H2Bub1 loss is an early contributor to clear cell ovarian cancer progression.

Epigenetic aberrations, including posttranslational modifications of core histones, are major contributors to cancer. Here, we define the status of histone H2B monoubiquitylation (H2Bub1) in clear cell ovarian carcinoma (CCOC), low-grade serous carcinoma, and endometrioid carcinomas. We report that clear cell carcinomas exhibited profound loss, with nearly all cases showing low or negative H2Bub1 expression. Moreover, we found that H2Bub1 loss occurred in endometriosis and atypical endometriosis, which are established precursors to CCOCs. To examine whether dysregulation of a specific E3 ligase contributes to the loss of H2Bub1, we explored expression of ring finger protein 40 (RNF40), ARID1A, and UBR7 in the same case cohort. Loss of RNF40 was significantly and profoundly correlated with loss of H2Bub1. Using genome-wide DNA methylation profiles of 230 patients with CCOC, we identified hypermethylation of RNF40 in CCOC as a likely mechanism underlying the loss of H2Bub1. Finally, we demonstrated that H2Bub1 depletion promoted cell proliferation and clonogenicity in an endometriosis cell line. Collectively, our results indicate that H2Bub1 plays a tumor-suppressive role in CCOCs and that its loss contributes to disease progression.

Facility level variation in the utilization of neoadjuvant chemotherapy is associated with higher surgical morbidity for patients with advanced stage epithelial ovarian carcinoma.

OBJECTIVE: Investigate outcomes for advanced stage epithelial ovarian cancer (EOC) patients based on facility-level utilization of neoadjuvant chemotherapy (NACT). METHODS: Stage III-IV EOC patients diagnosed between 2010 and 2016 were identified in the National Cancer Database. Percentage of patients managed with NACT was calculated for facilities, reporting ≥120 patients. Facilities with lowest and highest quartile of NACT rate comprised the low and high-utilizing groups. Clinico-pathological characteristics were collected, and appropriate statistical analysis performed. RESULTS: High- and low-utilizing facilities managed on average 54.1% and 25.4% of patients with NACT respectively. Patients managed at high-utilizing facilities were significantly more likely to be >65 (p = 0.029), have stage IV disease (p < 0.001) and comorbidities (p < 0.001). Patients managed with primary debulking surgery (PDS) at low-utilizing facilities were significantly more likely to be >65, have stage IV disease, and have comorbidities (all, p < 0.001). Patients undergoing PDS at low-utilizing facilities were significantly less likely to achieve complete gross resection (p < 0.001), and were significantly more likely to experience 90-day mortality (p < 0.001), and unplanned 30-day readmission (p < 0.001). After controlling for age, comorbidities, race, insurance status, stage, grade and histology, high-utilizing facilities trended towards better overall survival (OS) (HR: 0.92, 95% CI: 0.85-0.99). Overall, patients undergoing PDS had better OS compared to those who had NACT (median 42 vs 27 months, p < 0.001). CONCLUSIONS: Despite treating an EOC population with more advanced disease and comorbidities, high-utilizing facilities have lower surgical morbidity and mortality with no detrimental impact on long-term survival. Careful patient selection to minimize the morbidity and mortality associated with PDS is pivotal.

A Phase III Study of Pafolacianine Injection (OTL38) for Intraoperative Imaging of Folate Receptor-Positive Ovarian Cancer (Study 006).

PURPOSE: The adjunctive use of intraoperative molecular imaging (IMI) is gaining acceptance as a potential means to improve outcomes for surgical resection of targetable tumors. This confirmatory study examined the use of pafolacianine for real-time detection of folate receptor-positive ovarian cancer. METHODS: This phase III, open-label, 11-center study included subjects with known or suspected ovarian cancer, scheduled to undergo cytoreductive surgery. The objectives were to confirm safety and efficacy of pafolacianine (0.025 mg/kg IV), given ≥ 1 hour before intraoperative near-infrared imaging to detect macroscopic lesions not detected by palpation and normal white light. RESULTS: From March 2018 through April 2020, 150 patients received a single infusion of pafolacianine (safety analysis set); 109 patients with folate receptor-positive ovarian cancer comprised the full analysis set for efficacy. In 33.0% of patients (95% CI, 24.3 to 42.7; P < .001), pafolacianine with near-infrared imaging identified additional cancer on tissue not planned for resection and not detected by white light assessment and palpation, exceeding the prespecified threshold of 10%. Among patients who underwent interval debulking surgery, the rate was 39.7% (95% CI, 27.0 to 53.4; P < .001). The sensitivity to detect ovarian cancer was 83%, and the patient false-positive rate was 24.8%. Investigators reported achieving complete R0 resection in 62.4% (68 of 109) of patients. Drug-related adverse events were reported by 30% of patients (45 of 150) and most commonly included nausea, vomiting, and abdominal pain. No drug-related serious adverse events or deaths were reported. CONCLUSION: This phase III study of pafolacianine met its primary efficacy end point, identifying additional cancers not otherwise identified or planned for resection. Pafolacianine may offer an important real-time adjunct to current surgical approaches for ovarian cancer.

A prospective cross-sectional survey comparing patient and provider expectations regarding ovarian cancer prognosis.

Introduction: There is limited data comparing patient and physician expectations regarding ovarian cancer prognosis. Our primary objective was to compare physician and patient estimates of survival to 6 months, 1 year, and 5 years; secondary objectives included comparing provider and patient responses on the likelihood of requiring future treatments and categorizing patient and provider preferences regarding communication about prognosis. Methods: A prospective cross-sectional survey was delivered to 10 gynecologic oncology providers and 50 adult ovarian cancer patients from November 2015-April 2016 at one institution. Descriptive statistics were used to categorize survey answers and compare survey answers between patients and providers; multivariable logistic regression evaluated patient survey responses. Results: All providers (100%) believed treating providers should discuss prognosis and 90% reported having prognostic conversations with patients, compared to 63%, 37%, and 4% of patients who reported discussing prognosis, living wills/advance directives, and palliative care/hospice services, respectively, with their provider. Compared to their provider, patients gave significantly lower estimations of requiring any future therapy (mean score 84.6 vs 74, p <.001) and future chemotherapy (mean score 84.1 vs 69.8, p <.001) and significantly higher estimations of requiring future surgery (mean score 23.3 vs 40, p <.001), achieving remission (mean score 33.5 vs 47.5, p =.009), survival to 1 year (mean score 77.1 vs 86.4, p =.002), and survival to 5 years (mean score 40.5 vs 61.3, p <.001). Conclusions: Although gynecologic oncology providers believe it is important to discuss prognosis and end-of-life care, there are gaps in communication, knowledge, and expectations between providers and ovarian cancer patients.

Adjuvant chemotherapy for stage I high-intermediate risk endometrial carcinoma with lymph-vascular invasion.

OBJECTIVE: The goal of this study was to evaluate if addition of adjuvant chemotherapy to radiation therapy improves overall survival in patients with high-intermediate risk stage I endometrial carcinoma with lymphovascular invasion. METHODS: Patients diagnosed between January 2010 and December 2015 with FIGO (International Federation of Gynecology and Obstetrics) stage I endometrioid endometrial carcinoma with lymphovascular invasion who underwent hysterectomy with lymphadenectomy and met the GOG-99 criteria for high-intermediate risk were identified in the National Cancer Database. Patients who received adjuvant radiotherapy with or without adjuvant chemotherapy (administered within 6 months of surgery) and had at least 1 month of follow-up were selected for further analysis. Overall survival was compared with the log-rank test following stratification by type of radiation treatment. A Cox model was constructed to control for a priori selected confounders. RESULTS: A total of 2881 patients who met the inclusion criteria were identified; 2417 (83.9%) patients received radiation therapy alone while 464 (16.1%) received chemoradiation. Rate of adjuvant chemotherapy administration was comparable between patients who received vaginal brachytherapy alone (16.2%), and external beam radiation therapy (with or without vaginal brachytherapy) (15.8%), p=0.78. Rate of chemoradiation was higher for patients with grade 3 (28.8%) tumors compared with those with grade 2 (9.9%) and grade 1 (8.3%) tumors, p<0.001. After controlling for confounders for patients receiving external beam radiation, addition of chemotherapy was not associated with improved overall survival (HR 0.90, 95% CI 0.56 to 1.46). For patients receiving vaginal brachytherapy addition of chemotherapy was associated with better overall survival (HR 0.644, 95% CI 0.45 to 0.92). Benefit was limited to patients with grade 3 tumors, p=0.026; 4-year overall survival rate was 81.1% versus 74.9%. CONCLUSIONS: In patients with high-intermediate risk FIGO stage I endometrioid endometrial carcinoma and lymphovascular invasion, addition of chemotherapy to radiation therapy was associated with a survival benefit for patients with grade 3 tumors receiving vaginal brachytherapy.

A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45).

PURPOSE: ATHENA (ClinicalTrials.gov identifier: NCT03522246) was designed to evaluate rucaparib first-line maintenance treatment in a broad patient population, including those without BRCA1 or BRCA2 (BRCA) mutations or other evidence of homologous recombination deficiency (HRD), or high-risk clinical characteristics such as residual disease. We report the results from the ATHENA-MONO comparison of rucaparib versus placebo. METHODS: Patients with stage III-IV high-grade ovarian cancer undergoing surgical cytoreduction (R0/complete resection permitted) and responding to first-line platinum-doublet chemotherapy were randomly assigned 4:1 to oral rucaparib 600 mg twice a day or placebo. Stratification factors were HRD test status, residual disease after chemotherapy, and timing of surgery. The primary end point of investigator-assessed progression-free survival was assessed in a step-down procedure, first in the HRD population (BRCA-mutant or BRCA wild-type/loss of heterozygosity high tumor), and then in the intent-to-treat population. RESULTS: As of March 23, 2022 (data cutoff), 427 and 111 patients were randomly assigned to rucaparib or placebo, respectively (HRD population: 185 v 49). Median progression-free survival (95% CI) was 28.7 months (23.0 to not reached) with rucaparib versus 11.3 months (9.1 to 22.1) with placebo in the HRD population (log-rank P = .0004; hazard ratio [HR], 0.47; 95% CI, 0.31 to 0.72); 20.2 months (15.2 to 24.7) versus 9.2 months (8.3 to 12.2) in the intent-to-treat population (log-rank P < .0001; HR, 0.52; 95% CI, 0.40 to 0.68); and 12.1 months (11.1 to 17.7) versus 9.1 months (4.0 to 12.2) in the HRD-negative population (HR, 0.65; 95% CI, 0.45 to 0.95). The most common grade ≥ 3 treatment-emergent adverse events were anemia (rucaparib, 28.7% v placebo, 0%) and neutropenia (14.6% v 0.9%). CONCLUSION: Rucaparib monotherapy is effective as first-line maintenance, conferring significant benefit versus placebo in patients with advanced ovarian cancer with and without HRD.

Delay in adjuvant chemotherapy administration for patients with FIGO stage I epithelial ovarian carcinoma is associated with worse survival; an analysis of the National Cancer Database.

OBJECTIVE: The administration of adjuvant chemotherapy within 42 days from surgery is one of the proposed quality measures for patients with epithelial ovarian cancer (EOC). The aim of the present study was to evaluate the impact of chemotherapy delay in the survival of patients with stage I EOC. METHODS: The National Cancer Database was accessed, and patients diagnosed between 2004 and 2015 with FIGO stage I EOC who received multi-agent chemotherapy were identified. Overall survival (OS) was compared between patients who received chemotherapy <6 weeks and 6-12 weeks from surgery with the log-rank test following generation of Kaplan-Meier curves. Cox model was constructed to control for a priori selected confounders. RESULTS: A total of 8549 patients who received adjuvant chemotherapy at a median 35 days from surgery (interquartile range 19) were identified; 67.7% received adjuvant chemotherapy <6 weeks from surgery while 32.3% experienced a delay. Patients who experienced a delay were more likely to have comorbidities (18.4% vs 14.9%, p < 0.001), and be managed in non-academic facilities (57.1% vs 53.2%, p = 0.001). Patients who experienced a delay had worse OS compared to those who did not, p < 0.001; 5-year OS rates 85.7% and 89.7%, respectively. For patients with high-grade serous tumors, those who experienced a delay had a 5-yr OS of 81.9% compared to 88.6% for those who did not, p < 0.001. After controlling for age, race, presence of comorbidities, insurance status, tumor histology and grade, performance of lymphadenectomy and substage, chemotherapy delay was associated with worse survival (HR: 1.25, 95% CI: 1.10, 1.42). CONCLUSIONS: For patients with early stage EOC administration of adjuvant chemotherapy within 6 weeks from surgery was associated with better overall survival, especially for those with stage IC disease.

Disparities in cancer-specific and overall survival in black women with endometrial cancer: A Medicare-SEER study.

OBJECTIVES: To examine overall survival (OS) and cancer-specific survival (CSS) for different racial groups of women with surgically staged endometrial cancer by histologic subtype. METHODS: This is a retrospective cohort study of women with stage I-III endometrioid, serous, clear cell, and carcinosarcoma who underwent hysterectomy as primary surgical staging in the 2000-2016 SEER-Medicare database. OS and CSS outcomes were stratified by race (defined as White, Black, Other), stage, and histology. Survival was assessed with descriptive analyses, log-rank tests and unadjusted and adjusted multivariable cox regression models. RESULTS: Of the 24,142 women identified, 85.5% were White, 8.5% Black, and 6% other races. Receipt of adjuvant therapy differed only for stage III endometrioid: Black women were less likely to receive adjuvant treatment after hysterectomy (61.2% vs. 70.1% White, p = 0.03). For stage I, Black women had worse CSS for all histologies other than clear cell in unadjusted and adjusted analyses. For stage II, Black women had worse CSS for endometrioid histology in unadjusted analyses and similar OS. For stage III, Black women with endometrioid carcinoma had worse CSS and OS in unadjusted analyses, but no significant difference in CSS in adjusted analyses. "Other" race showed improved OS for Stage I endometrioid adenocarcinoma without significant differences in outcomes when compared to White women. CONCLUSION: Across histologies other than clear cell, Black women diagnosed with stage I endometrial cancer had consistently worse CSS, despite similar receipt of adjuvant therapy. Differences in CSS and OS at higher stages disappeared once accounting for treatment disparities.

Patterns of adjuvant treatment and survival outcomes in stage I uterine carcinosarcoma.

OBJECTIVE: To determine patterns in type and sequence of adjuvant treatment and associated differences in overall survival among women with Stage I uterine carcinosarcoma (UCS). METHODS: Women with stage I UCS from 2000 to 2015 were identified through the National Cancer Institute's Surveillance, Epidemiology and End Results database linked to Medicare-based claims follow-up data through 2016. Data including demographics, co-morbidities, surgical procedure, surgical pathology and type and sequence of adjuvant treatment were collected. The primary study outcome was overall survival (OS) by type and sequence of adjuvant therapy. Cancer specific survival was also analyzed. RESULTS: A total of 755 women with Stage I UCS were identified. Of these, 56.3% (n = 445) received adjuvant therapy, whereas 43.7% (n = 330) did not. In comparison to no adjuvant treatment, an overall survival benefit was noted with receipt of chemotherapy alone for women with Stage I disease (log rank p < 0.01). Pairwise comparisons did not show a benefit in OS of concurrent RT-chemo, sequential RT-chemo, or sequential chemo-RT, over chemotherapy alone (p > 0.05 for all). Likewise, radiation alone and no treatment were associated with worse OS compared to chemotherapy alone (p < 0.001 for both). Adjusted Cox regression models demonstrated an OS benefit only in the chemotherapy alone cohort for Stage I disease (HR 0.43 95% CI 0.32, 0.60, p < 0.0001), as well as for CSS (HR 0.41, 95 %CI 0.26, 0.62, p < 0.0001), compared to no treatment. CONCLUSIONS: In comparison to no adjuvant therapy, an overall survival and cancer-specific survival benefit was noted with receipt of chemotherapy alone in Stage I UCS.

Sports- and Physical Activity-Related Concussions, Binge Drinking and Marijuana Use among Adolescents: The Mediating Role of Depression and Suicidal Ideation.

BACKGROUND: Although past studies have examined the adverse impact of sports- and physical activity-related concussions (SPACs) on health and mental health outcomes, there is a dearth of research investigating the association between SPACs and binge drinking and marijuana use. OBJECTIVE: The objective of this study is to examine the cross-sectional association between SPACs and binge drinking and marijuana use among adolescents and whether symptoms of depression and suicidal ideation mediate this association. METHODS: Data for this study came from the 2017 and 2019 National Youth Risk Behavior Survey. An analytic sample of 17,175 adolescents aged 14-18 years (50.2% male) was analyzed using binary logistic regression. RESULTS: Of the 17,175 adolescents, 13.7% engaged in binge drinking and 19.3% used marijuana 30 days preceding the survey date. Approximately one in seven (14.1%) adolescents had SPACs during the past year. Upon controlling for the effects of other factors, adolescents who had SPACs had 1.74 times higher odds of engaging in binge drinking (AOR = 1.74, p<.001, 95% CI = 1.47-2.06) and 1.42 times higher odds of using marijuana (AOR = 1.42, p<.001, 95% CI = 1.24-1.62) than those who did not have SPACs. Symptoms of depression and suicidal ideation explained 12% of the association between SPACs and binge drinking, and 19% of the association between SPACs and marijuana use. CONCLUSIONS: Understanding the association between SPACs and substance use and mental health could contribute to early identification of adolescents who may engage in substance use.

The ATHENA COVID-19 Study: Cohort profile and first findings for people diagnosed with COVID-19 in Queensland, 1 January to 31 December 2020.

BACKGROUND: To date, there are limited Australian data on characteristics of people diagnosed with COVID-19 and on how these characteristics relate to outcomes. The ATHENA COVID-19 Study was established to describe health outcomes and investigate predictors of outcomes for all people diagnosed with COVID-19 in Queensland by linking COVID-19 notification, hospital, general practice and death registry data. This paper reports on the establishment and first findings for the ATHENA COVID-19 Study. METHODS: Part 1 of the ATHENA COVID-19 Study used Notifiable Conditions System data from 1 January 2020 to 31 December 2020, linked to: Emergency Department Collection data for the same period; Queensland Health Admitted Patient Data Collections (from 1 January 2010 to 30 January 2021); and Deaths Registrations data (from 1 January 2020 to 17 January 2021). RESULTS: To 31 December 2020, a total of 1,254 people had been diagnosed with SARS-CoV-2 infection in Queensland: half were female (49.8%); two-thirds (67.7%) were aged 20-59 years; and there was an over-representation of people living in less-disadvantaged areas. More than half of people diagnosed (57.6%) presented to an ED; 21.2% were admitted to hospital as an inpatient (median length of stay 11 days); 1.4% were admitted to an intensive care unit (82.4% of these required ventilation); and there were six deaths. Analysis of factors associated with these outcomes was limited due to small case numbers: people living in less-disadvantaged areas had a lower risk of being admitted to hospital (test for trend, p < 0.001), while those living in more remote areas were less likely than people living in major cities to present to an ED (test for trend: p=0.007), which may reflect differential health care access rather than health outcomes per se. Increasing age (test for trend, p < 0.001) and being a current/recent smoker (age-sex-adjusted relative risk: 1.61; 95% confidence interval: 1.00, 2.61) were associated with a higher risk of being admitted to hospital. CONCLUSION: Despite uncertainty in our estimates due to small numbers, our findings are consistent with what is known about COVID-19. Our findings reinforce the value of linking multiple data sources to enhance reporting of outcomes for people diagnosed with COVID-19 and provide a platform for longer term follow-up.

Oncologic outcomes of minimally invasive versus open radical hysterectomy for early stage cervical carcinoma and tumor size <2 cm: a systematic review and meta-analysis.

OBJECTIVE: To investigate the oncologic outcomes of patients with early-stage cervical carcinoma and tumor size <2 cm who underwent open or minimally invasive radical hysterectomy. METHODS: The Pubmed/Medline, Embase, and Web-of-Science databases were queried from inception to January 2021 (PROSPERO CRD 42020207971). Observational studies reporting progression-free survival and/or overall survival for patients who had open or minimally invasive radical hysterectomy for early-stage cervical carcinoma and tumor size <2 cm were selected. Level of statistical heterogeneity was evaluated with the I2 statistic. A random-effects model was used to compare progression and overall survival between the two groups and HR with 95% confidence intervals were calculated with the Der Simonian and Laird approach. Risk of bias and quality of included studies was assessed with the Newcastle-Ottawa scale. RESULTS: A total of 10 studies that met the inclusion criteria were included encompassing 4935 patients. Of these, 2394 (48.5%) patients had minimally invasive and 2541 (51.5%) patients had open radical hysterectomy; respectively. Patients who underwent minimally invasive hysterectomy had worse progression-free survival than those who had open surgery (HR 1.68, 95% CI 1.20, 2.36, I2 26%). Based on five studies, patients who had minimally invasive (n=1808) hysterectomy had a trend towards worse overall survival than those who had open surgery (n=1853) (HR 1.64, 95% CI 1.00 to 2.68, I2 15%). CONCLUSION: Based on a systematic review of the literature and meta-analysis of studies that control for confounders, for patients with cervical cancer and tumor size <2 cm, minimally invasive radical hysterectomy was associated with worse progression-free survival than laparotomy.

Role of lymphadenectomy for apparent early stage uterine sarcoma; a comprehensive analysis of the National Cancer Database.

OBJECTIVE: Investigate the role of lymphadenectomy for patients with apparent stage I uterine sarcoma. METHODS: The National Cancer Database was accessed and patients without a history of another tumor diagnosed between 2004 and 2015 with an apparent early stage leiomyosarcoma, adenosarcoma, low-grade endometrial stromal and high-grade endometrial stromal/undifferentiated sarcoma who underwent hysterectomy with or without lymphadenectomy were identified. Overall survival was assessed after stratification by histology with the log-rank test while Cox models were constructed to control for confounders. RESULTS: A total of 6412 patients with apparent early stage uterine sarcoma who underwent hysterectomy were identified; 2820 (44%) underwent lymphadenectomy. Rate of lymph node metastasis was 3.4% (42/1250) for patients with leiomyosarcoma, 2.3% (19/826) for those with adenosarcoma, 4.5% (21/463) for patients with low-grade endometrial stromal sarcoma and 7.9% (22/280) for those with high-grade endometrial stromal/undifferentiated sarcoma, p < 0.001. After controlling for confounders lymphadenectomy was not associated with better survival for patients with adenosarcoma (HR: 0.92, 95% CI: 0.73, 1.17), or low-grade endometrial stromal sarcoma (HR: 1.17, 95% CI: 0.73, 1.87). Patients with leiomyosarcoma who underwent lymphadenectomy had worse survival (HR: 1.15, 95% CI: 1.03, 1.28). Patients with high-grade endometrial stromal/undifferentiated sarcoma who underwent lymphadenectomy had better survival (HR: 0.66, 95% CI: 0.48, 0.89). CONCLUSIONS: Incidence of lymph node metastasis in apparent early stage uterine sarcoma is rare while the performance of lymphadenectomy was not associated with a clear survival benefit for all histologic subtypes except high-grade endometrial stromal/undifferentiated sarcoma.

Role of adjuvant radiation therapy after radical hysterectomy in patients with stage IB cervical carcinoma and intermediate risk factors.

OBJECTIVE: To investigate the outcomes of observation-alone versus adjuvant radiotherapy for patients with lymph node negative FIGO 2018 stage IB cervical carcinoma following radical hysterectomy with negative prognostic factors. METHODS: The National Cancer Database was accessed and patients with no history of another tumor, diagnosed with intermediate risk (defined as tumor size 2-4 cm with lymph-vascular invasion or tumor size >4 cm) pathological stage IB squamous, adenosquamous carcinoma or adenocarcinoma of the cervix between January 2010 and December 2015 who underwent radical hysterectomy with lymphadenectomy and had negative tumor margins were identified. Overall survival was assessed following generation of Kaplan-Meier curves and compared with the log-rank test. A Cox model was constructed to control for a priori selected confounders known to be associated with overall survival. RESULTS: A total of 765 patients were identified and adjuvant external beam radiotherapy was administered to 378 patients (49.4%). There was no difference in overall survival between patients who did and did not receive adjuvant radiotherapy, P=0.44: 4-year overall survival rates were 88.4% and 87.1% respectively. After controlling for patient age, histology, and surgical approach, the administration of adjuvant radiotherapy was not associated with better survival (HR 0.86, 95% CI 0.54 to 1.38). For patients who received adjuvant radiotherapy, there was no survival difference between those who did (n=219) and did not (n=159) receive concurrent chemotherapy, P=0.36: 4-year overall survival rates were 89.8% and 86.3%, respectively. CONCLUSION: In a large cohort of patients with lymph node negative, margin negative, stage IB cervical carcinoma, with negative prognostic factors, the administration of adjuvant external beam radiation therapy was not associated with a survival benefit compared with observation alone.

The impact of sentinel lymph node sampling versus traditional lymphadenectomy on the survival of patients with stage IIIC endometrial cancer.

OBJECTIVE: To investigate the survival of patients with lymph node positive endometrial carcinoma by type of surgical lymph node assessment. METHODS: Patients diagnosed between January 2012 and December 2015 with endometrial carcinoma and uterine confined disease and nodal metastases on final pathology who underwent minimally invasive hysterectomy were identified in the National Cancer Database. Patients who had sentinel lymph node biopsy alone or underwent systematic lymphadenectomy were selected. Overall survival was evaluated following generation of Kaplan-Meier curves and compared with the log rank test. A Cox model was constructed to evaluate survival after controlling for confounders. RESULTS: A total of 1432 patients were identified: 1323 (92.4%) and 109 (7.6%) underwent systematic lymphadenectomy and sentinel lymph node biopsy only, respectively. The rate of adjuvant treatment was comparable between patients who had sentinel lymph node biopsy alone and systematic lymphadenectomy (83.5% vs 86.6%, p=0.39). However, patients who had sentinel lymph node biopsy were less likely to receive chemotherapy alone (13.6% vs 36.6%, p<0.001) and more likely to receive radiation therapy alone (19.8% vs 5.4%, p<0.001) compared with patients who had systematic lymphadenectomy. There was no difference in overall survival between patients who had sentinel lymph node biopsy alone and systematic lymphadenectomy (p=0.27 from log rank test), and 3 year overall survival rates were 82.2% and 79.4%, respectively (p>0.05). After controlling for confounders, there was no difference in survival between the systematic lymphadenectomy and sentinel lymph node biopsy alone groups (hazard ratio 0.82, 95% confidence interval 0.46 to 1.45). CONCLUSIONS: Performance of sentinel lymph node biopsy alone was not associated with an adverse impact on survival in patients with lymph node positive endometrial cancer.

Outcomes of sentinel lymph node mapping for patients with FIGO stage I endometrioid endometrial carcinoma.

OBJECTIVE: Investigate the overall survival of patients with FIGO stage I endometrioid endometrial carcinoma who underwent sentinel lymph node biopsy (SLNBx). METHODS: Patients diagnosed between 2012 and 2015 with pathological stage I endometrioid endometrial carcinoma who underwent minimally invasive hysterectomy and had at least one month of follow-up were identified in the National Cancer Database (NCDB). Patients who underwent SLNBx or systematic lymphadenectomy (LND) (defined as at least 20 lymph nodes removed) were selected. Overall survival (OS) was evaluated following generation of Kaplan-Meier curves and compared with the log-rank test. A Cox model was constructed to evaluate survival after controlling for confounders. RESULTS: A total of 13,010 patients with endometrioid endometrial carcinoma who met the inclusion criteria were identified; 9861 (75.8%) and 3149 (24.2%) patients had systematic LND and SLNBx, respectively. Patients who had LND were more likely to receive radiation therapy (27.4% vs 19.3%, p < 0.001) and chemotherapy (13% vs 8.7%, p < 0.001) compared to those who had SLNBx. After controlling for patient age, race, insurance status, depth of myometrial invasion, tumor grade, tumor size, presence of lymph-vascular invasion and receipt of radiation therapy, the performance of SLNBx was not associated with worse survival (HR: 0.99, 95% CI: 0.80, 1.21). For high-intermediate risk patients (based on GOG-99 criteria) after controlling for confounders, performance of SLNBx was not associated with worse survival (HR: 1.07, 95% CI: 0.80, 1.44). For intermediate risk patients who did not receive external beam radiation therapy or chemotherapy after controlling for confounders, performance of SLNBx was not associated with worse survival (HR: 1.58, 95% CI: 0.94, 2.65). CONCLUSIONS: SLNBx had no negative impact on the survival of patients with FIGO stage I endometrioid endometrial carcinoma who undergo hysterectomy.

Is there a benefit of performing an omentectomy for clinical stage I high-grade endometrial carcinoma?

OBJECTIVES: Routine omentectomy is generally not performed in patients with endometrial cancer unless there is evidence of gross omental metastases. The aim of the current study was to evaluate the role of omentectomy in the staging of clinical stage I high-grade endometrial carcinoma and its impact on overall survival. METHODS: Patients in the National Cancer Database who presented between 2010 and 2015 with clinical stage I serous, clear cell, carcinosarcoma, or grade 3 endometrioid carcinoma and underwent hysterectomy with lymphadenectomy were selected. Patients who did and did not receive an omentectomy were identified and clinico-pathological characteristics were compared. Overall survival was evaluated for patients diagnosed between 2010 and 2014 who had at least one month of follow-up following generation of Kaplan-Meier curves and comparison with the log-rank test. A Cox model was constructed to control for confounders. RESULTS: A total of 9097 patients were identified, and 36.3% underwent an omentectomy. Patients who underwent omentectomy were more likely to be managed in academic institutions (50% vs. 44%, p < 0.001). They were also more likely to have an open surgery (48.2% vs. 27.2%, p < 0.001) and receive adjuvant chemotherapy (54.7% vs. 38.2%, p < 0.001). There was no difference in overall survival between patients who did and did not undergo omentectomy, p = 0.61; the 3-year OS rates were 82.3% and 82.2%, respectively. After controlling for confounders, the performance of an omentectomy was not associated with better survival (hazard ratio [HR]: 0.94, 95% confidence intervals [CI]: 0.84, 1.05). CONCLUSIONS: Routine omentectomy may not be associated with a survival benefit for patients with clinical stage I high-grade endometrial carcinoma.

Impact of past surgical history on perioperative outcomes in gynecologic surgery.

OBJECTIVE: We sought to determine if past surgical history is associated with perioperative outcomes for patients undergoing hysterectomy. METHODS: A retrospective cohort study was conducted at a single, tertiary, academic health system of women who underwent hysterectomy from May 2016 - May 2017. Past surgical history (PSH) involving any abdominal or pelvic surgery, baseline demographics and perioperative outcomes were collected. For purposes of analyses, PSH was defined using three algorithms: 1) any prior abdominopelvic surgery, 2) having had abdominopelvic surgeries likely to cause adhesive disease, 3) anatomic location of prior PSH (none; pelvic; abdominal; or abdominal+pelvic). Descriptive, bivariable and multivariable analyses were performed. RESULTS: 1256 patients underwent hysterectomy. In adjusted analyses, PSH defined by any prior abdominopelvic surgery was associated with length of stay (LOS) (2.1 days (95%CI 1.9, 2.2) vs. 1.8 (95%CI 1.6, 2.0), (p=0.02)). PSH of procedures likely to cause adhesive disease was associated with greater estimated blood loss (EBL) (243.2 mL (95%CI 208.1, 278.3) vs. 189.0 (95%CI 1734, 204.7), (p=0.01)), longer LOS (2.5 days (95%CI 2.2, 2.8) vs. 1.9 (95%CI 1.7, 2.0), (p<0.01)), and more readmissions (OR 2.4, 95%CI 1.3, 4.5) (p<0.01). PSH defined by anatomic location revealed a trend (p=0.07) towards greater EBL in those with prior pelvic or abdominal+pelvic surgery compared to none or abdominal only, whereas LOS, readmissions and operative times did not differ. Increased total number of prior open surgeries was associated with operative time (p<0.0001), EBL (p<0.0001), hospital LOS (p<0.0001) and readmission (p=0.026). CONCLUSIONS: Prior abdominopelvic surgery is associated with worse perioperative outcome measures in women undergoing hysterectomy.

Utilization and outcomes of sentinel lymph node biopsy in patients with early stage vulvar cancer.

OBJECTIVE: A retrospective cohort study comparing survival and perioperative outcomes of patients with early vulvar cancer who underwent sentinel lymph node biopsy versus standard lymphadenectomy METHODS: Patients diagnosed between January 2012 and December 2015 with vulvar squamous cell carcinoma of less than 4 cm in size, with invasion of at least 1 mm, who underwent sentinel lymph node biopsy, lymphadenectomy, or both were identified from the National Cancer Database. Overall survival was evaluated following generation of Kaplan-Meier curves and compared with the log-rank test for patients who had at least 1 month of follow-up. A Cox model was constructed to control for confounders. RESULTS: A total of 1583 patients were identified; 304 patients (19.2%) underwent sentinel lymph node biopsy alone. Sentinel lymph node biopsy utilization increased 13.9% between 2012 and 2015. Patients who underwent sentinel node biopsy alone were less likely to have comorbidities compared with those undergoing lymphadenectomy only or sentinel node biopsy with lymphadenectomy (25.3% vs 32.9% vs 31.9%, p=0.042), had smaller tumors (median 1.6 vs 2.0 vs 2.0 cm, p<0.001), and were less likely to have positive lymph nodes (11% vs 19.6% vs 28.1%, p<0.001). There was no difference in 3 year overall survival between the three groups (86.3% vs 82.1% vs 77.9%, p=0.26). After controlling for age, race, insurance, comorbidities, lymph node metastases, and tumor size, sentinel lymph node biopsy alone was not associated with worse overall survival compared with lymphadenectomy (HR 0.86, 95% CI 0.57 to 1.32). The sentinel node only group had shorter inpatient stays compared with lymphadenectomy only (median 1 vs 2 days, p<0.001) and a lower rate of unplanned readmission (1.7% vs 5.0%, p=0.010). CONCLUSIONS: The utilization of sentinel lymph node biopsy is increasing in the management of vulvar cancer and is associated with superior perioperative outcomes without impacting overall survival.