Publications by authors named "Matthew A Powell"

192 Publications

Immunotherapy as a treatment strategy in advanced stage and recurrent endometrial cancer: review of current phase III immunotherapy clinical trials.

Ther Adv Med Oncol 2021 16;13:17588359211001199. Epub 2021 Mar 16.

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Washington University School of Medicine, St. Louis, MO, USA.

The treatment of advanced stage, metastatic or recurrent endometrial cancer remains a clinically difficult scenario. Although combination carboplatin and paclitaxel is an effective standard-of-care regimen, alternate strategies have shown promise, particularly in biomarker select populations. In an effort to improve oncologic outcomes, investigators are exploring novel immunotherapy combinations. In this review, we discuss the clinical rationale and design of current phase III immuno-oncology clinical trials in patients with advanced stage or recurrent endometrial cancer.
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http://dx.doi.org/10.1177/17588359211001199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970168PMC
March 2021

Obese endometrial cancer survivors' perceptions of weight loss strategies and characteristics that may influence participation in behavioral interventions.

Gynecol Oncol Rep 2021 May 8;36:100719. Epub 2021 Feb 8.

Division of Gynecologic Oncology, Washington University in St. Louis School of Medicine, St. Louis, MO, United States.

We aimed to evaluate obese endometrial cancer (EC) survivors' perceptions of weight loss barriers and previously attempted weight loss methods and to identify characteristics that predicted willingness to enroll in a behavioral intervention trial. We administered a 27-question baseline survey at an academic institution to EC survivors with body mass index ≥ 30 kg/m. Survivors were asked about their lifestyles, previous weight loss attempts, perceived barriers, and were offered enrollment into an intervention trial. Data was analyzed using Fisher's Exact, Kruskal-Wallis, and univariate and multivariate regressions. 155 of 358 (43%) eligible obese EC survivors were surveyed. Nearly all (n = 148, 96%) had considered losing weight, and 77% (n = 120) had tried two or more strategies. Few had undergone bariatric surgery (n = 5, 3%), psychologic counseling (n = 2, 1%), or met with physical therapists (n = 9, 6%). Lower income was associated with difficulty in accessing interventions. Survivors commented that negative self-perceptions and difficulties with follow-through were barriers to weight loss, and fear of complications and self-perceived lack of qualification were deterrents to bariatric surgery. 80 (52%) of those surveyed enrolled in the trial. In a multivariate model, adjusting for race and stage, survivors without recurrence were 4.3 times more likely to enroll than those with recurrence. Most obese EC survivors have tried multiple strategies to lose weight, but remain interested in weight loss interventions, especially women who have never experienced recurrence. Providers should encourage weight loss interventions early, at the time of initial diagnosis, and promote underutilized strategies such as psychological counseling, physical therapy, and bariatric surgery.
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http://dx.doi.org/10.1016/j.gore.2021.100719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907756PMC
May 2021

A deficit-accumulation frailty index predicts survival outcomes in patients with gynecologic malignancy.

Gynecol Oncol 2021 Feb 26. Epub 2021 Feb 26.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, and Alvin J. Siteman Cancer Center, St. Louis, MO, United States of America. Electronic address:

Objective: To determine the association between scores from a 25-item patient-reported Rockwood Accumulation of Deficits Frailty Index (DAFI) and survival outcomes in gynecologic cancer patients.

Methods: A frailty index was constructed from the SEER-MHOS database. The DAFI was applied to women age ≥ 65 diagnosed with all types of gynecologic cancers between 1998 and 2015. The impact of frailty status at cancer diagnosis on overall survival (OS) was analyzed using Kaplan-Meier curves and Cox proportional hazards regression.

Results: In this cohort (n = 1336) the median age at diagnosis was 74 (range 65-97). Nine hundred sixty-two (72%) women were Caucasian and 132 (10%) were African-American. Overall, 651(49%) of patients were considered frail. On multivariate analysis, frail patients had a 48% increased risk for death (aHR 1.48; 95% CI 1.29-1.69; P < 0.0001). Each 10% increase in frailty index was associated with a 16% increased risk of death (aHR, 1.16; 95% CI, 1.11 to 1.21; P < 0.0001). In subgroup analyses of the varying cancer types, the association of frailty status with prognosis was fairly consistent (aHR 1.15-2.24). The DAFI was more prognostic in endometrial (aHR 1.76; 95% CI 1.41-2.18, P < 0.0001) and vaginal/vulvar (aHR 1.94; 95% CI 1.34-2.81, P = 0.0005) cancers as well as patients with loco-regional disease (aHR 1.94; 95% CI 1.62-2.33, P < 0.0001).

Conclusions: Frailty appears to be a significant predictor of mortality in gynecologic cancer patients regardless of chronological age. This measure of functional age may be of particular utility in women with loco-regional disease only who otherwise would have a favorable prognosis.
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http://dx.doi.org/10.1016/j.ygyno.2021.02.027DOI Listing
February 2021

Impact of employment and insurance status on distress in gynecologic oncology patients.

Gynecol Oncol 2021 Feb 2. Epub 2021 Feb 2.

Department of Psychiatry, Alvin J. Siteman Cancer Center, St. Louis, MO 63110, United States of America.

Objectives: To study associations among employment, insurance status, and distress in gynecologic oncology patients; and to evaluate the impact of being unemployed or having no/Medicaid insurance on different distress problem areas.

Methods: In this single institution, cross-sectional analysis of gynecologic oncology patients, we screened for distress and problem areas using the National Comprehensive Cancer Network distress thermometer and problem list at outpatient appointments between 6/2017-9/2017. Primary outcome was self-reported high distress (score ≥ 5). The distress problem list included 5 categories-practical, family, emotional, physical, and other. Employment status included employed, unemployed, homemaker, and retired. Logistic regression was used to predict high distress from employment and insurance statuses, adjusting for relevant covariates.

Results: Of 885 women, 101 (11.4%) were unemployed, and 53 (6.0%) uninsured or had Medicaid coverage. One in five patients (n = 191, 21.6%) indicated high distress. Unemployed patients were more likely than employed to endorse high distress [adjusted odds ratio (aOR) = 3.5, 95% confidence interval (CI) 2.2-5.7, p < 0.001]. Compared to employed patients, a greater proportion of unemployed patients endorsed distress related to practical (p < 0.05), emotional (p < 0.001), physical (p < 0.01), and other (p < 0.05) problems. Uninsured/Medicaid patients were more likely to endorse high distress (aOR = 2.8, 95% CI 1.5-5.1, p < 0.001) and report family (p < 0.001), emotional (p < 0.001), and other (p < 0.01) problems than patients who had Medicare/commercial insurance.

Conclusions: Gynecologic oncology patients who are unemployed or have no/Medicaid insurance face high distress that appears to arise from issues beyond practical problems, including financial and/or insurance insecurities.
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http://dx.doi.org/10.1016/j.ygyno.2021.01.038DOI Listing
February 2021

The role of endometrial sampling for surveillance of recurrence in postmenopausal patients with medically inoperable stage I endometrial cancer.

Gynecol Oncol Rep 2021 Feb 31;35:100694. Epub 2020 Dec 31.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, and Alvin J. Siteman Cancer Center, St. Louis, MO, USA.

It is unclear if surveillance for postmenopausal women with medically inoperable stage 1 endometrial cancer (EC) should differ depending on their management strategy. Thus, we investigated the utility of surveillance endometrial sampling among 53 postmenopausal women with medically inoperable, clinical stage I, grade 1 endometrioid EC who received either progestin therapy or radiation between 2009 and 2018, at a single academic institution. Frequency and results of endometrial sampling, as well as recurrence and survival rates were studied. Of 53 patients, 18 (34.0%) received progestin therapy and 35 (66.0%) radiation. Medically managed patients were treated with megestrol acetate (27.7%), a levonorgestrel intrauterine device (27.7%), or both (44.4%). Radiated patients were mostly treated with high-dose rate brachytherapy only (77.1%). Surveillance endometrial sampling (median procedures = 4, range 1-10) was strictly adhered to among all patients who received progestin therapy, but infrequently (6/35, 17.1%) performed among radiated patients, yielding no positive results. Three recurrences occurred over the median follow-up of 38 months. Two (11%) women in the progestin therapy group recurred locally and were diagnosed by endometrial sampling. One (3%) patient in the radiation group recurred distally in the lung 25.3 months after completing brachytherapy. We conclude that appropriate surveillance for women with medically inoperable, clinical stage I, grade 1 EC depends on the management strategy. For those treated with progestins, surveillance with endometrial sampling every 3-6 months can reveal local recurrence. However, given the excellent local control after radiation, endometrial sampling may not be warranted for women treated with definitive radiation.
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http://dx.doi.org/10.1016/j.gore.2020.100694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809387PMC
February 2021

The presence of an endometrioid component does not alter the clinicopathologic profile or survival of patients with uterine serous cancer: A gynecologic oncology group (GOG/NRG) study of 934 women.

Gynecol Oncol 2021 Mar 8;160(3):660-668. Epub 2021 Jan 8.

Washington University School of Medicine, St. Louis, MO, USA. Electronic address:

Objective: While most cases of endometrial cancer can readily be classified as pure endometrioid, pure serous, or another type, others show an apparent mixture of serous and endometrioid components, or indeterminate serous versus endometrioid features. Since serous histology carries a worse prognosis than endometrioid, Gynecologic Oncology Group protocol GOG-8032 was established to examine whether the presence of a non-serous component is a favorable feature in an otherwise serous cancer.

Methods: 934 women with serous cancer were prospectively identified among a larger group enrolled in GOG-0210. Six expert gynecologic pathologists classified each case as pure serous (SER, n=663), mixed serous and endometrioid (SER-EM-M, n=138), or indeterminate serous v. endometrioid (SER-EM-I, n=133) by H&E morphology. Follow-up data from GOG-0210 were analyzed.

Results: The subgroups did not differ on BMI, race, ethnicity, lymphovascular invasion, cervical invasion, ovary involvement, peritoneal involvement, omental involvement, FIGO stage, or planned adjuvant treatment. SER-EM-M patients were younger (p=0.0001) and less likely to have nodal involvement (p=0.0287). SER patients were less likely to have myoinvasion (p=0.0002), and more likely to have adnexal involvement (p=0.0108). On univariate analysis, age, serous subtype, race, and components of FIGO staging predicted both progression-free and overall survival. On multiple regression, however, serous subtype (SER, SER-EM-M, or SER-EM-I) did not significantly predict survival.

Conclusions: There were few clinicopathologic differences between cases classified as SER, SER-EM-M, and SER-EM-I. Cases with a mixture of serous and endometrioid morphology, as well as cases with morphology indeterminate for serous v. endometrioid type, had the same survival as pure serous cases. NCT#: NCT00340808.
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http://dx.doi.org/10.1016/j.ygyno.2020.12.040DOI Listing
March 2021

Carboplatin and Paclitaxel for Advanced Endometrial Cancer: Final Overall Survival and Adverse Event Analysis of a Phase III Trial (NRG Oncology/GOG0209).

J Clin Oncol 2020 11 29;38(33):3841-3850. Epub 2020 Sep 29.

The University of Chicago Medicine, Chicago, IL.

Purpose: Limitations of the paclitaxel-doxorubicin-cisplatin (TAP) regimen in the treatment of endometrial cancer include tolerability and cumbersome scheduling. The Gynecologic Oncology Group studied carboplatin plus paclitaxel (TC) as a noninferior alternative to TAP.

Methods: GOG0209 was a phase III, randomized, noninferiority, open-label trial. Inclusion criteria were stage III, stage IV, and recurrent endometrial cancers; performance status 0-2; and adequate renal, hepatic, and marrow function. Prior radiotherapy and/or hormonal therapy were permitted, but chemotherapy, including radiosensitization, was not. Patients were treated with doxorubicin 45 mg/m and cisplatin 50 mg/m (day 1), followed by paclitaxel 160 mg/m (day 2) with granulocyte colony-stimulating factor or paclitaxel 175 mg/m and carboplatin area under the curve 6 (day 1) every 21 days for seven cycles. The primary endpoint was overall survival (OS; modified intention to treat). Progression-free survival (PFS), health-related quality of life (HRQoL), and toxicity were secondary endpoints.

Results: From 2003 to 2009, 1,381 women were enrolled. Noninferiority of TC to TAP was concluded for OS (median, 37 41 months, respectively; hazard ratio [HR], 1.002; 90% CI, 0.9 to 1.12), and PFS (median, 13 14 months; HR, 1.032; 90% CI, 0.93 to 1.15). Neutropenic fever was reported in 7% of patients receiving TAP and 6% of those receiving TC. Grade > 2 sensory neuropathy was recorded in 26% of patients receiving TAP and 20% receiving TC ( = .40). More grade ≥ 3 thrombocytopenia (23% 12%), vomiting (7% 4%), diarrhea (6% 2%), and metabolic (14% 8%) toxicities were reported with TAP. Neutropenia (52% 80%) was more common with TC. Small HRQoL differences favored TC.

Conclusion: With demonstrated noninferiority to TAP, TC is the global first-line standard for advanced endometrial cancer.
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http://dx.doi.org/10.1200/JCO.20.01076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676887PMC
November 2020

Assessing Physician Adherence to Guidelines for Cervical Cancer Screening and Management of Abnormal Screening Results.

J Low Genit Tract Dis 2020 10;24(4):337-342

Division of Gynecologic Oncology, Washington University School of Medicine, Alvin J. Siteman Cancer Center, St. Louis, MO.

Objective: The aim of the study was to survey obstetrician-gynecologists' cervical cancer screening practices and management of cervical abnormalities to ascertain adherence to guidelines.

Methods: From January to July 2019, obstetrician-gynecologists at 5 St. Louis area hospitals were surveyed online about cervical cancer screening and management practices through 13 clinical vignettes. Survey scores and the American Society of Colposcopy and Cervical Pathology (ASCCP) app use were compared using Mann-Whitney tests.

Results: When screening 30- to 65-year-old participants, 114 (98%) of the 116 total participants used co-testing, but only 71 (61%) screened at 5-year intervals. None used primary human papillomavirus (HPV) testing. For 21- to 29-year-old participants, 17 (15%) screened with annual cytology, whereas 14 (12%) used annual or every 3-year co-testing. Forty eight (41%) screened younger than 21 years, regardless of risk factors or only if immunocompromised. Eleven (9%) continued screening after total hysterectomy for benign indications. Only 2 (2%) responded to all clinical vignettes in adherence to guidelines. More than 30% of participants would pursue unnecessary HPV testing and/or loop electrosurgical excision procedure for persistent low-grade cytology. Fifty eight (48%) incorrectly reported hysterectomy as management for adenocarcinoma in situ on biopsy. Participants would undertreat young women with high-grade abnormalities including high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia 3 (48, 41%) and high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia 1 (65, 56%). Forty one (35%) reported exiting women from screening prematurely. The median score for participants using the ASCCP app was significantly greater than those who did not (79% vs 71%, p = .002).

Conclusions: Midwestern obstetrician-gynecologists' adherence to the guidelines for cervical cancer screening and management of abnormal results is suboptimal. Although co-testing for women aged 30-65 years has been broadly adopted, primary HPV testing has not. Physicians overscreen, overtreat low-grade lesions, and undertreat high-grade lesions in young women.
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http://dx.doi.org/10.1097/LGT.0000000000000558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673488PMC
October 2020

A fellow-run clinic achieves similar patient outcomes as faculty clinics: A safe and feasible model for gynecologic oncology fellow education.

Gynecol Oncol 2020 10 19;159(1):209-213. Epub 2020 Jul 19.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, Alvin J. Siteman Cancer Center, St. Louis, MO, USA. Electronic address:

Objectives: Fellow involvement in patient care is important for education, but effect on patient care is unclear. Our aim was to compare patient outcomes in gynecologic oncology attending clinics versus a fellow training clinic at a large academic medical center.

Methods: A retrospective review of consecutive gynecologic oncology patients from six attending clinics and one faculty-supervised fellow clinic was used to analyze differences based on patient demographics, cancer characteristics, and practice patterns. Primary outcome was overall survival (OS); secondary outcomes included recurrence-free survival (RFS), postoperative complications and chemotherapy within the last 30 days of life. Survival analyses were performed using Kaplan-Meier curves with log-rank tests.

Results: Of 159 patients, 76 received care in the attending clinic and 83 in the fellow clinic. Patients in the fellow clinic were younger, less likely to be Caucasian, and more overweight, but cancer site and proportion of advanced stage disease were similar. Both clinics had similar rates of moderate to severe adverse events related to surgery (15% vs. 8%, p = .76), chemotherapy (21% vs. 23%, p = .40), and radiation (14% vs. 17%, p = .73). There was no difference in median RFS in the fellow compared to attending clinic (38 vs. 47 months, p = .78). OS on both univariate (49 months-fellow clinic, 60 months-attending clinic vs. p = .40) and multivariate analysis [hazard ratio 1.3 (0.57, 2.75), P = .58] was not significantly different between groups.

Conclusions: A fellow-run gynecologic oncology clinic designed to provide learning opportunities does not compromise patient outcomes and is a safe and feasible option for fellow education.
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http://dx.doi.org/10.1016/j.ygyno.2020.07.018DOI Listing
October 2020

Phase II study of axalimogene filolisbac (ADXS-HPV) for platinum-refractory cervical carcinoma: An NRG oncology/gynecologic oncology group study.

Gynecol Oncol 2020 09 6;158(3):562-569. Epub 2020 Jul 6.

Memorial Sloan-Kettering Cancer Center, Dept. of Medical Oncology, New York, NY 10021, United States of America. Electronic address:

Objective: Women with persistent, recurrent, and/or metastatic cervical cancer have a poor prognosis. Even with the availability of cisplatin plus paclitaxel and bevacizumab, median overall survival (OS) is only 17.0 months, with median post-progression survival of approximately seven months. We studied the therapeutic vaccine, Axalimogene filolisbac (ADXS-HPV), in women who had progressed following at least one prior line of therapy (Gynecologic Oncology Group protocol 265/NCT01266460).

Methods: Volunteers ≥18 years with advanced cervical cancer and GOG performance status score of 0 or 1 were eligible for participation in this 2-stage, phase II trial. In stage 1, women received up to three doses of ADXS-HPV (1 × 10 colony-forming units in 250 mL IV over 15 min every 28 days) and were monitored for tumor progression. In stage 2, women were treated until progression, intolerable adverse events (AEs), or voluntary withdrawal of consent. Co-primary endpoints were safety and proportion of volunteers surviving ≥12 months. An estimated, combined (stages 1 + 2) 12-month OS of 35% was calculated from historical GOG cohorts to declare ADXS-HPV sufficiently active in this platinum-pre-treated population. Secondary endpoints were OS and progression-free survival (PFS).

Results: Among 50 evaluable volunteers, the 12-month OS was 38% (n = 19). Median OS was 6.1 months (95% CI: 4.3-12.1) and median PFS was 2.8 months (95% CI: 2.6-3.0). The most common treatment-related AEs were fatigue, chills, fever, nausea, and anemia. The majority of AEs were grade 1 or 2 and resolved spontaneously or with appropriate treatment.

Conclusion: At the dose and schedule studied, ADXS-HPV immunotherapy was tolerable and met the protocol-specified benchmark for activity required to warrant further investigation in volunteers with cervical carcinoma.
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http://dx.doi.org/10.1016/j.ygyno.2020.06.493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487015PMC
September 2020

Long-term outcomes of intensity-modulated radiation therapy (IMRT) and high dose rate brachytherapy as adjuvant therapy after radical hysterectomy for cervical cancer.

Int J Gynecol Cancer 2020 08 11;30(8):1157-1161. Epub 2020 Jun 11.

Radiation Oncology, Washington University School of Medicine, St Louis, Missouri, USA

Objective: Compared with 3D-planned pelvic radiation, intensity-modulated radiation therapy (IMRT) has been shown to reduce acute toxicity in cervical cancer patients after radical hysterectomy. This study evaluated late toxicity and patterns of failure after post-operative pelvic IMRT interdigitated weekly with high dose rate brachytherapy.

Methods: This retrospective study included 53 cervical cancer patients treated between January 2006 and August 2019 with radical hysterectomy, lymphadenectomy, and post-operative IMRT and high dose rate brachytherapy. The decision to include chemotherapy was made by the treating gynecologic oncologist based on patient-specific criteria including positive pelvic lymph nodes, positive surgical margins, or positive parametrial invasion. The actuarial rates of genitourinary and gastrointestinal toxicity, vaginal cuff/regional nodal/distant failure, and overall survival were calculated using the Kaplan-Meier method.

Results: Median follow-up was 70 months (range 5.4-148) months and age at diagnosis was 47 (range 24-73) years. The 2018 International Federation of Gynecology and Obstetrics (FIGO) clinical stages were IB1 (n=19), IB2 (n=7), IIB (n=7), IIIC1 (n=19), and IIIC2 (n=1). Median radiation dose delivered in 160 cGy daily fractions was 5120 (range 4640-5120) cGy. Median brachytherapy dose prescribed to the vaginal surface delivered in six weekly fractions was 2400 (range 1200-4800) cGy. Concurrent chemotherapy was delivered in 35 (66%) patients. There were no acute grade 3 genitourinary or gastrointestinal toxicities. Late grade 3 occurred in two (3.8%) patients, including a small bowel obstruction and a ureteral stricture. The 5-year actuarial rate for gastrointestinal or genitourinary toxicity was 1.9%. There were no vaginal cuff recurrences. The 5-year actuarial rates for regional nodal failure, distant failure outside the radiation field, any failure, and overall survival were 11%, 11%, 14%, and 85%, respectively.

Conclusions: Post-operative IMRT with high dose rate brachytherapy for patients with cervical cancer is associated with excellent outcomes and limited rates of radiation-related non-hematologic toxicity.
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http://dx.doi.org/10.1136/ijgc-2020-001412DOI Listing
August 2020

Radiologic Assessment of Groin Lymph Nodes in Pelvic Malignancies.

Int J Gynecol Cancer 2020 07 2;30(7):947-953. Epub 2020 Jun 2.

Department of Radiation Oncology, Washington University in Saint Louis, Saint Louis, Missouri, USA

Introduction: Metastatic involvement of groin nodes can alter radiation therapy planning for pelvic tumors. F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) can identify nodal metastases; however, interpretation of PET/CT-positive nodes can be complicated by non-malignant processes. We evaluated quantitative metrics as methods to identify groin metastases in patients with pelvic tumors by comparison with standard subjective interpretive criteria, with pathology as the reference standard.

Methods: We retrospectively identified patients with vulvar, vaginal, or anal cancers who underwent F-FDG PET/CT before pathologic evaluation of groin nodes between 2007 and 2017. Because patho-radiologic correlation was not possible for every node, one index node identified on imaging was selected for each groin. For each index node, standardized uptake value measurements, total lesion glycolysis, metabolic tumor volume, CT-based volume, and short and long axes were measured. Multivariate logistic regression was used to identify metrics predictive for pathologically positive groins and generate a probabilistic model. Area under the receiver-operating characteristic curves (AUCs) for the model were compared with clinical interpretation from the diagnostic report via a Wald's χ test.

Results: Of 55 patients identified for analysis, 75 groins had pathologic evaluation resulting in 75 index groin nodes for analysis with 35 groins pathologically positive for malignancy. Logistic regression identified mean standardized-uptake-value (50% threshold) and short-axis length as the most predictive imaging metrics for metastatic nodal involvement. The probabilistic model performed better at predicting pathologic involvement compared with standard clinical interpretation on analysis (AUC 0.91, 95% CI 0.84 to 0.97 vs 0.80, 95% CI 0.71 to 0.89; p<0.01).

Discussion: Accuracy of F-FDG PET/CT for detecting groin nodal metastases in patients with pelvic tumors may be improved with the use of quantitative metrics. Improving prediction of nodal metastases can aid with appropriate selection of patients for pathologic node evaluation and guide radiation volumes and doses.
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http://dx.doi.org/10.1136/ijgc-2020-001363DOI Listing
July 2020

FIGO 2018 staging criteria for cervical cancer: Impact on stage migration and survival.

Gynecol Oncol 2020 06 2;157(3):639-643. Epub 2020 Apr 2.

Alvin J. Siteman Cancer Center, Washington University in St. Louis School of Medicine, United States of America; Division of Gynecology Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, United States of America.

Objective: To compare FIGO 2009 and FIGO 2018 cervical cancer staging criteria with a focus on stage migration and treatment outcomes.

Methods: This study is based on a database cohort of 1282 patients newly diagnosed with cervical cancer from 1997 to 2019. All underwent standard clinical examination and whole-body FDG-PET. Tumor stage was recorded using the FIGO 2009 system, which excluded surgical pathologic, FDG-PET and other advanced imaging findings, and then re-classified to the FIGO 2018 system, including surgical pathologic and imaging findings. Patient management was based on clinical, surgical, and imaging findings. Stage migration and prognosis were evaluated.

Results: The distribution per the 2009 staging system was stage I in 593 (46%), stage II in 342 (27%), stage III in 263 (21%), and stage IV in 84 (7%) and the 2018 staging system was stage I in 354 (28%), stage II in 156 (12%), stage III in 601 (47%), and stage IV in 171 (13%). No patients were down-staged. Stage migration occurred in 53% (676/1282) and was attributable to detection of occult lymph node metastasis in 520 (41%), occult distant metastasis in 90 (7%), and tumor size and extent in 66 (5%). The 5-year progression-free survivals (PFS) by FIGO 2009 versus FIGO 2018 were as follows: stage I, 80% vs. 87% (p = 0.02); stage II, 59% vs. 71% (p = 0.002); stage III, 35% vs. 55% (p < 0.001), and stage IV, 20% vs. 16% (p = 0.41).

Conclusion: Inclusion of surgical pathologic and imaging findings resulted in upward stage migration in the majority, mostly related to nodal and distant metastasis. While FIGO 2018 improves survival discriminatory ability for stages I and IV patients, survival remains heterogeneous among stage III substages.
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http://dx.doi.org/10.1016/j.ygyno.2020.03.027DOI Listing
June 2020

Racial disparities in uterine and ovarian carcinosarcoma: A population-based analysis of treatment and survival.

Gynecol Oncol 2020 04 4;157(1):67-77. Epub 2020 Feb 4.

Gynecologic Cancer Center of Excellence, Department of Obstetrics & Gynecology, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD, USA; Henry M Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA; John P Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD, USA. Electronic address:

Objective: To investigate racial disparities in uterine carcinosarcoma (UCS) and ovarian carcinosarcoma (OCS) in Commission on Cancer®-accredited facilities.

Methods: Non-Hispanic Black (NHB) and non-Hispanic White (NHW) women in the National Cancer Database diagnosed with stage I-IV UCS or OCS between 2004 and 2014 were eligible. Differences by disease site or race were compared using Chi-square test and multivariate Cox analysis.

Results: There were 2830 NHBs and 7366 NHWs with UCS, and 280 NHBs and 2586 NHWs with OCS. Diagnosis of UCS was more common in NHBs (11.5%) vs. NHWs (3.7%) and increased with age (P < .0001). OCS diagnosis remained <5% in both races and all ages. NHBs with UCS or OCS were more common in the South and more likely to have a comorbidity score ≥ 1, low neighborhood income and Medicaid or no insurance (P < .0001). Diagnosis at stage II-IV was more common in NHBs than NHWs with UCS but not OCS. NHBs with both UCS and OCS were less likely to undergo surgery and to achieve no gross residual disease with surgery (P = .002). Risk of death in NHB vs. NHW patients with UCS was 1.38 after adjustment for demographic factors and dropped after sequential adjustment for comorbidity score, neighborhood income, insurance status, stage and treatment by 4%, 16%, 7%, 19% and 10%, respectively, leaving 43.5% of the racial disparity in survival unexplained. In contrast, risk of death in NHBs vs. NHWs with OCS was 1.19 after adjustment for demographic factors and became insignificant after adjustment for comorbidity. Race was an independent prognostic factor in UCS but not in OCS.

Conclusions: Racial disparities exist in characteristics, treatment and survival in UCS and OCS with distinctions that merit additional research.
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http://dx.doi.org/10.1016/j.ygyno.2020.01.017DOI Listing
April 2020

Modified frailty index is predictive of wound complications in obese patients undergoing gynecologic surgery via a midline vertical incision.

Gynecol Oncol 2020 04 27;157(1):287-292. Epub 2020 Jan 27.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, Alvin J. Siteman Cancer Center. St Louis, MO, USA. Electronic address:

Objectives: There are limited methods to identify which obese patients will experience wound complications after undergoing gynecologic surgery. We sought to determine the association between frailty and postoperative wound complications and to develop a prediction model for wound complications in this patient population.

Methods: We reviewed prospectively collected data of obese patients undergoing laparotomy though midline vertical incisions from 7/2013-3/2016. Modified frailty index (mFI) was calculated using 11 comorbidities previously validated. The primary outcome was the composite rate of postoperative wound complication. Data was analyzed using Fisher exact test or Chi-square and t-tests or Kruskal-Wallis tests. Poisson regression models were used to generate relative risks. Prediction models were created with receiver-operator characteristic curve analysis.

Results: Of 163 patients included, 56 (34%) were considered frail. Wound complications occurred in 52 patients (31.9%): 28 (50%) frail and 24 (22.4%) non-frail patients (RR 2.23, 95%CI 1.29-3.85). Frail patients had significantly greater frequencies of wound breakdown (37.5% vs 15%, RR 2.51, 95%CI 1.31-4.81). After controlling for BMI, tobacco use, and maximum postoperative glucose, frailty remained an independent predictor of wound complication (aRR 1.88, 95%CI 1.04-3.40). The area under the curve for the predictive model incorporating frailty was 0.73 for wound complications.

Conclusion: Frailty is associated with wound complications in obese patients undergoing gynecologic surgery via a midline vertical incision and is a useful tool in identifying the most high risk patients. Further prospective research is necessary to incorporate mFI into preoperative planning and counseling.
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http://dx.doi.org/10.1016/j.ygyno.2019.11.008DOI Listing
April 2020

Second-line lenvatinib in patients with recurrent endometrial cancer.

Gynecol Oncol 2020 03 17;156(3):575-582. Epub 2020 Jan 17.

Division of Hematology and Oncology, Massachusetts General Hospital, Boston, MA, USA.

Objective: This study assessed the efficacy of lenvatinib, a multitargeted tyrosine kinase inhibitor, as second-line therapy in patients with unresectable endometrial cancer. The primary end point was the objective response rate (ORR) as assessed by independent radiologic review (IRR). Secondary end points included median progression-free survival (PFS), overall survival (OS), and clinical benefit rate. Exploratory end points examined the association of baseline levels of plasma biomarkers (50 circulating cytokine and/or angiogenic factors measured by immunoassays) with efficacy outcomes.

Methods: An international, open-label, single-arm, multicenter, phase 2 trial was conducted. Eligible patients had histologically confirmed unresectable endometrial cancer that relapsed after 1 prior systemic platinum-based chemotherapy. Patients received once-daily oral lenvatinib 24 mg in a 28-day dosing cycle.

Results: There were 133 patients in the study. By IRR, 19 patients had a confirmed objective response for an ORR of 14.3% (95% CI: 8.8-21.4). Durable stable disease (≥23 weeks) was observed in 31 patients (23.3%) and the clinical benefit rate was 37.6% (95% CI: 29.3-46.4). Median PFS was 5.6 months (95% CI: 3.7-6.3), and median OS was 10.6 months (95% CI: 8.9-14.9). The most common (any grade) treatment-related adverse events were fatigue/asthenia (48%), hypertension (49%), nausea/vomiting (32%), decreased appetite (32%), and diarrhea (31%). Lower baseline levels of angiopoietin-2 were associated with longer PFS, OS, and a higher ORR.

Conclusions: Patients with recurrent endometrial cancer treated with second-line lenvatinib experienced modest antitumor activity and treatment was generally well tolerated, with a safety profile consistent with previous studies.
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http://dx.doi.org/10.1016/j.ygyno.2019.12.039DOI Listing
March 2020

Impact of adjuvant treatment and prognostic factors in stage I uterine leiomyosarcoma patients treated in Commission on Cancer®-accredited facilities.

Gynecol Oncol 2020 04 15;157(1):121-130. Epub 2020 Jan 15.

Gynecologic Cancer Center of Excellence, Department of Obstetrics & Gynecology, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD, USA; The Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; John P Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. Electronic address:

Objectives: Determine the impact of adjuvant chemotherapy (ACT) and prognostic factors in surgically managed patients with stage I uterine leiomyosarcoma (ULMS).

Methods: Women who underwent hysterectomy and were diagnosed with stage I ULMS between 2010 and 2014 in the National Cancer Database were eligible for this observation study. Inverse probability of treatment weighting based on propensity score was used to balance clinical characteristics between ACT and no ACT patients. Hazard ratio (HR) and 95% confidence interval (CI) were estimated from Cox modeling.

Results: There were 1059 eligible patients with stage I ULMS including 514 treated with ACT and 545 with no ACT. Patient characteristics and tumor features varied in patients treated with ACT vs. no ACT (P < .0001). Multivariate survival analysis demonstrated that patient age, comorbidity score, tumor size, lymphovascular space invasion (LVSI) and grade were independent prognostic factors. After propensity score weighting to control for imbalance of prognostic clinical factors, adjusted five-year survival was 61.7% vs. 61.3% and restricted mean survival time was 39.7 vs. 40.6 months for ACT vs. no ACT, respectively. Risk of death in a weighted Cox analysis of overall survival was similar (HR = 1.08, 95% CI = 0.85-1.37, P = .054) for ACT vs. no ACT patients. Subset analysis demonstrated that survival was similar in ACT vs. no ACT patients categorized by age, tumor size and LVSI or with high grade or ungraded tumors. In contrast, patients with low grade tumors had worse 5-year survival (82.3% vs. 91.5%) and an increased risk of death (HR = 3.79, 95% CI = 1.15-12.40, P = .028) following ACT vs. no ACT.

Conclusions: ACT did not improve survival over no ACT in patients with stage I ULMS and was inferior in patients with low grade tumors.
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http://dx.doi.org/10.1016/j.ygyno.2019.12.008DOI Listing
April 2020

Molecular characterization of endometrial cancer and therapeutic implications.

Curr Opin Obstet Gynecol 2020 02;32(1):76-83

Division of Gynecologic Oncology, Washington University in St. Louis, St. Louis, Missouri, USA.

Purpose Of Review: The present article reviews molecular subtyping and genomic characterization of endometrial carcinoma, and the associated therapeutic and prognostic implications.

Recent Findings: Endometrial cancer has historically been classified through histology into endometrioid and nonendometrioid subtypes with poor prognostic predictability. Molecular classification through genomic analysis now allows for a major advance in characterization. Four distinct subgroups have been identified: polymerase (POLE) ultramutated, microsatellite unstable, copy number-low--microsatellite stable, and copy number-high-'serous-like'. These subtypes have prognostic implications and may aid in the identification of early-stage patients who are at high risk for recurrence. Through analysis of surrogate markers (POLE, MSI, and p53) and other validated molecular alterations (L1CAM), it is possible to obtain an integrated molecular risk profile that relates to prognosis. Studies utilizing this risk profile in order to identify patients who may benefit from adjuvant treatment for early-stage disease are on-going.

Summary: Molecular characterization of endometrial cancer into subgroups has enhanced prognostic and therapeutic implications, contrary to traditional risk stratification. Further development of an integrated molecular risk profile may identify patients who could most benefit from adjuvant treatment following surgery and tailor treatment decisions in the recurrent setting.
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http://dx.doi.org/10.1097/GCO.0000000000000602DOI Listing
February 2020

Low rates of cascade genetic testing among families with hereditary gynecologic cancer: An opportunity to improve cancer prevention.

Gynecol Oncol 2020 01 25;156(1):140-146. Epub 2019 Nov 25.

Division of Gynecologic Oncology, Washington Universiy, St. Louis, MO, USA. Electronic address:

Objective: Cascade genetic testing (CGT) of hereditary breast and ovarian cancer (HBOC) or Lynch Syndrome (LS) patients' relatives offers opportunities to prevent cancer, but CGT rates are not well described. We aimed to measure reported disclosure of genetic testing results and CGT rates in these families and evaluate patients' views of educational media.

Methods: Patients with HBOC or LS identified from germline genetic testing at an academic institution between 2011 and 2016 were surveyed regarding disclosure, testing among relatives, and perceptions of educational materials. Medical records and pedigrees provided numbers of total and first-degree relatives.

Results: Of 103 mutation carriers consented, 64 (63%) completed the survey an average of 38 months after receiving genetic testing results. Participants' mean age was 53 years, and thirty-one (48%) had a cancer diagnosis. The majority (86%) felt extremely or very comfortable sharing health information. Participants disclosed results to 87% of first-degree relatives, but reported that only 40% of first-degree relatives underwent testing. First-degree female relatives had significantly higher CGT rates than first-degree male relatives (59% versus 21%, P < 0.001). Participants with HBOC reported higher CGT rates than those with LS (49% versus 33%, P = 0.02). Participants did not identify any one educational medium as more helpful than the others for disclosing results.

Conclusion: Disclosure rates are high among HBOC and LS mutation carriers, but reported CGT rates are low. Gender- and mutation-specific barriers prevent patients' family members from undergoing CGT. Future studies should implement materials to address these barriers and improve CGT rates.
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http://dx.doi.org/10.1016/j.ygyno.2019.11.005DOI Listing
January 2020

Prospective follow-up of quality of life for participants undergoing risk-reducing salpingo-oophorectomy or ovarian cancer screening in GOG-0199: An NRG Oncology/GOG study.

Gynecol Oncol 2020 01 21;156(1):131-139. Epub 2019 Nov 21.

Gynecologic Medical Oncology Service, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, 10065, USA. Electronic address:

Background: Risk-reducing salpingo-oophorectomy (RRSO) and ovarian cancer screening (OCS) are management options for women at increased risk of ovarian cancer. Long-term effects of these interventions on quality of life (QOL) are not well understood.

Methods: GOG-0199 is a prospective cohort study of women at increased ovarian cancer risk who chose either RRSO or OCS as their risk management intervention. At study entry, 6, 12, 24 and 60 months of follow-up, participants completed the QOL questionnaire, which included the Medical Outcome Study Short Form-36, the Impact of Events Scales, the Center for Epidemiological Studies Depression Scale, the State-Trait Anxiety Inventory, the Functional Assessment of Cancer Therapy - Endocrine Subscale, and the Sexual Activity Questionnaire. QOL measures were compared between the RRSO and OCS cohort at baseline and over time.

Results: Five-hundred-sixty-two participants in the RRSO cohort and 1,010 in the OCS completed the baseline and at least one follow-up questionnaire. At baseline, participants selecting RRSO reported lower health-related QOL (HRQOL), greater ovarian cancer-related stress, greater anxiety, and more depressive symptomatology, which improved during follow-up, especially for ovarian cancer-related stress. Screening was not found to adversely impact HRQOL. Hormone-related menopausal symptoms worsened and sexual functioning declined during follow-up in both cohorts, but more so among participants who underwent RRSO.

Conclusions: HRQOL improved after surgery among women who chose RRSO and remained stable among participants undergoing screening. The adverse effects of RRSO and screening on short-term and long-term sexual activity and sexual functioning warrant consideration in the decision-making process for high-risk women.
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http://dx.doi.org/10.1016/j.ygyno.2019.10.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980744PMC
January 2020

A phase II randomized, double-blind trial of a polyvalent Vaccine-KLH conjugate (NSC 748933 IND# 14384) + OPT-821 versus OPT-821 in patients with epithelial ovarian, fallopian tube, or peritoneal cancer who are in second or third complete remission: An NRG Oncology/GOG study.

Gynecol Oncol 2019 12 22;155(3):393-399. Epub 2019 Oct 22.

Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA. Electronic address:

Objective: Early-phase data have demonstrated induction of antibody responses to a polyvalent vaccine conjugate (Globo-H, GM2, MUC1-TN, TF) with adjuvant OPT-821. We sought to determine if this combination decreases the hazard of progression or death compared to OPT-821 alone in patients with ovarian cancer in second/third clinical complete remission following chemotherapy. Secondary and translational objectives were overall survival (OS), safety, and immunogenicity.

Methods: From 2010-2013, patients were randomized (1:1) to receive OPT-821±vaccine-KLH conjugate subcutaneously at weeks 1, 2, 3, 7, 11, and then every 12 weeks (total 11). Dose delay or reduction was not permitted. Patients were removed for pre-defined dose-limiting toxicity.

Results: Of 171 patients randomized, 170 were treated. Most had disease of serous histology (85%), stage 3 disease at diagnosis (77%), and had received 2 prior regimens (68%). 32% received >6 treatment cycles [median 6, each arm (p = 0.33)]. 77% discontinued due to progression, 4% due to toxicity, and 1 due to myeloid dysplastic syndrome (MDS). Maximum toxicities included grade 4 MDS and depression/personality change (1 each, unlikely related), as well as grade 3 gastrointestinal disorders and others (n = 21, 4 related). Lesser adverse events were injection site reactions (82%) and fever (11%). Estimated HR for progression-free survival (PFS) of the vaccine + OPT-821 to OPT-821 arm was 0.98 (95% CI: 0.71-1.36). At a median follow-up of 60 months, median OS was 47 and 46 months, respectively.

Conclusions: Vaccine + OPT-821 compared to OPT-821 alone was modestly immunogenic and did not prolong PFS or OS. Multi-remission patients are a viable, well-defined population for exploring innovative consolidation and maintenance approaches.

Trial Registration: NCT00857545.
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http://dx.doi.org/10.1016/j.ygyno.2019.09.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900458PMC
December 2019

Optical Resolution Photoacoustic Microscopy of Ovary and Fallopian Tube.

Sci Rep 2019 10 4;9(1):14306. Epub 2019 Oct 4.

Biomedical Engineering, Washington University, St Louis, MO, 63130, USA.

Ovarian cancer is the leading cause of death among gynecological cancers, but is poorly amenable to preoperative diagnosis. In this study, we investigate the feasibility of "optical biopsy," using high-optical-resolution photoacoustic microscopy (OR-PAM) to quantify the microvasculature of ovarian and fallopian tube tissue. The technique is demonstrated using excised human ovary and fallopian tube specimens imaged immediately after surgery. Quantitative parameters are derived using Amira software. The parameters include three-dimensional vascular segment count, total volume and length, which are associated with tumor angiogenesis. Qualitative results of OR-PAM demonstrate that malignant ovarian tissue has larger and more tortuous blood vessels as well as smaller vessels of different sizes, while benign and normal ovarian tissue has smaller vessels of uniform size. Quantitative analysis shows that malignant ovaries have greater tumor vessel volume, length and number of segments, as compared with benign and normal ovaries. The vascular pattern of benign fallopian tube is different than that of benign ovarian tissue. Our initial results demonstrate the potential of OR-PAM as an imaging tool for fast assessment of ovarian tissue and fallopian tube and could avoid unnecessary surgery if the risk of the examined ovary is extremely low.
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http://dx.doi.org/10.1038/s41598-019-50743-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778126PMC
October 2019

Impact of tumor histology on detection of pelvic and para-aortic nodal metastasis with F-fluorodeoxyglucose-positron emission tomography in stage IB cervical cancer.

Int J Gynecol Cancer 2019 11 30;29(9):1351-1354. Epub 2019 Aug 30.

Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri, USA

Objective: F-fluorodeoxyglucose-positron emission tomography (FDG-PET) detection of metastatic nodal disease is useful for guiding cervical cancer treatment but the impact of tumor histology is unknown. This study reports the detection of FDG avid pelvic and para-aortic lymph nodes in patients with early stage cervical cancer with squamous carcinoma and adenocarcinoma tumor histology.

Methods: Patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB1-2 cervical cancer who underwent pre-surgical FDG-PET between March 1999 and February 2018 were identified in a tertiary academic center database. All patients had radical hysterectomy with pelvic and para-aortic lymph node dissection. Detection of pelvic and para-aortic lymph nodes by FDG-PET versus surgical dissection was compared. FDG-PET sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined and stratified by tumor histology.

Results: We identified 212 patients with early stage cervical cancer (84% FIGO IB1, 16% IB2) who underwent pre-surgical FDG-PET; 137 (65%) patients had squamous carcinoma and 75 (35%) patients had adenocarcinoma. PET/computed tomography was performed in 189 (89%) patients and 23 (11%) had PET only. Surgical dissection revealed positive pelvic and para-aortic lymph nodes in 25% and 3.3% of patients, respectively. For squamous carcinoma, sensitivity, specificity, PPV, and NPV of FDG-PET for pelvic nodal metastasis were 44%, 99%, 95%, and 78%, respectively. For adenocarcinoma, the corresponding results for pelvic nodal metastasis were 25%, 99%, 67%, and 92%, respectively. The overall values for sensitivity, specificity, PPV, and NPV of FDG-PET for para-aortic nodal metastasis were 29%, 99%, 67%, and 98%, respectively.

Discussion: Pelvic nodal metastasis was less likely to be detected by FDG-PET in patients with early stage adenocarcinoma than with squamous carcinoma.
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http://dx.doi.org/10.1136/ijgc-2019-000528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984174PMC
November 2019

Patients with endometrial cancer continue to lack understanding of their risks for cancer.

Gynecol Oncol Rep 2019 Aug 10;29:106-110. Epub 2019 Aug 10.

Division of Gynecologic Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA.

It is unclear if endometrial cancer (EC) patients are aware of their modifiable risk factors. We administered a 33-item questionnaire to EC patients at a university-based cancer center to assess their understanding of how comorbidities and lifestyle/sexual behaviors impact their cancer risk. We also inquired about their access to a primary care physician (PCP). Pearson's χ test or Fisher's exact test were used to assess differences in understanding based on a dichotomized Charlson comorbidity score, <7 vs ≥7. Of the 50 surveyed women (81% response rate), 39 reported hypertension (80%) and 36 (72%) diabetes. All had a PCP. Most were aware that obesity contributes to diabetes (43/48, 90%), hypertension (42/48, 88%), and heart attack (42, 88%), but only 19/49 (39%) knew that EC is more common in overweight/obese women. More than half lacked understanding of the following risks including modifiable risk factors-unhealthy diet (31, 62%), hormone replacement therapy (38, 76%), alcohol (30, 60%), and the protective effects of cigarette smoking (38, 76%). Most also incorrectly identified the following sexual health factors as risks for EC: early coitarche (30, 60%), or having an abortion (27, 54%), a sexually transmitted infection (35, 70%) or human immunodeficiency virus (34, 68%). Although EC patients recognize that obesity is linked to comorbidities, less than half are aware that it contributes to their cancer risk. Furthermore, responses to lifestyle/sexual health behaviors suggest women may lack understanding of global differences between endometrial and cervical cancer risk factors.
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http://dx.doi.org/10.1016/j.gore.2019.07.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710550PMC
August 2019

Risk of cervical and vaginal dysplasia after surgery for vulvar intraepithelial neoplasia or cancer: A 6 year follow-up study.

Gynecol Oncol 2019 10 30;155(1):88-92. Epub 2019 Jul 30.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, St Louis, MO, USA; Alvin J. Siteman Cancer Center, St Louis, MO, USA.

Objectives: To estimate the frequency of abnormal surveillance cytology leading to high-grade dysplasia after surgical management for high-grade vulvar intraepithelial neoplasia (VIN) and vulvar cancer and to determine whether prior hysterectomy reduces this risk.

Methods: Women who underwent surgery for high-grade VIN or vulvar cancer between 2006 and 2014 were identified retrospectively. Patients who underwent prior hysterectomy for any indication were included. Univariate and multivariate logistic regression analyses were used to identify clinical correlates of abnormal cytology after surgical treatment for VIN and vulvar cancer.

Results: During a median follow-up for 72 months, 302 women underwent surveillance with cytologic screening after vulvar surgery including 99 (33%) women with prior hysterectomy. 75 (25%) women had abnormal cytology results. Of those, 47 (63%) were low-grade and 28 (37%) were high-grade, including 2 (3%) cases of invasive cancer. The rates of high-grade vaginal intraepithelial neoplasia (VAIN), cervical intraepithelial neoplasia (CIN), or cancer were not significantly different despite prior hysterectomy (9% VAIN 2+, 7% CIN 2+). Multivariate analysis showed that correlates of high-grade cytology following treatment for VIN or vulvar cancer included non-white race [odds radio (OR) 3.6, 95% confidence interval (CI) 1.7-7.8], prior abnormal cytology (OR 3.5, 95% CI 1.6-7.6), and immunodeficiency (OR 3.4, 95% CI 1.3-8.8). Prior hysterectomy did not significantly decrease risk of high-grade cytology (OR 0.87, 95% CI 0.5-1.6).

Conclusions: Women treated surgically for VIN/vulvar cancer have an 8% risk of at least high-grade dysplasia from surveillance screening and prior hysterectomy does not mitigate the risk. Extrapolating from current guidelines, we recommend surveillance cytology screening at least 6-12 months after treatment.
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http://dx.doi.org/10.1016/j.ygyno.2019.07.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757628PMC
October 2019

Histogram analysis of en face scattering coefficient map predicts malignancy in human ovarian tissue.

J Biophotonics 2019 11 5;12(11):e201900115. Epub 2019 Aug 5.

Department of Biomedical Engineering, Washington University, St. Louis, Missouri.

Ovarian cancer is a heterogeneous disease at the molecular and histologic level. Optical coherence tomography (OCT) is able to map ovarian tissue optical properties and heterogeneity, which has been proposed as a feature to aid in diagnosis of ovarian cancer. In this manuscript, depth-resolved en face scattering maps of malignant ovaries, benign ovaries, and benign fallopian tubes obtained from 20 patients are provided to visualize the heterogeneity of ovarian tissues. Six features are extracted from histograms of scattering maps. All features are able to statistically distinguish benign from malignant ovaries. Two prediction models were constructed based on these features: a logistic regression model (LR) and a support vector machine (SVM). The optimal set of features is mean scattering coefficient and scattering map entropy. The LR achieved a sensitivity and specificity of 97.0% and 97.8%, and SVM demonstrated a sensitivity and specificity of 99.6% and 96.4%. Our initial results demonstrate the feasibility of using OCT as an "optical biopsy tool" for detecting the microscopic scattering changes associated with neoplasia in human ovarian tissue.
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http://dx.doi.org/10.1002/jbio.201900115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982142PMC
November 2019

Type II endometrial cancers with minimal, non-invasive residual disease on final pathology: What should we do next?

Gynecol Oncol Rep 2019 Aug 23;29:20-24. Epub 2019 May 23.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, United States of America.

There are minimal data regarding the management of high risk endometrial cancer histologies lacking invasive disease on the final pathology specimen. This study examines a cohort of these patients and assesses outcomes including time to recurrence and risk of death after management with and without adjuvant therapies. Endometrial cancer patients with minimal or no remaining invasive disease on final pathologic specimen from 1995 to 2010 were included. Surgical procedure was at the discretion of the operating physician. Electronic medical records were used to abstract relevant clinicopathologic data and standard statistical methods were employed. 70 patients met inclusion criteria, of which 26 were high grade histologies. Adjuvant therapies were given in 12 of 26 patients. 6/26 patients recurred, of which 50% were salvaged with therapy at time of recurrence. Overall deaths occurred in 3 of 26 patients in the high risk cohort. Less than half of the high risk cohort received adjuvant therapies after surgical management. No histologic type was found to increase risk of recurrence, and treatment with initial adjuvant therapy did not significantly reduce recurrence risk. Large scale prospective trials are needed to aid in management of this unique endometrial cancer population.
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http://dx.doi.org/10.1016/j.gore.2019.05.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541758PMC
August 2019

Adjuvant Chemotherapy plus Radiation for Locally Advanced Endometrial Cancer.

N Engl J Med 2019 06;380(24):2317-2326

From Northwestern University (D. Matei) and Loyola University (W.S.) - both in Chicago; NRG Oncology Statistical and Data Center, Roswell Park Comprehensive Cancer Center, Buffalo, NY (V.F., H.Q.H.); University of Kentucky, Lexington (M.E.R.); Washington University School of Medicine, Siteman Cancer Center, St. Louis (D. Mutch, M.A.P.); Women and Infants Hospital in Rhode Island-The Warren Alpert Medical School of Brown University, Providence (M.M.S., P.A.D.); Stephenson Cancer Center Gynecologic Cancers Clinic, University of Oklahoma Health Sciences Center, Oklahoma City (K.M.M.); Asan Medical Center, University of Ulsan, Songpa-gu, Seoul, South Korea (Y.M.K.); Ohio State University, Columbus (D.M.O.); Women's Cancer Center of Nevada, Las Vegas (N.M.S.); University of California Irvine Medical Center, Irvine (K.S.T.); Lewis Cancer and Research Pavilion at St. Joseph's-Candler, Savannah, GA (W.E.R.); Case Western Reserve University Hospital, Cleveland (J.N.); Dana-Farber Cancer Institute, Boston (U.A.M.); and the University of Texas Southwestern Medical Center, Dallas (D.S.M.).

Background: Stage III or IVA endometrial cancer carries a significant risk of systemic and locoregional recurrence.

Methods: In this randomized phase 3 trial, we tested whether 6 months of platinum-based chemotherapy plus radiation therapy (chemoradiotherapy) is associated with longer relapse-free survival (primary end point) than six cycles of combination chemotherapy alone in patients with stage III or IVA endometrial carcinoma. Secondary end points included overall survival, acute and chronic toxic effects, and quality of life.

Results: Of the 813 patients enrolled, 736 were eligible and were included in the analysis of relapse-free survival; of those patients, 707 received the randomly assigned intervention (346 received chemoradiotherapy and 361 received chemotherapy only). The median follow-up period was 47 months. At 60 months, the Kaplan-Meier estimate of the percentage of patients alive and relapse-free was 59% (95% confidence interval [CI], 53 to 65) in the chemoradiotherapy group and 58% (95% CI, 53 to 64) in the chemotherapy-only group (hazard ratio, 0.90; 90% CI, 0.74 to 1.10). Chemoradiotherapy was associated with a lower 5-year incidence of vaginal recurrence (2% vs. 7%; hazard ratio, 0.36; 95% CI, 0.16 to 0.82) and pelvic and paraaortic lymph-node recurrence (11% vs. 20%; hazard ratio, 0.43; 95% CI, 0.28 to 0.66) than chemotherapy alone, but distant recurrence was more common in association with chemoradiotherapy (27% vs. 21%; hazard ratio, 1.36; 95% CI, 1.00 to 1.86). Grade 3, 4, or 5 adverse events were reported in 202 patients (58%) in the chemoradiotherapy group and 227 patients (63%) in the chemotherapy-only group.

Conclusions: Chemotherapy plus radiation was not associated with longer relapse-free survival than chemotherapy alone in patients with stage III or IVA endometrial carcinoma. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00942357.).
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http://dx.doi.org/10.1056/NEJMoa1813181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6948006PMC
June 2019

Do gynecologic oncology patients with severely diminished renal function and urinary tract obstruction benefit from ureteral stenting or percutaneous nephrostomy?

Gynecol Oncol Rep 2019 May 24;28:136-140. Epub 2019 Apr 24.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri, United States of America.

Objective: To assess the renal outcomes of gynecologic oncology patients who present with hydronephrosis and acute kidney injury (AKI), have <20% renal function on diuretic renal scintigraphy, and undergo placement of a ureteral stent or percutaneous nephrostomy (PCN) tube.

Methods: This is a single-institution case series of gynecologic oncology patients who underwent diuretic renal scintigraphy from January 1, 2007, to June 1, 2017. Univariate and multivariate logistic analyses were used to assess predictors of <20% renal function. Recovery from AKI or elevated creatinine was reported for women with <20% renal function who received a unilateral ureteral stent or PCN tube on the same side as their more compromised kidney.

Results: Among 353 gynecologic oncology patients who underwent diuretic renal scintigraphy, 58 (16%) had renal function <20%. Mean age was 59.6 years, 17% had preexisting chronic kidney disease, and 44% had a diagnosis of cervical cancer. Renal atrophy on computed tomography scan (aOR 18.24, 95% CI 1.21-274.92) predicted renal function <20%. Of 10 women with <20% renal function who received a stent or PCN tube, 7 recovered from AKI or elevated creatinine.

Conclusions: Gynecologic oncology patients with <20% renal function may recover from AKI after placement of a stent or PCN tube, indicating that a diuretic renal scintigraphy cutoff of <20% renal function may be overly conservative. Future studies are warranted to determine optimal renal function cutoffs for stent/PCN tube placement in gynecologic oncology patients.
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http://dx.doi.org/10.1016/j.gore.2019.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488532PMC
May 2019