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.

Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer.

BACKGROUND: Data are limited regarding the use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors, such as veliparib, in combination with chemotherapy followed by maintenance as initial treatment in patients with high-grade serous ovarian carcinoma. METHODS: In an international, phase 3, placebo-controlled trial, we assessed the efficacy of veliparib added to first-line induction chemotherapy with carboplatin and paclitaxel and continued as maintenance monotherapy in patients with previously untreated stage III or IV high-grade serous ovarian carcinoma. Patients were randomly assigned in a 1:1:1 ratio to receive chemotherapy plus placebo followed by placebo maintenance (control), chemotherapy plus veliparib followed by placebo maintenance (veliparib combination only), or chemotherapy plus veliparib followed by veliparib maintenance (veliparib throughout). Cytoreductive surgery could be performed before initiation or after 3 cycles of trial treatment. Combination chemotherapy was 6 cycles, and maintenance therapy was 30 additional cycles. The primary end point was investigator-assessed progression-free survival in the veliparib-throughout group as compared with the control group, analyzed sequentially in the BRCA-mutation cohort, the cohort with homologous-recombination deficiency (HRD) (which included the BRCA-mutation cohort), and the intention-to-treat population. RESULTS: A total of 1140 patients underwent randomization. In the BRCA-mutation cohort, the median progression-free survival was 34.7 months in the veliparib-throughout group and 22.0 months in the control group (hazard ratio for progression or death, 0.44; 95% confidence interval [CI], 0.28 to 0.68; P<0.001); in the HRD cohort, it was 31.9 months and 20.5 months, respectively (hazard ratio, 0.57; 95 CI, 0.43 to 0.76; P<0.001); and in the intention-to-treat population, it was 23.5 months and 17.3 months (hazard ratio, 0.68; 95% CI, 0.56 to 0.83; P<0.001). Veliparib led to a higher incidence of anemia and thrombocytopenia when combined with chemotherapy as well as of nausea and fatigue overall. CONCLUSIONS: Across all trial populations, a regimen of carboplatin, paclitaxel, and veliparib induction therapy followed by veliparib maintenance therapy led to significantly longer progression-free survival than carboplatin plus paclitaxel induction therapy alone. The independent value of adding veliparib during induction therapy without veliparib maintenance was less clear. (Funded by AbbVie; VELIA/GOG-3005 ClinicalTrials.gov number, NCT02470585.).

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.

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.

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.

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.

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.

An increase in multi-site practices: The shifting paradigm for gynecologic cancer care delivery.

OBJECTIVE: To assess whether the number of practice sites per gynecologic oncologist (GO) and geographic access to GOs has changed over time. METHODS: This is a retrospective repeated cross-sectional study using the 2015-2019 Physician Compare National File. All GOs in the 50 United States and Washington, DC, who had completed at least one year of practice were included in the study. All practice sites with complete addresses were included. Linear regression analyses estimated trends in GOs' number of practice sites and geographic dispersion of practice sites. Secondary analyses assessed temporal trends in the number of geographic areas served by at least one GO. RESULTS: Although there was no significant change in the number of GOs from 2015 to 2019 (n = 1328), there was a significant increase in the number of practice sites (881 to 1416, p = 0.03), zip codes (642 to 984, p = 0.03), HSAs (404 to 536, p = 0.04), and HRRs (218 to 230, p = 0.03) containing a GO practice. The mean number of practice sites (1.64 versus 2.13, p < 0.001) and dispersion of practice sites (0.03 versus 0.43 miles, p = 0.049) per GO increased significantly. CONCLUSIONS: Between 2015 and 2019, an increasing number of GOs have multi-site practices, and more geographic regions contain a GO practice. Improvements in geographic access to GOs may represent improved access to care for many women in the US, but its effect on patients, physicians, and geographic disparities is unknown.

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.

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.

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.

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.

Performance of lymphadenectomy for apparent early stage malignant ovarian germ cell tumors in the era of platinum-based chemotherapy.

OBJECTIVES: To investigate the patterns of use and impact of lymphadenectomy (LND) on overall survival (OS) of patients with apparent early stage malignant ovarian germ cell tumors (MOGCTs). METHODS: Patients with apparent stage I MOGCT diagnosed between 2004 and 2015 were drawn from the National Cancer Database. The performance of LND was assessed from the pathology report. OS was evaluated using Kaplan-Meier curves, and compared with the log-rank test. A multivariate Cox analysis was performed to control for confounders. RESULTS: A total of 2774 patients were identified; 1426 (51.4%) underwent LND. The median number of lymph nodes (LN) removed was 9 (range 1-81); 48.3% of patients had at least 10 lymph nodes removed. The rate of regional lymph node metastasis was 10.3% (147 patients). There was no difference in OS, between patients who did (n = 1287) and did not (n = 1210) undergo LND, p = 0.81; 5-yr OS rates were 96.5% and 97.6% respectively. After controlling for patient age, insurance status, histology, presence of medical comorbidities, and receipt of chemotherapy, the performance of LND was not associated with better survival (HR: 1.33, 95% CI: 0.82, 2.14). CONCLUSIONS: While LN metastasis is common in apparent early stage MOGCTs, the performance of LND was not associated with a survival benefit.

Adjuvant chemotherapy for early stage endometrioid ovarian carcinoma: An analysis of the National Cancer Data Base.

INTRODUCTION: The benefit of adjuvant chemotherapy for Stage IC grade 1 and stage IA/IB grade 2 endometrioid ovarian adenocarcinoma (EOOC) remains unclear as the NCCN guidelines recommend either observation only or adjuvant chemotherapy. Therefore, we sought to determine whether patients with stage I EOOC had improved overall survival (OS) following receipt of adjuvant chemotherapy. METHODS: Patients with pathological stage I ovarian endometrioid adenocarcinoma diagnosed between 2004 and 2014 were identified from the National Cancer Database. Demographics, pathologic factors including tumor grade, and treatment information including receipt of adjuvant chemotherapy were collected. The impact of chemotherapy on OS was evaluated with Kaplan-Meier curves, and compared with log-rank tests. Multivariate Cox analysis was performed to control for confounders. RESULTS: A total of 4538 patients were identified and the median age was 55 years The rate of adjuvant chemotherapy use was 50.9%. Higher rates were noted among patients with stage IC and grade 3 tumors. Following stratification by tumor grade, substage and extent of lymphadenectomy, adjuvant chemotherapy was associated with a survival benefit for patients with grade 2 tumors who did not undergo (stage IA/IB: 95.7% vs 83%, p = 0.038; stage IC: 84.5% vs 84.8%, p = 0.39) or had limited lymphadenectomy (stage IA/IB: 96% vs 89.5%, p = 0.03; stage IC: 97.2% vs 83.9%, p = 0.001). A survival difference was also seen for patients with grade 3 tumors who did not undergo lymphadenectomy but did not reach statistical significance. CONCLUSION: Adjuvant chemotherapy was associated with an overall survival benefit for patients with inadequately-staged, grade 2 stage I ovarian endometrioid adenocarcinoma. A possible benefit for inadequately-staged patients with grade 3 tumors cannot be excluded.

Radical hysterectomy is not associated with a survival benefit for patients with stage II endometrial carcinoma.

OBJECTIVE: To evaluate the role of radical hysterectomy in the management of patients with stage II endometrial carcinoma. MATERIALS: Patients diagnosed between 2004 and 2015, with stage II (based on the revised FIGO staging) endometrial carcinoma who had hysterectomy and regional lymph node surgery were identified in the National Cancer Database. Those who had radical or modified radical (RH), or total hysterectomy (TH) were selected. Overall survival (OS) was assessed with 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 7552 patients who met the inclusion criteria were identified. Rate of RH was 10.5%. Those who underwent RH had longer hospital stay (median 3 vs 2 days, p < 0.001) and a higher 90-day (1.6% vs 0.8%, p = 0.05) mortality. There was no difference in OS between patients who had RH (n = 712) and SH (n = 5955) (p = 0.62); 5-year survival rates were 77.4% and 76.9%, respectively. After controlling for patient age (<65, ≥65 years), race (white, black, other/unknown), insurance status, presence of comorbidities, tumor size (<5, ≥5 cm, unknown), histology (endometrioid, non-endometrioid), performance of adequate lymphadenectomy, and receipt of adjuvant chemotherapy and radiation therapy, performance of radical hysterectomy was not associated with better survival (HR: 1.01, 95% CI: 0.85, 1.21). CONCLUSIONS: Radical hysterectomy was not associated with a survival benefit in a cohort of patients with stage II endometrial carcinoma.

Utilization and survival outcomes of sequential, concurrent and sandwich therapies for advanced stage endometrial cancers by histology.

OBJECTIVE: To determine the impact on overall survival (OS) of different modalities of adjuvant therapy for the treatment of stage III endometrial cancer (EC), by histology. METHODS: Stage 3 endometrioid (EAC), serous (SER), clear cell (CC), and carcinosarcoma (CS) patients who underwent primary surgical staging from 2000 to 2013 were identified in SEER-Medicare. Adjuvant therapy was defined by a 4-arm comparator grouping (none; RT only; CT only; combination RT), as well as by an 8-arm comparator grouping (none; RT only; CT only; concurrent CT-RT; concurrent CT-RT then CT; Serial CT-RT; serial RT-CT; sandwich). Modality of RT and CT were analyzed using Kaplan-Meier estimates, log rank tests, and multivariable cox modeling. RESULTS: Of 2870 cases identified (1798 EAC, 606 SER, 118 CC, 348 CS), 31.5% received no adjuvant therapy. The remainder received RT or CT alone, concurrent RT-CT, serial or sandwich modalities. OS differed by adjuvant therapy in adjusted and unadjusted models, when combining all histologies, and when stratifying by histology using both the 4-arm, and 8-arm comparator analyses (log rank p < .05, all). By histology, in adjusted analyses, sandwich modality had the greatest improvement in OS for endometrioid, but pairwise comparisons did not identify a superior chemotherapy-based regimen. For serous and clear cell, the greatest improvement in OS was seen with concurrent RT-CT, and for carcinosarcoma, CT alone. CONCLUSIONS: OS for advanced EC significantly differs by histology and mode of adjuvant therapy. Future studies should evaluate the efficacy of combination-based adjuvant therapy versus chemotherapy alone, by histologic subtype and molecular signature.

Effect of bilateral salpingo-oophorectomy on the overall survival of premenopausal patients with stage I low-grade endometrial stromal sarcoma; a National Cancer Database analysis.

OBJECTIVES: Investigate the prevalence of bilateral salpingo-oophorectomy (BSO) for women ≤50 years with early stage low-grade endometrial stromal sarcoma (LGESS) and its impact on overall survival (OS). METHODS: Women ≤50 years, diagnosed with stage I LGESS and managed with hysterectomy between 2004 and 2015 were identified from the National Cancer Database. Patient demographics were recorded and compared with the chi-square test. OS for patients diagnosed between 2004 and 2014 with at least one month of follow-up was assessed using Kaplan-Meier curves, and compared with the log-rank test. RESULTS: A total 743 patients with a median age of 44 years met the inclusion criteria. Use of radiatiotherapy (9%), chemotherapy (0.8%) and hormonal therapy (11%) was infrequent. BSO was performed in 541 (72.8%) patients. Patients who had ovarian preservation (OP) were younger (median age 43 vs 45 years, p < 0.001), less likely to have comorbidities (6.9% vs 12.4%, p = 0.034), or undergo LND (30.7% vs 44.4%, p = 0.001). There were no differences between the two groups in terms of substage or patient race. Five year OS rates for patients who did (n = 490) and did not (n = 191) undergo BSO were 96.2% and 97.1% and there was no difference in OS, p = 0.50. Even after controlling for presence of comorbidities performance of BSO was not associated with better survival (HR: 1.28, 95% CI: 0.51, 3.19). CONCLUSIONS: Ovarian function was preserved in approximately one third of women ≤50 years with stage I LGESS with no clear detriment to overall survival. As BSO is associated with long term health effects in this patient population OP could be considered in selected women with stage I LGESS.

Adjuvant treatment for patients with FIGO stage I uterine serous carcinoma confined to the endometrium.

OBJECTIVES: The role of adjuvant treatment for early-stage uterine serous carcinoma is not defined. The goal of this study was to investigate the impact of adjuvant treatment on survival of patients with tumors confined to the endometrium. METHODS: Patients diagnosed with stage I uterine serous carcinoma with no myometrial invasion between January 2004 and December 2015 who underwent hysterectomy with at least 10 lymph nodes removed were identified from the National Cancer Database. Adjuvant treatment patterns defined as receipt of chemotherapy and/or radiotherapy within 6 months from surgery were investigated and overall survival was evaluated using Kaplan-Meier curves, and compared with the log-rank test for patients with at least one month of follow-up. A Cox analysis was performed to control for confounders. RESULTS: A total of 1709 patients were identified; 833 (48.7%) did not receive adjuvant treatment, 348 (20.4%) received both chemotherapy and radiotherapy, 353 (20.7%) received chemotherapy only, and 175 (10.2%) received radiotherapy only. Five-year overall survival rates for patients who did not receive adjuvant treatment (n=736) was 81.9%, compared with 91.3% for those who had chemoradiation (n=293), 85.1% for those who received radiotherapy only (n=143), and 91.0% for those who received chemotherapy only (n=298) (p<0.001). After controlling for age, insurance status, type of treatment facility, tumor size, co-morbidities, and history of another tumor, patients who received adjuvant chemotherapy (HR 0.64, 95% CI 0.42, 0.96), or chemoradiation (HR 0.55, 95% CI 0.35, 0.88) had better survival compared with those who did not receive any adjuvant treatment, while there was no benefit from radiotherapy alone (HR 0.85, 95% CI 0.53, 1.37). There was no survival difference between chemoradiation and chemotherapy only (HR 1.15, 95% CI 0.65, 2.01). CONCLUSION: Adjuvant chemotherapy (with or without radiotherapy) is associated with a survival benefit for uterine serous carcinoma confined to the endometrium.

Advanced stage primary mucinous ovarian carcinoma. Where do we stand ?

OBJECTIVE: To evaluate factors associated with survival of patients with advanced stage mucinous ovarian carcinoma (MOC) using a large multi-institutional database. METHODS: Patients diagnosed between 2004 and 2014 with advanced stage (III-IV) MOC were identified within the National Cancer Database. Those without a personal history of another primary tumor who received cancer-directed surgery with a curative intent were selected for further analysis. Overall survival (OS) was evaluated with Kaplan-Meier curves, and compared with the log-rank test. Multivariate Cox analysis was performed to identify independent predictors of survival. RESULTS: A total of 1509 patients with a median age of 59 years (IQR 20) met the inclusion criteria: stage III (n = 1045, 69.3%) and stage IV disease (n = 464, 30.7%). Patients who received chemotherapy (n = 1065, 70.6%) had better OS compared to those who did not (n = 385, 25.5%), (median OS 15.44 vs 5.06 months, p < 0.001). The type of reporting facility (p = 0.65) and the year of diagnosis (p = 0.27) were not associated with OS. Presence of residual disease was strongly associated with OS (p < 0.001). After controlling for confounders, the administration of chemotherapy (HR 0.63, 95% CI 0.55, 0.72) was associated with better survival. CONCLUSION: Advanced stage MOC has an extremely poor prognosis. Patients who received chemotherapy had a small improvement in survival. Every effort to achieve complete gross resection should be performed. Given no improvement in survival outcomes over time, there is an eminent need for novel treatment options.

Adjuvant chemotherapy is not associated with a survival benefit for patients with early stage mucinous ovarian carcinoma.

OBJECTIVE: Primary mucinous ovarian carcinoma (MOC) is a rare histologic subtype of ovarian cancer. The benefit of adjuvant chemotherapy for patients with MOC is unclear. PATIENTS AND METHODS: Patients diagnosed with stage I mucinous ovarian cancer (MOC) between 2004 and 2015 were identified from the U.S National Cancer Database. Those with a history of another primary tumor were excluded. Factors independently associated with the receipt of chemotherapy were identified using logistic regression. Impact of chemotherapy on overall survival (OS) for patients diagnosed between 2004 and 2014 was assessed using was Kaplan-Meier curves, and compared with the log-rank test. A multivariate Cox analysis was performed to control for confounders. RESULTS: We identified 4811 patients with a median age at diagnosis of 51 years (IQR: 21). Chemotherapy was administered to 1488 (30.9%) patients; 20.2% and 60.2% for those with stage IA/IB and IC respectively, p < 0.001. Stage IC, larger tumor size, and high tumor grade, were associated with the receipt of chemotherapy. There was no difference in OS between patients who did (n = 1322) and did not (n = 2920) receive chemotherapy, p = 0.17; 5-year OS rate was 86.8% vs 89.7%, respectively. No difference was noted following stratification by substage (p = 0.46 for IA/IB and p = 0.11 for IC). After controlling for substage, patient age, type of insurance, tumor grade, performance of lymphadenectomy and the presence of co-morbidities, the administration of chemotherapy was not associated with better survival (HR:1.18, 95% CI: 0.85, 1.64). CONCLUSIONS: In a large cohort of patients with stage I MOC, receiving chemotherapy was not associated with a survival benefit.