient UFH, inpatient LMWH, and SCDs were less effective and more expensive than UFH×1 month. In the sensitivity analysis, cost rankings remained unchanged unless the baseline probability of VTE was assumed <6.5%, the cost of VTE treatment was <$20,000, or the cost of bleeding was >$4500. LMWH×1 month became least expensive when cost was decreased 38%.

Conclusion: Based on current evidence, extended prophylaxis with UFH is the least expensive and most effective strategy to prevent postoperative VTE following laparotomy for ovarian cancer.
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http://dx.doi.org/10.1016/j.ygyno.2011.06.014DOI Listing
September 2011

Adverse events associated with laparoscopy vs laparotomy in the treatment of endometrial cancer.

Am J Obstet Gynecol 2011 Aug 16;205(2):143.e1-6. Epub 2011 Mar 16.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University School of Medicine, Durham, NC, USA.

Objective: The objective of the study was to compare adverse event rates between laparoscopic vs open surgery for endometrial cancer.

Study Design: This was a retrospective cohort study comparing 107 women who underwent laparoscopy with 269 age- and body mass index-matched women who underwent laparotomy for treatment of endometrial cancer.

Results: Adverse event rates were similar between cohorts (37% laparoscopy vs 43% laparotomy, P=.248). Laparotomies had higher rates of cellulitis (16% vs 7%, P=.018) and open wound infection (9% vs 2%, P=.02), whereas laparoscopy had higher rates of sensory peripheral nerve deficit (5% vs 0%, P=.008) and lymphedema (7% vs 1%, P=.003). Laparoscopy was associated with longer mean operating room times but with shorter hospital stays and lower mean blood loss.

Conclusion: Laparoscopy was associated with decreased rates of surgical site infections but had an increased risk of peripheral sensory nerve deficits and lymphedema when compared with laparotomy.
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http://dx.doi.org/10.1016/j.ajog.2011.03.012DOI Listing
August 2011
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