Metronidazole and cefazolin vs cefazolin alone for surgical site infection prophylaxis in gynecologic surgery at a comprehensive cancer center.

BACKGROUND: Surgical site infection is one of the most common complications of gynecologic cancer surgery. Current guidelines recommend the administration of cefazolin preoperatively to reduce surgical site infection rates for patients undergoing clean-contaminated surgeries such as hysterectomy. OBJECTIVE: To evaluate the impact of a quality improvement project adding metronidazole to cefazolin for antibiotic prophylaxis on surgical site infection rate for women undergoing gynecologic surgery at a comprehensive cancer center. STUDY DESIGN: This retrospective, single-center cohort study included patients who underwent surgery in the gynecologic oncology department from May 2017 to June 2023. Patients with penicillin allergies and those undergoing concomitant bowel resections and/or joint cases were excluded. The preintervention group patients had surgery from May 2017 to April 2022, and the postintervention group patients had surgery from April 2022 to June 2023. The primary outcome was a 30-day surgical site infection rate. Sensitivity analyses were performed to compare surgical site infection rates on the basis of actual antibiotics received and for those who had a hysterectomy. Factors independently associated with surgical site infection were identified using a multivariable logistic regression model adjusting for confounding variables. RESULTS: Of 3343 patients, 2572 (76.9%) and 771 (23.1%) were in the pre-post intervention groups, respectively. Most patients (74.7%) had a hysterectomy performed. Thirty-four percent of cases were for nononcologic (benign) indications. Preintervention patients were more likely to receive appropriate preoperative antibiotics (95.6% vs 90.7%; P<.001). The overall surgical site infection rate before the intervention was 4.7% compared with 2.6% after (P=.010). The surgical site infection rate for all patients who underwent hysterectomy was 4.9% (preintervention) vs 2.8% (postintervention) (P=.036); a similar trend was seen for benign cases (4.4% vs 2.4%; P=.159). On multivariable analysis, the odds ratio for surgical site infection was 0.49 (95% confidence interval, 0.38-0.63) for the postintervention compared with the preintervention group (P<.001). In a sensitivity analysis (n=3087), the surgical site infection rate was 4.5% for those who received cefazolin alone compared with 2.3% for those who received cefazolin plus metronidazole, with significantly decreased odds of surgical site infection for the cefazolin plus metronidazole group (adjusted odds ratio, 0.40 [95% confidence interval, 0.30-0.53]; P<.001). Among only those who had a hysterectomy performed, the odds of surgical site infection were significantly reduced for those in the postintervention group (adjusted odds ratio, 0.63 [95% confidence interval, 0.47-0.86]; P=.003). CONCLUSION: The addition of metronidazole to cefazolin before gynecologic surgery decreased the surgical site infection rate by half, even after accounting for other known predictors of surgical site infection and differences in practice patterns over time. Providers should consider this combination regimen in women undergoing gynecologic surgery, especially for cases involving hysterectomy.

Efficacy, safety, and feasibility of Apixaban for postoperative venous thromboembolism prophylaxis following open gynecologic cancer surgery at a comprehensive cancer center.

OBJECTIVES: To evaluate safety, efficacy, and feasibility of apixaban for postoperative venous thromboembolism (VTE) prophylaxis following open gynecologic cancer surgery at a comprehensive cancer center. METHODS: This retrospective, cohort study included patients with gynecologic cancer who underwent open surgery between 3/2021 and 3/2023 and received 28-day postoperative VTE prophylaxis. Patients on therapeutic anticoagulation preoperatively were excluded. Predictors of 90- and 30-day VTE and 30-day bleeding events were determined using multivariable logistic regression, adjusting for known confounders. RESULTS: 452 patients were included in the cohort: 348 received apixaban and 104 received enoxaparin. Those who received enoxaparin were more likely to be American Society of Anesthesiologists class III/IV (compared to I/II) (p = 0.033), current or former smokers (p = 0.012) and have a higher BMI (p < 0.001), Charlson Comorbidity Index (p = 0.005), and age (p = 0.046). 30-day VTE rate was significantly lower in the apixaban group (0.6%) compared to the enoxaparin group (6.2%) (adjusted OR 0.13, 95% CI 0.03-0.56; p = 0.006). 90-day VTE rate was 2.7% and 6.2% in the apixaban and enoxaparin groups, respectively (adjusted OR 0.85, 95% CI 0.38-1.92; p = 0.704). Major bleeding complications (2.4% vs. 2.0%) and minor bleeding complications (0.9% vs. 3.0%) were similar in the apixaban and enoxaparin groups, respectively, on multivariate analyses. The median patient out of pocket cost was $10 (IQR 0.0-40.0) for apixaban and $20 (IQR 3.7-67.7) for enoxaparin (p = 0.001). CONCLUSIONS: Our findings along with previously published data suggest that apixaban should be considered the standard of care for VTE prophylaxis in patients undergoing open surgery for gynecologic malignancies.

Neuroendocrine neoplasms of the ovary: a review of 63 cases.

OBJECTIVE: To describe the clinicopathological characteristics and survival outcomes of ovarian neuroendocrine neoplasms from a curated registry. METHODS: This is a retrospective cross-sectional study of patients in our registry with confirmed ovarian neuroendocrine neoplasms. We excluded patients with small cell carcinoma not otherwise specified, small cell hypercalcemic type, and those with neuroendocrine 'features' or 'differentiation.' Clinicopathological characteristics were described in two separate groups: patients with carcinoid tumors and patients with neuroendocrine carcinomas. Progression-free and overall survival were estimated with the Kaplan-Meier product-limit estimator in these two groups, and multivariable analysis was done to identify predictors of survival for neuroendocrine carcinomas only. RESULTS: A total of 63 patients met inclusion criteria, 13 (21%) with carcinoid tumors and 50 (79%) with neuroendocrine carcinomas. In the carcinoid tumor group, one patient (8%) was misdiagnosed. Two patients (15%) had a recurrence and the 5-year overall survival rate was 80% (95% CI 45% to 100%), with a lower bound of the median survival of 4.8 years (95% CI). In the neuroendocrine carcinoma group, 23 patients (46%) were misdiagnosed, 16 of whom (69%) received therapy with the presumption of a non-neuroendocrine carcinoma diagnosis. Thirty patients (60%) had a recurrence, and the 5-year overall survival rate was 24% (10%, 38%), with a median survival of 1.6 years (1.3, 3.3). Patients with carcinomas stage III or IV had an increased risk of progression/recurrence (HR=5.6; 95% CI 1.9 to 17.0) and death (HR=8.1; 95% CI 2.2 to 29.7) compared with those with stage I or II. Pure histology was associated with an increased risk of progression/recurrence (HR=2.3; 95% CI 1.0 to 5.2) compared with admixed histology. CONCLUSION: Most patients had neuroendocrine carcinomas, which were associated with a higher recurrence rate and worse survival than carcinoid tumors. A high proportion of patients in both groups were initially misdiagnosed, and a new association with endometrial hyperplasia was observed. Neuroendocrine admixed histology is associated with a higher risk of progression.

Impact of pelvic radiation therapy in patients with early neuroendocrine cervical carcinoma and no residual disease in the radical hysterectomy specimen: a NeCTuR study.

OBJECTIVE: The impact of adjuvant pelvic radiation therapy on the rate and location of recurrences was evaluated in patients with early-stage (IA1-IB2) neuroendocrine cervical carcinoma who underwent prior conization or polypectomy with no residual disease and negative nodes in the subsequent upfront radical hysterectomy specimen. As a secondary objective, disease-free and overall survival were analyzed. METHODS: We searched the Neuroendocrine Cervical Tumor Registry (NeCTuR) to identify patients with clinical early-stage neuroendocrine cervical carcinoma with no residual disease in the specimen from upfront radical surgery and negative nodes. Patients who received pelvic radiation therapy were compared with those who did not, regardless of whether they received adjuvant chemotherapy. RESULTS: Twenty-seven patients met the inclusion criteria, representing 17% of all patients with clinical early-stage disease who underwent upfront radical hysterectomy included in the NeCTuR registry. The median age was 36.0 years (range 26.0-51.0). Six (22%) patients had stage IA, 20 (74%) had stage IB1, and one (4%) had stage IB2 disease. Seven (26%) patients received adjuvant radiation therapy and 20 (74%) did not. All seven patients in the radiation group and 14 (70%) in the no-radiation group received adjuvant chemotherapy (p=0.16). Fifteen percent (4/27) of patients had a recurrence, 14% (1/7) in the radiation group and 15% (3/20) in the no-radiation group (p=0.99). In the radiation group the recurrence was outside the pelvis, and in the no-radiation group, 67% (2/3) recurred outside the pelvis and 33% (1/3) recurred both inside and outside the pelvis (p=0.99). In the radiation group the 5-year disease-free and overall survival rates were 100% while, in the no-radiation group, the 5-year disease-free and overall survival rates were 81% (95% CI 61% to 100%) (p=0.99) and 80% (95% CI 58% to 100%) (p=0.95), respectively. CONCLUSIONS: For patients with no residual disease and negative nodes in the upfront radical hysterectomy specimen, our study did not find that pelvic radiation therapy improves survival.

Clinicopathologic characteristics, oncologic outcomes, and prognostic factors in neuroendocrine cervical carcinoma: a Neuroendocrine Cervical Tumor Registry study.

OBJECTIVE: To evaluate clinicopathologic features and oncologic outcomes of patients with neuroendocrine cervical carcinoma in an institutional neuroendocrine cervical tumor registry. METHODS: Retrospective study including patients with neuroendocrine cervical carcinomas diagnosed between 1986 and 2022. Patients were categorized into International Federation of Gynecology and Obstetrics 2018 stage groups: early-stage (IA1-IB2, IIA1); locally advanced (IB3, IIA2-IVA); and advanced (IVB). Clinicopathologic characteristics and oncologic outcomes were evaluated by stage. Survival was compared between patients diagnosed in 1986-2003 and those diagnosed in 2004-2016. Progression-free and overall survival were estimated using the Kaplan-Meier product-limit estimator. RESULTS: A total of 453 patients was included, 133 (29%) with early-stage, 226 (50%) with locally advanced, and 94 (21%) with advanced disease. Median age was 38 years (range 21-93). Sixty-nine percent (306/453) had pure and 32% (146/453) had mixed histology. The node positivity rate (surgical or radiological detection) was 19% (21/108) for tumors ≤2 cm, 37% (39/105) for tumors >2 to ≤4 cm, and 61% (138/226) for tumors >4 cm (p<0.0001). After primary treatment, rates of complete response were 86% (115/133) for early-stage, 65% (147/226) for locally advanced, and 19% (18/94) for advanced disease (p<0.0001). The recurrence/progression rate was 43% for early-stage, 69% for locally advanced, and 80% for advanced disease (p<0.0001). Five-year progression-free and overall survival rates were 59% (95% CI 50% to 68%) and 71% (95% CI 62% to 80%), respectively, for early-stage, 28% (95% CI 22% to 35%) and 36% (95% CI 29% to 43%), respectively, for locally advanced, and 6% (95% CI 0% to 11%) and 12% (95% CI 5% to 19%), respectively, for advanced disease. For early-stage disease, the 5-year progression-free survival rate was 68% for tumors ≤2 cm and 43% for tumors >2 to ≤4 cm (p=0.0013). Receiving cisplatin/carboplatin plus etoposide (HR=0.33, 95% CI 0.17 to 0.63, p=0.0008) and receiving curative radiotherapy (HR=0.32, 95% CI 0.17 to 0.6, p=0.0004) were positive predictors of survival for patients with advanced disease. CONCLUSION: Among patients with neuroendocrine cervical carcinomas, overall survival is favorable for patients with early-stage disease. However, most patients present with locally advanced disease, and overall survival remains poor in this subgroup. For patients with advanced disease, receiving cisplatin/carboplatin plus etoposide and curative radiation therapy is associated with improved overall survival.

RB1 alteration and poor prognosis in women with high-grade neuroendocrine carcinoma of the uterine cervix: a NeCTuR study.

OBJECTIVE: To describe the gene alteration status in high-grade neuroendocrine cervical carcinoma (NECC) specimens and to explore the potential association of unique gene alterations with survival. METHODS: Results from tumor-based molecular testing on specimens from women with high-grade NECC in the Neuroendocrine Cervical Tumor Registry were reviewed and analyzed. Tumor specimens could be from primary or metastatic sites and obtained at initial diagnosis, during treatment, or at recurrence. RESULTS: Molecular testing results were available for 109 women with high-grade NECC. The genes most frequently mutated were PIK3CA (mutated in 18.5% of patients), TP53 (17.4%), and MYC (14.5%). Other targetable alterations identified were alterations in KIT (7.3%), KRAS (7.3%), and PTEN (7.3%). Women with tumors having an RB1 alteration (6.4%) had a median overall survival (OS) of 13 months, compared to 26 months for women with tumors that did not have an RB1 alteration (p=0.003). None of the other genes evaluated were shown to be associated with OS. CONCLUSION: Although no individual alteration was found in a majority of tumor specimens from patients with high-grade NECC, a large proportion of women with this disease will have at least one targetable alteration. Treatments based on these gene alterations may offer additional targeted therapies for women with recurrent disease, who currently have very limited therapeutic options. Patients with tumors that harbor RB1 alterations have decreased OS.

Combination therapy with topotecan, paclitaxel, and bevacizumab improves progression-free survival in patients with recurrent high-grade neuroendocrine cervical cancer: a Neuroendocrine Cervical Tumor Registry (NeCTuR) study.

BACKGROUND: Recurrent high-grade neuroendocrine cervical cancer has a very poor prognosis and limited active treatment options. OBJECTIVE: This study aimed to evaluate the efficacy of the 3-drug regimen of topotecan, paclitaxel, and bevacizumab in women with recurrent high-grade neuroendocrine cervical cancer. STUDY DESIGN: This retrospective cohort study used data from the Neuroendocrine Cervical Tumor Registry (NeCTuR), which include data abstracted directly from medical records of women diagnosed with high-grade neuroendocrine carcinoma of the cervix from English- and Spanish-speaking countries. The study compared women with recurrent high-grade neuroendocrine cervical cancer who received the topotecan, paclitaxel, and bevacizumab regimen as first- or second-line therapy for recurrence and women with recurrent high-grade neuroendocrine cervical cancer who received chemotherapy but not the topotecan, paclitaxel, and bevacizumab regimen. Patients continued chemotherapy until disease progression or the development of unacceptable toxic effects. Progression-free survival from the start of therapy for recurrence to the next recurrence or death, overall survival from the first recurrence, and response rates were evaluated. RESULTS: The study included 62 patients who received the topotecan, paclitaxel, and bevacizumab regimen as first- or second-line therapy for recurrence and 56 patients who received chemotherapy but not the topotecan, paclitaxel, and bevacizumab regimen for recurrence. The median progression-free survival rates were 8.7 months in the topotecan, paclitaxel, and bevacizumab regimen group and 3.7 months in the non-topotecan, paclitaxel, and bevacizumab regimen group, with a hazard ratio for disease progression of 0.27 (95% confidence interval, 0.17-0.48; P<.0001). In the topotecan, paclitaxel, and bevacizumab regimen group, 15% of patients had stable disease, 39% of patients had a partial response, and 18% of patients had a complete response. Compared with patients in the non-topotecan, paclitaxel, and bevacizumab regimen group, significantly more patients in the topotecan, paclitaxel, and bevacizumab regimen group remained on treatment at 6 months (31% vs 67%, respectively; P=.0004) and 1 year (9% vs 24%, respectively; P=.02). The median overall survival rates were 16.8 months in the topotecan, paclitaxel, and bevacizumab regimen group and 14.0 months in the non-topotecan, paclitaxel, and bevacizumab regimen group, with a hazard ratio for death of 0.87 (95% confidence interval, 0.55-1.37). CONCLUSION: Combination therapy with topotecan, paclitaxel, and bevacizumab was an active regimen in women with recurrent high-grade neuroendocrine cervical cancer and improved progression-free survival while decreasing the hazard ratio for disease progression.

Definitive pelvic radiation therapy improves survival in stage IVB neuroendocrine cervical carcinoma: A NeCTuR study.

OBJECTIVE: To evaluate the survival impact of adding definitive pelvic radiation therapy (RT) to chemotherapy among patients with stage IVB neuroendocrine cervical carcinoma (NECC). METHODS: We retrospectively studied patients with FIGO 2018 stage IVB NECC diagnosed during 1998-2020 who received chemotherapy with or without definitive whole pelvic RT (concurrent or sequential). Demographic, oncologic, and treatment characteristics were summarized. Progression-free (PFS) and overall survival (OS) were plotted using the Kaplan-Meier method, and hazard ratios (HRs) were calculated using Cox regression. RESULTS: The study included 71 patients. Median age was 43 years (range, 24-75). Fifty-nine patients (83%) had pure neuroendocrine histology, and 57 (80%) had pretreatment tumor size >4 cm. Fifty-six patients (79%) received chemotherapy alone with (n = 15) or without (n = 41) palliative pelvic RT, and 15 (21%) received chemotherapy and definitive pelvic RT (chemo+RT). Median follow-up time was 20.1 months (range, 11.3-170.3) for the chemo+RT group and 13.5 months (range, 0.9-73.6) for the chemotherapy-alone group. Median PFS was 10.3 months (95% CI, 7.5-∞) for the chemo+RT group vs 6.6 months (95% CI, 6.1-8.7) for the chemotherapy-alone group (p = 0.0097). At 24 months, the PFS rate was 24% for chemo+RT vs 7.8% for chemotherapy alone. Median OS was 20.3 months (95% CI, 18.5-∞) for the chemo+RT group vs 13.6 months (95% CI, 11.3-19.2) for the chemotherapy-alone group (p = 0.0013). At 24 months, the OS rate was 49.2% for chemo+RT vs 21.5% for chemotherapy alone. In a Cox regression model, definitive RT was associated with improved PFS (HR, 0.44; 95% CI, 0.23-0.83; p = 0.0119) and OS (HR, 0.31; 95% CI, 0.14-0.65; p = 0.0022). CONCLUSIONS: Addition of definitive pelvic RT to chemotherapy may improve survival in patients with stage IVB NECC.

Comparison of Internal Patient Satisfaction Scores at a Cancer Center With Star Ratings on Online Physician-Rating Websites.

PURPOSE: Patients have been increasingly using physician-rating websites (PRWs); however, few studies have analyzed the validity of star ratings on PRWs. We aimed to compare PRW patient satisfaction scores with internally generated patient satisfaction scores (internal scores) of physicians at a large quaternary cancer center. METHODS: We collected internal scores and PRW scores for physicians at MD Anderson Cancer Center. Internal scores were based on patient responses to the Clinician and Group Consumer Assessment of Healthcare Providers and Systems patient experience (CG-CAHPS) survey. Only physicians with an internal score on the basis of ≥ 30 patient reviews were included. The median numbers of reviews and median scores were compared between internal data and four PRWs (Google, HealthGrades, Vitals, and WebMD). Both internally and on PRWs, possible scores ranged from 1 (least satisfied) to 5 (most satisfied). RESULTS: Of 640 physicians with an internal score, 510 (79.7%) met the inclusion criteria. For these 510 physicians, the median (IQR) number of internal reviews was 49.5 (30-93) and the median (IQR) internal score was 4.89 (4.81-4.93); the median number of reviews on PRWs ranged from 2 to 7, and the median score on PRWs ranged from 4.40 to 5.00. No physician had an internal score < 4, but the proportions with score < 4 on PRWs ranged from 16% to 30%. CONCLUSION: Internal patient satisfaction scores were higher and calculated from more reviews than PRW patient satisfaction scores and correlated weakly with PRW scores. Given that patients rely on PRWs when evaluating potential physicians, we recommend publishing internal scores online to give patients more complete information regarding physician performance.

Role of radical hysterectomy in patients with early-stage high-grade neuroendocrine cervical carcinoma: a NeCTuR study.

OBJECTIVE: Patients with early-stage, high-grade neuroendocrine cervical carcinoma typically undergo radical hysterectomy with pelvic lymphadenectomy followed by adjuvant radiotherapy and/or chemotherapy. To explore the role of radical surgery in patients with this disease, who have a high likelihood of undergoing postoperative adjuvant therapy, we aimed to determine the rate of parametrial involvement and the rate of parametrial involvement without other indications for adjuvant treatment in these patients. METHODS: We retrospectively studied patients in the Neuroendocrine Cervical Tumor Registry (NeCTuR) at our institution to identify those with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IA1-IB2, high-grade neuroendocrine cervical carcinoma who underwent up-front radical surgery with or without adjuvant therapy. RESULTS: One hundred patients met the inclusion criteria. The median age was 35 years (range 22-65), and 51% (51/100) had pure high-grade neuroendocrine carcinoma. No patient had a tumor >4 cm or suspected parametrial or nodal disease before surgery. Ten patients (10%) had microscopic parametrial compromise in the final surgical specimens. Ninety-four (94%) patients underwent nodal assessment, and 19 (19%) had positive nodes. Ten patients underwent both sentinel lymph node biopsy and pelvic lymphadenectomy, and none had false-negative findings. Patients with parametrial compromise were more likely to have positive pelvic nodes (80% vs 12%, p<0.0001), and a positive vaginal margin (20% vs 1%, p=0.03). All patients with parametrial compromise had lymphovascular space invasion (100% vs 73%, p=0.10). Of the 100 patients, 95 (95%) were recommended adjuvant therapy and 89 (89%) were known to have received it. Adjuvant pelvic radiotherapy reduced the likelihood of local recurrence by 62%. CONCLUSIONS: In carefully selected patients with high-grade neuroendocrine cervical carcinoma, the rate of microscopic parametrial involvement is 10%. As most patients receive adjuvant treatment, we hypothesize that simple hysterectomy may be adequate when followed by adjuvant radiotherapy with concurrent cisplatin and etoposide followed by additional chemotherapy.

Ovarian mucinous neoplasms, intestinal type, in premenopausal patients, develop in abnormal ovaries.

Although several studies have addressed different aspects of mucinous neoplasms arising in the ovary, such as their clinicopathologic features, immunohistochemical profile, and molecular characteristics, no study has presented an analysis of the ovarian tissue where these neoplasms arise. In this study, we included 196 cases of intestinal-type ovarian mucinous neoplasms in premenopausal patients. Our main goal was to perform a rigorous examination of the ovarian tissue surrounding these neoplasms. We also reviewed the clinicopathologic features of these cases. For comparison, the background ovarian tissue in 85 cases of ovarian serous neoplasm and in 29 cases of metastatic neoplasms to the ovary, as well as 57 normal ovaries, was examined. All the patients in this study, which included those with mucinous and with serous neoplasms primary in the ovary, those with metastatic tumors to the ovaries, and those with normal ovaries, were also premenopausal. Patients affected by ovarian mucinous neoplasms ranged in age from 13 to 52 years (median = 36 years). Nulligravidity was seen in 50%, 32%, and 22% of patients with mucinous carcinomas, mucinous borderline neoplasms, and mucinous cystadenomas, respectively. Ovarian mucinous intestinal neoplasms arise in abnormal ovaries characterized by two important features: (1) an abnormal ovarian cortex, seen in 95% of the cases, which is hypocellular or with no distinction between the cellular cortex and medulla, and (2) a remarkable paucity of primordial follicles. The abnormalities detected in the background ovarian tissue might provide insights into the tumorigenesis of these neoplasms and might facilitate their distinction from metastasis to the ovary, in premenopausal patients.

Implementation of a sentinel lymph node mapping algorithm for endometrial cancer: surgical outcomes and hospital charges.

INTRODUCTION: The purpose of this study was to compare operative times, surgical outcomes, resource utilization, and hospital charges before and after the implementation of a sentinel lymph node (SLN) mapping algorithm in endometrial cancer. METHODS: All patients with clinical stage I endometrial cancer were identified pre- (2012) and post- (2017) implementation of the SLN algorithm. Clinical data were summarized and compared between groups. Total hospital charges incurred on the day of surgery were extracted from the hospital financial system for each patient and all charges were adjusted to 2017 US dollars. RESULTS: A total of 203 patients were included: 71 patients in 2012 and 130 patients in 2017. There was no difference in median age, body mass index, or stage. In 2012, 35/71 patients (49.3%) underwent a lymphadenectomy. In 2017, SLN mapping was attempted in 120/130 patients (92.3%) and at least one SLN was identified in 110/120 (91.7%). Median estimated blood loss was similar between groups (100 mL vs 75 mL, p=0.081). There was a significant decrease in both median operative time (210 vs 171 min, p=0.007) and utilization of intraoperative frozen section (63.4% vs 14.6%, p<0.0001). No significant differences were noted in intraoperative (p=1.00) or 30 day postoperative complication rates (p=0.30). The median total hospital charges decreased by 2.73% in 2017 as compared with 2012 (p=0.96). DISCUSSION: Implementation of an SLN mapping algorithm for high- and low-risk endometrial cancer resulted in a decrease in both operative time and intraoperative frozen section utilization with no change in surgical morbidity. While hospital charges did not significantly change, further studies are warranted to assess the true cost of SLN mapping.

Prospective pilot trial with combination of propranolol with chemotherapy in patients with epithelial ovarian cancer and evaluation on circulating immune cell gene expression.

OBJECTIVE: To determine the feasibility of pharmacologic beta-adrenergic blockade in women with newly diagnosed stage II-IV epithelial ovarian cancer (EOC) throughout primary treatment. METHODS: Patients initiated propranolol prior to beginning chemotherapy or surgery. Feasibility was assessed as proportion able to complete 6 chemotherapy cycles while on adrenergic suppression. Descriptive statistics summarized surveys, and paired changes were analyzed using signed rank tests. Random-intercept Tobit models examined immune response. RESULTS: Median age was 59.9; 88.5% were stage IIIC/IV; and 38.5% underwent primary debulking. Thirty-two patients were enrolled; 3 excluded because they never took propranolol; an additional 3 didn't meet inclusion criteria, leaving 26 evaluable. Eighteen of 26 (69%), 90% credible interval (CI) of 53-81%, completed 6 chemotherapy cycles plus propranolol (an 82% posterior probability that the true proportion of success is ≥60%). Among the 23 patients with baseline and six month follow up data, overall QOL, anxiety, and depression improved (P < 0.05) and leukocyte expression of pro-inflammatory genes declined (P = 0.03) after completion of therapy. Decrease from baseline of serum IL-6 and IL-8 preceded response to chemotherapy (P < 0.0014). Change from baseline IL-10 preceded complete response. CONCLUSION: Use of propranolol during primary treatment of EOC is feasible and treatment resulted in decrease in markers of adrenergic stress response. In combination with chemotherapy, propranolol potentially results in improved QOL over baseline.

Frequency and characteristics of drowsiness, somnolence, or daytime sleepiness in patients with advanced cancer.

INTRODUCTION: Cancer-related drowsiness (CRD) is a distressing symptom in advanced cancer patients (ACP). The aim of this study was to determine the frequency and factors associated with severity of CRD. We also evaluated the screening performance of Edmonton Symptom Assessment Scale-drowsiness (ESAS-D) item against the Epworth Sedation Scale (ESS). METHOD: We prospectively assessed 180 consecutive ACP at a tertiary cancer hospital. Patients were surveyed using ESAS, ESS, Pittsburgh Sleep Quality Index, Insomnia Severity Index, and Hospital Anxiety Depression Scale. RESULT: Ninety of 150 evaluable patients had clinically significant CRD (ESS); median (interquartile ratio): ESS. 11 (7-14); ESAS-D. 5 (2-6); Pittsburgh Sleep Quality Index. 8 (5-11); Insomnia Severity Index. 13 (5-19); Stop Bang Scoring 3 (2-4), and Hospital Anxiety Depression Scale-D 6 (3-10). ESAS-D was associated with ESAS (r, p) sleep (0.38, <0.0001); pain (0.3, <0.0001); fatigue (0.51, <0.0001); depression (0.39, <0.0001); anxiety (0.44, <0.0001); shortness of breath (0.32, <0.0001); anorexia (0.36, <0.0001), feeling of well-being [(0.41, <0.0001), ESS (0.24, 0.001), and opioid daily dose (0.19, 0.01). Multivariate-analysis showed ESAS-D was associated with fatigue (odds ratio [OR] = 9.08, p < 0.0001), anxiety (3.0, p = 0.009); feeling of well-being (OR = 2.27, p = 0.04), and insomnia (OR = 2.35; p = 0.036). Insomnia (OR = 2.35; p = 0.036) cutoff score ≥3 (of 10) resulted in a sensitivity of 81% and 32% and specificity of 70% and 44% in the training and validation samples, respectively. SIGNIFICANCE OF RESULTS: Clinically significant CRD is frequent and seen in 50% of ACP. CRD was associated with severity of insomnia, fatigue, anxiety, and worse feeling of well-being. An ESAS-D score of ≥3 is likely to identify most of the ACP with significant CRD.

Characteristics and outcomes of patients with recurrent ovarian cancer undergoing early phase immune checkpoint inhibitor clinical trials.

OBJECTIVE: To describe the clinical outcomes associated with the use of checkpoint inhibitor therapy in recurrent ovarian malignancy. METHODS: Women with recurrent ovarian cancer treated with an immune checkpoint inhibitor between 1/2012 and 8/2017 were included. RECIST criteria determined disease status, and immune related adverse events (irAE) were graded per trial protocols. Predictors of response, irAE, progression free survival (PFS) and overall survival (OS) were investigated. RESULTS: Forty-four women were included with a median age of 53 years, median of 4 prior lines of chemotherapy, and most commonly high grade serous pathology (59.1%). 3 patients had partial response and 3 had pseudoprogression, for a response rate of 14.2%. In subset analysis of high grade serous (HGSOC) pathology, platinum sensitivity at time of checkpoint inhibitor therapy was correlated with response (p = 0.01). There were 28 grade 3/4 irAEs in 21 patients (47.7%). Combination therapy rather than monotherapy predicted irAE (OR 5.7, CI 1.6-20.9, p = 0.02). The most common severe irAE was elevation in hepatic or pancreatic enzymes in 12 total patients (13.6% each). Interestingly, the number of genes mutated was protective from hepatic/pancreatic AE (p = 0.02). CONCLUSIONS: While response rate was similar to prior literature, in patients with HGSOC platinum sensitivity at time of checkpoint inhibitor initiation was correlated to response. Grade 3/4 hepatic and pancreatic enzyme elevations were more common in ovarian cancer patients than has been previously reported in other tumor types. The number of genes mutated was inversely correlated to risk of this type of irAEs but not to total irAEs.

Bilateral salpingectomy with delayed oophorectomy for ovarian cancer risk reduction: A pilot study in women with BRCA1/2 mutations.

OBJECTIVE: Risk-reducing salpingo-oophorectomy (RRSO) reduces ovarian cancer risk in BRCA1/2 mutation carriers, but the adverse effects of the associated early-onset surgical menopause are problematic. Despite suggestive evidence, no data demonstrate whether bilateral salpingectomy alone lowers the risk of developing ovarian cancer in BRCA mutation carriers. We conducted a pilot study of bilateral salpingectomy with delayed oophorectomy (BS/DO) in BRCA mutation carriers to determine the safety and acceptability of the procedure. METHODS: In this prospective, multicenter, non-randomized pilot study, pre-menopausal BRCA1/2 mutation carriers aged 30 to 47 years chose screening, RRSO, or BS/DO. For those undergoing BS/DO, the delayed oophorectomy was recommended at age 40 years for BRCA1 and age 45 years for BRCA2 patients. We compared surgical and psychosocial outcomes between time points and between arms. RESULTS: Of the 43 patients enrolled, 19 (44%) chose BS/DO, 12 (28%) chose RRSO, and 12 (28%) chose screening. The cohort was 37% BRCA1 carriers and 63% BRCA2 carriers. One serous tubal intraepithelial carcinoma (STIC) was found in an RRSO patient, and no cases of occult ovarian cancers were found. There were no surgical complications. Twelve months after surgery, responses on the Cancer Worry Scale indicated decreased worry in the BS/DO (P < 0.0001) and RRSO (P = 0.01) arms, while responses on the State Anxiety Inventory indicated decreased anxiety in the BS/DO arm (P = 0.02) compared with preoperative responses. CONCLUSIONS: In this pilot study, BRCA mutation carriers who underwent bilateral salpingectomy had no intraoperative complications, were satisfied with their procedure choice, and had decreased cancer worry and anxiety after the procedure.

Incidence of Lymph Node Metastases in Women With Low-Risk Early Cervical Cancer (<2 cm) Without Lymph-Vascular Invasion.

OBJECTIVE: To determine the incidence of lymph node metastasis in women with low-risk cervical cancer stage IA2 or IB1 (<2 cm) without lymph-vascular space invasion. METHODS: A multicenter retrospective study was performed in patients who underwent radical or simple hysterectomy, conization, or trachelectomy plus pelvic lymphadenectomy for cervical cancer between January 2000 and June 2016. RESULTS: A total of 271 patients were included in the study. Median age and body mass index were 46 years (range, 23-77 years) and 24 kg/m (range, 18-48 kg/m), respectively. Twenty-two patients had stage IA2 (8.1%), and 249 (91.9%) had stage IB1. The median tumor size was 14 mm (range, 5-20 mm). Tumor grades were 1 (n = 63 [23.2%]), 2 (n = 120 [44.3%]), 3 (n = 63 [23.2%]), and unknown (25 [9.2%]). Median depth stromal invasion was 6 mm (range, 3-20 mm). Histologic subtypes included squamous (n = 171 [63.1%]), adenocarcinoma (n = 92 [33.9%]), and adenosquamous (n = 8 [3.0%]). Overall incidence of lymph node metastasis was 2.9% (n = 8). The incidence of lymph node involvement in G1, G2, and G3 was 0% (0/63), 5% (6/120), and 3.1% (2/63), respectively. No patient with stage IA2 (regardless of grade or histology) or G1 cervical cancer less than 2 cm (stage IB1) had lymph node metastasis. CONCLUSIONS: Patients with stage IA2 or IB1 (G1) with tumor size of less than 2 cm and no lymph-vascular space invasion may not need lymph node evaluation. On the other hand, 95% and 98% of patients with grade 2 or 3 tumors, respectively, could potentially undergo an unnecessary lymphadenectomy. Further studies with bigger sample size are required to confirm these results.

Genomic Rearrangement Signatures and Clinical Outcomes in High-Grade Serous Ovarian Cancer.

Background: To identify clinically relevant genomic rearrangement signatures in high-grade serous ovarian cancer (HGSOC), we conducted a retrospective analysis of sequenced HGSOC whole-tumor genomes. Methods: Clinical data and whole-genome sequencing (WGS) reads were obtained for primary HGSOC tumors sequenced by the Australian Ovarian Cancer Study (AOCS; n = 80). Genomic rearrangements were identified, and non-negative matrix factorization (NMF) was used to extract rearrangement signatures. The cohort was then dichotomized around the median signature contribution, and overall survival (OS) was analyzed. An independent cohort from The Cancer Genome Atlas (TCGA) ovarian cancer study (n = 490) was also examined. The TCGA cohort was dichotomized around the median similarity between tumor copy number profile and a prognostic rearrangement signature, and OS was analyzed. Outcomes were assessed using Kaplan-Meier and multivariable Cox regression methods. All statistical tests were two-sided. Results: We identified five genomic rearrangement signatures (Ov.RS1-5) in HGSOC. Ov.RS3 exhibited 10 kilobase to 10 megabase deletions and tandem duplications, and patients whose tumors exhibited a high contribution from Ov.RS3 had poor OS. The median OS was 22.7 months (95% confidence interval [CI] = 20.2 to 39.0 months) in the Ov.RS3-high group vs 38.2 months (95% CI = 22.7 to 69.1 months) in the Ov.RS3-low group (hazard ratio [HR] = 1.86, 95% CI = 1.12 to 3.09, P = .02). For the independent TCGA cohort, median OS rates were 38.0 months (95% CI = 35.3 to 41.4 months) in the Ov.RS3 high-similarity group vs 48.9 months (95% CI = 44.1 to 57.1 months) in the Ov.RS3 low-similarity group (HR = 1.54, 95% CI = 1.21 to 1.97, P < .001). Conclusion: A novel genomic rearrangement signature is associated with poor prognosis in HGSOC.