Publications by authors named "Paola A Gehrig"

135 Publications

Endometrial cancer: A society of gynecologic oncology evidence-based review and recommendations.

Gynecol Oncol 2021 Mar 27;160(3):817-826. Epub 2021 Jan 27.

Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Medicine, Stony Brook University Cancer Center, Stony Brook, NY, United States of America.

Introduction: In 2014, the Society of Gynecologic Oncology's Clinical Practice Committee published a clinical update reviewing the treatment of women with endometrial cancer. At that time, there had been significant advances in the diagnosis, work-up, surgical management, and available treatment options allowing for more optimal care of affected women. Despite these advances, the incidence of endometrial cancer as well as the deaths attributable to the disease have continued to rise; from 1987 to 2014 there has been a 75% increase in cases and almost 300% increase in endometrial cancer deaths. Fortunately, since then, there has been progress in the treatment of patients with endometrial cancer with increased utilization of molecular pathology, greater understanding of genetic predisposition, enhanced methods for lymph node assessment, a broader understanding of the efficacy of radiation and chemotherapy, and a more efficient approach to survivorship and surveillance. The purpose of this document is to present a comprehensive review of this progress.

Manuscript Development Process: The authors reviewed the available evidence, contributed to the development of this manuscript, provided critical review of the guidelines, and finalized the manuscript recommendations. The review was also presented to and approved by the Society of Gynecologic Oncology (SGO) Clinical Practice Committee, SGO Publications Committee, and the SGO board members prior to submission for publication. The recommendations for this manuscript were developed by a panel of gynecologic oncologists who were members of the SGO Clinical Practice and Education Committees. Panelists reviewed and considered evidence from current uterine cancer literature. The terminology used in these guidelines was adopted from the ASCCP management guidelines [1] using a two-part rating system to grade the strength of recommendation and quality of evidence (Table 1). The rating for each recommendation is given in parentheses.
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http://dx.doi.org/10.1016/j.ygyno.2020.12.021DOI Listing
March 2021

Endometrial cancer: A society of gynecologic oncology evidence-based review and recommendations, part II.

Gynecol Oncol 2021 Mar 13;160(3):827-834. Epub 2021 Jan 13.

Department of Obstetrics, Gynecology and Reproductive Medicine, Stony Brook University Cancer Center, Stony Brook, NY, United States of America.

In 2014, the Society of Gynecologic Oncology's Clinical Practice Committee published a clinical update reviewing the treatment of women with endometrial cancer. At that time, there had been significant advances in the diagnosis, work-up, surgical management, and available treatment options allowing for more optimal care of affected women. This manuscript, Part II in a two-part series, includes specific recommendations on treatment of recurrent disease, post treatment surveillance and survivorship, considerations for younger women, and special situations. Part I covered histopathology and molecular pathology, risk factors, presentation and diagnostic approach, surgical approach and adjuvant therapy.
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http://dx.doi.org/10.1016/j.ygyno.2020.12.024DOI Listing
March 2021

Accuracy of preoperative cross-sectional imaging in cervical cancer patients undergoing primary radical surgery.

Gynecol Oncol 2021 Feb 16;160(2):384-388. Epub 2020 Nov 16.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC, United States of America.

Objective: We aim to describe the false negative (FN) and false positive (FP) rates of preoperative cross-sectional imaging (PCI) prior to radical surgery for cervical cancer.

Methods: A retrospective cohort study of patients who underwent radical hysterectomy for early-stage cervical cancer from January 2010 until December 2017 at a single tertiary care center was performed. Patients were included if they underwent preoperative PCI and radical surgery. Patient demographics and clinicopathologic information were recorded from medical record review. Descriptive statistics were used.

Results: Overall, 106 patients met inclusion criteria. Eighty-four percent (89/106) of patients had no suspicion for metastatic disease on PCI, while 16% (17/106) had suspicion for metastatic disease. Of the 89 without suspicion for metastatic disease on PCI, 16% (14/89) had a false negative study with metastatic disease identified on final surgical pathology. False negative rates by modality were 16% (11/70) for PET/CT and 6% (2/33) for diagnostic CT. Of the 17 cases with suspicion for metastatic disease on imaging, 53% (9/17) were false positive studies with no metastatic disease identified histologically. False positive rates by modality were 7% (5/70) for PET/CT and 12% (4/33) for diagnostic CT.

Conclusion: PCI is a tool to help identify patients who are optimal candidates for radical surgery. In this sample, the false negative rate was 16%, and false positive rate was 53% for PCI among women who underwent primary radical surgery. Further study is needed to explore preoperative testing that may more accurately identify optimal surgical candidates.
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http://dx.doi.org/10.1016/j.ygyno.2020.11.001DOI Listing
February 2021

Are There Survival Differences Between Women with Equivalent Residual Disease After Interval Cytoreductive Surgery Compared with Primary Cytoreductive Surgery for Advanced Ovarian and Peritoneal Cancer?

Ann Surg Oncol 2020 Nov 5. Epub 2020 Nov 5.

Obstetrics and Gynecology, University of North Carolina Hospitals, Women's Hospital, Chapel Hill, NC, USA.

Objective: The aim of this study was to investigate survival differences between equivalent residual disease [complete gross resection (CGR), minimal residual disease (MRD), suboptimal] at the time of primary debulking surgery (PDS) and interval debulking surgery (IDS).

Methods: The National Cancer Database was used to identify patients from 2010 to 2015 with stage IIIC/IV primary peritoneal or ovarian cancer who had residual disease recorded. Propensity score matching (PSM) was used to correct for differences in characteristics between the PDS and IDS groups.

Results: Of 8683 patients with advanced ovarian cancer, 4493 (52%), 2546 (29%), and 1644 (19%) had CGR, MRD, or suboptimal resection, respectively. From 2010 to 2015, the number of patients undergoing IDS increased 27% (p < 0.001), and there was an 18% increase in CGRs (p = 0.005). The increased use of IDS from 2010 to 2015 was associated with increased CGRs (p = 0.02) and decreased MRD (p = 0.001), but not with decreased suboptimal resections (p = 0.18). IDS, even after PSM, was associated with inferior overall survival [OS; hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.03-1.22, p = 0.008]. A CGR at PDS had prolonged median OS compared with a CGR at IDS (51 vs. 44 months, p < 0.001). Additionally, MRD at PDS had worse median OS compared with a CGR at IDS (41 vs. 44 months, p = 0.03), but improved median OS compared with MRD at IDS (median OS 35 months, p = 0.05).

Conclusion: The use of IDS continues to rise in the US, and is associated with improved surgical outcomes but not necessarily similar oncologic outcomes. There should be continued efforts to improve cytoreductive outcomes in women with advanced ovarian and peritoneal malignancies.
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http://dx.doi.org/10.1245/s10434-020-09304-wDOI Listing
November 2020

Uterine Cellular Blue Nevus Arising in Mullerian and Pelvic Dendritic Melanocytosis: Case Report of a Rare Phenomenon to Be Distinguished From Uterine Melanoma.

Int J Gynecol Pathol 2020 Sep 11. Epub 2020 Sep 11.

School of Medicine (C.J.C.) Department of Obstetrics and Gynecology, Residency Program (A.F.) Department of Obstetrics and Gynecology, Gynecology Oncology Division (L.B., P.A.G.) Department of Pathology and Laboratory Medicine (S.O., P.B.G.) Department of Dermatology, Dermatopathology (P.B.G.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

A 37-yr-old woman presented to the gynecology clinic with abnormal uterine bleeding in the setting of known, large uterine fibroids. Preoperative endometrial biopsy identified atypical melanocytic cells concerning for uterine melanoma. Care was transferred to the gynecologic oncology service for hysterectomy. Intraoperative findings included macular, blue-black pigmentation of the peritoneum of the bladder and cervix, which was resected and sent for frozen section, confirming melanocytic neoplasia. The hysterectomy revealed multiple tan leiomyomas up to 12 cm, and a distinct 3 cm black, incompletely circumscribed mass in the endomyometrium composed of bland spindled cells with delicate melanin granules. The tumor cells were positive for Sox-10, BAP1, and Mart-1 (Melan-A) and negative for PRAME, PD-L1, and BRAFV600E by immunostains. Microscopic elements of similar melanocytes and melanophages were found in the cervix and bladder peritoneum. Molecular analysis of the uterine tumor identified a GNA11 mutation but no TERT or BAP1 mutation. The uterine melanocytic tumor has characteristic findings of a cellular blue nevus arising in association with dendritic melanocytosis of Mullerian and pelvic tissues, a rarely seen benign phenomenon that should be distinguished from malignant melanoma of the upper genital tract.
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http://dx.doi.org/10.1097/PGP.0000000000000715DOI Listing
September 2020

Adjuvant treatment improves overall survival in women with high-intermediate risk early-stage endometrial cancer with lymphovascular space invasion.

Int J Gynecol Cancer 2020 11 7;30(11):1738-1747. Epub 2020 Aug 7.

Division of Gynecologic Oncology, Women's Health Institute, Cleveland Clinic, Cleveland, Ohio, USA

Background: Adjuvant therapy in early-stage endometrial cancer has not shown a clear overall survival benefit, and hence, patient selection remains crucial.

Objective: To determine whether women with high-intermediate risk, early-stage endometrial cancer with lymphovascular space invasion particularly benefit from adjuvant treatment in improving oncologic outcomes.

Methods: A multi-center retrospective study was conducted in women with stage IA, IB, and II endometrial cancer with lymphovascular space invasion who met criteria for high-intermediate risk by Gynecologic Oncology Group (GOG) 99. Patients were stratified by the type of adjuvant treatment received. Clinical and pathologic features were abstracted. Progression-free and overall survival were evaluated using multivariable analysis.

Results: 405 patients were included with the median age of 67 years (range 27-92, IQR 59-73). 75.0% of the patients had full staging with lymphadenectomy, and 8.6% had sentinel lymph node biopsy (total 83.6%). After surgery, 24.9% of the patients underwent observation and 75.1% received adjuvant therapy, which included external beam radiation therapy (15.1%), vaginal brachytherapy (45.4%), and combined brachytherapy + chemotherapy (19.1%). Overall, adjuvant treatment resulted in improved oncologic outcomes for both 5-year progression-free survival (77.2% vs 69.6%, HR 0.55, p=0.01) and overall survival (81.5% vs 60.2%, HR 0.42, p<0.001). After adjusting for stage, grade 2/3, and age, improved progression-free survival and overall survival were observed for the following adjuvant subgroups compared with observation: external beam radiation (overall survival HR 0.47, p=0.047, progression-free survival not significant), vaginal brachytherapy (overall survival HR 0.35, p<0.001; progression-free survival HR 0.42, p=0.003), and brachytherapy + chemotherapy (overall survival HR 0.30 p=0.002; progression-free survival HR 0.35, p=0.006). Compared with vaginal brachytherapy alone, external beam radiation or the addition of chemotherapy did not further improve progression-free survival (p=0.80, p=0.65, respectively) or overall survival (p=0.47, p=0.74, respectively).

Conclusion: Adjuvant therapy improves both progression-free survival and overall survival in women with early-stage endometrial cancer meeting high-intermediate risk criteria with lymphovascular space invasion. External beam radiation or adding chemotherapy did not confer additional survival advantage compared with vaginal brachytherapy alone.
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http://dx.doi.org/10.1136/ijgc-2020-001454DOI Listing
November 2020

Recurrence Rates in Patients With Cervical Cancer Treated With Abdominal Versus Minimally Invasive Radical Hysterectomy: A Multi-Institutional Retrospective Review Study.

J Clin Oncol 2020 04 7;38(10):1030-1040. Epub 2020 Feb 7.

University of Wisconsin, Madison, WI.

Purpose: To compare the disease-free survival (DFS) between open and minimally invasive radical hysterectomies (RH) performed in academic medical institutions.

Methods: Retrospective multi-institutional review of patients undergoing RH for stage IA1 (with lymphovascular invasion), IA2, and IB1 squamous, adenocarcinoma, or adenosquamous carcinoma between January 1, 2010 and December 31, 2017.

Results: Of 815 patients, open RH was performed in 255 cases (29.1%) and minimally invasive RH in 560 cases (70.9%). There were 19 (7.5%) recurrences in the open RH and 51 (9.1%) recurrences in the minimally invasive group ( = .43). Risk-adjusted analysis revealed that minimally invasive RH was independently associated with an increased hazard of recurrence (aHR, 1.88; 95% CI, 1.04 to 3.25). Other factors independently associated with an increased hazard of recurrence included tumor size, grade, and adjuvant radiation. Conization before surgery was associated with lower recurrence risk (aHR, 0.4; 95% CI, 0.23 to 0.71). There was no difference in OS in the unadjusted analysis (HR, 1.14; 95% CI, 0.61 to 2.11) or after risk adjustment (aHR, 1.01; 95% CI, 0.5 to 2.2). Of 264 patients with tumors ≤ 2 cm on final pathology (excluding those with no residual tumor on final pathology), 2/82 (2.4%) recurred in the open RH group and 16/182 (8.8%) in the minimally invasive RH group ( = .058). In propensity score matching analysis, 7/159 (4.4%) recurrences were noted in the open RH group and 18/156 (11.5%) in the minimally invasive RH group ( = .019). Survival analysis revealed an increased risk of recurrence in the minimally invasive group in propensity-matched cohort (HR, 2.83; 95% CI, 1.1 to 7.18).

Conclusion: In this retrospective series, patients undergoing minimally invasive radical hysterectomy, including those with tumor size ≤ 2 cm on final pathology, had inferior DFS but not overall survival in the entire cohort.
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http://dx.doi.org/10.1200/JCO.19.03012DOI Listing
April 2020

Adjuvant therapy for early stage, endometrial cancer with lymphovascular space invasion: Is there a role for chemotherapy?

Gynecol Oncol 2020 03 14;156(3):568-574. Epub 2020 Jan 14.

The Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Objectives: Lymphovascular space invasion (LVSI) is an independent risk factor for recurrence and poor survival in early-stage endometrioid endometrial cancer (EEC), but optimal adjuvant treatment is unknown. We aimed to compare the survival of women with early-stage EEC with LVSI treated postoperatively with observation (OBS), radiation (RAD, external beam and/or vaginal brachytherapy), or chemotherapy (CHEMO)+/-RAD.

Methods: This was a multi-institutional, retrospective cohort study of women with stage I or II EEC with LVSI who underwent hysterectomy+/-lymphadenectomy from 2005 to 2015 and received OBS, RAD, or CHEMO+/-RAD postoperatively. Progression-free survival and overall survival were evaluated using Kaplan-Meier estimates and Cox proportional hazards models.

Results: In total, 478 women were included; median age was 64 years, median follow-up was 50.3 months. After surgery, 143 (30%) underwent OBS, 232 (48.5%) received RAD, and 103(21.5%) received CHEMO+/-RAD (95% of whom received RAD). Demographics were similar among groups, but those undergoing OBS had lower stage and grade. A total of 101 (21%) women recurred. Progression-free survival (PFS) was improved in both CHEMO+/-RAD (HR = 0.18, 95% CI: 0.09-0.39) and RAD (HR = 0.31, 95% CI: 0.18-0.54) groups compared to OBS, though neither adjuvant therapy was superior to the other. However, in grade 3 tumors, the CHEMO+/-RAD group had superior PFS compared to both RAD (HR 0.25; 95% CI: 0.12-0.52) and OBS cohorts (HR = 0.10, 95% CI: 0.03-0.32). Overall survival did not differ by treatment.

Conclusions: In early-stage EEC with LVSI, adjuvant therapy improved PFS compared to observation alone. In those with grade 3 EEC, adjuvant chemotherapy with or without radiation improved PFS compared to observation or radiation alone.
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http://dx.doi.org/10.1016/j.ygyno.2019.12.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388269PMC
March 2020

Sarcopenia as a predictor of survival and chemotoxicity in patients with epithelial ovarian cancer receiving platinum and taxane-based chemotherapy.

Gynecol Oncol 2020 03 10;156(3):695-700. Epub 2020 Jan 10.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, United States of America.

Objectives: Severe skeletal muscle loss (sarcopenia) is associated with poor cancer outcomes, including reduced survival and increased treatment toxicity. Our goal was to evaluate if sarcopenia was associated with worse survival outcomes and chemotoxicity in EOC patients undergoing primary platinum and taxane-based chemotherapy.

Methods: EOC patients diagnosed between 06/2000 and 02/2017 who received treatment with platinum and taxane-based chemotherapy were included. CT abdominal images closest to the time of diagnosis were retrospectively evaluated for skeletal muscle area at the 3rd lumbar vertebrae. Measurements were obtained with use of TomoVision® radiological software (SliceOmatic - version 5.0, Quebec, Canada). Sarcopenia was defined as Skeletal Muscle Index (SMI) ≤ 41. Data analysis included Kaplan-Meier plots to assess survival, and unpaired t-tests were used to compare the means by groups.

Results: 201 EOC patients were evaluated. Sixty-four percent (128/201) met criteria for sarcopenia (SMI ≤ 41) at time of diagnosis. The mean overall survival did not differ between patients with SMI > 41 and SMI ≤ 41 (36.5 vs 40.8 months, p = 0.4, respectively). No difference in frequency of dose reduction, dose delay, hospital admissions, changes in regimen, blood transfusion, or toxicity was noted. There was no difference in distribution of toxicity grade.

Conclusion: Sarcopenia was not associated with worse survival outcomes or chemotoxcity in EOC patients receiving first-line platinum and taxane-based chemotherapy in this cohort. Future prospective studies should focus on interventions to prevent or reverse sarcopenia and possibly increase ovarian cancer survival, performance status, and quality of life.
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http://dx.doi.org/10.1016/j.ygyno.2020.01.003DOI Listing
March 2020

Defining the learning curve for successful staging with sentinel lymph node biopsy for endometrial cancer among surgeons at an academic institution.

Int J Gynecol Cancer 2020 03 6;30(3):346-351. Epub 2020 Jan 6.

OBGYN, Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Background: Sentinel lymph node (SLN) biopsy is increasingly used in endometrial cancer staging; however, success of the technique is variable, and the learning curve needs to be better understood. Success is defined as identification of a SLN specimen containing nodal tissue in bilateral hemi-pelvises.

Objective: To assess the learning curve of surgeons at an academic institution in performing successful SLN mapping and biopsy during robotic staging for endometrial cancer.

Methods: After institutional review board approval, patients who underwent staging with robotic SLN mapping using indocyanine green at a single academic program between July 2012 and December 2017 were identified. Demographic, pathologic, and surgical data were retrospectively collected from the medical records. Descriptive and comparative statistics were performed. Surgeon rates of successful bilateral SLN mapping and removal of lymphoid-containing SLN specimens were compared. A logistic model was used to analyze the probability of successful SLN mapping and removal of lymph node-containing tissue with increasing number of procedures performed.

Results: Three hundred and seventeen patients met the eligibility criteria. Most had early-stage, low-grade endometrial cancer. A total of 194 (61%) patients had successful bilateral mapping. Among seven surgeons, a plateau in rates of successful bilateral mapping was achieved after 40 cases. No linear correlation was seen between the number of surgeries performed and the rate of removal of lymph node-containing tissue among surgeons. Each additional 10 procedures performed was associated with a 5% and an 11% increase in the odds of successful SLN mapping and removal of lymph node-containing tissue, respectively.

Discussion: The successful removal of lymph node-containing specimens appears to be a surgeon-specific phenomenon. The plateau of the learning curve for successful bilateral mapping seems to be reached at around 40 cases. These first 40 cases offer a time for auditing of individual rates of SLN mapping and removal to identify surgeons who may benefit from procedure-specific remediation.
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http://dx.doi.org/10.1136/ijgc-2019-000942DOI Listing
March 2020

Prospective Evaluation of Multinational Association of Supportive Care in Cancer Risk Index Score for Gynecologic Oncology Patients With Febrile Neutropenia.

Am J Clin Oncol 2019 02;42(2):138-142

Department of Obstetrics and Gynecology, Section of Gynecologic Oncology.

Background: The Multinational Association of Supportive Care of Cancer (MASCC) risk-index score has been validated as a stratification tool for febrile neutropenia (FN) risk in a heterogeneous group of cancer patients; recently, it has been deemed a suitable tool in gynecologic oncology patients in a retrospective study. This is a prospective multi-institutional study wherein we sought to validate MASCC score for stratifying FN morbidity in gynecologic oncology patients.

Methods: IRB approval was obtained at 4 institutions for prospective data collection of gynecologic cancer patients admitted with FN from 3/1/2013 to 9/1/2014. Participating institutions have a policy of inpatient management of FN patients receiving chemotherapy. Deidentified data was compiled and processed at the leading institution.

Results: In total, 31 patients met inclusion criteria. Most had advanced stage disease (67%). 100% of patients were receiving chemotherapy (57% for primary, 43% for recurrent disease). 55% had a positive culture. Median MASCC score was 21 (range, 10 to 26); 58% of patients were considered low risk. High risk patients more often had one (11% vs. 38%, P=0.09) or multiple (6% vs. 23%, P=0.28) severe complications, ICU admission (0% vs. 15%, P=0.17), and delay in next chemotherapy cycle (33% vs. 54%, P=0.25). No patients died from FN during the study period.

Conclusions: This pilot data suggests that MASCC score may be a promising tool for determining suitability of outpatient management of FN in gynecologic oncology patients. Larger studies are warranted to achieve statistically significant results, which may enable us to effectively utilize this risk stratification tool for cost containment and avoidance of nosocomial infections.
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http://dx.doi.org/10.1097/COC.0000000000000498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345587PMC
February 2019

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

Gynecol Oncol 2018 02 19;148(2):329-335. Epub 2017 Dec 19.

Department of Health Policy and Management, Gillings School of Global Public Health, University of North Carolina, United States.

Objective: Advanced stage epithelial ovarian cancer (AEOC) can be treated with either neoadjuvant chemotherapy (NACT) or primary cytoreductive surgery (PCS). Although randomized controlled trials show that NACT is non-inferior in overall survival compared to PCS, there may be improvement in short-term morbidity. We sought to investigate the cost-effectiveness of NACT relative to PCS for AEOC from the US Medicare perspective.

Methods: A cost-effectiveness analysis using a Markov model with a 7-month time horizon comparing (1) 3cycles of NACT with carboplatin and paclitaxel (CT), followed by interval cytoreductive surgery, then 3 additional cycles of CT, or (2) PCS followed by 6cycles of CT. Input parameters included probability of chemotherapy complications, surgical complications, treatment completion, treatment costs, and utilities. Model outcomes included costs, life-years gained, quality-adjusted life-years (QALYs) gained, and incremental cost-effectiveness ratios (ICER), in terms of cost per life-year gained and cost per QALY gained. We accounted for differences in surgical complexity by incorporating the cost of additional procedures and the probability of undergoing those procedures. Probabilistic sensitivity analysis (PSA) was performed via Monte Carlo simulations.

Results: NACT resulted in a savings of $7034 per patient with a 0.035 QALY increase compared to PCS; therefore, NACT dominated PCS in the base case analysis. With PSA, NACT was the dominant strategy more than 99% of the time.

Conclusions: In the short-term, NACT is a cost-effective alternative compared to PCS in women with AEOC. These results may translate to longer term cost-effectiveness; however, data from randomized control trials continues to mature.
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http://dx.doi.org/10.1016/j.ygyno.2017.12.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002777PMC
February 2018

Surgical readmission and survival in women with ovarian cancer: Are short-term quality metrics incentivizing decreased long-term survival?

Gynecol Oncol 2017 12 21;147(3):607-611. Epub 2017 Sep 21.

University of North Carolina, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Chapel Hill, NC, United States; Lineberger Clinical Cancer Center, University of North Carolina, Chapel Hill, NC, United States.

Objectives: To determine the association between treatment with neoadjuvant chemotherapy (NACT) or primary debulking surgery (PDS) and readmission after surgical hospitalization as well as overall survival among women with stage IIIC epithelial ovarian cancer (EOC).

Methods: We identified incident cases of stage IIIC EOC treated with both chemotherapy and surgery in the National Cancer Database (NCDB) from 2006 to 2012. 30-day readmissions were categorized as planned or unplanned. Log binomial models were used to estimate risk ratios and 95% confidence intervals. Survival analysis was performed using cox proportional hazards models.

Results: We identified 20,853 women with stage IIIC EOC. 15.6% (n=3242) were treated with NACT and 11.6% (n=2427) were readmitted within 30days of surgery, 59% (n=1421) were unplanned. NACT was associated with a 48% reduction in the risk of any readmission (aRR 0.52 95%CI 0.45-0.60) compared to PDS with adjustment for age, race, insurance, histology, year of diagnosis, and Charlson co-morbidity index score. However, in the same population, receipt of neoadjuvant chemotherapy was also associated with a 33% increase in the rate of death (HR 1.33 95%CI 1.29-1.40) with adjustment for the same factors.

Conclusions: Among women with stage IIIC EOC, NACT is associated with both decreased rates of readmission and decreased survival compared to PDS. While selection bias may account for some of the observed differences in survival, the current focus on short-term hospital-wide quality metrics, such as postoperative readmission, in the ovarian cancer population, may be creating incentives inconsistent with long-term goals.
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http://dx.doi.org/10.1016/j.ygyno.2017.09.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5996754PMC
December 2017

Sexual Health Before Treatment in Women with Suspected Gynecologic Malignancy.

J Womens Health (Larchmt) 2017 12 22;26(12):1326-1332. Epub 2017 Aug 22.

1 Division of Urogynecology, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina.

Objectives: Sexual health in survivors of gynecologic cancer has been studied; however, sexual health in these women before treatment has not been thoroughly evaluated. The objective of our study was to describe the pretreatment characteristics of sexual health of women with suspected gynecologic cancer before cancer treatment.

Materials And Methods: We performed a cross-sectional analysis of women with a suspected gynecologic cancer, who were prospectively enrolled in a hospital-based cancer survivorship cohort from August 2012 to June 2013. Subjects completed the validated Patient-Reported Outcomes Measurement Information System Sexual Function and Satisfaction Questionnaire. Pretreatment sexual health was assessed in terms of sexual interest, desire, lubrication, discomfort, orgasm, enjoyment, and satisfaction.

Results: Of 186 eligible women with suspected gynecologic cancer, 154 (82%) completed the questionnaire pretreatment. Mean age was 58.1 ± 13.3 years. Sexual health was poor: 68.3% reported no sexual activity, and 54.7% had no interest in sexual activity. When comparing our study population to the general U.S. population, the mean pretreatment scores for the subdomains of lubrication and vaginal discomfort were similar, while sexual interest was significantly lower and global satisfaction was higher. In a linear regression model, controlling for cancer site, age remained significantly associated with sexual function while cancer site did not.

Conclusions: Problems with sexual health are prevalent in women with suspected gynecologic malignancies before cancer treatment. Increasing awareness of the importance of sexual health in this population will improve quality of life for these women.
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http://dx.doi.org/10.1089/jwh.2016.6307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824658PMC
December 2017

Hospital readmission after ovarian cancer surgery: Are we measuring surgical quality?

Gynecol Oncol 2017 08 16;146(2):368-372. Epub 2017 May 16.

University of North Carolina, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Chapel Hill, NC, United States; Lineberger Clinical Cancer Center, University of North Carolina, Chapel Hill, NC, United States.

Objectives: Readmission after surgery is a quality metric hypothesized to reflect the quality of care in the index hospitalization. We examined the link between readmissions and a surrogate of surgical quality - major postoperative complication - among ovarian cancer patients.

Methods: Patients who underwent surgery for ovarian cancer between 2012 and 2013 were identified from the National Surgical Quality Improvement Project (NSQIP). Major complications were defined as grade 3 or ≥complications on the validated Claviden-Dindo scale and included both NSQIP and non-NSQIP defined complications based on readmission ICD-9 code. Readmissions and complications within 30-days of surgery were analyzed using rate ratios and modified Poisson regression.

Results: We identified 2806 ovarian cancer patients of whom 9.1% (n=259) experienced an unplanned readmission. Overall major complication rate was 10.9% (n=307). Major complications in the index hospitalization were not associated with subsequent readmission (RR 1.2, 95% CI 0.7-1.9). Overall, 41.4% of readmissions were not attributable to any major postoperative complication. Of the unplanned readmissions, 55.2% (n=143) never experienced a NSQIP-defined major complication. Of these 143 patients, the reason for readmission was known for 107 patients and was: 28.0% non-NSQIP-defined major complications; 16.8% cancer or other medical factors; 22.4% minor complications; and 32.7% symptoms without a diagnosis of complication.

Conclusions: Forty percent of unplanned readmissions after ovarian cancer surgery occur among patients who have not experienced a major postoperative complication. Quality metric benchmarks and efforts to decrease readmissions should account for this high percentage of readmissions not associated with a major complication.
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http://dx.doi.org/10.1016/j.ygyno.2017.05.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5614497PMC
August 2017

Nonoperative management of atypical endometrial hyperplasia and grade 1 endometrial cancer with the levonorgestrel intrauterine device in medically ill post-menopausal women.

Gynecol Oncol 2017 07 18;146(1):34-38. Epub 2017 Apr 18.

Department of Obstetrics & Gynecology, University of Virginia, Charlottesville, VA, United States.

Objective: To assess the endometrial response rates to treatment with the levonorgestrel intrauterine device in post-menopausal women with atypical hyperplasia/endometrial intraepithelial neoplasia and grade 1 endometrioid (AH/EC) endometrial carcinoma who are not surgical candidates.

Methods: Chart review was undertaken of patients with AH/EC who underwent levonorgestrel intrauterine device insertion by a gynecologic oncologist within two academic health systems between 2002 and 2013. When available, tissue blocks were evaluated with immunohistochemical staining for progesterone receptor expression.

Results: A total of 41 patients received treatment for AH/EC with the levonorgestrel intrauterine device. Follow up sufficient to assess response occurred in 36 women (88%). Complete response was documented in 18 of 36 women (50%), no response in 8 patients (22%), partial response in 3 women (8%) and progression of disease in 7 patients (19%). Four of 18 patients with complete response (22%) later experienced relapse of hyperplasia or cancer. Four patients (10%) died during the study period: none had evidence of metastatic disease and 1 of the 4 woman died of perioperative complications following hysterectomy for stage I disease. Patients responding to treatment had significantly lower progesterone receptor expression on post-treatment biopsies.

Conclusions: Intrauterine levonorgestrel is a viable treatment option for post-menopausal women with AH/EC who are poor candidates for standard surgical management. The response rate in this series is similar to published reports in premenopausal patients and includes cases of disease recurrence following conversion to benign endometrium.
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http://dx.doi.org/10.1016/j.ygyno.2017.04.006DOI Listing
July 2017

Perioperative sexual interest in women with suspected gynecologic malignancies.

Gynecol Oncol 2017 07 12;146(1):109-113. Epub 2017 Apr 12.

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, United States.

Objectives: For women with gynecologic cancer, the impact of surgery on sexual interest and desire in the immediate and later postoperative period is not well characterized. The objective of this study was to report the perioperative trends of changing sexual interest and desire in a cohort of women undergoing surgery for suspected gynecologic malignancies.

Methods: This is an ancillary analysis of a cohort study analyzing health-related outcomes in women who underwent primary surgical management of a suspected gynecologic malignancy between 10/2013 and 10/2014. Subjects completed the Patient-Reported Outcomes Measurement Information System Sexual Function and Satisfaction Questionnaire (PROMIS-SFQ) preoperatively and questions on sexual interest and desire at one, three, and six months postoperatively. Bivariate tests and multiple linear regression were used to analyze data.

Results: Of 231 women who completed a baseline PROMIS-SFQ, 187 (81%) completed one-month, 170 (74%) three-month, and 174 (75%) six-month follow-up interviews. Following surgery, 71% of enrolled subjects were diagnosed with a malignancy. Women age <55 had a greater decrease in sexual interest from baseline to one month than women age >55 (-5.5±1.0 vs -2.3±0.9, p=0.02). In a multivariable analysis, age <55 remained associated with a larger decrease in sexual interest at one month postoperatively (-4.6, 95% CI: -1.8, -7.4), as did having cancer vs benign disease for women of all ages (-5.6, 95% CI: -9.6, -1.5).

Conclusions: This study provides new data regarding the timing and magnitude of changes in sexual interest following gynecologic oncology procedures.
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http://dx.doi.org/10.1016/j.ygyno.2017.04.001DOI Listing
July 2017

Variation in neoadjuvant chemotherapy utilization for epithelial ovarian cancer at high volume hospitals in the United States and associated survival.

Gynecol Oncol 2017 06 31;145(3):500-507. Epub 2017 Mar 31.

Division of Family Planning, Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC, United States.

Objective: To estimate variation in the use of neoadjuvant chemotherapy by high volume hospitals and to determine the association between hospital utilization of neoadjuvant chemotherapy and survival.

Methods: We identified incident cases of stage IIIC or IV epithelial ovarian cancer in the National Cancer Database from 2006 to 2012. Inclusion criteria were treatment at a high volume hospital (>20 cases/year) and treatment with both chemotherapy and surgery. A logistic regression model was used to predict receipt of neoadjuvant chemotherapy based on case-mix predictors (age, comorbidities, stage etc). Hospitals were categorized by the observed-to-expected ratio for neoadjuvant chemotherapy use as low, average, or high utilization hospitals. Survival analysis was performed.

Results: We identified 11,574 patients treated at 55 high volume hospitals. Neoadjuvant chemotherapy was used for 21.6% (n=2494) of patients and use varied widely by hospital, from 5%-55%. High utilization hospitals (n=1910, 10 hospitals) had a median neoadjuvant chemotherapy rate of 39% (range 23-55%), while low utilization hospitals (n=2671, 14 hospitals) had a median rate of 10% (range 5-17%). For all ovarian cancer patients adjusting for clinical and socio-demographic factors, treatment at a hospital with average or high neoadjuvant chemotherapy utilization was associated with a decreased rate of death compared to treatment at a low utilization hospital (HR 0.90 95% CI 0.83-0.97 and HR 0.85 95% CI 0.75-0.95).

Conclusions: Wide variation exists in the utilization of neoadjuvant chemotherapy to treat stage IIIC and IV epithelial ovarian cancer even among high volume hospitals. Patients treated at hospitals with low rates of neoadjuvant chemotherapy utilization experience decreased survival.
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http://dx.doi.org/10.1016/j.ygyno.2017.03.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503107PMC
June 2017

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

J Minim Invasive Gynecol 2017 Jul - Aug;24(5):757-763. Epub 2017 Feb 22.

Gynecology Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina.

Study Objective: To confirm the safety and feasibility outcomes of robotic radical parametrectomy and pelvic lymphadenectomy and compare the clinicopathological features of women requiring adjuvant treatment with the historical literature.

Design: Retrospective cohort study and review of literature (Canadian Task Force classification II-2).

Setting: Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill.

Patients: All patients who underwent robotic radical parametrectomy with upper vaginectomy (RRPV), and pelvic lymphadenectomy for occult cervical cancer discovered after an extrafascial hysterectomy at our institution between January 2007 and December 2015.

Interventions: RRPV and pelvic lymphadenectomy for occult cervical cancer discovered after an extrafascial hysterectomy. We also performed a literature review of the literature on radical parametrectomy after occult cervical carcinoma.

Measurements And Main Results: Seventeen patients with invasive carcinoma of the cervix discovered after extrafascial hysterectomy underwent RRPV with bilateral pelvic lymphadenectomy. There were 2 intraoperative complications, including 1 bowel injury and 1 bladder injury. One patient required a blood transfusion of 2 units. Three patients underwent adjuvant treatment with chemoradiation with radiation-sensitizing cisplatin. One of these patients had residual carcinoma on the upper vagina, 1 patient had positive parametria and pelvic nodes, and 1 patient had positive pelvic lymph nodes. No patients experienced recurrence, and 1 patient died from unknown causes at 59.4 months after surgery. We analyzed 15 studies reported in the literature and found 238 women who underwent radical parametrectomy; however, no specific preoperative pathological features predicted outcomes, the need for adjuvant treatment, or parametrial involvement.

Conclusion: RRPV is a feasible and safe treatment option. As reflected in the literature, RRPV can help avoid empiric adjuvant chemoradiation; however, no pathological features predict the need for adjuvant treatment after surgery.
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http://dx.doi.org/10.1016/j.jmig.2017.02.016DOI Listing
January 2018

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

Gynecol Oncol 2017 03 3;144(3):531-535. Epub 2017 Jan 3.

University of North Carolina, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Chapel Hill, NC, United States; Lineberger Clinical Cancer Center, University of North Carolina, Chapel Hill, NC, United States.

Objectives: To evaluate progression-free survival (PFS) and overall survival (OS) outcomes in women diagnosed with uterine papillary serous carcinoma (UPSC) who have had (UPSCBR+) or have not had (UPSCBR-) an antecedent history of breast cancer and to correlate their outcomes to prior tamoxifen exposure.

Methods: Data were collected for women diagnosed with UPSC at two academic institutions between January 1997 and July 2012. Patient demographics, tumor histology, stage, and treatments were recorded. Patients were divided into two groups: those with and without a personal history of breast cancer. Within the UPSCBR+ cohort, we identified those with a history of tamoxifen use. Cox regression modeling was used to explore associations between selected covariates of interest and the time-to-event outcomes of PFS and OS.

Results: Of 323 patients with UPSC, 46 (14%) were UPSCBR+. Of these, 15 (33%) had a history of tamoxifen use. UPSCBR+ patients were older than UPSCBR- (median years, 72 vs. 68, p=0.004). UPSCBR+ women showed no significant difference in PFS or OS compared to UPSCBR- (p=0.64 and p=0.73 respectively), even after controlling for age (p=0.15 and p=0.48 respectively). Within the UPSCBR+ cohort, there was no difference in PFS or OS with or without tamoxifen exposure (p=0.98 and p=0.94 respectively).

Conclusions: There was no difference in PFS or OS between the UPSCBR+ and UPSCBR- cohorts. We did not demonstrate significant OS or PFS differences in women who took tamoxifen prior to their endometrial cancer diagnosis. These findings have implications for counseling, and should be encouraging to women who are facing their second cancer diagnosis.
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http://dx.doi.org/10.1016/j.ygyno.2016.12.024DOI Listing
March 2017

Discrete microfluidics for the isolation of circulating tumor cell subpopulations targeting fibroblast activation protein alpha and epithelial cell adhesion molecule.

NPJ Precis Oncol 2017 25;1. Epub 2017 Jul 25.

BioEngineering Program, The University of Kansas, Lawrence, KS 66047, USA.

Circulating tumor cells consist of phenotypically distinct subpopulations that originate from the tumor microenvironment. We report a circulating tumor cell dual selection assay that uses discrete microfluidics to select circulating tumor cell subpopulations from a single blood sample; circulating tumor cells expressing the established marker epithelial cell adhesion molecule and a new marker, fibroblast activation protein alpha, were evaluated. Both circulating tumor cell subpopulations were detected in metastatic ovarian, colorectal, prostate, breast, and pancreatic cancer patients and 90% of the isolated circulating tumor cells did not co-express both antigens. Clinical sensitivities of 100% showed substantial improvement compared to epithelial cell adhesion molecule selection alone. Owing to high purity (>80%) of the selected circulating tumor cells, molecular analysis of both circulating tumor cell subpopulations was carried out in bulk, including next generation sequencing, mutation analysis, and gene expression. Results suggested fibroblast activation protein alpha and epithelial cell adhesion molecule circulating tumor cells are distinct subpopulations and the use of these in concert can provide information needed to navigate through cancer disease management challenges.
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http://dx.doi.org/10.1038/s41698-017-0028-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871807PMC
July 2017

Sebaceous carcinoma of the vulva: A case report and review of the literature.

Gynecol Oncol Rep 2016 Nov 29;18:40-41. Epub 2016 Oct 29.

University of North Carolina at Chapel Hill, Gynecologic Oncology, United States; University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, United States.

•Sebaceous carcinoma (SC) is rare with only nine cases reported in the literature.•Extraocular SC likely has similar prognosis to ocular SC.•Reporting of vulvar SC should include detailed pathologic information so that risk factor associations can be made.
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http://dx.doi.org/10.1016/j.gore.2016.10.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5099323PMC
November 2016

Glutaminase inhibitor compound 968 inhibits cell proliferation and sensitizes paclitaxel in ovarian cancer.

Am J Transl Res 2016 15;8(10):4265-4277. Epub 2016 Oct 15.

Division of Gynecological Oncology, University of North CarolinaChapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North CarolinaChapel Hill, NC, USA.

Objective: Our overall goal was to investigate the anti-tumor activity of the glutaminase 1 (GLS1) Inhibitor compound 968 in ovarian cancer cells. The human ovarian cancer cell lines, HEY, SKOV3 and IGROV-1 were used. Cell proliferation was assessed by MTT assay after treatment with compound 968. Cell cycle progression and Annexin V expression were evaluated using Cellometer. Western blotting was performed to determine changes in GLS1, cellular stress and cell cycle checkpoints. Reactive oxygen species (ROS) and glutamate dehydrogenase (GDH) activity were assessed by ELISA assay. Compound 968 significantly inhibited cell proliferation and the expression of GLS1 in a dose-dependent manner in all three ovarian cancer cell lines. Compound 968 induced G1 phase cell cycle arrest and apoptosis. Treatment with compound 968 increased ROS levels and induced the protein expression of calnexin, binding immunoglobulin protein (BiP) and protein kinase RNA-like endoplasmic reticulum kinase (PERK). Deprivation of glutamine increased the sensitivity of cells to paclitaxel, and compound 968 sensitized cells to the anti-proliferative effects of paclitaxel. Compound 968 inhibited cell growth in ovarian cancer cells through induction of G1 phase cell cycle arrest, apoptosis and cellular stress, suggesting that targeting GLS1 provide a novel therapeutic strategy for ovarian cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095319PMC
October 2016

The effect of celecoxib on tumor growth in ovarian cancer cells and a genetically engineered mouse model of serous ovarian cancer.

Oncotarget 2016 Jun;7(26):39582-39594

Division of Gynecological Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Our objective was to evaluate the effect of the COX-2 inhibitor, celecoxib, on (1) proliferation and apoptosis in human ovarian cancer cell lines and primary cultures of ovarian cancer cells, and (2) inhibition of tumor growth in a genetically engineered mouse model of serous ovarian cancer under obese and non-obese conditions. Celecoxib inhibited cell proliferation in three ovarian cancer cell lines and five primary cultures of human ovarian cancer after 72 hours of exposure. Treatment with celecoxib resulted in G1 cell cycle arrest, induction of apoptosis, inhibition of cellular adhesion and invasion and reduction of expression of hTERT mRNA and COX-2 protein in all of the ovarian cancer cell lines. In the KpB mice fed a high fat diet (obese) and treated with celecoxib, tumor weight decreased by 66% when compared with control animals. Among KpB mice fed a low fat diet (non-obese), tumor weight decreased by 46% after treatment with celecoxib. In the ovarian tumors from obese and non-obese KpB mice, treatment with celecoxib as compared to control resulted in decreased proliferation, increased apoptosis and reduced COX-2 and MMP9 protein expression, as assessed by immunohistochemistry. Celecoxib strongly decreased the serum level of VEGF and blood vessel density in the tumors from the KpB ovarian cancer mouse model under obese and non-obese conditions. This work suggests that celecoxib may be a novel chemotherapeutic agent for ovarian cancer prevention and treatment and be potentially beneficial in both obese and non-obese women.
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http://dx.doi.org/10.18632/oncotarget.8659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129955PMC
June 2016

NT1014, a novel biguanide, inhibits ovarian cancer growth in vitro and in vivo.

J Hematol Oncol 2016 Sep 21;9(1):91. Epub 2016 Sep 21.

Division of Gynecologic Oncology, University of North Carolina, Chapel Hill, NC, USA.

Background: NT1014 is a novel biguanide and AMPK activator with a high affinity for the organic cation-specific transporters, OCT1 and OCT3. We sought to determine the anti-tumorigenic effects of NT1014 in human ovarian cancer cell lines as well as in a genetically engineered mouse model of high-grade serous ovarian cancer.

Methods: The effects of NT1014 and metformin on cell proliferation were assessed by MTT assay using the human ovarian cancer cell lines, SKOV3 and IGROV1, as well as in primary cultures. In addition, the impact of NT1014 on cell cycle progression, apoptosis, cellular stress, adhesion, invasion, glycolysis, and AMPK activation/mTOR pathway inhibition was also explored. The effects of NT1014 treatment in vivo was evaluated using the K18 - gT121; p53; Brca1 (KpB) mouse model of high-grade serous ovarian cancer.

Results: NT1014 significantly inhibited cell proliferation in both ovarian cancer cell lines as well as in primary cultures. In addition, NT1014 activated AMPK, inhibited downstream targets of the mTOR pathway, induced G1 cell cycle arrest/apoptosis/cellular stress, altered glycolysis, and reduced invasion/adhesion. Similar to its anti-tumorigenic effects in vitro, NT1014 decreased ovarian cancer growth in the KpB mouse model of ovarian cancer. NT1014 appeared to be more potent than metformin in both our in vitro and in vivo studies.

Conclusions: NT1014 inhibited ovarian cancer cell growth in vitro and in vivo, with greater efficacy than the traditional biguanide, metformin. These results support further development of NT1014 as a useful therapeutic approach for the treatment of ovarian cancer.
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http://dx.doi.org/10.1186/s13045-016-0325-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5031332PMC
September 2016

JQ1 suppresses tumor growth via PTEN/PI3K/AKT pathway in endometrial cancer.

Oncotarget 2016 Oct;7(41):66809-66821

Division of Gynecological Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Overexpression of c-Myc is associated with worse outcomes in endometrial cancer, indicating that c-Myc may be a promising target for endometrial cancer therapy. A novel small molecule, JQ1, has been shown to block BRD4 resulting in inhibition of c-Myc expression and tumor growth. Thus, we investigated whether JQ1 can inhibit endometrial cancer growth in cell culture and xenograft models. In PTEN-positive endometrial cancer cells, JQ1 significantly suppressed cell proliferation via induction of G1 phase arrest and apoptosis in a dose-dependent manner, accompanied by a sharp decline in cyclin D1 and CDK4 protein expression. However, PTEN-negative endometrial cancer cells exhibited intrinsic resistance to JQ1, despite significant c-Myc inhibition. Moreover, we found that PTEN and its downstream PI3K/AKT signaling targets were modulated by JQ1, as evidenced by microarray analysis. Silencing of PTEN in PTEN-positive endometrial cancer cells resulted in resistance to JQ1, while upregulation of PTEN in PTEN-negative endometrial cancer cells increased sensitivity to JQ1. In xenografts models of PTEN-positive and PTEN-knock-in endometrial cancer, JQ1 significantly upregulated the expression of PTEN, blocked the PI3K/AKT signaling pathway and suppressed tumor growth. These effects were attenuated in PTEN-negative and PTEN-knockdown xenograft models. Thus, JQ1 resistance appears to be highly associated with the status of PTEN expression in endometrial cancer. Our findings suggest that targeting BRD4 using JQ1 might serve as a novel therapeutic strategy in PTEN-positive endometrial cancers.
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http://dx.doi.org/10.18632/oncotarget.11631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341839PMC
October 2016

Does the Robotic Platform Reduce Morbidity Associated With Combined Radical Surgery and Adjuvant Radiation for Early Cervical Cancers?

Int J Gynecol Cancer 2016 10;26(8):1485-9

*University of North Carolina at Chapel Hill; and Division of Gynecologic Oncology, Lineberger Comprehensive Cancer Center, Chapel Hill, NC.

Objective: Open radical hysterectomy followed by adjuvant radiation for cervical cancer has been associated with significant rates of morbidity. Radical hysterectomy is now often performed robotically. We sought to examine if the robotic platform decreased the morbidity associated with radical hysterectomy followed by adjuvant radiation.

Materials/methods: A retrospective cohort of patients with cervical cancer undergoing radical hysterectomy from 1995 to 2013 was evaluated. Complications were assessed using electronic record review and graded. χ tests and Student t tests were used for analysis.

Results: Overall, 243 patients underwent radical hysterectomy for cervical cancer. Surgical approach was 43% open and 57% robotic. Eighty-three patients (34.2%) required adjuvant radiation. Overall, radical hysterectomy plus adjuvant radiation was associated with increased risk of complication (29%) compared to radical hysterectomy alone (7%) (P < 0.001). Complications included lymphedema (n = 18), bowel-associated complications (n = 10), and urinary complications (n = 7). There was no difference in time to initiation of radiation between open and robotic surgery (43 vs 47 days; P = 0.33). There was no difference in grade 2/3 complications in patients receiving adjuvant radiation between open and robotic surgery (27.5% vs 27.9%; P = 0.97). Patients undergoing open surgery followed by radiation experienced a trend toward increased adhesion-related complications, such as bowel obstruction and ureteral stricture (10% vs 2.3%; P = 0.19); whereas patients undergoing robotic surgery followed by radiation experienced a trend toward increased lymphedema (19% vs 8%; P = 0.20).

Conclusions: We found no difference in long-term complications between patients who underwent robotic surgery compared to open radical hysterectomy with adjuvant radiation. There may be fewer adhesion-related complications with robotic surgery. However, as many radiation-related complications occur at later time points, continued follow-up to evaluate for potential differences between the 2 groups is necessary.
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http://dx.doi.org/10.1097/IGC.0000000000000775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030127PMC
October 2016

Buformin exhibits anti-proliferative and anti-invasive effects in endometrial cancer cells.

Am J Transl Res 2016 15;8(6):2705-15. Epub 2016 Jun 15.

Division of Gynecologic Oncology, University of North Carolina at Chapel HillChapel Hill, NC. USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel HillChapel Hill, NC. USA.

Objective: Biguanides are anti-diabetic drugs that are thought to have anti-tumorigenic effects. Most pre-clinical studies have focused on metformin for cancer treatment and prevention; however, buformin may be potentially more potent than metformin. Given this, our goal was to evaluate the effects of buformin on cell growth, adhesion and invasion in endometrial cancer cell lines.

Methods: The ECC-1 and Ishikawa endometrial cancer cell lines were used. Cell proliferation was assessed by MTT assay. Apoptosis and cell cycle analysis was performed by FITC Annexin V assay and propidium iodide staining, respectively. Adhesion was analyzed using the laminin adhesion assay. Invasion was assessed using the transwell invasion assay. The effects of buformin on the AMPK/mTOR pathway were determined by Western immunoblotting.

Results: Buformin and metformin inhibited cell proliferation in a dose-dependent manner in both endometrial cancer cell lines. IC50s were 1.4-1.6 mM for metformin and 8-150 μM for buformin. Buformin induced cell cycle G1 phase arrest in the ECC-1 cells and G2 phase arrest in the Ishikawa cells. For both ECC-1 and Ishikawa cells, treatment with buformin resulted in induction of apoptosis, reduction in adhesion and invasion, activation of AMPK and inhibition of phosphorylated-S6. Buformin potentiated the anti-proliferative effects of paclitaxel in both cell lines.

Conclusion: Buformin has significant anti-proliferative and anti-metastatic effects in endometrial cancer cells through modulation of the AMPK/mTOR pathway. IC50 values were lower for buformin than metformin, suggesting that buformin may be more potent for endometrial cancer treatment and worthy of further investigation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931164PMC
July 2016

Intraoperative Handoffs and Postoperative Complications Among Patients Undergoing Gynecologic Oncology Operations.

J Healthc Qual 2017 Jul/Aug;39(4):e42-e48

There is evidence that systems-based factors influence surgical outcomes of intraoperative and postoperative morbidity. The goal of this study was to provide an exploratory analysis of systems-based variables and their associations with surgical outcomes in gynecologic oncology patients. We merged electronic records from operating room software with billing claims from major surgeries performed from 2011 to 2013, at a tertiary care academic medical center. Univariate and bivariate analyses were performed to evaluate the relationship between baseline demographic and clinical covariates (age, comorbidity, procedure type, and surgeon volume), the main exposure variables (case start time, case order, and personnel handoffs), and the primary outcome of 30-day postoperative complications. Multiple logistic regression models were created to analyze the contributing effect of each systemic variable on postoperative complications. The overall rate of postoperative complications among patients was 31.4% (n = 182). Although traditional risk factors of comorbidity, procedure type, and case length were the strongest primary drivers of complication risk, there was a significant relationship between handoffs among surgical scrub technicians and postoperative complications (odds ratio: 2.12; 95% CI: 1.00-4.47). As a novel finding in surgical quality and safety research, this supports greater efforts into integrating key staffing information into studies of systemic variables and surgical outcomes.
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http://dx.doi.org/10.1097/JHQ.0000000000000042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5183519PMC
April 2018

Who presents satisfied? Non-modifiable factors associated with patient satisfaction among gynecologic oncology clinic patients.

Gynecol Oncol 2016 08 11;142(2):299-303. Epub 2016 Jun 11.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC, United States; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States; Department of Health Policy and Management, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, United States.

Objective: To examine associations between non-modifiable patient factors and patient satisfaction (PS) among women presenting to a gynecologic oncology clinic.

Methods: This is a cross sectional analysis of patients presenting for surgical management by a gynecologic oncologist at a tertiary care academic medical center. The Patient Satisfaction Questionnaire (PSQ-18) that measures PS in seven domains of health care was administered. Scores were converted to "satisfied" versus "unsatisfied/equivocal". Demographic and medical factors were obtained from the medical record. Chi-square, t-tests, and multivariable logistic regression were used.

Results: 208 patients completed the baseline patient satisfaction questionnaire and the median PSQ-18 score was 70.5 (range: 42-90). Median age was 58years (range: 22-93). Several non-modifiable factors were associated with PS. White patients had higher interpersonal PS than minorities (86% v 65%, p=0.002). The uninsured had lower interpersonal (60% v 86%, p=0.003) and accessibility PS (33% v 67%, p=0.03). Increasing education and less time travelled to care were both associated with higher interpersonal (p=0.03, p=0.05) and accessibility PS (p=0.01, p=0.01). There was no association between clinical factors (BMI, comorbidities, cancer) and PS. In multivariable analysis, the strongest predictor of interpersonal PS was white race while the strongest predictors of accessibility PS were time travelled to care and insurance status.

Conclusions: Patient satisfaction scores among patients presenting to a gynecologic oncology clinic are associated with non-modifiable demographic, financial and geographic factors. Pay for performance measures that use summed patient satisfaction scores may penalize hospitals for patient-mix driven differences.
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http://dx.doi.org/10.1016/j.ygyno.2016.06.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4961557PMC
August 2016