Homologous recombination deficiency should be tested for in patients with advanced stage high-grade serous ovarian cancer aged 70 years and over.

OBJECTIVE: Due to limited data on homologous recombination deficiency (HRD) in older patients (≥ 70 years) with advanced stage high grade serous ovarian cancer (HGSC), we aimed to determine the rates of HRD at diagnosis in this age group. METHODS: From the Phase 3 trial VELIA the frequency of HRD and BRCA1/2 pathogenic variants (PVs) was compared between younger (< 70 years) and older participants. HRD and somatic(s) BRCA1/2 pathogenic variants (PVs) were determined at diagnosis using Myriad myChoice® CDx and germline(g) BRCA1/2 PVs using Myriad BRACAnalysis CDx®. HRD was defined if a BRCA PV was present, or the genomic instability score (GIS) met threshold (GIS ≥ 33 & ≥ 42 analyzed). RESULTS: Of 1140 participants, 21% were ≥ 70 years. In total, 26% (n = 298) had a BRCA1/2 PV and HRD, 29% (n = 329) were HRD/BRCA wild-type, 33% (n = 372) non-HRD, and 12% HR-status unknown (n = 141). HRD rates were higher in younger participants, 59% (n = 476/802), compared to 40% (n = 78/197) of older participants (GIS ≥ 42) [p < 0.001]; similar rates demonstrated with GIS ≥ 33, 66% vs 48% [p < 0.001]. gBRCA PVs observed in 24% younger vs 8% of older participants (p < 0.001); sBRCA in 8% vs 10% (p = 0.2559), and HRD (GIS ≥ 42) not due to gBRCA was 35% vs 31% (p = 0.36). CONCLUSIONS: HRD frequency was similar in participants aged < 70 and ≥ 70 years (35% vs 31%) when the contribution of gBRCA was excluded; rates of sBRCA PVs were also similar (8% v 10%), thus underscoring the importance of HRD and BRCA testing at diagnosis in older patients with advanced HGSC given the therapeutic implications.

Multi-institutional Validation of a Vaginal Hysterectomy Simulation Model for Resident Training.

STUDY OBJECTIVE: The purpose of the research was to both develop a vaginal hysterectomy model with surgically pertinent anatomic landmarks and assess its validity for simulation training. DESIGN: A low-cost, reproducible vaginal hysterectomy model with relevant anatomic landmarks for key surgical steps. SETTING: Nine academic and community-based obstetrics and gynecology residency programs. PARTICIPANTS: One hundred sixty-nine obstetrics and gynecology residents. INTERVENTIONS: A vaginal hysterectomy model with surgically pertinent anatomic landmarks was developed and tested for construct validity. MEASUREMENTS AND MAIN RESULTS: Of the 184 available residents, 169 (91%) participated in this study and performed a vaginal hysterectomy procedure on the described model. The validated objective 7-item global rating scale (GRS) and the 13-item task-specific checklist (TSC) were used as tools to assess performance. The median TSC and GRS scores correlated with year of training, prior experience, and trainee confidence. In addition, the TSC scores also correlated with the GRS scores (p <.001) with regard to performance and resident year of training. Receiver Operator Curves for identification of the residents meeting national residency accreditation minimum numbers for vaginal hysterectomy using the GRS and TSC scores had an area under the curve of 0.89 and 0.83, respectively. CONCLUSION: This reduced-cost vaginal hysterectomy model offers high construct validity and pertinence for simulation.

Implementation of an abdominal closure bundle to reduce surgical site infection in patients on a gynecologic oncology service undergoing exploratory laparotomy.

OBJECTIVE: Surgical site infections (SSI) are associated with increased morbidity, mortality, and healthcare costs. This study investigated whether implementation of an abdominal closure bundle reduces surgical site infection rates. We aimed to identify sub-populations that would benefit the most from this intervention. METHODS: We conducted a retrospective cohort study of all patients that underwent exploratory laparotomy by a Gynecologic Oncologist from January 1, 2011 to April 1, 2017. The abdominal closure bundle was implemented on May 6, 2014. SSI rates were assessed overall and within subgroups. RESULTS: 875 patients were included in the analysis. Overall, SSI rate was reduced, albeit not significantly, from 48/471 (10.2%) to 32/404 (7.9%) (p=0.148) with implementation of the closing bundle. In patients that underwent a tumor debulking procedure, SSI was noted in 36/277 (13.0%) in the pre-bundle group and 14/208 (6.7%) in the post-bundle cohort (p=0.017). In patients with malignant pathology, the pre-bundle cohort had an SSI rate of 38/282 (13.5%), which reduced to 18/215 (8.4%) in the post-bundle group (p=0.049). In patients with FIGO stage III or IV disease, the SSI rate was reduced from 21/114 (18.4%) to 8/87 (8.4%) with implantation of the closure bundle (p=0.028). In patients with intra-operative ascites, SSI rate decreased from 19/119 (15.9%) pre-bundle to 4/104 (3.8%) in the post-bundle group (p=0.002). CONCLUSIONS: Implementation of an abdominal closure bundle was not associated with a significant reduction in overall SSI rate. However, multiple subpopulations associated with advanced gynecologic cancer benefited from this intervention.

Pre-operative assessment and post-operative outcomes of elderly women with gynecologic cancers, primary analysis of NRG CC-002: An NRG oncology group/gynecologic oncology group study.

INTRODUCTION: CC-002 is a prospective cooperative group study conducted by NRG Oncology to evaluate whether a pre-operative GA-GYN score derived from a predictive model utilizing components of an abbreviated geriatric assessment (GA) is associated with major post-operative complications in elderly women with suspected ovarian, fallopian tube, primary peritoneal or advanced stage papillary serous uterine (GYN) carcinoma undergoing primary open cytoreductive surgery. METHODS: Patients 70 years or older with suspected advanced gynecologic cancers undergoing evaluation for surgery were eligible. A GA-GYN score was derived from a model utilizing the GA as a pre-operative tool. Patients were followed for six weeks post-operatively or until start of chemotherapy. Post-operative events were recorded either directly as binary occurrence (yes or no) using CTCAE version 4.0. RESULTS: There were 189 eligible patients, 117 patients with primary surgical intervention and 37 patients undergoing interval cytoreduction surgery. The association between higher GA-GYN score and major postoperative complications in patients undergoing primary surgery was not significant (p = 0.1341). In a subgroup analysis of patients with advanced staged malignant disease who underwent primary cytoreductive surgery, there was a trend towards an association with the GA-GYN score and post-operative complications. CONCLUSION: The pre-operative GA-GYN score derived from a predictive model utilizing components of an abbreviated geriatric assessment was not predictive of major post-operative complications in elderly patients undergoing primary open cytoreductive surgery. However, there was an association between GA-GYN score and post-operative complications in a subgroup of patients with advanced staged malignant disease.

Neoadjuvant chemotherapy for newly diagnosed, advanced ovarian cancer: Society of Gynecologic Oncology and American Society of Clinical Oncology Clinical Practice Guideline.

PURPOSE: To provide guidance to clinicians regarding the use of neoadjuvant chemotherapy and interval cytoreduction among women with stage IIIC or IV epithelial ovarian cancer. METHODS: The Society of Gynecologic Oncology and the American Society of Clinical Oncology convened an Expert Panel and conducted a systematic review of the literature. RESULTS: Four phase III clinical trials form the primary evidence base for the recommendations. The published studies suggest that for selected women with stage IIIC or IV epithelial ovarian cancer, neoadjuvant chemotherapy and interval cytoreduction are non-inferior to primary cytoreduction and adjuvant chemotherapy with respect to overall and progression-free survival and are associated with less perioperative morbidity and mortality. RECOMMENDATIONS: All women with suspected stage IIIC or IV invasive epithelial ovarian cancer should be evaluated by a gynecologic oncologist prior to initiation of therapy. The primary clinical evaluation should include a CT of the abdomen and pelvis, and chest imaging (CT preferred). Women with a high perioperative risk profile or a low likelihood of achieving cytoreduction to <1cm of residual disease (ideally to no visible disease) should receive neoadjuvant chemotherapy. Women who are fit for primary cytoreductive surgery, and with potentially resectable disease, may receive either neoadjuvant chemotherapy or primary cytoreductive surgery. However, primary cytoreductive surgery is preferred if there is a high likelihood of achieving cytoreduction to <1cm (ideally to no visible disease) with acceptable morbidity. Before neoadjuvant chemotherapy is delivered, all patients should have confirmation of an invasive ovarian, fallopian tube, or peritoneal cancer. Additional information is available at www.asco.org/NACT-ovarian-guideline and www.asco.org/guidelineswiki.

Utility of ultrasound and MRI in prenatal diagnosis of placenta accreta: a pilot study.

OBJECTIVE: The purpose of this study was to evaluate transabdominal pelvic ultrasound and MRI for the prenatal diagnosis of placenta accreta. MATERIALS AND METHODS: A historical cohort pilot study was performed at our institution to identify women at risk of placenta accreta who had undergone both prenatal ultrasound and MRI. Findings at ultrasound and MRI were compared with the final diagnosis, which was established with clinical findings at delivery and pathologic examination of specimens. Volume measurements were made of low-signal-intensity intraplacental bands on T2-weighted MR images. Risk factors for placental insufficiency were recorded. RESULTS: Thirteen patients at risk of placenta accreta underwent both sonography and MRI. Nine of these patients had abnormal placentation. With ultrasound, abnormal placentation was correctly identified in six of nine patients (67%) and the absence of accreta in two of four patients (50%). With MRI, abnormal placentation was correctly identified in seven of nine patients (78%) and the absence of accreta in three of four patients (75%). The volumes of low-signal-intensity bands were significantly different in the patients with abnormal placentation and those without placenta accreta (p = 0.047), and band volumes were significantly different among patients with accreta, increta, and percreta (p < 0.0005). CONCLUSION: The accuracy of MRI may improve if volumes of low-signal-intensity bands are calculated, MRI is performed before 30 weeks' gestation, and risk factors for placental insufficiency are recognized.

Implementation of an enhanced recovery protocol in gynecologic oncology.

Enhanced Recovery after Surgery (ERAS) is an evidence-based approach that aims to reduce narcotic use and maintain anabolic balance to enable full functional recovery. Our primary aim was to determine the effect of ERAS on narcotic usage among patients who underwent exploratory laparotomy by gynecologic oncologists. We characterized its effect on length of stay, intraoperative blood transfusions, bowel function, 30-day readmissions, and postoperative complications. A retrospective cohort study was performed at Abington Hospital-Jefferson Health in gynecologic oncology. Women who underwent an exploratory laparotomy from 2011 to 2016 for both benign and malignant etiologies were included before and after implementation of our ERAS protocol. Patients who underwent a bowel resection were excluded. A total of 724 patients were included: 360 in the non-ERAS and 364 in the ERAS cohort. An overall reduction in narcotic usage, measured as oral morphine milliequivalents (MMEs) was observed in the ERAS relative to the non-ERAS group, during the entire hospital stay (MME 34 versus 68, p < 0.001 and within 72 h postoperatively (MME 34 versus 60, p < 0.005). A shorter length of stay and earlier return of bowel function were also observed in the ERAS group. No differences in 30-day readmissions (p = 0.967) or postoperative complications (p = 0.328) were observed. This study demonstrated the benefits of ERAS in Gynecologic Oncology. A significant reduction of postoperative narcotic use, earlier return of bowel function and a shorter postoperative hospital stay was seen in the ERAS compared to traditional perioperative care.

Disparities Among Cervical Cancer Patients Receiving Brachytherapy.

OBJECTIVE: To evaluate the effects of race and insurance status on the use of brachytherapy for treatment of cervical cancer. METHODS: This is a retrospective cohort study of the National Cancer Database. We identified 25,223 patients diagnosed with stage IB2 through IVA cervical cancer who received radiation therapy during their primary treatment from 2004 to 2015. A univariate analysis was used to assess covariate association with brachytherapy. A multivariable regression model was used to evaluate the effect of race and insurance status on rates of brachytherapy treatment. The Cox proportional hazards model and the multiplicative hazard model were used to evaluate overall survival. P<.05 indicated a statistically significant difference for comparisons of primary and secondary outcomes. RESULTS: Non-Hispanic black patients received brachytherapy at a significantly lower rate than non-Hispanic white patients (odds ratio [OR] 0.93; 95% CI 0.86-0.99; P=.036); Hispanic (OR 0.93; 95% CI 0.85-1.02; P=.115) and Asian (OR 1.13; 95% CI 0.99-1.29; P=.074) patients received brachytherapy at similar rates. Compared with patients with private insurance, those who were uninsured (OR 0.72; 95% CI 0.65-0.79; P<.001), had Medicaid (OR 0.83; 95% CI 0.77-0.89; P<.001) or Medicare insurance (OR 0.85; 95% CI 0.78-0.92; P<.001) were less likely to receive brachytherapy. Brachytherapy was not found to be a mediator of race and insurance-related disparities in overall survival. CONCLUSION: Racial and insurance disparities exist for those who receive brachytherapy, with many patients not receiving the standard of care, but overall survival was not affected.

Long-term trajectories of psychological adaptation among women diagnosed with gynecological cancers.

OBJECTIVE: Women diagnosed with gynecological cancers may cope with a difficult treatment regimen that includes multiple abdominal surgeries and courses of chemotherapy and/or radiation. Little attention has been paid to identifying what factors place women at risk for long-term problems with psychological adaptation. The goal of the present study was to identify a set of demographic, medical, and predisposing factors as well as cognitive and social processing strategies that predict the trajectory of psychological distress and well-being among women diagnosed with gynecological cancer. METHODS: One hundred thirteen women on active treatment for gynecological cancer completed measures at baseline, 3, 6, and 9 months afterward. RESULTS: Women with poorer physician-rated performance status and self-reported functional impairment, women who were Caucasian, women who have received previous psychological treatments, women who were less expressive of positive emotions, women who had unsupportive friends and family, and women who were less able to find something positive in the cancer experience reported poorer adaptation. CONCLUSIONS: This study identified a set of risk factors for poor long-term psychological adaptation among women diagnosed with gynecological cancers. Healthcare professionals working with these women can use these risk factors to screen for patients who may require additional psychological services.

Coping and communication-enhancing intervention versus supportive counseling for women diagnosed with gynecological cancers.

This study compared the efficacy of 2 psychological interventions, a coping and communication-enhancing intervention (CCI) and supportive counseling (SC), in reducing depressive symptoms and cancer-specific distress of women diagnosed with gynecological cancer. Demographic, medical, and psychological moderators of intervention effects were evaluated. Three hundred fifty-three women with gynecological cancer were randomly assigned to 7 sessions of CCI, 7 sessions of SC, or usual care. Intent-to-treat growth curve analyses indicated that participants assigned to CCI and SC reported lower depressive symptoms than participants assigned to usual care at the 6- and 9-month follow-ups. Women with greater than average increases in physician-rated physical symptoms and/or women who were more expressive of positive emotions benefited more from SC than women with lower than average increases in symptom scores and/or women who were less expressive of positive emotions. These findings suggest that both interventions may be effective in treating depressive symptoms among patients with gynecological cancer. Future research should evaluate whether bolstering both psychological interventions with additional intervention sessions and topics in the disease trajectory will result in persistent long-term effects.

Tumor cell-specific BRCA1 and RASSF1A hypermethylation in serum, plasma, and peritoneal fluid from ovarian cancer patients.

Because existing surgical and management methods can consistently cure only early-stage ovarian cancer, novel strategies for early detection are required. Silencing of tumor suppressor genes such as p16INK4a, VHL, and hMLH1 have established promoter hypermethylation as a common mechanism for tumor suppressor inactivation in human cancer and as a promising target for molecular detection in bodily fluids. Using sensitive methylation-specific PCR, we screened matched tumor, preoperative serum or plasma, and peritoneal fluid (washes or ascites) DNA obtained from 50 patients with ovarian or primary peritoneal tumors for hypermethylation status of the normally unmethylated BRCA1 and RAS association domain family protein 1A tumor suppressor genes. Hypermethylation of one or both genes was found in 34 tumor DNA (68%). Additional examination of one or more of the adenomatous polyposis coli, p14ARF, p16INK4a, or death associated protein-kinase tumor suppressor genes revealed hypermethylation in each of the remaining 16 tumor DNA, which extended diagnostic coverage to 100%. Hypermethylation was observed in all histologic cell types, grades, and stages of ovarian tumor examined. An identical pattern of gene hypermethylation was found in the matched serum DNA from 41 of 50 patients (82% sensitivity), including 13 of 17 cases of stage I disease. Hypermethylation was detected in 28 of 30 peritoneal fluid DNA from stage IC-IV patients, including 3 cases with negative or atypical cytology. In contrast, no hypermethylation was observed in nonneoplastic tissue, peritoneal fluid, or serum from 40 control women (100% specificity). We conclude that promoter hypermethylation is a common and relatively early event in ovarian tumorigenesis that can be detected in the serum DNA from patients with ovary-confined (stage IA or B) tumors and in cytologically negative peritoneal fluid. Analysis of tumor-specific hypermethylation in serum DNA may enhance early detection of ovarian cancer.

Neoadjuvant Chemotherapy for Newly Diagnosed, Advanced Ovarian Cancer: Society of Gynecologic Oncology and American Society of Clinical Oncology Clinical Practice Guideline.

PURPOSE: To provide guidance to clinicians regarding the use of neoadjuvant chemotherapy and interval cytoreduction among women with stage IIIC or IV epithelial ovarian cancer. METHODS: The Society of Gynecologic Oncology and the American Society of Clinical Oncology convened an Expert Panel and conducted a systematic review of the literature. RESULTS: Four phase III clinical trials form the primary evidence base for the recommendations. The published studies suggest that for selected women with stage IIIC or IV epithelial ovarian cancer, neoadjuvant chemotherapy and interval cytoreduction are noninferior to primary cytoreduction and adjuvant chemotherapy with respect to overall and progression-free survival and are associated with less perioperative morbidity and mortality. RECOMMENDATIONS: All women with suspected stage IIIC or IV invasive epithelial ovarian cancer should be evaluated by a gynecologic oncologist prior to initiation of therapy. The primary clinical evaluation should include a CT of the abdomen and pelvis, and chest imaging (CT preferred). Women with a high perioperative risk profile or a low likelihood of achieving cytoreduction to < 1 cm of residual disease (ideally to no visible disease) should receive neoadjuvant chemotherapy. Women who are fit for primary cytoreductive surgery, and with potentially resectable disease, may receive either neoadjuvant chemotherapy or primary cytoreductive surgery. However, primary cytoreductive surgery is preferred if there is a high likelihood of achieving cytoreduction to < 1 cm (ideally to no visible disease) with acceptable morbidity. Before neoadjuvant chemotherapy is delivered, all patients should have confirmation of an invasive ovarian, fallopian tube, or peritoneal cancer. Additional information is available at www.asco.org/NACT-ovarian-guideline and www.asco.org/guidelineswiki.

Prevalence and predictors of psychological distress among women with ovarian cancer.

PURPOSE: To identify the prevalence of psychological distress among women with ovarian cancer and to examine the association between these symptoms of distress and demographic and medical variables. PATIENTS AND METHODS: Participants were 143 women with ovarian cancer. Forty-eight percent of participants had been diagnosed with advanced-stage disease (stage III or IV) and most (80%) were currently receiving treatment. Psychological distress was assessed with the following measures: the Beck Depression Inventory, the Mental Health Inventory, the Impact of Events Scale, and a questionnaire regarding mental health service use. RESULTS: Approximately one fifth of women reported moderate to severe levels of distress, and more than half reported high stress responses to their cancer and its treatment. Most participants (60%) were not using any mental health services or psychotropic medications. There was also evidence to suggest that younger patients, patients with more advanced or recurrent disease, and patients who had more recently been diagnosed with ovarian cancer experienced greater psychological distress. CONCLUSION: These findings indicate that psychological distress and high stress responses to cancer are prevalent among women with ovarian cancer, suggesting they should be carefully evaluated to determine whether treatment for these symptoms is warranted.

p16 expression in squamous lesions of the female genital tract.

The aim of this study was to examine the role of p16 in the pathogenesis of squamous carcinoma of the gynecologic tract. Squamous carcinoma and carcinoma in situ from the female genital tract were examined for the expression of p16 by paraffin immunohistochemistry. About 74% (40/54) of cases showed p16 expression. By primary site, 77% (23/30) of cervical, 67% (6/9) of vaginal and 85% (11/13) of vulvar primaries expressed p16, but two endometrial primary squamous carcinomas were negative (0/2). In addition, p16 was not identified in non-dysplastic tissue and low grade dysplasia. In cases where there were matched vaginal or vulvar and cervical primaries in a given patient, there was concordant positive p16 expression. It is concluded that p16 is frequently expressed in squamous carcinoma of the cervix, vagina and vulva, but not seen in cases of benign and low grade lesions. It may be a marker of transformation from a low to a high grade lesion. More cases of endometrial primaries need to be studied to see if these evolve by a p16-independent pathway.

Immunohistochemical confirmation of pulmonary papillary adenocarcinoma metastatic to ovaries.

Metastatic papillary adenocarcinomas of the ovary are rare compared to primary ovarian papillary serous carcinomas. We report a case of pulmonary papillary adenocarcinoma metastatic to the ovary and show how this tumor can be differentiated immunohistochemically from an ovarian primary. Paraffin blocks of the ovarian tumor were analyzed for carcinoembryonic antigen, CA 125, surfactant, E-cadherin, N-cadherin, and vimentin. These markers are useful in differentiating epithelial tumors of lung versus ovarian origin. The papillary tumor showed expression of carcinoembryonic antigen, surfactant, and E-cadherin, but was negative for CA 125, N-cadherin, and vimentin. These findings support a lung carcinoma metastatic to the ovary.

Prophylactic and risk-reducing bilateral salpingo-oophorectomy: recommendations based on risk of ovarian cancer.

Women who do not have a documented germline mutation or who do not have a strong family history suspicious for a germline mutation are considered to be at average risk of ovarian cancer. Women who have confirmed deleterious BRCA1 and BRCA2 germline mutations are high risk of ovarian cancer. In addition, women who have a strong family history of either ovarian or breast cancer may carry a deleterious mutation and must be presumed to be at higher-than-average risk, even if they have not been tested, because there could be other mutations that are either untested or yet undiscovered that confirm higher-than-average risk of these diseases. We reviewed studies pertaining to prophylactic bilateral salpingo-oophorectomy in women at average risk of ovarian cancer who are undergoing hysterectomy for benign disease. We also reviewed the role of prophylactic bilateral salpingo-oophorectomy in preventing ovarian cancer based on the level of risk of the patient. For women at average risk of ovarian cancer who are undergoing a hysterectomy for benign conditions, the decision to perform prophylactic bilateral salpingo-oophorectomy should be individualized after appropriate informed consent, including a careful analysis of personal risk factors. Several studies suggest an overall negative health effect when prophylactic bilateral salpingo-oophorectomy is performed before the age of menopause. Ovarian conservation before menopause may be especially important in patients with a personal or strong family history of cardiovascular or neurological disease. Conversely, women at high risk of ovarian cancer should undergo risk-reducing bilateral salpingo-oophorectomy.