Financial toxicity of withdrawn poly (ADP-ribose) polymerase inhibitor indications for ovarian cancer.

OBJECTIVE: We sought to quantify exposure to and financial impacts of PARPi treatments for eventually withdrawn ovarian cancer indications. METHODS: We identified in Optum's de-identified Clinformatics® Data Mart database 1695 patients with ovarian cancer diagnoses who received olaparib, rucaparib, or niraparib between January 2015 and September 2021. We describe PARPi use and out-of-pocket (OOP), total health care, and PARPi spending among ovarian cancer patients with 3 or more prior lines of therapy (LOT). RESULTS: Of the 1695 patients who received PARPi, 254 were estimated to have been heavily pretreated and exposed to eventually withdrawn indications. Cumulative total medical and pharmacy costs for these patients were $53,392,184; PARPi costs accounted for 34%. Median PARPi cost per patient was $43,347. Cumulative out-of-pockets costs totaled $533,281. CONCLUSIONS: Potential patient harm, including financial toxicity, might have been mitigated through more stringent drug approval requirements.

Financial toxicity: A practical review for gynecologic oncology teams to understand and address patient-level financial burdens.

Financial toxicity describes the adverse impact patients experience from the monetary and time costs of cancer care. The financial burden patients experience comes from substantially increased out-of-pocket spending that often occurs concurrent with reduced income due to sick leave from work. Financial toxicity is common affecting approximately half of patients with a gynecological cancer depending on the validated instrument used for measurement. Financial toxicity is experienced by patients in three domains: economic hardship affecting patients' material conditions (i.e., medical debt), psychological response (i.e., distress), and health-related coping behaviors that patients adopt (i.e., foregoing care due to costs). Higher financial toxicity among cancer patients has been associated with decreased quality of life, impaired adherence to recommended care, and worse overall survival. In this review, we describe the current literature on financial toxicity, including how it can be assessed with validated tools, the downstream impact on patients, risk factors, and employment concerns of survivors. Whenever possible, we highlight data from research featuring patients with gynecologic cancer specifically. We also review studies with interventions aimed to mitigate financial toxicity and offer the reader real world examples of interventions currently being used. Lastly, we provide an overview of health policy developments relevant to financial toxicity and advocate for innovation in the development and implementation of strategies to decrease the financial toxicity patients experience following a diagnosis of gynecologic cancer.

Association of body mass index with early age at diagnosis of endometrial intraepithelial neoplasia.

OBJECTIVE: Elevated body mass index (BMI) is a risk factor for endometrioid endometrial cancer and its precursor, endometrial intraepithelial neoplasia (EIN). Our objective was to describe the association between BMI and age at EIN diagnosis. METHODS: We conducted a retrospective study of patients diagnosed with EIN from 2010 to 2020 at a large academic medical center. Patient characteristics were stratified by menopausal status and compared using a chi-square or t-test. We used linear regression to determine the parameter estimate (ß) and 95% confidence interval for the association between BMI and age at diagnosis. RESULTS: We identified 513 patients with EIN; 503 (98%) had complete medical records. Premenopausal patients were more likely to be nulliparous and to have polycystic ovary syndrome than postmenopausal patients (both p ≤ 0.001). Postmenopausal patients were more likely to have hypertension, type 2 diabetes, and hyperlipidemia (all p ≤ 0.02). There was a significant linear association between BMI and age at diagnosis in premenopausal patients (ß = -0.19 (95% CI: -0.27, -0.10). In premenopausal patients, for every 1-unit increase in BMI, age at diagnosis decreased by 0.19 years. No association was observed in postmenopausal patients. CONCLUSIONS: In a large cohort of patients with EIN, increasing BMI was associated with an earlier age at diagnosis in premenopausal patients. This data suggests consideration of endometrial sampling in younger patients with known risk factors for excess estrogen exposure.

Factors associated with increased financial toxicity after the completion of radiation treatment for gynecologic cancer.

PURPOSE: We evaluated financial toxicity (FT) in patients with gynecologic cancer treated with radiation and assessed the impact of the COVID-19 pandemic on patients' financial wellbeing. METHODS: Patients completed a survey 1 month after completing radiation from August 2019-March 2020 and November 2020-June 2021. The survey included the COmprehensive Score for Financial Toxicity (COST) tool, EQ-5D to measure quality of life (QOL) and pandemic-related questions for the second survey period. High FT was COST score ≤ 23. RESULTS: Of 97 respondents (92% response rate), 49% completed the survey pre-pandemic and 51% after; the majority were white (76%) and had uterine cancer (64%). Sixty percent received external beam radiation with or without brachytherapy; 40% had only brachytherapy. High FT was associated with worse QOL (r = -0.37, P < 0.001), younger age and type of insurance (both p ≤ 0.03). Respondents with high FT were 6.0 (95% CI 1.0-35.9) times more likely to delay/avoid medical care, 13.6 (95% CI 2.9-64.3) times more likely to borrow money, and 6.9 (95% CI 1.7-27.2) times as likely to reduce spending on basic goods. The pandemic cohort had a smaller proportion of respondents with high FT than the pre-pandemic cohort (20% vs. 35%, p = 0.10) and a higher median COST score (32 (IQR 25-35) vs. 27 (IQR 19-34), p = 0.07). CONCLUSION: Privately insured, younger respondents who received radiation for gynecologic cancer were at risk for FT. High FT was associated with worse QOL and economic cost-coping strategies. We observed less FT in the pandemic cohort, though not statistically different from the pre-pandemic cohort.

Financial toxicity in pregnancy and postpartum.

INTRODUCTION: The financial burden of pregnancy in the United States can be high and is associated with worse mental health and birth outcomes. Research on the financial burden of health care, such as the development of the COmprehensive Score for Financial Toxicity (COST) tool, has been conducted primarily among patients with cancer. This study aimed to validate the COST tool and use it to measure financial toxicity and its impacts among obstetric patients. METHODS: We used survey and medical record data from obstetric patients at a large medical center in the United States. We validated the COST tool using common factor analysis. We used linear regression to identify risk factors for financial toxicity and to investigate associations between financial toxicity and patient outcomes including satisfaction, access, mental health, and birth outcomes. RESULTS: The COST tool measured two distinct constructs of financial toxicity in this sample: current financial toxicity and concern over future financial toxicity. Racial/ethnic category, insurance, neighborhood deprivation, caregiving, and employment were associated with current financial toxicity (P < 0.05 for all). Only racial/ethnic category and caregiving were associated with concern over future financial toxicity (P < 0.05 for all). Both current and future financial toxicity were associated with worse patient-provider communication, depressive symptoms, and stress (P < 0.05 for all). Financial toxicity was not associated with birth outcomes or keeping obstetric visits. CONCLUSIONS: The COST tool captures two constructs among obstetric patients, current and future financial toxicity, both of which are associated with worse mental health and patient-provider communication.

Endometrial stripe thickness: a preoperative marker to identify patients with endometrial intraepithelial neoplasia who may benefit from sentinel lymph node mapping and biopsy.

OBJECTIVES: The goal of our study was to identify preoperative factors in patients with endometrial intraepithelial neoplasia that are associated with concurrent endometrial cancer to select patients who may benefit from sentinel lymph node (SLN) assessment at the time of hysterectomy. METHODS: Retrospective single institution cohort study of patients with a preoperative diagnosis of endometrial intraepithelial neoplasia who underwent hysterectomy with or without staging from January 2010 to July 2020. Modified Poisson regression was used to calculate risk ratios (RR) and 95% confidence intervals (CI). RESULTS: Of 378 patients with a preoperative diagnosis of endometrial intraepithelial neoplasia, 275 (73%) had endometrial intraepithelial neoplasia and 103 (27%) had invasive cancer on final pathology. Age (p=0.003), race (p=0.02), and hypertension (p=0.02) were significantly associated with concurrent endometrial cancer. The median preoperative endometrial stripe was significantly greater in the endometrial cancer group (14 mm (range 10-19)) than in the endometrial intraepithelial neoplasia group (11 mm (range 8-16); p=0.002). A preoperative endometrial stripe ≥20 mm was associated with double the risk of endometrial cancer on final pathology (crude RR 2.0, 95% CI 1.3 to 2.9) and preoperative endometrial stripe ≥15 mm was 2.5 times more likely to be associated with high risk Mayo criteria on final pathology (crude RR 2.5, 95% CI 1.2 to 5.2). Of those with concurrent endometrial cancer, 5% were stage IB, 29% had tumors >2 cm, and 1% had grade 3 histology. Only 3% of all patients underwent lymph node evaluation. CONCLUSIONS: In a large cohort of patients with a preoperative diagnosis of endometrial intraepithelial neoplasia, less than a third had invasive cancer and even fewer had pathologic features considered high risk for nodal metastasis, arguing against the use of routine SLN dissection in these patients. Endometrial stripe ≥15 mm may be a useful preoperative marker to identify patients at higher risk for concurrent endometrial cancer and may be an important criterion for use of selective SLN dissection in carefully selected patients with endometrial intraepithelial neoplasia.

Crowdsourcing to measure financial toxicity in gynecologic oncology.

OBJECTIVE: To utilize a novel crowdsourcing method to measure financial toxicity and its effects among a national cohort of gynecologic cancer patients. METHODS: Crowdsourcing methods were used to administer an online survey to women in the United States with gynecologic cancers. We used the Comprehensive Score for Financial Toxicity (COST) tool to measure financial toxicity and the EQ-5D-3L to measure quality of life (QOL). Based on prior work, we defined high financial toxicity as a COST score ≤ 23. We assessed correlation of COST scores with QOL. We used log-binomial regression to examine associations between high financial toxicity and cost-coping strategies. RESULTS: Among the final study sample of 334 respondents, 87% were white, median age at diagnosis was 55 (interquartile range 47-63), 52% had stage III or IV disease and 90% had private insurance or Medicare. Median COST score was 24 (interquartile range 15-32) and 49% of respondents reported high financial toxicity. Greater financial toxicity was correlated with worse QOL (p < 0.001). Participants reporting high financial toxicity were more likely to use cost-coping strategies, including spending less on basic goods (RR: 3.3; 95% CI: 2.1-5.1), borrowing money or applying for financial assistance (RR: 4.0; 95% CI: 2.4-6.9), and delaying or avoiding care (RR: 5.6; 95% CI: 2.6-12.1). CONCLUSIONS: Crowdsourcing is an effective tool to measure financial toxicity. Nearly half of respondents reported high financial toxicity, which was significantly associated with worse QOL, utilization of cost-coping strategies and delays or avoidance of care.

Evaluating meaningful levels of financial toxicity in gynecologic cancers.

OBJECTIVE: The Comprehensive Score for Financial Toxicity (COST) is a validated instrument measuring the economic burden experienced by patients with cancer. We evaluated the frequency of financial toxicity at different COST levels and stratified risk factors and associations with cost-coping strategies by financial toxicity severity. METHODS: We analyzed previously collected survey data of gynecologic oncology patients from two tertiary care institutions. Both surveys included the COST tool and questions assessing economic and behavioral cost-coping strategies. We adapted a proposed grading scale to define three groups: no/mild, moderate, and severe financial toxicity and used χ2, Fisher's exact test, and Wilcoxon rank sum test to compare groups. We used Poisson regression to calculate crude and adjusted risk ratios for cost-coping strategies, comparing patients with moderate or severe to no/mild financial toxicity. RESULTS: Among 308 patients, 14.9% had severe, 32.1% had moderate, and 52.9% had no/mild financial toxicity. Younger age, non-white race, lower education, unemployment, lower income, use of systemic therapy, and shorter time since diagnosis were associated with worse financial toxicity (all p<0.05). Respondents with moderate or severe financial toxicity were significantly more likely to use economic cost-coping strategies such as changing spending habits (adjusted risk ratio (aRR) 2.7, 95% CI 1.8 to 4.0 moderate; aRR 3.6, 95% CI 2.4 to 5.4 severe) and borrowing money (aRR 5.5, 95% CI 1.8 to 16.5 moderate; aRR 12.7, 95% CI 4.3 to 37.1 severe). Those with severe financial toxicity also had a significantly higher risk of behavioral cost-coping through medication non-compliance (aRR 4.6, 95% CI 1.2 to 18.1). CONCLUSIONS: Among a geographically diverse cohort of gynecologic oncology patients, nearly half reported financial toxicity (COST <26), which was associated with economic cost-coping strategies. In those 14.9% of patients reporting severe financial toxicity (COST <14) there was also an increased risk of medication non-compliance, which may lead to worse health outcomes in this group.

Germline mutations of SMARCA4 in small cell carcinoma of the ovary, hypercalcemic type and in SMARCA4-deficient undifferentiated uterine sarcoma: Clinical features of a single family and comparison of large cohorts.

OBJECTIVE: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) and SMARCA4-deficient undifferentiated uterine sarcoma (SMARCA4-DUS) are rare and aggressive tumors, primarily affecting pre- and perimenopausal women. Inactivating SMARCA4 mutations are thought to be the driving molecular events in the majority of these tumors. Here, we report the clinical course of a family with germline SMARCA4 mutation and compare large cohorts of these rare tumor types. METHODS: We extracted clinico-pathological medical record data for the family with germline SMARCA4 mutation. Clinico-genomic data from SCCOHT and SMARCA4-DUS cohorts were retrospectively extracted from the archives of a large CLIA-certified reference molecular laboratory. RESULTS: We identified a single family with an inherited germline SMARCA4 mutation, in which two different family members developed either SCCOHT or SMARCA4-DUS, both of whom died within one year of diagnosis, despite aggressive surgical, chemotherapy and immunotherapy treatment. Retrospective comparative analysis of large SCCOHT (n = 48) and SMARCA4-DUS (n = 17) cohorts revealed that SCCOHT patients were younger (median age: 28.5 vs. 49.0) and more likely to have germline SMARCA4 alterations (37.5% vs. 11.8%) than SMARCA4-DUS patients. CONCLUSIONS: Growing understanding of the role SMARCA4 plays in the pathogenesis of these rare cancers may inform recommended genetic testing and counseling in families with these tumor types.

Adoption of enhanced recovery after laparotomy in gynecologic oncology.

INTRODUCTION: Enhanced recovery after surgery (ERAS) pathways combine a comprehensive set of peri-operative practices that have been demonstrated to hasten patient post-operative recovery. We aimed to evaluate the adoption of ERAS components and assess attitudes towards ERAS among gynecologic oncologists. METHODS: We developed and administered a cross-sectional survey of attending, fellow, and resident physicians who were members of the Society of Gynecologic Oncology in January 2018. The χ2 test was used to compare adherence to individual components of ERAS. RESULTS: There was a 23% survey response rate and we analyzed 289 responses: 79% were attending physicians, 57% were from academic institutions, and 64% were from institutions with an established ERAS pathway. Respondents from ERAS institutions were significantly more likely to adhere to recommendations regarding pre-operative fasting for liquids (ERAS 51%, non-ERAS 28%; p<0.001), carbohydrate loading (63% vs 16%; p<0.001), intra-operative fluid management (78% vs 32%; p<0.001), and extended duration of deep vein thrombosis prophylaxis for malignancy (69% vs 55%; p=0.003). We found no difference in the use of mechanical bowel preparation, use of peritoneal drainage, or use of nasogastric tubes between ERAS and non-ERAS institutions. Nearly all respondents (92%) felt that ERAS pathways were safe. DISCUSSION: Practicing at an institution with an ERAS pathway increased adoption of many ERAS elements; however, adherence to certain guidelines remains highly variable. Use of bowel preparation, nasogastric tubes, and peritoneal drainage catheters remain common. Future work should identify barriers to the implementation of ERAS and its components.

Financial toxicity in gynecologic oncology.

OBJECTIVES: Financial toxicity is increasingly recognized as an adverse outcome of cancer treatment. Our objective was to measure financial toxicity among gynecologic oncology patients and its association with demographic and disease-related characteristics; self-reported overall health; and cost-coping strategies. METHODS: Follow-up patients at a gynecologic oncology practice completed a survey including the COmprehensive Score for Financial Toxicity (COST) tool and a self-reported overall health assessment, the EQ-VAS. We abstracted disease and treatment characteristics from medical records. We dichotomized COST scores into low and high financial toxicity and assessed the correlation (r) between COST scores and self-reported health. We calculated risk ratios (RR) and 95% confidence intervals (CI) for the associations of demographic and disease-related characteristics with high financial toxicity, as well as the associations between high financial toxicity and cost-coping strategies. RESULTS: Among 240 respondents, median COST score was 29. Greater financial toxicity was correlated with worse self-reported health (r = 0.47; p < 0.001). In the crude analysis, Black or Hispanic race/ethnicity, government-sponsored health insurance, lower income, unemployment, cervical cancer and treatment with chemotherapy were associated with high financial toxicity. In the multivariable analysis, only government-sponsored health insurance, lower income, and treatment with chemotherapy were significantly associated with high financial toxicity. High financial toxicity was significantly associated with all cost-coping strategies, including delaying or avoiding care (RR: 7.3; 95% CI: 2.8-19.1). CONCLUSIONS: Among highly-insured gynecologic oncology patients, many respondents reported high levels of financial toxicity. High financial toxicity was significantly associated with worse self-reported overall health and cost-coping strategies, including delaying or avoiding care.

Adnexal mass staging CT with a disease-specific structured report compared to simple structured report.

OBJECTIVES: To assess a disease-specific structured report (dsSR) for CT staging of ovarian malignancy compared to a simple structured report (sSR). METHODS: This is a HIPAA-compliant, IRB-approved study with waiver of informed consent. An adnexal mass-specific structured reporting CT template was developed in collaboration between gynecologic oncologists and diagnostic radiologists. The study population included 24 consecutive women who had a staging CT prior to undergoing debulking surgery for a primary ovarian malignancy. Objective evaluation by radiologists for the presence of 19 key features and subjective evaluation by gynecologic oncologists were performed to assess the clarity and usefulness for procedural planning of dsSR and sSR. Accuracy, sensitivity, and specificity were assessed using operating room notes and pathology reports as the reference standard. RESULTS: Fewer key features were missing from dsSR than sSR: 0.2 ± 0.8 (range 0-2) vs.10.2 ± 1.7 (range 7-14), respectively (p < 0.0001). Compared to sSR, gynecologic oncologists deemed dsSR more helpful (4.3 ± 0.7 vs. 3.7 ± 0.8, p < 0.0001) and easier to understand (4.3 ± 0.6 vs. 3.9 ± 0.7, p = 0.0057) (on a scale 0-5, 0 not helpful/very difficult to understand; 5 extremely helpful/very clear to understand). Gynecologic oncologists reported a higher rate of potential to modify their surgical approach based on dsSR (33-42%) compared to sSR (13-17%), p = 0.004. CONCLUSIONS: Disease-specific structured reports were more reliable than simple structured reports in describing key features essential for procedural planning. dsSR was described as more helpful and easier to understand and more likely to lead to modification of the surgical approach by gynecologic oncologists compared to sSR. KEY POINTS: • Disease-specific structured report is easier to understand and more helpful for planning gynecological surgery as compared with simple structured report. • Disease-specific structured report for pre-operative evaluation of ovarian cancer provides better documentation of essential features required for surgical planning as compared with simple structured report. • Disease-specific structured report has the potential to modify the surgical approach as assessed by gynecologic oncologists.

Pilot of an International Collaboration to Build Capacity to Provide Gynecologic Oncology Surgery in Botswana.

OBJECTIVES: Gynecologic malignancies are the leading cause of cancer death among women in Botswana. Twenty-five percent of cervical cancers present at a stage that could be surgically cured; however, there are no gynecologic oncologists to provide radical surgeries. A sustainable model for delivery of advanced surgery is essential to advance treatment for gynecologic malignancies. METHODS/MATERIALS: A model was developed to provide gynecologic oncology surgery in Botswana, delivered by US-based gynecologic oncologists in four 2-week blocks per year. A pilot gynecologic oncology campaign was planned at a district hospital. Eligible patients were identified through the gynecologic oncology multidisciplinary clinic at the regional referral hospital, where gynecologic oncology treatment planning is provided. Local providers were invited to participate to build local surgical capacity. RESULTS: One US-based gynecologic oncologist, 2 gynecologists, and 2 surgeons working in Botswana participated in the pilot campaign. Sixteen operations were performed over 7 days. Indications included cervical cancer (4), ovarian cancer (3), vulvar cancer (1), complex atypical hyperplasia (1), pre-invasive cervical disease (2), and benign disease (3), as well as 2 obstetric emergencies. The only gynecologic oncology complication was a case of bleeding requiring transfusion and postoperative intensive care unit admission. Follow-up care was coordinated through the gynecologic oncology multidisciplinary clinic. CONCLUSIONS: Periodic gynecologic oncology campaigns in settings otherwise lacking local capacity to perform advanced surgery are a feasible model to create access and build local capacity. Strong local collaboration is essential. Future strategies to increase impact include recruitment of more gynecologic oncologists to increase service and training availability.

Endosalpingiosis: More than just an incidental finding at the time of gynecologic surgery?

OBJECTIVE: To describe the clinical characteristics of patients with endosalpingiosis (ES) and examine its association with endometriosis and gynecologic malignancies. METHODS: We queried the medical record for patients who underwent gynecologic surgery (Gynecologic Surgery Cohort (GSC), n=58,161) from 1998 to 2013 at a single institution for the presence of "endosalpingiosis" (ES). Demographic and clinical characteristics were collected for patients with pathologically confirmed ES (n=838). Within GSC, we compared the frequency of endometriosis and gynecologic malignancies with and without ES. We estimated the expected distribution of ovarian cancer subtypes using cases from the New England Case Control Study (NECC). We used chi-square tests to test for significant differences in frequency distributions and unconditional logistic regression to calculate multivariate odds ratios for the association between ES and ovarian cancer subtypes. RESULTS: We observed concurrent endometriosis (p<0.0001), uterine cancer (p<0.0001), and ovarian cancer (p<0.0001) more frequently in women with ES. Women from the GSC with ES and ovarian cancer were more likely to have serous borderline (OR=10.2, 95% CI=5.1-20.7), clear cell (OR=3.0, 95% CI=1.1-8.0), and invasive mucinous tumors (OR=5.0, 95% CI=1.5-16.6) as compared to ovarian cancer cases from the NECC without ES, after accounting for age, race, menopausal status, parity, tubal ligation, and endometriosis. CONCLUSION: Women with ES are more likely to also be diagnosed with endometriosis, uterine, and ovarian cancers. Further study is needed to understand these associations so we may appropriately counsel patients with ES diagnosed at time of gynecologic surgery.

Solitary Fibrous Tumor of the Uterus Presenting With Lung Metastases: A Case Report.

We describe the case of an 81-yr-old woman who presented with bilateral pulmonary nodules in the setting of a large uterine mass, concerning for a gynecologic malignancy such as leiomyosarcoma. However, fine-needle aspiration of a lung nodule revealed a spindle cell neoplasm consistent with solitary fibrous tumor (SFT), a rare mesenchymal neoplasm characterized by a patternless architecture of spindle cells and branching ectatic vessels. Total abdominal hysterectomy demonstrated a primary SFT of the uterus. Both the lung lesion and uterine mass were positive for STAT6, a sensitive and specific biomarker for SFT. SFT infrequently metastasizes and only rarely occurs in the uterus. These tumors are considered to have uncertain malignant potential, and the diagnosis of "malignant" SFT requires the presence of >4 mitoses per 10 high-power fields. The uterine SFT we report did not meet this criterion for malignancy, emphasizing that this entity can behave aggressively even without increased mitoses or atypical histology. To our knowledge, this is the first reported case of a uterine SFT with metastasis to the lung. We discuss the differential diagnosis for the finding of multiple pulmonary spindle cell lesions in the setting of a uterine mass.

The Role of Endometrial Biopsy in the Preoperative Detection of Uterine Leiomyosarcoma.

STUDY OBJECTIVE: To assess the sensitivity of preoperative endometrial biopsy in detection of uterine leiomyosarcoma (ULMS). STUDY DESIGN: Retrospective analysis of a prospectively collected database (Canadian Task Force III). SETTING: Two academic tertiary referral centers. PATIENTS: All cases of ULMS treated at participating institutions between January 2005 and August 2012 were identified following IRB approval. INTERVENTIONS: Abstracted data included demographics, preoperative evaluation, presenting symptom, surgical management, pathology and clinical outcomes. Chi-square tests were used for statistical analysis. MEASUREMENTS AND MAIN RESULTS: 329 cases were identified, of which 152 cases had complete pathologic data available for review. Sixty-eight (45%) of 152 patients had endometrial sampling prior to surgery. Patients with postmenopausal bleeding were significantly more likely to be biopsied preoperatively (51.6% vs 9.5%, p = <.0001). Of those sampled, 43 (63%) underwent endometrial pipelle biopsies and 25 (37%) had dilation and curettage. Endometrial sampling was significantly more likely to detect a concern for malignancy in patients who presented with postmenopausal bleeding (72.7% vs 32.3%, p = 0.002), however it was less likely to detect malignancy in patients with abnormal premenopausal bleeding (31.8% vs 64.3%, p = .02), compared to other presenting symptoms. Overall, 51.5% of patients with ULMS on final pathology had preoperative endometrial biopsies in which leiomyosarcoma or atypical spindle cell proliferation were diagnosed, whereas 35.5% of the pre-operative biopsies identified ULMS specifically. CONCLUSIONS: The sensitivity of an endometrial biopsy to detect ULMS is low, illustrating the difficulty of diagnosing ULMS preoperatively. As expected, the probability that an endometrial biopsy will detect ULMS or a related worrisome pathological finding is higher for patients with post-menopausal bleeding. Thus, benign endometrial biopsy results, particularly in pre-menopausal patients, should be interpreted with caution if there is suspicion for leiomyosarcoma. However, a positive or suspicious result can play an important role in the subsequent management of patients with ULMS, even if the absolute numbers of affected patients are small.

Genomic aberrations in cervical adenocarcinomas in Hong Kong Chinese women.

Although the rates of cervical squamous cell carcinoma have been declining, the rates of cervical adenocarcinoma are increasing in some countries. Outcomes for advanced cervical adenocarcinoma remain poor. Precision mapping of genetic alterations in cervical adenocarcinoma may enable better selection of therapies and deliver improved outcomes when combined with new sequencing diagnostics. We present whole-exome sequencing results from 15 cervical adenocarcinomas and paired normal samples from Hong Kong Chinese women. These data revealed a heterogeneous mutation spectrum and identified several frequently altered genes including FAT1, ARID1A, ERBB2 and PIK3CA. Exome sequencing identified human papillomavirus (HPV) sequences in 13 tumors in which the HPV genome might have integrated into and hence disrupted the functions of certain exons, raising the possibility that HPV integration can alter pathways other than p53 and pRb. Together, these provisionary data suggest the potential for individualized therapies for cervical adenocarcinoma based on genomic information.

Does plastic surgical consultation improve the outcome of patients undergoing radical vulvectomy for squamous cell carcinoma of the vulva?

OBJECTIVES: To analyze margin status and prognostic factors for complications in patients undergoing vulvectomy for invasive squamous cell cancer (iSCC) with and without plastic-assisted closure. METHODS: Demographic and clinical data were collected on 94 patients with iSCC who underwent vulvectomy between 2004 and 2013. All pathology slides were re-reviewed by two gynecologic pathologists. Data were analyzed using XLSTAT-Pro v2014.2.02. RESULTS: Of 88 eligible patients, 15 (17%) had plastic-assisted vulvar closure and 73 (83%) did not. There were significantly more patients in the plastics group with recurrent disease (53% v 10%) and history radiation therapy prior to surgery (40% versus 5%). Plastic-assisted closure was associated with larger tumors (3.73 cm versus 2.03 cm, p<0.01) and a higher frequency of adequate margins (53% versus 29%, p=0.06). For tumors≥3.0 cm, plastic-assisted closure was significantly associated with adequate margins (44% versus 6%, p=0.03). Prior radiation use was associated with plastic-assisted closure, larger tumors, older age, and recurrent disease. Complications occurred in 36 patients (41%) and significantly more occurred in those with plastic-assisted closure (67% versus 36%, p=0.04). On multivariate analysis including age, tumor size, recurrent disease, plastic-assisted closure, and history of radiation, only history of radiation therapy was a significant predictor of complications (OR=17, 95%CI 2.05-141.35; p=0.01). CONCLUSIONS: Plastic-assisted vulvectomy closure was more often utilized in cases involving past radiation therapy and larger tumors. Plastic-assisted closure significantly increased the frequency of adequate margins in tumors≥3 cm and did not impact complications.

Endosalpingiosis as it relates to tubal, ovarian and serous neoplastic tissues: an immunohistochemical study of tubal and Müllerian antigens.

OBJECTIVE: The origins and clinical significance of endosalpingiosis (ES), ectopic tubal epithelium, are not well understood. These investigations aim to characterize ES as it relates to normal fallopian tube, ovarian surface and serous neoplasms. METHODS: A retrospective review of pathology reports from all prophylactic gynecologic surgeries from 2000 to 2010 was performed to assess the frequency of ES. Twenty-one archival specimens of ES, 6 normal fallopian tubes, 9 normal ovaries, 21 serous neoplasms and a commercially available ovarian tissue microarray were subjected to immunohistochemistry (IHC) with 11 tubal and Müllerian antigens. IHC staining was evaluated with a quantitative scoring system and scores were analyzed using MINITAB statistical software. RESULTS: ES was noted in 3.5% of pathologic specimens from 464 prophylactic surgeries. The majority of antigens showed no significant differences (p > 0.05) in median IHC scores between ES and normal fallopian tube epithelium (nFTE), while they were significantly different (p < 0.05) from the ovarian surface epithelium (OSE). Median IHC scores were unchanged in ES tissues regardless of the location of ES or the presence of a concurrent serous neoplasm. Three antigens emerged as contemporary tubal and ES biomarkers: phospho-Smad2, BCL2 and FOXJ1. All 3 biomarkers were expressed in ES, nFTE and serous neoplasms, but not in OSE or other tumor types. CONCLUSION: This study provides immunophenotypic evidence that ES is more similar to the nFTE than OSE. Further, ES biomarker expression closely resembles serous neoplasms strengthening the growing body of evidence that all Müllerian serous carcinomas arise from tubal-like epithelium.

What is the optimal treatment for obese patients with advanced ovarian carcinoma?

OBJECTIVE: The purpose of this study was to compare primary debulking surgery (PDS) vs neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS) among obese patients. STUDY DESIGN: Medical records of patients with a body mass index (BMI) of ≥30 kg/m(2) with ovarian/fallopian tube/primary peritoneal carcinoma between January 2005 and December 2010 were reviewed. Patients were separated by PDS or NACT-IDS. Preoperative characteristics, surgical procedures, and postoperative and oncologic outcomes were compared. RESULTS: Of 117 patients, 95 women (81.2%) underwent PDS, and 22 women (18.8%) underwent NACT-IDS. Patients who underwent NACT-IDS were more likely to have stage IV disease (63.6% vs 26.3%; P = .001) and a low surgical complexity score (n = 14; 63.6%). There were no other differences between groups with respect to preoperative characteristics or postoperative morbidity. Compared with the NACT-IDS group, the PDS group had an improved progression-free survival (PFS; 15 vs 11 months; P = .006) and overall survival (OS; 53 vs 32 months; P = .036). Seventy-eight patients (66.7%) had a BMI of 30-34.9 kg/m(2). Within this subset of obese patients, the PDS group had an improved PFS (15 vs 10 months; P = .011) and OS (58 vs 32 months; P = .033), compared with the NACT-IDS group. Among patients with a BMI of ≥35 kg/m(2), there was no difference in PFS (14 vs 12 months; P = .316) or OS (38 vs 32 months; P = .640) when the PDS and NACT-IDS groups were compared. CONCLUSION: Patients with a BMI of 30-34.9 kg/m(2) who undergo PDS have improved oncologic outcomes, compared with those women who undergo NACT-IDS. Patients with a BMI of ≥35 kg/m(2) who undergo PDS have similar oncologic outcomes to those who undergo NACT-IDS. Complication rates were similar at all BMIs, regardless of treatment approach.