Publications by authors named "Saketh R Guntupalli"

51 Publications

Beyond Sedlis-A novel histology-specific nomogram for predicting cervical cancer recurrence risk: An NRG/GOG ancillary analysis.

Gynecol Oncol 2021 Sep 1;162(3):532-538. Epub 2021 Jul 1.

Johns Hopkins University School of Medicine, Baltimore, MD, United States of America. Electronic address:

Purpose: The Sedlis criteria define risk factors for recurrence warranting post-hysterectomy radiation for early-stage cervical cancer; however, these factors were defined for squamous cell carcinoma (SCC) at an estimated recurrence risk of ≥30%. Our study evaluates and compares risk factors for recurrence for cervical SCC compared with adenocarcinoma (AC) and develops histology-specific nomograms to estimate risk of recurrence and guide adjuvant treatment.

Methods: We performed an ancillary analysis of GOG 49, 92, and 141, and included stage I patients who were surgically managed and received no neoadjuvant/adjuvant therapy. Multivariable Cox proportional hazards models were used to evaluate independent risk factors for recurrence by histology and to generate prognostic histology-specific nomograms for 3-year recurrence risk.

Results: We identified 715 patients with SCC and 105 with AC; 20% with SCC and 17% with AC recurred. For SCC, lymphvascular space invasion (LVSI: HR 1.58, CI 1.12-2.22), tumor size (TS ≥4 cm: HR 2.67, CI 1.67-4.29), and depth of invasion (DOI; middle 1/3, HR 4.31, CI 1.81-10.26; deep 1/3, HR 7.05, CI 2.99-16.64) were associated with recurrence. For AC, only TS ≥4 cm, was associated with recurrence (HR 4.69, CI 1.25-17.63). For both histologies, there was an interaction effect between TS and LVSI. For those with SCC, DOI was most associated with recurrence (16% risk); for AC, TS conferred a 15% risk with negative LVSI versus a 25% risk with positive LVSI.

Conclusions: Current treatment standards are based on the Sedlis criteria, specifically derived from data on SCC. However, risk factors for recurrence differ for squamous cell and adenocarcinoma of the cervix. Histology-specific nomograms accurately and linearly represent risk of recurrence for both SCC and AC tumors and may provide a more contemporary and tailored tool for clinicians to base adjuvant treatment recommendations to their patients with cervical cancer.
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http://dx.doi.org/10.1016/j.ygyno.2021.06.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405564PMC
September 2021

Assessing Inequities in Cervical Cancer Quality of Care and Survival Related to Ethnicity and Socioeconomic Factors.

J Low Genit Tract Dis 2021 Jul;25(3):205-209

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO.

Objective: This study aimed to assess the effect that race and socioeconomic factors have on the provision of care to cervical cancer patients based on National Comprehensive Cancer Network (NCCN) recommended treatment guidelines.

Materials And Methods: To do this, we completed a retrospective cohort study using the American College of Surgeon's Nation Cancer Database from 2004 to 2016. We identified all reported cases of cervical cancer in that period. Two cohorts were created using self-reported racial demographic data, Hispanic- and White, non-Hispanic-identified patients. Our primary outcome variables were adherence to NCCN-recommended treatment and 5-year overall survival. Adherence to NCCN-recommended treatment was determined by the provision of surgical and/or radiation and/or chemotherapy treatment based on the clinical stage at time of diagnosis and the presence or absence of lymphovascular space invasion. We used bivariate analyses to compare baseline characteristics between the 2 cohorts, multivariable logistic regression to identify independent predictors of 5-year survival, and Cox proportional hazards models to compute survival by group.

Results: The difference in NCCN-adherent care between the 2 cohorts was found to be not statistically significant (p = .880). A log rank (Mantel-Cox) χ2 test showed that there was a statistically significant difference between the 2 groups in overall survival with the Hispanic-identified patients living longer (p < .001). Our study is limited by the effect large databases confer on finding statistical significance.

Conclusions: Hispanic-identified women with cervical cancer receive NCCN-compliant care and live longer than their White, non-Hispanic counterparts.
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http://dx.doi.org/10.1097/LGT.0000000000000611DOI Listing
July 2021

Highlights from the recent 2020 Annual Global IGCS Meeting.

Gynecol Oncol 2021 May 27;161(2):333-335. Epub 2021 Feb 27.

Department of Obstetrics and Gynaecology, University of Pretoria, Hatfield 0028, South Africa. Electronic address:

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http://dx.doi.org/10.1016/j.ygyno.2021.02.008DOI Listing
May 2021

Post hoc analyses of GOG 9923: Does BRCA status affect toxicities?: An NRG oncology study.

Gynecol Oncol 2021 May 17;161(2):512-515. Epub 2021 Feb 17.

Stephenson Cancer Center at the University of Oklahoma, Oklahoma City, OK, United States of America. Electronic address:

Objective: To evaluate how women with epithelial ovarian cancer (EOC), dichotomized by BRCA status, tolerate intravenous (IV) or intraperitoneal (IP) chemotherapy given with veliparib and bevacizumab (bev) on a GOG phase I study (GOG 9923, NCT00989651).

Methods: This is an unplanned, post hoc analysis of an IRB approved, multi-institutional, prospective study (GOG 9923). Clinical characteristics and toxicity data based on BRCA status were evaluated and descriptive statistics were used to summarize baseline patient characteristics and toxicities. The Kaplan Meier method was used to generate survival estimates.

Results: Four hundred twenty-four patients were evaluable. Patients were treated with IV carboplatin, paclitaxel, and bev every 21 days (regimen 1), weekly IV paclitaxel with carboplatin and bev (regimen 2) or IV paclitaxel and bev with IP cisplatin (regimen 3). Bev was continued as maintenance in all arms. Within each of these regimens, veliparib was given either twice daily for the entirety of each cycle (continuous) or on days -2 to 5 (intermittent). Ten percent of patients treated on regimen 1, 12% on regimen 2, and 19.8% on regimen 3 had BRCA-associated tumors. Patients with BRCA-associated tumors, when compared to wild type, experienced similar rates of anemia, febrile neutropenia (, abdominal pain, colonic perforation, nausea, vomiting, and peripheral sensory neuropathy. Median progression free survival (PFS) was not significantly different between BRCA-associated and wild type cancers (HR 0.96, CI 0.65-1.42), though this study's primary aim was not to evaluate outcomes.

Conclusions: Germline BRCA mutations positively affect chemosensitivity in EOC, but whether differences in toxicities among BRCA-associated and BRCA wild type tumors existed was previously not reported. In this population with newly diagnosed ovarian cancer no differences in reported toxicity between the two groups was observed.
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http://dx.doi.org/10.1016/j.ygyno.2021.01.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084973PMC
May 2021

Treatment of epithelial ovarian cancer.

BMJ 2020 11 9;371:m3773. Epub 2020 Nov 9.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Denver, CO, USA

Ovarian cancer is the third most common gynecologic malignancy worldwide but accounts for the highest mortality rate among these cancers. A stepwise approach to assessment, diagnosis, and treatment is vital to appropriate management of this disease process. An integrated approach with gynecologic oncologists as well as medical oncologists, pathologists, and radiologists is of paramount importance to improving outcomes. Surgical cytoreduction to R0 is the mainstay of treatment, followed by adjuvant chemotherapy. Genetic testing for gene mutations that affect treatment is the standard of care for all women with epithelial ovarian cancer. Nearly all women will have a recurrence, and the treatment of recurrent ovarian cancer continues to be nuanced and requires extensive review of up to date modalities that balance efficacy with the patient's quality of life. Maintenance therapy with poly ADP-ribose polymerase inhibitors, bevacizumab, and/or drugs targeting homologous recombination deficiency is becoming more widely used in the treatment of ovarian cancer, and the advancement of immunotherapy is further revolutionizing treatment targets.
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http://dx.doi.org/10.1136/bmj.m3773DOI Listing
November 2020

Cost-effectiveness of apixaban for prevention of venous thromboembolic events in patients after gynecologic cancer surgery.

Gynecol Oncol 2020 11 25;159(2):476-482. Epub 2020 Aug 25.

Division of Family Planning, Department of Obstetrics and Gynecology, University of Colorado School of Medicine Anschutz Medical Campus, Aurora, CO, USA. Electronic address:

Objective: The cost-effectiveness of apixaban was compared with enoxaparin for prevention of postoperative venothromboembolic events (VTE) in gynecologic oncology patients. Current guidelines recommend thromboprophylaxis with low molecular weight heparin for 28 days following gynecologic cancer surgery, but recent trials suggest that oral apixaban may be a safe, patient-preferred alternative. Apixaban was superior to enoxaparin in a Canadian cost-effectiveness analysis using orthopedics trial data.

Methods: Medication costs, adherence rates, event rates, event costs, and utility decrements were estimated using prior clinical trial data and literature review for input into a short-term decision model to simulate outcomes in a hypothetical cohort of 1000 patients. Incremental cost-effectiveness ratios (ICERs) were calculated as net cost difference per quality-adjusted life year (QALY) gained. Input values at which net costs and QALYs were equivalent and ICERs at upper and lower bounds were evaluated.

Results: Using aggregated costs, apixaban was less expensive and more effective than enoxaparin, and remained so or had high value in all scenarios on sensitivity analysis. Examining disaggregated ICERs, apixaban was cost-effective for deep venous thrombosis (DVT); of high value for clinically-relevant non-major bleeding (CRNMB) ($411); low value for major bleeding ($183,465), VTE-related death ($2,711,229), and all-cause mortality ($297,522); and not cost-effective for pulmonary embolism prevention.

Conclusions: Apixaban is more cost-effective than enoxaparin for the prevention of postoperative VTE in patients with gynecologic cancer. This appears to be driven largely by DVT and CRNMB prevention.
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http://dx.doi.org/10.1016/j.ygyno.2020.07.096DOI Listing
November 2020

Adherence to postoperative thromboprophylactic medication among gynecologic oncology patients: A subanalysis.

Gynecol Oncol 2020 09 6;158(3):754-759. Epub 2020 Jul 6.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Colorado School of Medicine Anschutz Medical Campus, Aurora, CO, USA.

Introduction: Venous thromboembolism (VTE) is a major cause of morbidity and mortality among gynecologic cancer patients, especially in the immediate postoperative period. We sought to identify patterns related with patient non-adherence to postoperative prophylactic anticoagulation.

Methods: Participant data (N = 400) were reviewed from a previously conducted randomized controlled trial comparing the safety and efficacy of prophylactic postoperative anticoagulation with enoxaparin versus apixaban among gynecologic oncology patients. Variables hypothesized to be related to medication adherence were pre-selected by the study authors, and adherence was defined as missing ≤2 days of medication (4 pills or 2 injections) in 28 days postoperatively. For univariate comparisons and multivariate modeling, the threshold for statistical significance was set at p < .05.

Results: Non-adherence (N = 64) was associated with lower quality of life (QOL) score, history of anxiety disorder, decreased medication satisfaction, taking more medications at baseline, higher baseline heart rate, fewer total intraoperative procedures, not undergoing radical hysterectomy and/or lymph node dissection, not meeting 2-week postoperative milestones, and 28-day emergency department (ED) visit or readmission. African American race, lower mental QOL, difficulty remembering to take medication, and 28-day ED visit or readmission were predictive of non-adherence in a multivariate model. Patients taking enoxaparin versus apixaban more frequently attributed non-adherence to pain or bruising (25.0% vs. 3.1%, P = .01).

Conclusion: Our findings provide new insights into factors associated with medication adherence that are particularly relevant to gynecologic oncology patients after surgery. Preoperative interventions to identify patients with these risk factors for more intensive followup of postoperative anticoagulation regimen may help increase medication adherence.
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http://dx.doi.org/10.1016/j.ygyno.2020.06.505DOI Listing
September 2020

Safety and Efficacy of Apixaban vs Enoxaparin for Preventing Postoperative Venous Thromboembolism in Women Undergoing Surgery for Gynecologic Malignant Neoplasm: A Randomized Clinical Trial.

JAMA Netw Open 2020 06 1;3(6):e207410. Epub 2020 Jun 1.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Colorado School of Medicine at Denver, Aurora.

Importance: Current guidelines recommend a 28-day course of enoxaparin for thromboprophylaxis after surgery for gynecologic cancer. The high cost of this medication and the low adherence rates observed in prior studies provide an opportunity to benefit patients by demonstrating the safety of a more cost-effective, easier to use thromboprophylactic.

Objective: To investigate the safety and efficacy of an oral treatment alternative for thromboprophylaxis in postoperative patients with gynecologic cancer.

Design, Setting, And Participants: This was a patient-based, multicenter, open-label, blinded, end point, randomized clinical trial conducted May 2015 to March 2019 in outpatient and inpatient gynecologic oncology settings. Women undergoing surgery for suspected or confirmed gynecologic cancer were approached for recruitment. The trial compared rates of major bleeding and clinically relevant nonmajor bleeding events during a 90-day follow-up period in patients taking apixaban or enoxaparin for postoperative thromboprophylaxis using a modified intent-to-treat analysis. Data analysis was performed from October to December 2019.

Interventions: Women were randomized to 28 days of apixaban (2.5 mg orally twice daily) or enoxaparin (40 mg subcutaneously daily).

Main Outcomes And Measures: The primary outcome was major bleeding and clinically relevant nonmajor bleeding events. Secondary outcomes included incidence of venous thromboembolic events, adverse events, medication adherence, participant quality of life, and medication satisfaction.

Results: Of 500 women recruited for the study, 400 were enrolled and randomized (median age, 58.0 years; range, 18.0-89.0 years); 204 received apixaban and 196 received enoxaparin. Treatment groups did not differ in terms of race/ethnicity, cancer stage, or surgery modality (open vs robotic). There were no statistically significant differences between the apixaban and enoxaparin groups in terms of rates of major bleeding events (1 patient [0.5%] vs 1 patient [0.5%]; odds ratio [OR], 1.04; 95% CI, 0.07-16.76; P > .99), clinically relevant nonmajor bleeding events (12 patients [5.4%] vs 19 patients [9.7%]; OR, 1.88; 95% CI, 0.87-4.1; P = .11), venous thromboembolic events (2 patients [1.0%] vs 3 patients [1.5%]; OR, 1.57; 95% CI, 0.26-9.50; P = .68), adverse events, medication adherence, or quality of life between the groups. Participant satisfaction was significantly greater in the apixaban group with regard to ease of taking the medication (186 patients [98.9%] vs 110 patients [58.8%]; OR, 0.06; 95% CI, 0.01-0.25; P < .001) and pain associated with taking the medication (4 patients [2.1%] vs 92 patients [49.2%]; OR, 9.20; 95% CI, 2.67-31.82; P < .001).

Conclusions And Relevance: These findings suggest that oral apixaban is a potentially safe, less painful, and easier-to-take alternative to subcutaneous enoxaparin for thromboprophylaxis after surgery for gynecologic cancer. The efficacy of apixaban to prevent venous thromboembolic events is hypothesized as being equivalent.

Trial Registration: ClinicalTrials.gov Identifier: NCT02366871.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.7410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320298PMC
June 2020

Safety and Efficacy of Apixaban vs Enoxaparin for Preventing Postoperative Venous Thromboembolism in Women Undergoing Surgery for Gynecologic Malignant Neoplasm: A Randomized Clinical Trial.

JAMA Netw Open 2020 06 1;3(6):e207410. Epub 2020 Jun 1.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Colorado School of Medicine at Denver, Aurora.

Importance: Current guidelines recommend a 28-day course of enoxaparin for thromboprophylaxis after surgery for gynecologic cancer. The high cost of this medication and the low adherence rates observed in prior studies provide an opportunity to benefit patients by demonstrating the safety of a more cost-effective, easier to use thromboprophylactic.

Objective: To investigate the safety and efficacy of an oral treatment alternative for thromboprophylaxis in postoperative patients with gynecologic cancer.

Design, Setting, And Participants: This was a patient-based, multicenter, open-label, blinded, end point, randomized clinical trial conducted May 2015 to March 2019 in outpatient and inpatient gynecologic oncology settings. Women undergoing surgery for suspected or confirmed gynecologic cancer were approached for recruitment. The trial compared rates of major bleeding and clinically relevant nonmajor bleeding events during a 90-day follow-up period in patients taking apixaban or enoxaparin for postoperative thromboprophylaxis using a modified intent-to-treat analysis. Data analysis was performed from October to December 2019.

Interventions: Women were randomized to 28 days of apixaban (2.5 mg orally twice daily) or enoxaparin (40 mg subcutaneously daily).

Main Outcomes And Measures: The primary outcome was major bleeding and clinically relevant nonmajor bleeding events. Secondary outcomes included incidence of venous thromboembolic events, adverse events, medication adherence, participant quality of life, and medication satisfaction.

Results: Of 500 women recruited for the study, 400 were enrolled and randomized (median age, 58.0 years; range, 18.0-89.0 years); 204 received apixaban and 196 received enoxaparin. Treatment groups did not differ in terms of race/ethnicity, cancer stage, or surgery modality (open vs robotic). There were no statistically significant differences between the apixaban and enoxaparin groups in terms of rates of major bleeding events (1 patient [0.5%] vs 1 patient [0.5%]; odds ratio [OR], 1.04; 95% CI, 0.07-16.76; P > .99), clinically relevant nonmajor bleeding events (12 patients [5.4%] vs 19 patients [9.7%]; OR, 1.88; 95% CI, 0.87-4.1; P = .11), venous thromboembolic events (2 patients [1.0%] vs 3 patients [1.5%]; OR, 1.57; 95% CI, 0.26-9.50; P = .68), adverse events, medication adherence, or quality of life between the groups. Participant satisfaction was significantly greater in the apixaban group with regard to ease of taking the medication (186 patients [98.9%] vs 110 patients [58.8%]; OR, 0.06; 95% CI, 0.01-0.25; P < .001) and pain associated with taking the medication (4 patients [2.1%] vs 92 patients [49.2%]; OR, 9.20; 95% CI, 2.67-31.82; P < .001).

Conclusions And Relevance: These findings suggest that oral apixaban is a potentially safe, less painful, and easier-to-take alternative to subcutaneous enoxaparin for thromboprophylaxis after surgery for gynecologic cancer. The efficacy of apixaban to prevent venous thromboembolic events is hypothesized as being equivalent.

Trial Registration: ClinicalTrials.gov Identifier: NCT02366871.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.7410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320298PMC
June 2020

Patient-reported outcomes at discontinuation of anti-angiogenesis therapy in the randomized trial of chemotherapy with bevacizumab for advanced cervical cancer: an NRG Oncology Group study.

Int J Gynecol Cancer 2020 05 28;30(5):596-601. Epub 2020 Feb 28.

University of California Irvine School of Medicine, Orange, California, USA.

Introduction: To describe patient-reported outcomes and toxicities at time of treatment discontinuation secondary to progression or toxicities in advanced/recurrent cervical cancer patients receiving chemotherapy with bevacizumab.

Methods: Summarize toxicity, grade, and health-related quality of life within 1 month of treatment discontinuation for women receiving chemotherapy with bevacizumab in GOG240.

Results: Of the 227 patients who received chemotherapy with bevacizumab, 148 discontinued study protocol treatment (90 for disease progression and 58 for toxicity). The median survival time from treatment discontinuation to death was 7.9 months (95% CI 5.0 to 9.0) for those who progressed versus 12.1 months (95% CI 8.9 to 23.2) for those who discontinued therapy due to toxicities. The most common grade 3 or higher toxicities included hematologic, gastrointestinal, and pain. Some 57% (84/148) of patients completed quality of life assessment within 1 month of treatment discontinuation. Those patients who discontinued treatment due to progression had a mean decline in the FACT-Cx TOI of 3.2 points versus 2.2 in patients who discontinued therapy due to toxicity. This was a 9.9 point greater decline in the FACT-Cx TOI scores than those who discontinued treatment due to progression (95% CI 2.8 to 17.0, p=0.007). The decline in quality of life was due to worsening physical and functional well-being. Those who discontinued treatment due to toxicities had worse neurotoxicity and pain.

Discussion: Patients who discontinued chemotherapy with bevacizumab for toxicity experienced longer post-protocol survival but significantly greater declination in quality of life than those with progression. Future trial design should include supportive care interventions that optimize physiologic function and performance status for salvage therapies.
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http://dx.doi.org/10.1136/ijgc-2019-000869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780262PMC
May 2020

African American women with advanced-stage ovarian cancer have worse outcomes regardless of treatment type.

Int J Gynecol Cancer 2020 07 26;30(7):1018-1025. Epub 2020 Feb 26.

Obstetrics and Gynecology, University of Colorado at Denver - Anschutz Medical Campus, Aurora, Colorado, USA.

Objective: There has been an increase in the use of neoadjuvant chemotherapy in recent years. Our objective was to determine if African American women are more likely to receive neoadjuvant chemotherapy than primary debulking surgery, when compared to their Caucasian counterparts, and the impact of such an approach on oncologic outcomes.

Methods: A retrospective cohort study was performed using the National Cancer Database (NCDB). Women aged 18-90 years, diagnosed with stage IIIC or IV epithelial ovarian cancer between January 2010 through December 2014 were included. Women with unknown treatment or treatments outside of neoadjuvant chemotherapy or primary debulking surgery were excluded. Only women of Caucasian, African American, or Hispanic origin who received either neoadjuvant chemotherapy or primary debulking surgery were included; all other races were excluded. Descriptive statistics were computed, and continuous variables were assessed for normality. Groups were compared using ANOVA or non-parametric medians tests for continuous variables, and chi-squared tests were used for dichotomous or categorical variables. Logistic regression was used to identify predictors of treatment. A p value of 0.05 was considered statistically significant.

Results: A total of 19 838 women with stage IIIC and IV epithelial ovarian cancer met the inclusion criteria. A total of 14 988 (75.6%) were treated with primary debulking surgery, while 4850 women (24.4%) were treated with neoadjuvant chemotherapy. Of those treated with neoadjuvant chemotherapy, 24.5% were white, 27.0% were African American, and 22.1% were Hispanic (p=0.005), and when adjusted for confounders, being African American was a predictor of receiving neoadjuvant chemotherapy (adjusted odds ratio (aOR) 1.29, 95% CI 1.10 to 1.51). Ninety-day mortality rates were higher in African American women compared with Caucasian and Hispanic women (2.9% vs 2.0% vs 1.6%, p=0.013). There were no differences in 30-day mortality, 90-day mortality, or status at last contact in African American women, when comparing neoadjuvant chemotherapy and primary debulking surgery. In Caucasian women, outcomes were worse in women receiving neoadjuvant chemotherapy.

Conclusions: Compared to other races, African American women with advanced ovarian cancer are more likely to receive neoadjuvant chemotherapy than primary debulking surgery and had a higher 90-day mortality rate. In African American women there was no difference in outcomes based on treatment type.
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http://dx.doi.org/10.1136/ijgc-2019-000555DOI Listing
July 2020

Hysterectomy in Residency Training: The New Numbers Game?

Obstet Gynecol 2020 02;135(2):266-267

Dr. Guntupalli is Director of the Division of Gynecologic Oncology in the Department of Obstetrics and Gynecology at the University of Colorado School of Medicine-Denver, Denver, Colorado; email:

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http://dx.doi.org/10.1097/AOG.0000000000003680DOI Listing
February 2020

A phase I study of intravenous or intraperitoneal platinum based chemotherapy in combination with veliparib and bevacizumab in newly diagnosed ovarian, primary peritoneal and fallopian tube cancer.

Gynecol Oncol 2020 01 7;156(1):13-22. Epub 2019 Nov 7.

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

Background: Improvements in disease free survival for epithelial ovarian, peritoneal or fallopian tube cancer (EOC) will only come with improved primary therapy. Incorporation of poly-ADP-ribose inhibitors (PARPi) in the frontline setting may represent one strategy. This study sought to determine the maximum tolerated and feasible doses of the PARPi veliparib in combination with chemotherapy for EOC.

Methods: A phase I, 3 + 3 dose escalation evaluated dose-limiting toxicities (DLTs) in cycles 1-2. Once <2/6 patients experienced a DLT, that dose level expanded to evaluate feasibility over 4 cycles. This study opened 10/2009 and closed 8/2016. Eligible patients had untreated, stage II-IV EOC. Veliparib was added either continuous (day 1-21) or intermittent (day - 2 to 5) during 6 cycles of chemotherapy. Three chemotherapy backbones were evaluated (2 intravenous (q3week and weekly) and 1 intraperitoneal (IP)) all inclusive of bevacizumab with and as maintenance to 22 cycles.

Findings: Dose evaluations for 424 treated patients were available. Regimen 1 (q3 week), continuous (Reg1c) the maximum tolerated dose (MTD) was 250 mg veliparib BID and feasible dose was 150 mg BID. For regimen 1, intermittent (Reg1i) the MTD and feasible dose were 400 and 250 mg BID. For Reg2c (weekly paclitaxel) the MTD and feasible dose were 150 mg BID. For Reg2i the MTD and feasible dose were 250 and 150 mg BID. For Reg3c (IP) the MTD and feasible dose were 150 mg BID and for Reg3i (IP), the MTD and feasible dose were 400 mg and 300 mg BID.

Interpretation: The feasible dose for Reg1c, 2c, 2i and 3c was 150 mg po BID. For Reg1i and 3i the dose was pushed to 250 and 300 mg po BID respectively. There is no apparent difference in efficacy between continuous and intermittent dosing indicating that the higher doses achieved in intermittent dosing may not be needed. (NCT00989651).

Funding: National Cancer Institute.
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http://dx.doi.org/10.1016/j.ygyno.2019.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048389PMC
January 2020

Intrauterine Device Use and Ovarian Cancer Risk: A Systematic Review and Meta-analysis.

Obstet Gynecol 2019 10;134(4):791-800

Divisions of Gynecologic Oncology and Family Planning, Department of Obstetrics and Gynecology, and the Health Sciences Library, University of Colorado Anschutz Medical Campus, Aurora, Colorado.

Objective: To explore the relationship between intrauterine device (IUD) use and risk of ovarian cancer through systematic review of the literature and meta-analysis.

Data Sources: We searched MEDLINE, EMBASE, Cochrane Library, Web of Science Core Collection from inception to June 2018. For the MEDLINE search, we included the MeSH terms "intrauterine devices" AND "ovarian neoplasms," however also searching "intrauter*," "ovar*" and "fallopian tube," as well as "cancer" and "carcinoma" as keywords to include all possible variations. Similar search terms were used in the other databases. We also searched ClinicalTrials.gov.

Methods Of Study Selection: Case-control and cohort studies that collected individual level data on IUD use and ovarian cancer diagnosis were critically reviewed and data extracted. Review of abstracts from 399 articles through systematic database review and an additional 200 articles through Google Scholar identified a total of 15 studies with individual level data regarding IUD use and incident ovarian cancer. On critical review, 11 of these studies were used for meta-analysis. All case reports and reviews were excluded.

Tabulation, Integration, And Results: The data were harmonized and weighted and summary odds ratios (ORs) were calculated. Covariates were identified evaluated separately. A random-effects meta-analysis was performed to confirm minimal bias. Harmonization and weighting of the data revealed an OR association between ever use of an IUD and incident ovarian cancer to be 0.68 (95% CI 0.62-0.75). There were no significant differences found between covariates. Heterogeneity among all studies was found to be I=68%.

Conclusion: Intrauterine device use is associated with a reduced incidence of ovarian cancer based on a review of existing retrospective data. Unfortunately, prospective investigation into the role of IUDs in ovarian cancer prevention is limited.
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http://dx.doi.org/10.1097/AOG.0000000000003463DOI Listing
October 2019

Recurrence, death, and secondary malignancy after ovarian conservation for young women with early-stage low-grade endometrial cancer.

Gynecol Oncol 2019 10 16;155(1):39-50. Epub 2019 Aug 16.

Department of Obstetrics and Gynecology, Niigata University School of Medicine, Niigata, Japan.

Objective: To examine the association between ovarian conservation and oncologic outcome in surgically-treated young women with early-stage, low-grade endometrial cancer.

Methods: This multicenter retrospective study examined women aged <50 with stage I grade 1-2 endometrioid endometrial cancer who underwent primary surgery with hysterectomy from 2000 to 2014 (US cohort n = 1196, and Japan cohort n = 495). Recurrence patterns, survival, and the presence of a metachronous secondary malignancy were assessed based on ovarian conservation versus oophorectomy.

Results: During the study period, the ovarian conservation rate significantly increased in the US cohort from 5.4% to 16.4% (P = 0.020) whereas the rate was unchanged in the Japan cohort (6.3-8.7%, P = 0.787). In the US cohort, ovarian conservation was not associated with disease-free survival (hazard ratio [HR] 0.829, 95% confidence interval [CI] 0.188-3.663, P = 0.805), overall survival (HR not estimated, P = 0.981), or metachronous secondary malignancy (HR 1.787, 95% CI 0.603-5.295, P = 0.295). In the Japan cohort, ovarian conservation was associated with decreased disease-free survival (HR 5.214, 95% CI 1.557-17.464, P = 0.007) and an increased risk of a metachronous secondary malignancy, particularly ovarian cancer (HR 7.119, 95% CI 1.349-37.554, P = 0.021), but was not associated with overall survival (HR not estimated, P = 0.987). Ovarian recurrence or metachronous secondary ovarian cancer occurred after a median time of 5.9 years, and all cases were salvaged.

Conclusion: Our study suggests that adoption of ovarian conservation in young women with early-stage low-grade endometrial cancer varies by population. Ovarian conservation for young women with early-stage, low-grade endometrial cancer may be potentially associated with increased risks of ovarian recurrence or metachronous secondary ovarian cancer in certain populations; nevertheless, ovarian conservation did not negatively impact overall survival.
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http://dx.doi.org/10.1016/j.ygyno.2019.08.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537353PMC
October 2019

The perceptions of gynecologic oncology fellows on readiness for subspecialty training following OB/GYNRESIDENCY.

Gynecol Oncol Rep 2019 May 20;28:104-108. Epub 2019 Mar 20.

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Colorado School of Medicine, Denver, CO, United States of America.

A recent survey of fellowship program directors (PD) within gynecologic oncology (GO) noted concerns regarding the abilities of incoming fellows. The objective of this study was to evaluate the perceptions of current and former fellows in gynecologic oncology of their readiness for fellowship training. A previously used survey was modified and distributed in 2016 to current and former fellows in GO. The survey explored domains of independent practice, psychomotor ability, clinical evaluation and scholarship. A standard Likert scale was employed and domains/responses were tailored to the subspecialty. A total of 150 current and recently former fellows responded to the survey, for a response rate of 38.7%. Nearly 70% of respondents reported being able to independently perform a hysterectomy when starting fellowship, and nearly 50% felt they could perform lysis of adhesions either without assistance. Although nearly 95% reported having had the opportunity to develop a plan of action for patients on labor and delivery, only 40.7% felt able to independently manage postoperative complications without assistance. Common themes that emerged in the open-ended responses pertained to self-perception of inadequate surgical skills and knowledge specific to gynecologic oncology. Although the majority of current and former fellows in gynecologic oncology report feeling prepared for fellowship, themes noted in the open-ended responses suggest a lack of confidence in surgical skills and clinical knowledge.
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http://dx.doi.org/10.1016/j.gore.2019.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451191PMC
May 2019

Molecular markers in recurrent stage I, grade 1 endometrioid endometrial cancers.

Gynecol Oncol 2019 06 22;153(3):517-520. Epub 2019 Mar 22.

University of Colorado Denver Aurora, Department of Gynecologic Oncology, CO, United States of America.

Objectives: Stage I, grade 1 endometrial cancers have low recurrence rates and often do not receive adjuvant therapy. We compared recurrent cases to matched non-recurrent controls to evaluate for molecular markers associated with higher risk of recurrence.

Methods: A case-control study including all cases of recurrent stage I, grade 1 endometrioid endometrial cancer at one institution in a ten-year period. Cases were matched to controls by age, BMI, weight and stage. Molecular testing and immunohistochemistry were performed on archival tumor specimens: microsatellite instability (MSI-H), mismatch repair status, POLE mutational status, and next-generation sequencing.

Results: 15 stage I, grade 1 endometrial cancer cases with recurrent disease and available tumor specimens were identified. CTNNB1 and MSI-H were present at significantly higher rates in cases than controls (CTNNB1 60% vs. 28%, OR 3.9, 95%CI 1.1-14.7, p = 0.04 and MSI-H 53% vs. 21%, OR 4.4, 95%CI 1.1-17.0, p = 0.03). POLE mutations were found in 0% of cases vs. 7% of controls (p = 0.54). Among specimens demonstrating microsatellite stability (MSS), 100% of cases vs. 26% of controls had CTNNB1 mutations (p < 0.001). CTNNB1 wild type tumors were MSI-H in 100% of cases vs. 19% of controls (p < 0.001).

Conclusions: Compared to controls, CTNNB1 mutation is present at significantly higher rates in recurrent stage I, grade 1 endometrial cancers and is found most commonly in MSS tumors. MSI-H is also present at significantly higher rates in recurrent cases. These markers may be useful for prognostic risk stratification and adjuvant therapy decision-making in this otherwise low-risk population.
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http://dx.doi.org/10.1016/j.ygyno.2019.03.100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005911PMC
June 2019

What Is New in Venous Thromboembolism Prophylaxis in Gynecologic Surgery?: Best Articles From the Past Year.

Obstet Gynecol 2019 03;133(3):577-578

Dr. Guntupalli is from the Department of Obstetrics and Gynecology at the University of Colorado School of Medicine, Denver, Colorado; email:

This month we will review the latest data on prevention of incidence of venous thromboembolism (VTE), which includes both deep venous thrombosis and pulmonary embolism, in patients undergoing gynecologic surgery. Dr. Guntupalli discusses four recent publications, which are concluded with a "bottom-line" that is the take-home message. A complete reference for each can be found on on this page along with direct links to abstracts.
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http://dx.doi.org/10.1097/AOG.0000000000003143DOI Listing
March 2019

Nomogram for Predicting Individual Survival After Recurrence of Advanced-Stage, High-Grade Ovarian Carcinoma.

Obstet Gynecol 2019 02;133(2):245-254

Cleveland Clinic Foundation and Case Western Reserve University, Cleveland, Ohio; NRG Oncology Statistics and Data Management Center, Roswell Park Cancer Institute, Buffalo, New York; The Ohio State University, Columbus, Ohio; the University of Minnesota, Minneapolis, Minnesota; Duke University Hospital; Durham, North Carolina; the University of California at Irvine, Orange, California; the University of Iowa Hospital, Iowa City, Iowa; Washington University in St. Louis School of Medicine, St. Louis, Missouri; ANZGOG, Australia-New Zealand Gynaecological Oncology Group, Sydney, Australia; the University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Community Health Network and Indiana University School of Medicine, Indianapolis, Indiana; Walter Reed Army Medical Center; Bethesda, Maryland; Tacoma General Hospital, Tacoma, Washington; Moffitt Cancer Center, Tampa, Florida; the University of Colorado School of Medicine at Denver, Aurora, Colorado; Cancer Treatment Centers of America, Philadelphia Pennsylvania; NYU Clinical Cancer Center, New York, New York; Johns Hopkins University/Sidney Kimmel Cancer Center, Baltimore, Maryland; US Oncology Research, Arizona Oncology, Tucson, Arizona; the University of Pennsylvania Medical Center, Philadelphia, Pennsylvania; and The Ohio State University Medical Center, Columbus, Ohio.

Objective: To analyze clinical prognostic factors for survival after recurrence of high-grade, advanced-stage ovarian-peritoneal-tubal carcinoma and to develop a nomogram to predict individual survival after recurrence.

Methods: We retrospectively analyzed patients treated in multicenter Gynecologic Oncology Group protocols for stage III and IV ovarian-peritoneal-tubal carcinoma who underwent primary debulking surgery, received chemotherapy with paclitaxel and a platinum compound, and subsequently developed recurrence. Prognostic factors affecting survival were identified and used to develop a nomogram, which was both internally and externally validated.

Results: There were 4,739 patients included in this analysis, of whom, 84% had stage III and 16% had stage IV ovarian carcinoma. At a median follow-up of 88.8 months (95% CI 86.2-92.0 months), the vast majority of patients (89.4%) had died. The median survival after recurrence was 21.4 months (95% CI 20.5-21.9 months). Time to recurrence after initial chemotherapy, clear cell or mucinous histology, performance status, stage IV disease, and age were significant variables used to develop a nomogram for survival after recurrence, which had a concordance index of 0.67. The time to recurrence alone accounted for 85% of the prognostic information. Similar results were found for patients who underwent second look laparotomy and had a complete pathologic response or received intraperitoneal chemotherapy.

Conclusion: For individuals with advanced-stage ovarian carcinoma who recur after standard first-line therapy, estimated survivals after recurrence are closely related to the time to recurrence after chemotherapy and prognostic variables can be used to predict subsequent survival.

Clinical Trial Registration: ClinialTrials.gov, NCT00002568, NCT00837993, NCT00002717, NCT01074398, and NCT00011986.
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http://dx.doi.org/10.1097/AOG.0000000000003086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6551603PMC
February 2019

Radiation therapy is not an independent risk factor for decreased sexual function in women with gynecologic cancers.

Rep Pract Oncol Radiother 2018 Sep-Oct;23(5):331-336. Epub 2018 Aug 13.

Department of Obstetrics and Gynecology, University of Colorado Denver, Aurora, CO, USA.

Aim: To evaluate the associations of external beam radiation therapy (EBRT) and intracavitary brachytherapy (IB) with decreased sexual function.

Background: There's inconsistent evidence on whether radiation for gynecologic cancers has an impact on sexual health. IB, an underutilized treatment modality, is thought to have less adverse effects than EBRT.

Materials And Methods: A cross-sectional study examining decreased sexual function following radiation for gynecologic cancers. A decrease in sexual function was measured as a change in the Female Sexual Function Index (FSFI) from before to after treatment, with a significant decrease determined by Reliable Change Index Statistic (RCIS). Chi-square and -tests were employed.

Results: 171 women completed the survey; 35% ( = 60) received radiation, of whom 29 received EBRT and IB (48%), 15 EBRT alone (25%), 16 IB alone (27%). Women who received radiation had similar rates of decreased sexual function as women who did not (47% vs. 38%,  = 0.262). EBRT and IB had similar rates of decreased sexual function compared to women with no radiation (50% vs. 38%  = 0.166 and 47% vs. 38%  = 0.309). Women experiencing decreased sexual function were more likely to be under 50 years old (OR 5.4, 95%CI 1.6-18.1), have received chemotherapy (OR 5.7, 95%CI 1.4-22.9), and have cervical cancer (OR 7.8, 95%CI 2.1-28.8).

Conclusions: Treatment with EBRT or IB does not appear to impair sexual function in women with gynecologic cancer. Age less than 50, concurrent chemotherapy, and cervical cancer may place women with gynecologic cancer at higher risk for decreased sexual function following radiation.
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http://dx.doi.org/10.1016/j.rpor.2018.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097409PMC
August 2018

Minority Race Predicts Treatment by Non-gynecologic Oncologists in Women with Gynecologic Cancer.

Ann Surg Oncol 2018 Nov 13;25(12):3685-3691. Epub 2018 Aug 13.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO, USA.

Background: Outcomes of women with gynecologic cancer are superior when treated by gynecologic oncologists. The National Surgical Quality Improvement Program (NSQIP) began identifying gynecologic surgeon subspecialty in 2014. We sought to identify characteristics and outcomes of women treated by general gynecologists in comparison with women treated by gynecologic oncologists.

Patients And Methods: Patients undergoing hysterectomy for gynecologic malignancy in 2014 and 2015 were abstracted from the NSQIP database. Patient characteristics, morbidities, surgeon specialty, and operative outcomes were captured.

Results: 7271 hysterectomies were performed for malignant disease, and 669 were performed by generalists. In comparison with generalists, gynecologic oncologists operated on patients who were older (P < 0.001), more likely to be White [odds ratio (OR) 2.1, P < 0.001], had disseminated cancer (OR 3.1, P < 0.001), had ascites (OR 2.6, P < 0.001), and were classified as American Society of Anesthesiologists (ASA) class ≥ 3 (OR 1.7, P < 0.001). Gynecologic oncologists were also more likely to have hospital readmissions (OR 1.7, P = 0.004) and perform lymph node dissections for endometrial cancer (OR 2.2, P < 0.001). On multivariable analysis, older age [adjusted OR (aOR) 1.0, P = 0.021], White race (aOR 2.0, P < 0.001), presence of disseminated cancer (aOR 2.5, P < 0.001), presence of ascites (aOR 1.8, P = 0.036), and ASA class ≥ 3 (aOR 1.6, P < 0.001) remained independent predictive factors for having a gynecologic oncology surgeon.

Conclusions: The majority of gynecologic cancer cases are performed by gynecologic oncologists. Generalists are more likely to operate on minority patients and patients with fewer comorbidities. Further efforts to ensure access to specialized cancer care for all patients are needed.
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http://dx.doi.org/10.1245/s10434-018-6694-0DOI Listing
November 2018

Receipt of adjuvant endometrial cancer treatment according to race: an NRG Oncology/Gynecologic Oncology Group 210 Study.

Am J Obstet Gynecol 2018 11 7;219(5):459.e1-459.e11. Epub 2018 Aug 7.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Background: Black women with endometrial cancer are more likely to die of their disease compared with white women with endometrial cancer. These survival disparities persist even when disproportionately worse tumor characteristics among black women are accounted. Receipt of less complete adjuvant treatment among black patients with endometrial cancer could contribute to this disparity.

Objective: We assessed the hypothesis that black women with endometrial cancer are less likely than their white counterparts to receive adjuvant treatment within subgroups defined by tumor characteristics in the NRG Oncology/Gynecology Oncology Group 210 Study.

Study Design: Our analysis included 615 black and 4283 white women with endometrial cancer who underwent hysterectomy. Women completed a questionnaire that assessed race and endometrial cancer risk factors. Tumor characteristics were available from pathology reports and central review. We categorized women as low-, intermediate-, or high-risk based on the European Society for Medical Oncology definition. Adjuvant treatment was documented during postoperative visits and was categorized as no adjuvant treatment (54.3%), radiotherapy only (16.5%), chemotherapy only (15.2%), and radiotherapy plus chemotherapy (14.0%). We used polytomous logistic regression to estimate odds ratios and 95% confidence intervals for multivariable-adjusted associations between race and adjuvant treatment in the overall study population and stratified by tumor subtype, stage, or European Society for Medical Oncology risk category.

Results: Overall, black women were more likely to have received chemotherapy only (odds ratio, 1.40; 95% confidence interval, 1.04-1.86) or radiotherapy plus chemotherapy (odds ratio, 2.01; 95% confidence interval, 1.54-2.62) compared with white women in multivariable-adjusted models. No racial difference in the receipt of radiotherapy only was observed. In tumor subtype-stratified models, black women had higher odds of receiving radiotherapy plus chemotherapy than white women when diagnosed with low-grade endometrioid (odds ratio, 2.04; 95% confidence interval, 1.06-3.93) or serous tumors (odds ratio, 1.81; 95% confidence interval, 1.07-3.08). Race was not associated with adjuvant treatment among women who had been diagnosed with other tumor subtypes. In stage-stratified models, we observed no racial differences in the receipt of adjuvant treatment. In models that were stratified by European Society for Medical Oncology risk group, black women with high-risk cancer were more likely to receive radiotherapy plus chemotherapy compared with white women (odds ratio, 1.41; 95% confidence interval, 1.03-1.94).

Conclusion: Contrary to our hypothesis, we observed higher odds of specific adjuvant treatment regimens among black women as compared with white women within specific subgroups of endometrial cancer characteristics.
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http://dx.doi.org/10.1016/j.ajog.2018.08.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6239903PMC
November 2018

Fellow Perceptions of Residency Training in Obstetrics and Gynecology.

J Surg Educ 2019 Jan - Feb;76(1):93-98. Epub 2018 Aug 7.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, Colorado.

Objective: To evaluate the perceptions of current and former fellows in obstetrics and gynecology (OBG) subspecialties of their readiness for fellowship training.

Methods: A previously used survey was modified and distributed in 2016 to current and former fellows in gynecologic oncology, maternal-fetal medicine, reproductive endocrinology-infertility, and female pelvic medicine and reconstructive surgery. The survey explored domains of professionalism, independent practice, psychomotor ability, clinical evaluation, and scholarship. A standard Likert scale was employed and domains/responses were tailored to each subspecialty. Standard statistical models were utilized.

Results: A total of 478 fellows responded to the survey. Nearly 75% of fellows from each specialty reported feeling prepared or very prepared for fellowship. More than 65% of fellows from each specialty reported feeling very prepared to perform core surgical procedures. More than 90% of respondents reported having opportunities during residency to independently develop a plan of action for patients on labor and delivery. Fewer respondents reported opportunities to independently manage postoperative complications-40.7% of gynecologic oncology and 44.7% of female pelvic medicine and reconstructive surgery reported having such opportunities, whereas 91.9% of maternal-fetal medicine respondents reported having had such opportunities. While 46.4% of respondents received education on scientific writing during residency, 80% reported writing a manuscript as a resident.

Conclusions: The majority of current and former fellows in OBG subspecialties report feeling prepared for fellowship in terms of clinical and surgical skills. Their feedback reveals opportunities for improvement of independent practice in gynecologic scenarios, as well as formal education on scientific research, for OBG residencies.
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http://dx.doi.org/10.1016/j.jsurg.2018.06.013DOI Listing
June 2020

Fellow perceptions of residency training in obstetrics and gynecology.

Am J Obstet Gynecol 2018 04 17;218(4):461-462. Epub 2018 Jan 17.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Denver, CO. Electronic address:

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http://dx.doi.org/10.1016/j.ajog.2018.01.021DOI Listing
April 2018

Risk of metachronous ovarian cancer after ovarian conservation in young women with stage I cervical cancer.

Am J Obstet Gynecol 2017 11 27;217(5):580.e1-580.e10. Epub 2017 Jun 27.

Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, NY.

Background: While there is an increasing trend of ovarian conservation at the time of surgical treatment for young women with stage I cervical cancer, the risk for subsequent ovarian cancer after ovarian conservation has not been well studied.

Objective: We sought to examine the incidence of and risk factors for metachronous ovarian cancer among young women with stage I cervical cancer who had ovarian conservation at the time of hysterectomy.

Study Design: The Surveillance, Epidemiology, and End Results Program was used to identify women aged <50 years who underwent hysterectomy with ovarian conservation for stage I cervical cancer from 1983 through 2013 (n = 4365). Time-dependent analysis was performed for ovarian cancer risk after cervical cancer diagnosis.

Results: Mean age at cervical cancer diagnosis was 37 years, and the majority of patients had stage IA disease (68.2%) and squamous histology (72.9%). Median follow-up time was 10.8 years, and there were 13 women who developed metachronous ovarian cancer. The 10- and 20-year cumulative incidences of metachronous ovarian cancer were 0.2% (95% confidence interval, 0.1-0.4) and 0.5% (95% confidence interval, 0.2-0.8), respectively. Mean age at the time of diagnosis of metachronous ovarian cancer was 47.5 years, and stage III-IV disease was seen in 55.6%. Age (≥45 vs <45 years, hazard ratio, 4.22; 95% confidence interval, 1.16-15.4; P = .018), ethnicity (non-white vs white, hazard ratio, 4.29; 95% confidence interval, 1.31-14.0; P = .009), cervical cancer histology (adenocarcinoma or adenosquamous vs squamous, hazard ratio, 3.50; 95% confidence interval, 1.17-10.5; P = .028), and adjuvant radiotherapy use (yes vs no, hazard ratio, 3.69; 95% confidence interval, 1.01-13.4; P = .034) were significantly associated with metachronous ovarian cancer risk. The presence of multiple risk factors was associated with a significantly increased risk of metachronous ovarian cancer compared to the no risk factor group: 1 risk factor (hazard ratio range, 2.96-8.43), 2 risk factors (hazard ratio range, 16.6-31.0), and 3-4 risk factors (hazard ratio range, 62.3-109), respectively.

Conclusion: Metachronous ovarian cancer risk after ovarian conservation for women with stage I cervical cancer is <1%. Older age, non-white ethnicity, adenocarcinoma or adenosquamous histology, and adjuvant radiotherapy may be associated with an increased metachronous ovarian cancer risk.
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http://dx.doi.org/10.1016/j.ajog.2017.06.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523226PMC
November 2017

Surgical-pathological findings in type 1 and 2 endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study on GOG-210 protocol.

Gynecol Oncol 2017 06 6;145(3):519-525. Epub 2017 Apr 6.

Department of Obstetrics & Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States. Electronic address:

Objective: To report clinical and pathologic relationships with disease spread in endometrial cancer patients.

Methods: Surgical candidates with uterine cancer (adenocarcinoma or carcinosarcoma) who were eligible to participate in a surgical pathological study to create a clinically annotated tissue biorepository to support translational and clinical research studies. All patients were to undergo a hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic and para-aortic lymphadenectomy. From 2003-2007, open eligibility enrollment was conducted, and from 2007-2011, eligibility was restricted to enrich underrepresented patients or those at high risk.

Results: This report details clinical pathological relationships associated with extra uterine disease spread of 5866 evaluable patients including those with endometrioid histology as well as papillary serous, clear cell and carcinosarcoma histologies. Review of unrestricted enrollment was constructed in an effort to capture a cross-section population representative of endometrial cancers seen by the GOG participating members. Evaluation of this group of patients suggested the more natural incidence of different surgical pathological findings as well as demographic information. The addition of 2151 patients enrolled during the restricted time interval allowed a total of 1630 poor histotype patients available for further analysis. As expected, endometrioid (E) cancers represented the largest enrollment and particularly E grade 1 and 2 (G1 and 2) were more frequently confined to the uterus. Grade 3 (G3) endometrioid cancers as well as the poor histotype (papillary serous, clear cell and carcinosarcoma) had a much greater propensity for extant disease.

Conclusions: This study confirms the previously reported surgical pathological findings for endometrioid cancers but in addition, using a large database of papillary serous, clear cell and carcinosarcoma, surgical pathological findings substantiate the categorization of poor histotypes for these cancers.
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http://dx.doi.org/10.1016/j.ygyno.2017.03.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702929PMC
June 2017

Nonsteroidal Anti-inflammatory Drugs and Endometrial Carcinoma Mortality and Recurrence.

J Natl Cancer Inst 2017 03;109(3):1-10

Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Background: Recent data suggest that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with reductions in endometrial cancer risk, yet very few have examined whether their use is related to prognosis among endometrial cancer patients.

Methods: Study subjects comprised 4374 participants of the NRG Oncology/Gynecology Oncology Group 210 Study with endometrial carcinoma who completed a presurgical questionnaire that assessed history of regular prediagnostic NSAID use and endometrial cancer risk factors. Recurrences, vital status, and causes of death were obtained from medical records and cancer registries. Fine-Gray semiproportional hazards regression estimated adjusted subhazard ratios (HRs) and 95% confidence intervals (CIs) for associations of NSAID use with endometrial carcinoma-specific mortality and recurrence. Models were stratified by endometrial carcinoma type (ie, type I [endometrioid] vs type II [serous, clear cell, or carcinosarcoma]) and histology.

Results: Five hundred fifty endometrial carcinoma-specific deaths and 737 recurrences occurred during a median of five years of follow-up. NSAID use was associated with 66% (HR = 1.66, 95% CI = 1.21 to 2.30) increased endometrial carcinoma-specific mortality among women with type I cancers. Associations were statistically significant for former and current users, and strongest among former users who used NSAIDs for 10 years or longer (HR = 2.23, 95% CI = 1.19 to 4.18, two-sided P trend = .01). NSAID use was not associated with recurrence or endometrial carcinoma-specific mortality among women with type II tumors.

Conclusions: In this study, use of NSAIDs was associated with increased endometrial carcinoma-specific mortality, especially in patients with type I tumors. Barring a clear biologic mechanism by which NSAIDs would increase the risk of cause-specific mortality, cautious interpretation is warranted.
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http://dx.doi.org/10.1093/jnci/djw251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161320PMC
March 2017

Sexual and Marital Dysfunction in Women With Gynecologic Cancer.

Int J Gynecol Cancer 2017 03;27(3):603-607

*Department of Obstetrics and Gynecology, University of Colorado Cancer Center, Aurora, CO; †Department of Obstetrics and Gynecology, Loma Linda University Cancer Center, Loma Linda, CA; ‡Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, NY; and §Department of Obstetrics and Gynecology, Denver Health Medical Center, Denver, CO.

Objective: Sexual dysfunction can be a long-term issue for women with gynecologic cancer. This study assesses the extent of sexual and marital dysfunction women face following treatment of a gynecologic cancer.

Methods: A cross-sectional study of women with gynecologic cancer was conducted using a 181-item survey. Sexual dysfunction was measured by change in the Female Sexual Function Index score; marital dysfunction was measured by change in Intimate Bond Measure from prediagnosis to posttreatment. Paired t tests and Fisher exact test were used to compare women with dysfunction to those without dysfunction.

Results: Three hundred twenty women were enrolled (mean age, 56.0 [SD, 12.0] years). Among all women, sexual function declined from a score of 21.3 (SD, 10.4) prior to 15.3 (SD, 10.2) (P < 0.001), and sexual activity decreased from 6.1 (SD, 6.8) to 2.6 (SD, 4.9) times per month following treatment (P < 0.001). Among the 208 women who were sexually active at the time of study, sexual dysfunction after treatment was associated with younger age (50.9 [SD, 11.7] years to 57.3 [SD, 12.3] years), ovarian (40.7% vs 30.7%) or cervical (21.0% vs 10.2%) cancer diagnosis, chemotherapy treatment (72.8% vs 50.4%), and being in a relationship (97.3% vs 82.7%). Among women in relationships, 27% experienced marital dysfunction.

Conclusions: Women who are younger, have an ovarian or cervical cancer diagnosis, receive chemotherapy, or are in a committed relationship are at particularly high risk of sexual dysfunction. These women should be provided information about the risks associated with their cancer treatment.
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http://dx.doi.org/10.1097/IGC.0000000000000906DOI Listing
March 2017

Histopathology Discrepancy of Preoperative Endometrial Sampling and Final Specimen: How Does This Influence Selective Lymph Node Dissection?

Int J Gynecol Cancer 2017 02;27(2):297-301

Department of Obstetrics & Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO.

Objective: Preoperative histology is a major component in the perioperative selective lymph node (LN) dissection decision process. Discrepancy between preoperative endometrial sampling and final specimen histopathology is generally accepted. The goals of this project are to determine if discrepancy of histopathology is associated with alteration of adjuvant treatment or outcome.

Materials And Methods: We performed a retrospective cross-sectional analysis of all patients undergoing surgery for endometrial cancer at a single institution from 2010 to 2014. All patients had preoperative endometrial sampling. Histopathology discrepancy was evaluated for potential in variation of perioperative LN dissection. Criteria for not performing LN dissection was defined as preoperative endometrioid histology, grade 1 or 2 lesion, myometrial invasion of 50% or less, and primary tumor diameter 2 cm or less.

Results: A total of 352 patients were identified; 44 were excluded because of no preoperative pathology or no residual disease on final pathology. Discrepancy of histopathology was noted in 64/308 (20.8%; 95% confidence interval [CI], 16.2%-25.3%) patients. Preoperative endometrioid histology was noted in 272 patients, and 17/272 (6.3%; 95% CI, 3.4%-9.1%) had preoperative sampling reviewed as a grade 1 or 2 endometrioid lesion and final specimen was upgraded to grade 3. Downstaging occurred in 3/272 (1.1%; 95% CI, 0%-2.3%) patients with preoperative grade 3 lesion and final specimen demonstrated grade 1 or 2 disease. All 3 patients' primary tumor diameter was greater than 2 cm and therefore received LN dissection. Histopathological discrepancy that would alter perioperative LN dissection decision based on the aforementioned criteria occurred in 2/272 (0.7%; 95% CI, 0%-1.8%).

Conclusions: Despite a 20% discrepancy of preoperative and postoperative histopathology, discrepancy that would alter a perioperative decision for LN dissection occurs in only 0.7% of cases in this retrospective single-institutional experience. Myometrial invasion and tumor size may be more influential than histology in LN selection criteria.
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http://dx.doi.org/10.1097/IGC.0000000000000866DOI Listing
February 2017
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