Validation of the surprise question in gynecologic oncology: A one-question screen to promote palliative care integration and advance care planning.

OBJECTIVE: The "surprise question" ("Would you be surprised if this patient died in the next year?") has been shown to be predictive of 12-month mortality in multiple populations, but has not been studied in gynecologic oncology (GO) patients. We sought to evaluate the prognostic performance of the surprise question in GO patients among physician and non-physician providers. METHODS: GO providers at two tertiary care centers were asked the surprise question about a cohort of their patients undergoing chemotherapy or radiation. Demographic and clinical information was chart abstracted. Mortality data were collected at one year; relative risk of death at one year based on response to the surprise question was then calculated. RESULTS: 32 providers (12 MDs, 7 APPs, 13 RNs) provided 942 surprise question assessments for 358 patients. Fifty-seven % had ovarian cancer and 54% had recurrent disease. Eighty-three (24%) patients died within a year. Patients whose physician answered "No" to the surprise question had a 43% one-year mortality (compared to 10% for "Yes"). Overall RR of 12-month mortality for "No" was 3.76 (95% CI 2.75-5.48); this association remained significant in all provider types. Among statistically significant predictors of 12-month mortality (including recurrent disease and >2 prior lines of chemotherapy), the surprise question had the highest RR. CONCLUSIONS: The surprise question is a simple, one question tool that effectively identifies GO patients increased risk of 12-month mortality. The surprise question could be used to identify patients for early referral to palliative care and initiation advance care planning.

Emerging biomarkers in ovarian granulosa cell tumors.

OBJECTIVE: Although the majority of ovarian granulosa cell tumors can be successfully managed with surgery, a subset require chemotherapy for residual and recurrent disease. The benefit of chemotherapy in this population, however, remains controversial. There is therefore interest in the development of more tolerable and effective treatment options for advanced ovarian granulosa cell tumors. We report the use of immunohistochemistry to investigate how biomarkers could inform clinical trials in granulosa cell tumors with an emphasis on emerging androgen antagonistic, immunotherapeutic, and anti-angiogenic approaches. METHODS: Immunohistochemistry for androgen receptor, the immune markers programmed cell death ligand 1, indoleamine-2,3 dioxygenase, and cluster of differentiation 8, and the vascular marker cluster of differentiation 31 were evaluated on formalin-fixed paraffin-embedded whole tissue sections from 29 cases of adult-type granulosa cell tumors. Results were evaluated with clinicopathologic variables including recurrence. RESULTS: 59% of granulosa cell tumors were androgen receptor-positive, suggesting a potential role for anti-androgen therapy in this tumor type. In contrast, the targetable immune modulatory molecules programmed cell death ligand 1 and indoleamine-2,3 dioxygenase were scarcely expressed, with no cases showing tumorous programmed cell death ligand 1 and a single case demonstrating very focal tumorous indoleamine-2,3 dioxygenase staining. A minority of cases expressed programmed cell death ligand 1 in occasional tumor-associated macrophages and indoleamine-2,3 dioxygenase in peritumoral vessels. Tumor-infiltrating cytotoxic T cells were also scarce in granulosa cell tumors, arguing against a significant role for immunotherapy in the absence of additional immunostimulation. Cluster of differentiation 31 immunostaining revealed a range of vascular densities across granulosa cell tumors, and future studies evaluating the role of vascular density as a predictor of response to angiogenesis inhibition are warranted. None of the biomarkers investigated were significantly correlated with recurrence, and the only clinicopathologic feature significantly correlated with outcome was stage at presentation. CONCLUSIONS: Biomarker data suggest that many ovarian granulosa cell tumors could be candidates for anti-androgen therapy, while the potential role for immunotherapy appears more limited. Vascular density could be useful for identifying optimal candidates for angiogenesis inhibition. Incorporation of these biomarkers into clinical trials could help optimize patient selection.

Cervical cancer care in rural Virginia: The impact of distance from an academic medical center on outcomes & the role of non-specialized radiation centers.

OBJECTIVE: To determine whether distance to a tertiary care facility affects outcomes for locally advanced cervical cancer and to evaluate the impact of receiving care at non-specialized centers in rural communities. METHODS: Retrospective, single institution study of patients with locally advanced cervical cancer managed with chemo-radiation from January 1, 2000 to June 1, 2014. Kaplan-Meier survival curves and Cox proportional hazard models were used to compare progression free and overall survival for patients by median distance to the tertiary care facility (<72 miles or >72 miles) and facility where treatment was received. RESULTS: 180 patients met inclusion criteria. There was no difference in PFS or OS between the travel distance cohorts. When compared by location of external beam radiation, patients treated at outside facilities were older (p = 0.02) and significantly more likely to be insured (95.6% versus 71.7%, p < 0.0002). There were more recurrences among patients treated at outside facilities (31.1% versus 15.8%) but this was non-significant (p = 0.24). On multivariable analysis, FIGO stage and insurance status were associated with overall survival. Uninsured patients had a significantly increased hazard risk of death as compared to privately insured patients (HR 3.85 95% CI 3.07-4.64, p = 0.0008). CONCLUSIONS: Median distance to a tertiary care facility had no significant impact on PFS or OS, however treating facility for radiation may influence recurrence rates. Having non-private insurance or being uninsured is significantly associated with increased risk of death and speaks to the many barriers these patients face.

Hormone replacement therapy after treatment for cervical cancer: Are we adhering to standard of care?

OBJECTIVE: The aim of this study was to assess hormone replacement therapy (HRT) and bone care health maintenance practices for cervical cancer patients with iatrogenic menopause, and, secondarily, to investigate the potential impact of specific demographic and clinical factors. METHODS: Women diagnosed with iatrogenic menopause due to cervical cancer treatment between January 1, 2005 and December 31, 2015 were identified from the University of Virginia's tumor registry. Univariable data were analyzed using Wilcoxon rank sum, Chi square, and Fisher's exact test; multivariable analysis was conducted using logistic regression. RESULTS: Two hundred and two women were included for analysis. Ninety-seven of these women (48.0%) received counseling and/or a prescription for HRT. After multivariable analysis, older age at diagnosis (adjusted OR 0.940, 95% CI 0.890-0.993, p=0.0270) and uninsured payer status (adjusted OR 0.455, 95% CI 0.212-0.977, p=0.0435) were associated with a decreased likelihood of receiving counseling or a prescription for HRT. A longer duration of follow-up was associated with the primary outcome with an adjusted OR of 1.011 (95% CI 1.001-1.020, p=value 0.0252). Dual-energy X-ray absorptiometry scans (DEXA) were infrequent and received by only 17/197 (8.6%) of all women. CONCLUSIONS: Fewer than half of all women received counseling and/or a prescription for HRT after diagnoses of iatrogenic menopause, and disparities were noted based on insurance status. These findings reflect a need for clearer guidelines on HRT during survivorship and improved efforts to reduce disparities in the distribution of survivorship care.

Margins for cervical and vulvar cancer.

Surgery is the primary treatment for vulvar cancer as well as early-stage carcinoma of the cervix. This article reviews the significance of margin status after surgery on overall survival, need for further surgical intervention, and role for possible adjuvant therapy. It summarizes the abundant literature on margin status in vulvar cancer and highlights the need for further investigation on the prognostic significance of margins in cervical cancer. In addition, it reviews other important operative considerations.

Chemotherapy alone may have equivalent survival as compared to suboptimal surgery in advanced endometrial cancer patients.

OBJECTIVE: To describe outcomes in patients with advanced endometrial cancer treated with chemotherapy only and compare them to patients treated with a combination of chemotherapy and surgery. METHODS: Retrospective chart review for all patients diagnosed with stage III and IV endometrial cancer from January 1, 2000 to December 31, 2015. We abstracted relevant demographic and clinical data. Kaplan-Meier analysis was used to create survival curves; Cox proportional hazards regression model was used to identify prognostic factors. RESULTS: Ninety-six patients met inclusion criteria; the median age was 64.5. Seventy patients were treated with combination therapy and 26 with chemotherapy alone. For the entire group, median overall survival (OS) was significantly different between groups (22.3 months surgery versus 9.8 months chemotherapy only, p = 0.0002). After multivariable analysis, having carcinosarcoma (HR 3.84 95% CI 2.64-5.03, p = 0.03), having grade 3 disease (HR 4.95 95% CI 3.70-6.18, p = 0.01), and having chemotherapy only (HR 4.13 95% CI 3.23-5.02, p = 0.002) were associated with increased mortality. When analysis was restricted to just patients who had a suboptimal debulking or chemotherapy alone, median OS was equivalent similar at 9.4 and 9.8 months (p = 0.46). CONCLUSION: For advanced endometrial cancer patients, surgery in addition to chemotherapy confers a survival advantage except when optimal debulking cannot be achieved.

Genetic counseling referral for ovarian cancer patients: a call to action.

The hereditary contribution to ovarian cancer has been increasingly recognized over the past decade, with a 2014 Society of Gynecologic Oncology (SGO) recommendation for all women with epithelial ovarian cancer to be considered for genetic testing. The objective of the study was to determine if disparities exist in genetic referrals and characterize referral patterns over time. A retrospective cohort study included all women diagnosed with invasive epithelial ovarian cancer at the University of Virginia from 2004 to 2015. Clinicopathologic data were abstracted from the electronic medical record and analyzed for association with genetic referral and testing. We identified 696 cases, with a median age of 62 years and a median follow up of 25.2 months (range 1-115). Thirty-four percent were referred for genetic counseling with an 80% genetic testing rate in those women. Referrals increased from a rate of 8% in 2004 to 68% in 2015. On multivariable analysis, papillary serous histology (OR 1.6, 95% CI 1.0-2.6), stage III disease (OR 3.4, 95% CI 1.6-7.5), ovarian cancer family history (OR 2.6, 95% CI 1.5-4.6), breast cancer family history (OR 1.7, 95% CI 1.1-2.5), and diagnosis after 2014 (OR 2.3, 95% CI 1.3-4.1) remained significantly associated with genetics referral. Older age and living > 100 miles away were associated with decreased referral (OR 0.97, 95% CI 0.95-0.99 per year and OR 0.49, 95% CI 0.28-0.86). As only 68% of women with epithelial ovarian cancer were referred in 2015 innovative strategies such as Medicare coverage for counseling are still needed to universalize testing.

Endometrial cancer in an increasingly obese population: Exploring alternative options when surgery may not cut it.

OBJECTIVES: The study objectives were to describe outcomes of obese patients with early endometrial cancer following primary non-surgical treatment, assess predictors of response, and estimate the increased surgical risk for these women. METHODS: Retrospective chart review identified women with early stage endometrial cancer at a single institution with BMI ≥ 30 kg/m2 who did not undergo surgery as primary treatment modality due to obesity and medical co-morbidities. Clinicopathologic factors were abstracted, characteristics of responders vs. non-responders compared and the National Surgical Quality Improvement Program (NSQIP) surgical risk calculator utilized to quantify surgical risks. RESULTS: Fifty-one patients were identified, with a mean BMI of 49.0 kg/m2. The NSQIP calculator predicted a significantly higher complication rate for our cohort compared to the expected average risk for hysterectomy (18.8% vs 7.2%, p < .0001). The majority of patients were treated with radiation alone (49%), followed by hormone therapy (45.1%). Response rates were 38.1% for women treated with hormones and 63.6% in the radiation group (p = .063). No significant differences were identified between responders and non-responders with regard to NSQIP scores, BMI, co-morbidities or age. Among those with persistent or progressive disease, 87.5% responded to secondary treatment. Only one death was from cancer progression. Two individuals died following treatment complications (one surgical, one chemotherapy); the remaining twelve deaths were due to pre-existing co-morbidities. CONCLUSIONS: Hormone and radiation therapy are both viable options for obese patients deemed to have too significant risk of surgical complications. Pursuing surgical intervention in this population may do more harm than good.

Ovarian carcinoma initially presenting as breast cancer two years prior to diagnosis: A case report and review of literature.

•Ovarian cancer presenting as a primary breast cancer two years prior•Ovarian cancer with metastases to breast is rare.•Metastases to the breast generally present as a recurrence.•Delay in diagnosis likely due to chemotherapy given for breast disease.