Search

The purpose of this study is to compare ultrasonographic ovarian mass scoring systems in pregnant women.This multicenter study included women with an ovarian mass during pregnancy who were evaluated using ultrasound and underwent surgery in 11 referral hospitals. The ovarian mass was evaluated and scored using three different scoring systems(International Ovarian Tumor Analysis Assessment of Different NEoplasias in the adnexa[IOTA ADNEX], Sassone, and Lerner). The final diagnosis was made histopathologically. Receiver operating characteristic(ROC) curves were generated for each scoring system.During the study period, 236 pregnant women underwent surgery for an ovarian mass, including 223 women(94.5%) with a benign ovarian mass and 13 women(5.5%) with a malignant ovarian mass. Among 10 ultrasound image findings, six findings were different between benign and ovarian masses(maximal diameter of mass, maximal diameter of solid mass, wall thickness of mass, inner wall structure, thickness of septations, and papillarity). In all three scoring systems, the ovarian mass scores were significantly higher in malignant masses than in benign masses, with the highest area under the ROC curve(AUROC) in the Sassone scoring system(AUROC: 0.831 for Sassone, 0.710 for Lerner vs 0.709 for IOTA ADNEX; p 0.05, between the Sassone and Lerner/ IOTA ADNEX). A combined model was developed with the six different ultrasound findings, and the AUROC of the combined model was 0.883(p = not significant between the combined model and Sassone).In pregnant women, malignant ovarian tumors can be predicted with high accuracy using either the Sassone scoring system or the combined model.

Objective to profile patients with vaginal intraepithelial neoplasia (VAIN), to evaluate natural history and to identify risk factors for persistence, progression and recurrence. Methods At West China Second University Hospital, all patients with histologically confirmed VAIN over a five-year period with minimum follow-up of 6 months were retrospectively identified. Demographics, medical history and clinical information related to the diagnosis and treatment were extracted. Clinical outcomes included normalization, persistence, progression and recurrence. We evaluated risk factors by univariate and multivariate analyses. Results A total of 1478 patients fulfilled the inclusion criteria with a median follow-up of 14 months (range, 6–60 months). In 86.6% of patients, VAIN went into normalization, 6.4% persisted, 3.5% progressed and 3.5% recurred. Besides, 24 (7.1%) VAIN 3 patients and 4 (0.8%) progressed to cancer, accounting for 85.7% and 14.3% of cancer cases, respectively. VAIN 3 patients treated with excision yielded superior outcomes. Risk factors for persistence were HPV 16, 56, 59 and 43 infections, for progression were prior hysterectomy for cervical lesions and HPV 56 infection, for recurrence were HPV 61 infection. Conclusion Although VAIN will regress in most patients, there are still risks of persistence, recurrence and progression, even malignancy. Therefore, a long-term follow-up is recommended. Patients with VAIN 3 are at higher risk of progressing to cancer and excision is preferred. HPV 16, 56, 59 and 43 infections might associate with an increased risk of persistence and patients with prior hysterectomy for cervical lesions tend to progress.

Objective To develop a novel diagnostic nomogram model to predict malignancy in patients with ovarian masses. Methods In total, 1277 patients with ovarian masses were retrospectively analyzed. Receiver operating characteristic (ROC) analysis was performed to identify valuable predictive factors. Univariate and multivariate logistic regression analyses were used to identify risk factors for ovarian cancer. Subsequently, a predictive nomogram model was developed. The performance of the nomogram model was assessed by its calibration and discrimination in a validation cohort. Decision curve analysis (DCA) was applied to assess the clinical net benefit of the model. Results Overall, 496 patients (38.8%) had ovarian cancer. Eighteen parameters were significantly different between the malignant and benign groups. Five parameters were identified as being most optimal for predicting malignancy, including age, carbohydrate antigen 125, fibrinogen-to-albumin ratio, monocyte-to-lymphocyte ratio, and ultrasound result. These parameters were incorporated to establish a nomogram model, and this model exhibited an area under the ROC curve (AUC) of 0.937 (95% confidence interval [CI], 0.920–0.954). The model was also well calibrated in the validation cohort and showed an AUC of 0.925 (95%CI, 0.896–0.953) at the cut-off point of 0.298. DCA confirmed that the nomogram model achieved the best clinical utility with almost the entire range of threshold probabilities. The model has demonstrated superior efficacy in predicting malignancy compared to currently available models, including the risk of ovarian malignancy algorithm, copenhagen index, and the risk of malignancy index. More importantly, the nomogram established here showed potential value in identification of early-stage ovarian cancer. Conclusion The cost-effective and easily accessible nomogram model exhibited favorable accuracy for preoperative prediction of malignancy in patients with ovarian masses, even at early stages.

Objective To estimate the diagnostic value of tumor and immune related proteins in the discrimination between benign and malignant adnexal masses, and between different subgroups of tumors. Methods In this exploratory diagnostic study, 254 patients with an adnexal mass scheduled for surgery were consecutively enrolled at the University Hospitals Leuven (128 benign, 42 borderline, 22 stage I, 55 stage II-IV, and 7 secondary metastatic tumors). The quantification of 33 serum proteins was done preoperatively, using multiplex high throughput immunoassays (Luminex) and electrochemiluminescence immuno-assay (ECLIA). We calculated univariable areas under the Receiver Operating Characteristic Curves (AUCs). To discriminate malignant from benign tumors, multivariable ridge logistic regression with backward elimination was performed, using bootstrapping to validate the resulting AUCs. Results CA125 had the highest univariable AUC to discriminate malignant from benign tumors (0.85, 95% confidence interval 0.79-0.89). Combining CA125 with CA72.4 and HE4 increased the AUC to 0.87. For benign vs borderline tumors, CA125 had the highest univariable AUC (0.74). For borderline vs stage I malignancy, no proteins were promising. For stage I vs II-IV malignancy, CA125, HE4, CA72.4, CA15.3 and LAP had univariable AUCs ≥0.80. Conclusions The results confirm the dominant role of CA125 for identifying malignancy, and suggest that other markers (HE4, CA72.4, CA15.3 and LAP) may help to distinguish between stage I and stage II-IV malignancies. However, further research is needed, also to investigate the added value over clinical and ultrasound predictors of malignancy, focusing on the differentiation between subtypes of malignancy.

SCCOHT is an aggressive malignancy linked to alterations of SMARCA4. We describe the diagnosis and therapy of a 32 year old who received multi-agent chemotherapy and underwent a second look operation with HIPEC followed by high-dose chemotherapy with stem cell transplant. Supportive care, oncofertility, and genetic counseling are described.

Introduction Management of a woman with a pelvic mass is complicated by difficulty in discriminating malignant from benign disease. Many serum biomarkers have been examined to determine their sensitivity for detecting malignancy. This study was designed to evaluate if the addition of biomarkers to HE4 and CA125, as used in the Risk of Malignancy Algorithm (ROMA), can improve the detection of EOC. Methods This was an IRB approved, prospective clinical trial examining serum obtained from women diagnosed with a pelvic mass who subsequently underwent surgery. Serum biomarker levels for CA125, HE4, YKL-40, transthyretin, ApoA1, Beta-2-microglobulin, transferrin, and LPA were measured. Logistic regression analysis was performed for various marker combinations, ROC curves were generated, and the area under the curves (AUCs) were determined. Results A total of 184 patients met inclusion criteria with a median age of 56 years (Range 20–91). Final pathology revealed there were 103 (56.0%) benign tumors, 4 (2.2%) LMP tumors, 61 EOC (33.1%), 2 (1.1%) non-EOC ovarian cancers, 6 (3.3%) gynecologic cancers with metastasis to the ovary and 8 (4.3%) non-gynecologic cancers with metastasis to the ovary. The combination of HE4 and CA125 (i.e. ROMA) achieved an AUC of 91.2% (95% CI: 86.0–96.4) for the detection of EOC vs benign disease. The combination of CA125, HE4, YKL-40, transthyretin, ApoA1, Beta 2 microglobulin, transferrin, LPA and menopausal status achieved the highest AUC of 94.6% (95% CI: 90.1–99.2) but this combination was not significantly better than the HE4 and CA125 combination alone (p = 0.078). Conclusions The addition of select further serum biomarkers to HE4 and CA125 does not add to the performance of the dual marker combination for the detection of ovarian cancer.

Uterine leiomyosarcoma is the most common type of uterine sarcoma. It is an extremely aggressive malignancy associated with a poor overall prognosis. Women affected may vary in age, but are most often diagnosed in their perimenopausal years. Presenting symptoms may be vague and mimic other benign uterine conditions. Preoperative diagnosis of leiomyosarcoma is difficult and often only made at time of surgical resection. These rare mesenchymal tumors are characterized by cytologic atypia, a high mitotic index, and tumor necrosis on histologic inspection. Management of early stage disease entails hysterectomy and complete surgical resection of gross tumor, though routine oophorectomy or lymph node dissection do not appear to confer much clinical benefit. Adjuvant therapy for early stage disease remains controversial as multiple clinical trials have failed to demonstrate benefit on overall survival. Recently, progress has been made in regards to therapy for advanced and recurrent disease. Novel chemotherapeutics, targeted therapies such as olaratumab and pazopanib, and new immunotherapies such as nivolumab and pembrolizumab have demonstrated promise in these previously difficult drug-resistant patients. In this article, we provide a detailed review of uterine leiomyosarcoma including epidemiology, clinical presentation, diagnosis, and pathologic characteristics. We then go on detail management strategies, including options for adjuvant therapy, and highlight new and developing regimens in the field.

Objectives To explore pre-operative factors and their impact on overall survival (OS) in a modern cohort of patients who underwent pelvic exenteration (PE) for gynecologic malignancies. Methods A retrospective review was performed for all patients who underwent a PE from 1/1/2010 through 12/31/2018 at our institution. Inclusion criteria were exenteration due to recurrent or progressive carcinoma of the uterus, cervix, vagina or vulva, with histologically confirmed complete surgical resection of the malignancy. Exclusion criteria included PE for palliation of symptoms without recurrence, and for ovarian or rare histologic malignancies. Univariable and multivariable analysis were performed to identify factors predicting prolonged survival. Results Overall, 71 patients met the inclusion criteria. Median age at time of exenteration was 62 years (range, 28–86 years). Vulvar cancer was the most common primary diagnosis (32%); 30% had cervical cancer; 23%, uterine cancer; 15%, vaginal cancer. Median OS was 55.1 months (95% confidence interval (CI): 36-not estimable) with a median follow-up time of 40.8 months (95% CI: 1–116.1). On univariable analysis, age > 62 years (hazard ratio (HR) 2.71, 95% CI 1.27–5.79), American Society of Anesthesia (ASA) 3–4 (HR: 3.41 (95% CI 1.03–11.29), and vulvar cancer (HR 4.19 (95% CI 1.17–14.96) predicted worse OS. Tumor size and prior progression-free interval (PFI) did not meet statistical significance in OS analyses. On multivariable analysis, there were no significant factors associated with worse OS. Conclusions PE performed with curative intent may be considered a treatment option in well-counseled, carefully selected patients, irrespective of tumor size and PFI before exenteration.

Objectives: This study aimed to evaluate the diagnostic performances of the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA) in the preoperative prediction of ovarian cancer.Methods: In a prospective cohort study, data were collected from 475 patients with ovarian masses diagnosed by gynecologic examination / ultrasound who were hospitalized at the Departments of Obstetrics and Gynecology, Hue University of Medicine and Pharmacy Hospital and Hue Central Hospital, Vietnam, between January 2018 and June 2020. ROMA and CPH-I were calculated based on measurements of serum carbohydrate antigen (CA-125) and human epididymis protein (HE4). The final diagnosis was based on clinical features, radiologic and histologic findings, and the International Federation of Gynecology and Obstetrics (FIGO) 2014 stages of ovarian cancer were recorded. Matching the values of ROMA and CPH-I to postoperative histopathology reports resulted in the preoperative prediction values.Results: Among the 475 women, 408 had benign tumors, 5 had borderline tumors and 62 had malignant tumors. The two indices showed similar discriminatory performances with no significant differences (p > 0.05). At an optimal cut-off, the sensitivities/specificities of ROMA and CPH-I for ovarian cancer diagnosis were 74.2% and 91.8%, 87.1% and 78.5%, respectively. The optimal cut-off for CPH-I was 1.89%. The areas under the ROC curves (AUCs) of ROMA and CPH-I were 0.882 (95% CI: 0.849 – 0.909) and 0.898 (95% CI: 0.867 – 0.924), respectively.Conclusions: The introduction of the Copenhagen Index to help stratify the malignancy risk of ovarian tumors, irrespective of menopausal status, might be applied as a simple alternative with a similar efficacy to ROMA in clinical practice.

To assess the diagnostic performance and inter-observer agreement of the American College of Radiology (ACR) Ovarian-Adnexal Reporting and Data System Ultrasound (O-RADS US).From January 2016 to December 2018 a total of 1054 adnexal lesions in 1035 patients with pathologic results from two hospitals were retrospectively included. Each lesion was assigned to an O-RADS US category according to the criteria. Kappa (κ) statistics were applied to assess inter-observer agreement between a less experienced and an expert radiologist.Of the 1054 adnexal lesions, 750 were benign and 304 were malignant. The malignancy rates of O-RADS 5, O-RADS 4, O-RADS 3, and O-RADS 2 lesions were 89.57%, 34.46%, 1.10%, and 0.45% respectively. Area under the receiver operating characteristic curve was 0.960 (95% CI, 0.947-0.971). The optimal cutoff value for predicting malignancy wasO-RADS 3 with a sensitivity and specificity of 98.7% (95% CI, 0.964-0.996) and 83.2% (95% CI, 0.802-0.858) respectively. When sub-classifying multilocular cysts and smooth solid lesions in O-RADS 4 lesions as O-RADS 4a lesions and the rest cystic lesions with solid components as O-RADS 4b lesions, the malignancy rate were 17.02% and 42.57% respectively, which showed better risk stratification (P0.001). The inter-observer agreement between a less-experienced and an expert radiologist of O-RADS categorization was good (κ = 0.714).The ACR O-RADS US provides effective malignancy risk stratification for adnexal lesions with high reliability for radiologists with different experience. Sub-grouping of O-RADS 4 lesions into two groups facilitated better stratification of the intermediate risk.

Objective Small cell neuroendocrine carcinoma of the cervix (SCNEC) is a lethal malignancy and little treatment progress has been made for decades. We sought to map its genetic profiles, and identify whether SCNEC harbor mutations and potential targets for therapeutic interventions. Methods Primary tumor tissue and blood samples were obtained from 51 patients with SCNEC. The next-generation sequencing was carried out to detect mutations of 520 cancer-related genes, including the entire exon regions of 312 genes and the hotspot mutation regions of 208 genes. Quantitative multiplex PCR was performed for the detection of seven high-risk HPV types. Results Of the 51 detected patients, 92.16% were positive for HPV 18. Ninety-eight percent of cases harbored genetic alterations. Two cases were observed with hypermutated phenotype and determined as MSI-H/dMMR. Genetic mutations were clustering in RTK/RAS(42.86%), PI3K-AKT(38.78%), p53 pathway(22.45%) and MYC family(20.41%). Mutations in genes involved in the p53 pathway indicate a poorer prognosis (3-year OS, 33.5% vs 59.9%, p = 0.031). A total of seven patients harboring mutations in homogeneous recombination repair (HRR) genes were reported. In addition, IRS2 and SOX2 were amplified in 14.9% and 6.12% of SCNEC patients, respectively. Conclusions SCNEC is specifically associated with HPV 18 infection. Its genetic alterations are characterized by a combined feature of high-risk HPV driven events and mutations observed in common neuroendocrine carcinoma. We identified several targetable mutated genes, including KRAS, PIK3CA, IRS2, SOX2, and HRR genes, indicating the potential efficacy of target therapies in these patients. MSI-H/dMMR individuals may benefit from checkpoint blockade therapies.

Objectives: To characterize the effect that a ban on elective surgery had for patients who were scheduled for surgery with a gynecologic oncologist during the first coronavirus disease 19 (COVID-19) outbreak in New York City. Methods: Patients who were scheduled to undergo surgery by a gynecologic oncologist at one of three campuses of a New York City based academic hospital during the ban on elective surgery between March 16, 2020 and June 15, 2020 were included. Patients with benign disease were excluded. Data on patient demographics, perioperative characteristics, nature of surgical delay, and post-operative treatment were abstracted from patient charts. Standard of care was considered met if surgical procedures occurred for suspected malignant and pre-invasive disease, or if an appropriate treatment plan and follow up was documented for malignant cases. Kruskal-Wallis and chi-square test of independence were performed with significance set at p Results: A total of 196 patients were scheduled to undergo a surgical procedure during the ban on elective surgery, of which 146 were for malignant, suspected malignant or pre-invasive disease. The majority of cases (42.4%) occurred in patients with known malignancy, followed by suspected malignancy (37.7%) and pre-invasive disease (19.9%). Forty percent of patients experienced one or more surgical delay, 9.6% experienced 2 or more surgical delays and 1.4% experienced three or more surgical delays. Of patients who experienced surgical delays, 75.9% experienced hospital-initiated delays and 24.1% experienced patient-initiated delays. There were no differences between hospital versus patient initiated delays by White vs non-White race (p=0.167). Eight percent of delays were due to a patient with known or suspected COVID-19. The median time from surgical consultation to proposed date of surgery was 20 days for both known malignancy and suspected malignancy, and 34.5 days for pre-invasive disease (p=0.005). Similarly, the median time from surgical consultation to actual date surgery was 23 days for patients with known or suspected malignancy compared to 64 days for preinvasive disease (p=0.011). Of eight patients undergoing treatment for ovarian cancer, 50% underwent primary debulking and 50% underwent neoadjuvant chemotherapy. Among all scheduled cases, the standard of care was met in 89.7% of cases. Standard of care treatment was achieved with a documented alternative plan in 6.1% of cases and with a non-surgical plan in 3% of cases. Download : Download high-res image (503KB) Download : Download full-size image Conclusions: During the ban on elective surgery in New York City during the first outbreak of the COVID-19 pandemic, many patients experienced minor surgical delays, but the majority of patients with known or suspected malignancies obtained appropriate, timely care. Ten percent of patients did not receive standard of care.

Objectives: The objectives of this study were to evaluate ovarian masses across multiple imaging models in series and in parallel with a second-generation multivariate index assay (MIA2G), and to develop a reliable protocol for ovarian malignancy risk stratification. Methods: This is an ongoing randomized controlled trial in Filipino women with ovarian masses in the University of the Philippines - Philippine General Hospital. A comprehensive analysis was performed between various imaging risk classifier methods: IOTA (International Ovarian Tumor Analysis) - Simple Rules, IOTA - LR1, IOTA LR - 2, IOTA-Adnex, Sassone, and Lerner; and a biochemical algorithm: MIA2G (OVERA). The sensitivity, specificity, positive and negative predictive values, and correct classification rate in classifying benign or malignant lesions were computed, as well as their interval estimates. The histopathologic findings served as the ‘gold’ standard or variable that represented ‘true’ presence of disease. Individual screening performances were assessed using parallel testing between the MIA2G (with conventional cut-off at 5.0) and various imaging risk classifier methods. However, based on previous local data, a higher cut-off at 7.0 was observed such that an additional analysis with the adjusted cut-off was also computed. Similarly, these diagnostic criteria were evaluated in series with the imaging tests followed by the MIA2G at both cut offs (5.0 and 7.0). Download : Download high-res image (657KB) Download : Download full-size image Results: There were 410 tumors identified from 343 women included in the study. Around 20% (67/343) had bilateral masses and only 72% (246/343) of women had histopathologic findings available. The observed study prevalence of women with confirmed malignancy was 31.5% (108/343, 26.6 to 36.7%) and much higher than the expected prevalence of the general population. The MIA2G was noted to be high-risk in 73% (251/343) of all the evaluable subjects using the traditional cut-off at greater than 5.0; but at a higher cut-off of 7.0, this resulted in only 40% (138/343) being classified as high-risk. The individual imaging test sensitivity, specificity, and predictive values calculated showed that the optimal imaging methods were IOTA-LR1, IOTA-LR2 and IOTA-Simple Rules, but the latter had a significant number of inconclusive results. When combined with imaging models in parallel, the conventional MIA2G cut-off (5.0), was noted to perform poorer than the adjusted cut-off (7.0). On the other hand, serial testing showed higher accuracy for imaging tests combined with the conventional MIA2G cut off (5.0). Conclusions: In this investigation, ultrasound imaging models and MIA2G are complementary and when used in combination, these provide a better understanding of the malignant potential of an ovarian tumor. MIA2G combined with IOTA-LR2 was the most reliable combination. For parallel testing, an adjusted MIA2G cut-off (7.0) increased overall test accuracy and sensitivity. In serial testing, the conventional MIA2G cut-off (5.0) resulted in overall higher test accuracy and specificity. Applied to our local setting, where the choice of imaging model used for pre-operative evaluation will vary according to the health provider's experience in performing such tests and where there are no standard protocols on the use of biochemical assays, inclusion of such findings in practice guidelines will significantly affect malignancy risk stratification and clinical outcome.

Objectives: An international consensus panel has defined locally advanced cervical cancers as a high priority malignancy during the COVID-19 pandemic and recommends prompt initiation of definitive treatment and completion of treatment (PMID 32563593). The objective of this study was to study the clinical outcomes of patients (pts) with cervical cancer treated with definitive chemoradiation (CRT) and brachytherapy (BT) at our institution in 2019 (pre-COVID) and in 2020 (peri-COVID). Methods: This was a retrospective cohort study of pts with FIGO Stage IB2-IVA cervical cancer at our institutions from 1/2019 to 10/2020. Pts received CRT followed by intracavitary brachytherapy (IC) with two operative insertions one week apart, or interstitial (IS) BT with one operative insertion. BT treatment was planned using image-guided CT or MR delineation. Pre-COVID was defined by initiation of CRT between 1/2019-12/2019, and peri-COVID was defined by initiation between 1/2020-10/2020. Process changes peri-COVID included limited on-site staff (e.g., minimal OR staff, no trainees, remote physics team), universal implementation of COVID-19 testing prior to surgery, and CT instead of MR-delineation based treatment. Outcomes of interest were time to treatment initiation and completion and differences in treatment planning modality or dosimetry. Fisher's exact and Mann Whitney U tests were used with significance p Results: Thirty pts were included, with 18 patients undergoing treatment pre-COVID and 12 peri-COVID. The median age at diagnosis pre-COVID was 57.7 (range 23-77) and for peri-COVID, 45.5 (range 28-62, p=0.06). There were no differences in non-English speaking pts (44% vs 59%, p=0.71) or uninsured pts (11% vs 33%, p=0.184) between the two cohorts. Median time to initiation of treatment from biopsy diagnosis was 52 days (range 13-209) in 2019 and for peri-COVID, 55.5 (range 20-173, p=0.71). During COVID, three pts had delayed initiation to treatment >100 days: two related to fertility and one due to fear of COVID-19. For this pt, tumor size progressed from 2.3cm to 4.2 cm maximal dimension. One pt treated in 2020 tested positive following treatment and did not require hospital admission. All pts completed CRT with RT: 24 pts pelvic RT (45 Gy), 3 pelvic and para-aortic RT (45 Gy with 57.5 Gy concomitant boost to nodes), 8 pts pelvic RT (45Gy) with sequential parametrial boost (50.4-59.4 Gy) using IMRT with no dose differences between pre and peri-COVID (Table 1). No pts required treatment breaks and the median overall treatment time was 50 days (range 31-85) in 2019 vs 50 days (range 43-63) in 2020 (p=0.710). Download : Download high-res image (105KB) Download : Download full-size image Conclusions: Despite the significant burden of the COVID-19 pandemic on our health care system, all cervical cancer pts receiving CRT met standard of care including CRT and BT within the recommended time frame with no significant differences in treatment parameters pre- and peri-COVID.

Objectives: For women with suspicious ovarian cysts of varying risk of malignancy, treatment often involves minimally invasive surgery (MIS). While there are a number of benefits to MIS, there is an increased risk of ovarian capsule rupture during the procedure compared to laparotomy. Capsule rupture has the potential to seed the abdominal cavity with malignant cells. This upstaging is associated with a 10-15% decrease in progression free survival. As the utilization of MIS has increased, there has been a corresponding increase in capsule rupture. We developed a decision model to compare the risks, benefits and effectiveness of MIS versus laparotomy in women with ovarian masses. Methods: A decision model was created to simulate the clinical trajectory of a hypothetical cohort of 10,000 women aged 45 years with ovarian masses concerning for malignancy who were undergoing surgical management. The initial decision point in the model was performance of surgery via laparotomy or an MIS approach. The second node was whether the cyst ruptured intra-operatively. The base case analysis estimated outcomes if the risk of malignancy was 5%. Based on population data, the risk of rupture was 21% for those undergoing laparotomy versus 26% in those who underwent MIS. Model probabilities, costs and utility values were derived with assumptions drawn from published literature and administrative data sources. The effectiveness was calculated in terms of average quality adjusted life years (QALYs) gained. The primary outcome was incremental cost-effectiveness ratios (ICERs), expressed in 2018 US dollars/QALYs. One-way sensitivity analyses were performed to vary the assumptions across a range of plausible values. Results: MIS was the least costly strategy at $6,350, compared to a cost of $13,892 for laparotomy. In our hypothetical cohort, there were 64 cases of ovarian rupture in the MIS group and 53 in the open group (Table 1). There were 26 cancer related deaths in the MIS group and 25 in the laparotomy group. MIS was more effective than laparotomy (188,462 QALYs for MIS versus 187,631 QALYs for open) and MIS was cost-effective with an ICER of $-81,025/QALYs compared to laparotomy. In one-way sensitivity analyses, the probability of cancer and risk of rupture did not substantially impact the cost-effectiveness. Download : Download high-res image (50KB) Download : Download full-size image Conclusions: MIS constitutes cost-effective management strategy for women with suspicious ovarian masses even though it is associated with both an increased risk of cyst rupture and death from ovarian cancer.

Objectives: In recent years, the Risk of Ovarian Malignancy Algorithm (ROMA) score has emerged as a useful tool in the triage of women with pelvic masses. Previously, triage of women with pelvic masses to management by either benign gynecology or gynecologic oncology was performed with an initial clinical risk assessment (ICRA) alone, involving a detailed history, exam, basic laboratory tests, and imaging. We sought to determine whether use of ROMA, which is calculated using CA125, HE4, and menopausal status for triage of women with pelvic masses, provides cost savings compared to triage based on ICRA alone. Methods: A health-economic decision model was developed to assess clinical and cost differences associated with referrals for patients presenting to their gynecologist or primary care physician with an adnexal mass. In our study, we modeled the differences of two clinical pathways that included 1) use of ICRA alone and 2) use of ROMA as a determining factor in referral to a gynecologic oncologist. Using previously reported accuracy rates and patient characteristics from a prospective, multicenter, blinded clinical trial (ClinicalTrial. gov identifier NCT00987649), we assessed triage of women with a pelvic mass using ICRA alone or ROMA and modeled the related lab testing, imaging, surgical procedures, and associated costs. Costs were estimated using current Medicare reimbursement rates. Results: A total of 423 patients with pelvic masses were included. Total healthcare costs for patients triaged for epithelial ovarian cancer (EOC) using ICRA alone were higher than when triaged by ROMA ($2,461,301 vs $2,428,628), a cost savings of 1.3%. While lab costs increased 55% when using ROMA ($16,006 vs $24,809), all other costs decreased, including total laparoscopy ($1,931,568 vs $1,896,314, -1.8% difference), total laparotomy ($436,910 vs $430,689, -1.4% difference), and total surgery ($2,368,479 vs $2,327,003, -1.8% difference) (Table 1). Repeat surgeries resulting from false negative ICRA were also reduced when using ROMA (8 vs 3), a 64% decrease. Notably, total healthcare costs were further reduced when including patients with low malignant potential (LMP) tumors ($2,646,738 vs $2,558,834, -3.3% difference) and analysis of all cancers ($2,847,829 vs $2,728,247, -4.2% difference). A similar reduction in repeat surgeries was noted in patients with LMP tumors (19 for ICRA, 7 for ROMA, -61% difference) and in all cancers (29 for ICRA, 14 for ROMA, -53% difference). Download : Download high-res image (119KB) Download : Download full-size image Conclusions: Triage of women with a pelvic mass using the more sensitive ROMA score compared to ICRA alone lowers overall healthcare costs. With fewer false negatives than ICRA alone, the ROMA score improves initial detection of malignancy and reduces second surgical treatments in women with pelvic masses.

Objectives: To investigate racial differences in uterine cancer histology in non-Hispanic Back (NHB) and non-Hispanic White (NHW) women with one or more cancer diagnoses as an extension of prior studies that excluded cases with multiple malignancies. Download : Download high-res image (552KB) Download : Download full-size image Methods: Women in the 18-region Surveillance, Epidemiology and End Results registry with an invasive uterine cancer diagnosed between 1975 and 2015 as a first or second of multiple malignancies relative a single malignancy were evaluated. Median age at diagnosis was compared using Wilcoxon test. Proportions between histologic and racial groups were compared using Chi-square test. Age-adjusted odds ratio (AOR) and 95% confidence interval (CI) for each high-risk uterine cancer histology were calculated for NHBs vs NHWs. Results: There were 237,823 with an invasive uterine cancer including 177,869 as a single diagnosis, 29,594 as a first of multiple malignancies and 30,380 as a second of multiple malignancies. The distribution of NHBs by the setting of the uterine cancer diagnosis was 10.1% as a single malignancy, 6.7% as a first of multiple malignancies and 8.5% as second of multiple malignancies. The median age for the uterine cancer diagnosis in NHBs vs NHWs was 3 vs 5 years younger when identified as a single or first malignancy compared with as a second malignancy, respectively (Table 1). The proportion of both NHBs and NHWs with grade 3 endometrioid cancer, serous cancer and carcinosarcoma was consistently higher in both NHBs and NHWs when diagnosed as a second malignancy compared with a single or first malignancy (P Conclusions: Racial differences in uterine serous cancer, clear cell cancer, carcinosarcoma and leiomyosarcoma but not in grade 3 endometrioid cancer were smaller in women with a prior cancer diagnosis and may reflect the impact of factors including ancestral admixture, germline vs. somatic alterations, genetic modifiers, epigenetic regulators, exposure to prior cancer treatment, cancer screening and social health determinants.

Objectives: While malignant peritoneal cytology is not the component of the current cancer staging schema, the collection of a peritoneal cytologic sample at the time of hysterectomy-based surgical staging for endometrial cancer is highly endorsed by multiple societies and organizations. Suspicious peritoneal cytology refers to the result of peritoneal cytology testing that is insufficient in either quality or quantity for a definitive diagnosis of malignancy. This study examined characteristics and survival outcomes related to suspicious peritoneal cytology in endometrial cancer. Methods: A population-based retrospective study by querying the National Cancer Institute's Surveillance, Epidemiology, and End Results Program was conducted. A total of 41,229 women with stage I-III endometrial cancer who had peritoneal cytologic sampling at hysterectomy from 2010 to 2016 were examined. A Cox proportional hazard regression model and a competing risk analysis with Fine-Gray model were fitted to assess survival outcome related to suspicious peritoneal cytology. Results: Suspicious peritoneal cytology was seen in 702 (1.7%) cases. On multivariable analysis, tumors related to suspicious peritoneal cytology had distinct characteristic for T and N stages compared to negative or malignant peritoneal cytology (all, P Download : Download high-res image (87KB) Download : Download full-size image Conclusions: Our study suggests that suspicious peritoneal cytology may be a prognostic factor for decreased survival in endometrial cancer. The results of our analysis call for a development of further studies highlighting the significance of suspicious peritoneal cytology in endometrial cancer.

Objective As a protective response, during starvation organisms withdraw energy from growth and reproduction to focus on cellular maintenance. Cancer cells cannot undergo this differential response which has been theorized as an adjunct to improve both the effect of chemotherapy treatment and reduce treatment side effects. We sought to investigate the feasibility and effect of short-term fasting in patients receiving chemotherapy for gynecologic malignancy. Methods A randomized control trial was conducted of women with gynecologic malignancies receiving at least 6 planned chemotherapy cycles. Fasting patients maintaining a water-only fast for 24 h before and 24 h following each chemotherapy cycle were compared to nonfasting patients. Treatment related side effects and quality of life (QOL) was assessed using NCCN-FACT FOSI-18 questionnaire. Results Analysis included data from 120 cycles of chemotherapy. The majority of patients had stage 3 and 4 malignancy requiring multi-agent chemotherapy. Eleven patients had ovarian, 8 had uterine, and 1 had cervical cancer. Ninety percent received taxane and platinum-based doublet therapy. Weight loss and unanticipated hospitalizations were similar between treatment groups. Fewer dose reductions or delays were seen in the fasting group. There was no significant difference in mean QOL scores, but fasting group QOL scores improved over the course of treatment to a level that reached the minimal clinically important difference. Conclusion A 48-h fast is well tolerated without increasing weight loss, hospital admissions, or chemotherapy dose reduction/delays. Fasting resulted in fewer treatment modifications and improved quality of life scores over the course of treatment.

Objective Vulvar cancer is a rare malignancy in the aging population, and optimizing treatment strategies requires large-scale investigation of the clinicopathological features of this disease. In Japan, no such surveys have been conducted in the past 30 years. This large-scale retrospective multi-center study aimed to examine the clinicopathological features of vulvar cancer in Japan. Methods Upon obtaining ethical approval by the participating institutions' review boards, the medical records of patients with vulvar cancer, who were treated between 2001 and 2010 were reviewed. The impact of clinicopathological factors on overall survival (OS) was investigated using a multivariate Cox regression model. Results After applying the inclusion and exclusion criteria, 1068 patients treated in 108 centers were included. The median age was 72 years. The disease was in stage I in 402 patients (37.6%), stage II in 249 patients (23.3%), stage III in 252 patients (23.6%), and stage IV in 165 patients (15.4%). Squamous cell carcinoma, Paget's disease, adenocarcinoma, and other diseases were diagnosed in 773 (72.4%), 154 (14.4%), 59 (5.5%), and 82 (7.7%) patients, respectively. Positive inguino-femoral lymph nodes were found in 265 (24.8%) patients. The 5-year OS rate for stage I, II, III, and IV vulvar cancer were 85.6%, 75.1%, 48.8%, and 40.0%, respectively. Conclusion Our study shows that advanced age, disease stage, histological diagnosis, tumor diameter, and lymph node metastases significantly affect the OS of patients with vulvar cancer in Japan.

OBJECTIVES: Reducing anastomotic leak rates after rectosigmoid resection and anastomosis is a priority in patients undergoing gynecologic oncology surgery. Therefore, we investigated the implications of performing near-infrared angiography (NIR) via proctoscopy to assess anastomotic perfusion at the time of rectosigmoid resection and anastomosis. METHODS: We identified all patients who underwent rectosigmoid resection and anastomosis for a gynecologic malignancy between January 1, 2013 and December 31, 2018. NIR proctoscopy was assessed via the PINPOINT Endoscopic Imaging System (Stryker). RESULTS: A total of 410 patients were identified, among whom NIR was utilized in 133 (32.4%). There were no statistically significant differences in age, race, BMI, type of malignancy, surgery, histology, FIGO stage, hypertension, diabetes, or preoperative chemotherapy between NIR and non-NIR groups. All cases of rectosigmoid resection underwent stapled anastomosis. The anastomotic leak rate was 2/133 (1.5%) in the NIR cohort compared with 13/277 (4.7%) in the non-NIR cohort (p=0.16). Diverting ostomy was performed in 9/133 (6.8%) NIR and 53/277 (19.9%) non-NIR patients (p

To identify the predictors of coexisting adnexa malignancy (CAM) before surgery for patients with G1/G2 endometrioid endometrial cancer (EEC).Patients with G1/G2 EEC who received surgery in Fudan University Shanghai Cancer Center from 1996 to 2017 were enrolled. Univariate and multivariate logistic regression were performed to identify the predictors for CAM, and the nomogram was constructed and evaluated the discrimination and calibration.Among the 1511 patients in the study cohort, 66 (4.4%) coexisted adnexa malignancy (51 metastatic and 15 synchronous primaries). In the univariate logistic regression analysis, CA125 level (35 U/ml), histologic grades, myometrial invasion depth in magnetic resonance imaging (MRI), adnexal involvement in MRI/surgical exploration (SEP) were found to be significant predictors for CAM (P .001, 0.047, 0.011,0.001, respectively). The multivariate analysis demonstrated that high CA125 level (P .001; OR: 2.945; 95%CI: 1.700-5.101), deep myometrial invasion (P = .011; OR: 2.194; 95%CI: 1.200-4.011), and suspected adnexal involvement in MRI/SEP (P .001; OR: 11.524; 95%CI: 6.726-19.744) were independent predictors for CAM (AUC = 0.786). In 338 patients with MMR results, eighty-seven (25.7%) were detected MSI-high. There were 5.7% (5/87) patients diagnosed with CAM in the MSI-high group compared with 4.4% (11/251) in the MSS group.A nomogram with pre- and intra-operative factors was constructed to predict CAM in G1/G2 EEC patients, which may help clinicians in decision-making for ovarian preservation for these patients.

Squamous cell carcinoma of the vulva is a rare female malignancy, with an incidence increasing with age. Unfortunately, one third of the patients are diagnosed with locally advanced disease, which constitutes a clinical challenge for the clinicians who treat these patients. The main challenges are represented by: 1. The primary site of the disease, which can be proximal to anatomical structures like the anal canal posteriorly, or the urethra and the bladder anteriorly, that in some circumstances cannot be spared without a bowel and/or urinary stoma; 2. The locoregional nodes that can be involved by the tumor, and they can be bulky, fixed or ulcerated; 3. The clinical condition of the patient, who may carry several comorbidities. Treatment modalities include radiation with or without chemotherapy, and surgery. In order to preserve the bowel and the urinary function without a permanent stoma, a personalized management with a multimodality approach is warranted. In this systematic review, we first clarify the different definitions of "locally advanced vulvar carcinoma". Secondly, we evaluated the different treatment modalities described in the literature, and the impact of the different treatment strategies on prognosis and on preservation of bowel/urinary function. Finally, we offer a possible algorithm that may help the clinicians in treating patients with these uncommon and challenging situations with a multidisciplinary approach.

Objectives In South Africa, where HIV prevalence among adults is 18.9%, cervical carcinoma is the second most common malignancy in women. However, oncology services are considerably more accessible in South Africa than in many neighbouring countries. This study reports five-year overall survival in a cohort of HIV-positive and -negative cervix carcinoma patients undergoing primary radiotherapy at a single institution in South Africa. Methods Prospective cohort study of all locally advanced cervix carcinoma patients referred for radiotherapy (EBRT) from July 2007 to November 2011. Overall survival (OS) was the primary end-point. Results A total of 492 patients commenced treatment with radical intent, including 71 HIV-positive patients (14.4%) and 421 HIV-negative patients (85.6%). Of the 433 who were prescribed standard fractionation EBRT, 384 were prescribed concurrent platinum-based chemotherapy (88.7%). Fewer HIV-positive than HIV-negative patients (58.5% vs. 76.1%; p = 0.007) completed ≥4 cycles. The OS of HIV-negative patients was 49.5% (95%CI; 44.6%–54.4%) at 5 years. The OS of HIV-positive patients was significantly lower, 35.9% (95% CI; 23.9%–48.0%) at 5 years (p = 0.002). In our Cox models, factors affecting outcome were HIV infection, stage IIIB disease, presence of hydronephrosis, and delivery of concurrent chemotherapy. Conclusion In our large cohort, HIV-positive patients had poorer survival than HIV-negative patients, however nearly 40% survived 5 years, justifying provision of the best standard of care to HIV-positive patients with cervical carcinoma.

Background Because of conflicting reports regarding the relationship between pelvic inflammatory disease (PID) and ovarian cancer, we performed an updated meta-analysis to investigate the association between PID and the risk of this malignancy. Methods Embase, PubMed, and Web of Science were searched up until November 1, 2019. Hazard ratios (HRs), along with 95% confidence intervals (CIs), were calculated to analyse outcomes. Results We included 16 studies in this meta-analysis. PID was associated with an increased risk of ovarian cancer (HR 1.18, 95% CI 1.13 to 1.22; I2 = 41%). In subgroup analyses according to ethnicity, study design, tumour invasiveness, and type of ovarian cancer, PID was significantly associated with ovarian cancer in all subgroups. The lowest heterogeneity (I2 = 0% to 38%) was observed for associations between PID and ovarian cancer in Asian patients (HR 1.25, 95% CI 1.10 to 1.42), ovarian cancer in case-control studies (HR 1.15, 95% CI 1.08 to 1.23), invasive ovarian cancer (HR 1.25, 95% CI 1.20 to 1.30), borderline ovarian cancer (HR 1.28, 95% CI 1.19 to 1.37), and non-serous ovarian cancer (HR 1.15, 95% CI 1.07 to 1.24). Conclusions This updated meta-analysis demonstrated that PID is associated with an increased risk of ovarian cancer. Future large, well-designed studies are necessary to corroborate our findings.

PURPOSE. Brachytherapy is integral to vaginal cancer treatment and is typically delivered using an intracavitary single-channel vaginal cylinder (SCVC) or an interstitial brachytherapy (ISBT) applicator. Multi-channel vaginal cylinder (MCVC) applicators allow for improved organ-at-risk (OAR) sparing compared to SCVC while maintaining target coverage. We present clinical outcomes of patients treated with image-based high dose-rate (HDR) brachytherapy using a MCVC. METHODS AND MATERIALS. Sixty patients with vaginal cancer (27% primary vaginal and 73% recurrence from other primaries) were treated with combination external beam radiotherapy (EBRT) and image-based HDR brachytherapy utilizing a MCVC if residual disease thickness was 7 mm or less after EBRT. All pts received 3D image-based BT to a total equivalent dose of 70–80 Gy. RESULTS. The median high-risk clinical target volume was 24.4 cm(3) (interquartile range [IQR], 14.1), with a median dose to 90% of 77.2 Gy (IQR, 2.8). After a median follow-up of 45 months (range, 11–78), the 4-year local-regional control, distant control, DFS, and OS rates were 92.6%, 76.1%, 64.0%, and 67.2%, respectively. The 4-year LRC rates were similar between the primary vaginal (92%) and recurrent (93%) groups (p = 0.290). Pts with lymph node positive disease had a lower rate of distant control at 4 years (22.7% vs. 89.0%, p < 0.001). There were no Grade 3 or higher acute complications. The 4-year rate of late Grade 3 or higher toxicity was 2.7%. CONCLUSIONS. Clinical outcomes of pts with primary and recurrent vaginal cancer treated definitively in a systematic manner with combination EBRT with image-guided HDR BT utilizing a MCVC applicator demonstrate high rates of local control and low rates of severe morbidity. The MCVC technique allows interstitial implantation to be avoided in select pts with ≤7 mm residual disease thickness following EBRT while maintaining excellent clinical outcomes with extended 4-year follow-up in this rare malignancy.

Objective Extra-pulmonary small cell carcinomas of the gynecologic tract (EPSCC-GTs) are a rare group of aggressive malignancies associated with poor prognoses and limited treatment options. Here, we review the clinical and molecular aspects of EPSCC-GTs and discuss how understanding their molecular features can assist in their diagnosis and the identification of novel effective treatments. Methods We searched PubMed and Scopus for articles using the following keywords: "small cell carcinoma" in combination with "neuroendocrine", "ovary", "vagina", "fallopian tube", "vulva", "endometrium", "uterus", "cervix", or "gynecologic". Articles were limited to those published in English from January 1984 to October 2017. Results EPSCC-GTs account for 2% of all gynecologic malignancies. The molecular features of EPSCC-GTs are largely understudied and unknown, with the exception of small cell carcinoma (SCC) of the ovary, hypercalcemic type (SCCOHT) and SCC of the cervix (SCCC). In nearly all cases, SCCOHT displays mutation in a single gene, SMARCA4 , a member of the SWI/SNF chromatin remodeling complex. The loss of expression of the SWI/SNF protein SMARCA2 is another feature of SCCOHT. Dual negative staining for SMARCA2 and SMARCA4 is specific for SCCOHT and is generally used by gynecologic pathologists for the accurate diagnosis of this malignancy. Mutational analysis of SCCC has shown alterations in PIK3CA , KRAS and TP53 , of which the last is the most common, although other actionable mutations have been identified. The molecular features of other EPSCC-GTs are largely unknown. Conclusions Due to their rarity, the majority of EPSCC-GTs are understudied and poorly understood. As demonstrated in the case of SCCOHT, unraveling the mutational profiles of these tumors can lead to improved diagnosis and the identification of novel therapeutic targets.

Objective To analyze whole exome sequencing (WES) data on ovarian clear cell carcinoma (OCCC) in Korean patients via the technique of next generation sequencing (NGS). Genomic profiles were compared between endometriosis-associated OCCC (EMS-OCCC) and Non-EMS-OCCC. Methods We used serum samples and cancer tissues, stored at the Seoul National University Hospital Human Biobank, that were initially collected from women diagnosed with OCCC between 2012 and 2016. In total, 15 patients were enrolled: 5 with pathologically confirmed EMS-OCCC and 10 with Non-EMS-OCCC. We performed NGS WES on 15 fresh frozen OCCC tissues and matched serum samples, enabling comprehensive genomic characterization of OCCC. Results OCCC was characterized by complex genomic alterations, with a median of 178 exonic mutations (range, 111-25,798) and a median of 343 somatic copy number variations (range, 43-1,820) per tumor sample. In all, 54 somatic mutations were discovered across 14 genes, including PIK3CA (40%), ARID1A (40%), and KRAS (20%) in the 15 Korean OCCCs. Copy number gains in NTRK1 (33%), MYC (40%), and GNAS (47%) and copy number losses in TET2 (73%), TSC1 (67%), BRCA2 (60%), and SMAD4 (47%) were frequent. The significantly altered pathways were associated with proliferation and survival (including the PI3K/AKT, TP53, and ERBB2 pathways) in 87% of OCCCs and with chromatin remodeling in 47% of OCCCs. No significant differences in frequencies of genetic alterations were detected between EMS-OCCC and Non-EMS-OCCC groups. Conclusion We successfully characterized the genomic landscape of 15 Korean patients with OCCC. We identified potential therapeutic targets for the treatment of this malignancy.

Objectives: The American Society of Clinical Oncology (ASCO) recommends early palliative care assessment (PCA) for patients with advanced or recurrent malignancy. We report initial findings of a protocol designed to meet this standard. Methods: We used key stakeholders from a multi-disciplinary team of gynecologic oncologists and palliative care providers to inform an initiative to increase compliance with the ASCO recommendation. As a result, in April of 2020, a quality improvement protocol was initiated whereby a palliative care consult was ordered for all patients with a gynecologic cancer diagnosis admitted to the gynecologic oncology service. Admissions for 23-hour observation and those who did not receive outpatient care from the gynecology oncology team were excluded. Admissions meeting the inclusion criteria 3 months prior to protocol initiation (PPI) were compared to admissions in months 4-6 after protocol initiation (API) to allow for a 3 month wash out period. A retrospective chart review was completed to identify clinicodemographic characteristics for each admission. The primary outcome was completion of inpatient PCA calculated per admission. Secondary outcomes were palliative care and hospice interventions, and advanced care documentation (code status, power of attorney or living will). T-test, Fisher's exact test, relative risk (RR) and exact binomial confidence intervals (CIs) were used. Results: There were 152 admissions, 82 PPI and 70 API. The mean age was 61 years (±13), the majority were White (49%) or Black (39%), had a primary diagnosis of ovarian/primary peritoneal (37%) or uterine cancer (32%) and had advanced/recurrent disease (93%). The majority were medical admissions (n=91, 62%) with 10 (7%) for radiation and 44 (30%) for postoperative care. The demographics of admissions PPI and API are summarized in Table 1. PCA was significantly higher API versus PPI (63% vs. 38%, RR 1.95, 95% CI 1.26-3.02). Additionally, API admissions were more likely to receive follow-up outpatient PCA referrals (20% vs 5%, p=0.005). Death (inpatient or outpatient) was more commonly observed in Black patients compared to White (61% vs 39%, p=0.049). Of the 24 patients who died during the study period, 7 died inpatient. Notably all patients who died inpatient were Black (0% White vs 0% other vs 100% Black p=0.03). Documentation of goals of care discussions, code status, or power of attorney did not change after protocol implementation (RR 1.14, CI 0.90-1.41). Conclusions: This universal palliative care consultation protocol improved the frequency of PCA on an inpatient gynecologic oncology service and increased outpatient PCA referrals, but did not achieve complete compliance. Early observations have also identified a potential disparity in frequency and location of death that warrants further exploration. The next phase of this QI initiative will explore and address barriers to achieving universal PCA.

Objectives: Minimally invasive surgery (MIS) is the standard of care for gynecologic and gynecologic oncology conditions. For large specimen retrieval, morcellation is a controversial option due to concerns of undetected malignancy and dissemination. Our objective was to compare safety and discharge outcomes for patients with mini-laparotomy (ML) versus morcellation for large specimen retrieval during robotic cases. Methods: In this retrospective cohort study of patients who underwent robotic gynecologic surgery (RGS) from January 2013 to June 2016, we compared intraoperative and postoperative outcomes for patients undergoing ML or morcellation. Mode of specimen delivery was at the discretion of the surgeon. The ML group consisted of patients who at the completion of RGS underwent an abdominal ML incision and the morcellation group consisted of patients who underwent manual or power morcellation for specimen delivery. Outcomes were analyzed using Mann-Whitney U test, Chi-squared/Fisher's exact tests, and multivariate logistic models. Results: Of the 2,126 patients undergoing RGS, 154 (7.2%) underwent a ML for specimen retrieval and 834 (39.2%) underwent specimen removal with morcellation. Median age was greater for the ML compared to morcellation (45 [IQR 37.1-52.8] vs 40 [IQR 35.0-46.0]; p Download : Download high-res image (80KB) Download : Download full-size image Conclusions: Despite increased EBL and operative time, ML for specimen retrieval does not affect postoperative outcomes such as time to discharge, wound infection, complications, need for blood transfusion, or re-admission rates. These results highlight that ML may play an important role when removing large specimens while still enabling patients to have a successful MIS procedure and same day discharge.

Objectives: High quality sleep is important for maintaining immune function, wound healing, and physical and emotional well-being. Our objective was to determine the quality of sleep in women admitted for post-operative recovery after surgical management for a suspected gynecologic malignancy. Methods: We surveyed women who were admitted to the hospital for at least one midnight after undergoing a surgical procedure for a suspected gynecologic malignancy between September 2020 and October 2020. The Pittsburgh Sleep Quality Index (19 item self-report questionnaire) was used to assess baseline sleep quality in the month prior to the planned procedure. The Richards-Campbell Sleep Questionnaire (5 item self-report survey) was used to assess nightly sleep quality during the subject's hospitalization. A chart review was also completed to assess for patient or surgical factors associated with poor sleep. Results: Twenty-three patients met the study criteria, of which 20 (87%) agreed to participate. The mean age was 58 (SD = 15), the mean BMI was 32.2 (SD = 8.3). Eighty percent of patients underwent surgery for confirmed malignancy, with uterine cancer (30%) and ovarian cancer (25) comprising the majority of diagnoses. The median admission length was 2 days interquartile range (IQR = 1-4.5), fifty percent of patients underwent an open procedure. Based on Pittsburgh Sleep Quality Index (PSQI) results, 15 patients (75%) reported poor sleep quality in the month prior to their surgery. The total RCSQ score was the worst on the first post-operative day (38.3, SD = 28.3). Sleep quality improved on post-operative day 2 (67.3, SD = 12.2), but then declined over the remainder of the hospitalization. Conclusions: Sleep quality is poor in women hospitalized after surgery with gynecologic oncologists. Sleep is an under recognized factor in optimizing postoperative recovery. The high prevalence of poor sleep during hospital-based post-operative recovery among gynecologic oncology patients warrants the development of evidence-based interventions for improving sleep and sleep quality.

Objectives: Opportunistic bilateral oophorectomy (BO) is often considered in patients undergoing benign hysterectomy, but the degree to which BO reduces the incidence of ovarian cancer in this population remains unclear and is important for patient decision-making. Methods: We performed a population-based cohort study of all women (≥20 years) undergoing hysterectomy for benign indications from 1996-2015 in Ontario, Canada, followed to December 2019. Patients with ovarian pathology at hysterectomy, previous breast or gynecologic cancer, or evidence of genetic susceptibility to malignancy were excluded. Ovarian cancers and deaths were ascertained from the Ontario Cancer Registry. Inverse probability of treatment weighted Fine & Gray subdistribution hazard models were used to examine the effect of BO on ovarian cancer incidence and death, while accounting for competing risks and adjusting for demographic factors, gynecologic conditions, and comorbidities. Results: We identified 249,924 patients (BO 61,203 [25%]; ovarian conservation 188,721 [75%]) with median age 45 years (interquartile range [IQR] 40-52). Over median follow-up of 14 years (IQR 9-19), 584 women developed ovarian cancer (0.2%) and 17,052 died (6.8%) from any cause. Baseline characteristics were balanced after IPT weighting (standardized differences Conclusions: BO results in a small absolute reduction in incident ovarian cancer among women undergoing benign hysterectomy. Population-average risk estimates derived in this study are generalizable, directly address the limitations of previous work, and should be used to counsel patients preoperatively.

This work was supported by Cancer Research UK (CRUK) (grant number C19335/A21351, to MJG and HK) . The metabolomics infrastructure in the Division of Cancer, Imperial College London is supported by the Imperial College Experimental Can-cer Medicine Centre, the This work was supported by Cancer Research UK (CRUK) (grant number C19335/A21351, to MJG and HK) . The metabolomics infrastructure in the Division of Cancer, Imperial College London is supported by the Imperial College Experimental Can-cer Medicine Centre, the Imperial College Cancer Research UK Centre and the NIHR Imperial Biomedical Research Centre (APS & HK) . The co-ordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Im-perial Biomedical Research Centre (BRC) . The national cohorts are sup-ported by: Danish Cancer Society (Denmark) ; Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France) ; German Cancer Aid, German Cancer Research Center (DKFZ) , German Institute of Human Nutrition PotsdamRehbruecke (DIfE) , Federal Ministry of Education and Research (BMBF) (Germany) ; Associazione Italiana per la Ricerca sul CancroAIRCItaly, Compagnia di SanPaolo and National Research Council (Italy) ; Dutch Ministry of Public Health, Welfare and Sports (VWS) , Netherlands Can-cer Registry (NKR) , LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland) , World Cancer Research Fund (WCRF) , Statistics Netherlands (The Netherlands) ; Health Research Fund (FIS) -Instituto de Salud Carlos III (ISCIII) , Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology-ICO (Spain) ; Swedish Cancer Society, Swedish Research Council and County Councils of Skkne and Vasterbotten (Sweden) ; Cancer Research UK (14136 to EPICNorfolk; C8221/A29017 to EPICOxford) , Medical Research Council (1000143 to EPICNorfolk; MR/M012190/1 to EPICOxford) . (United Kingdom) ., Background. Endometrial cancer is strongly associated with obesity and dysregulation of metabolic factors such as estrogen and insulin signaling are causal risk factors for this malignancy. To identify additional novel metabolic pathways associated with endometrial cancer we performed metabolomic analyses on pre-diagnostic plasma samples from853 case-control pairs fromthe European Prospective Investigation into Cancer and Nutrition (EPIC). Methods. A total of 129metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexoses, and sphingolipids) were measured by liquid chromatography-mass spectrometry. Conditional logistic regression estimated the associations of metabolites with endometrial cancer risk. An analysis focusing on clusters of metabolites using the bootstrap lasso method was also employed. Results. After adjustment for body mass index, sphingomyelin [SM] C18:0was positively (OR1SD: 1.18,95%CI: 1.05–1.33), and glycine, serine, and free carnitine (C0) were inversely (OR1SD: 0.89, 95% CI: 0.80–0.99; OR1SD: 0.89, 95% CI: 0.79–1.00 and OR1SD: 0.91, 95% CI: 0.81–1.00, respectively) associated with endometrial cancer risk. Serine, C0 and two sphingomyelins were selected by the lasso method in >90% of the bootstrap samples. The ratio of esterified to free carnitine (OR1SD: 1.14, 95% CI: 1.02–1.28) and that of short chain to free acylcarnitines (OR1SD: 1.12, 95% CI: 1.00–1.25) were positively associated with endometrial cancer risk. Further adjustment for C-peptide or other endometrial cancer risk factors only minimally altered the results. Conclusion. These findings suggest that variation in levels of glycine, serine, SMC18:0 and free carnitine may represent specific pathways linked to endometrial cancer development. If causal, these pathways may offer novel targets for endometrial cancer prevention., Cancer Research UK C19335/A21351, Imperial College Experimental Cancer Medicine Centre Imperial College Cancer Research UK Centre, NIHR Imperial Biomedical Research Centre, World Health Organization, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Danish Cancer Society, Ligue Contre le Cancer (France) Institut Gustave Roussy (France) Mutuelle Generale de l'Education Nationale (France), Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe, German Cancer Research Center (DKFZ) (Germany) German Institute of Human Nutrition PotsdamRehbruecke (DIfE) (Germany), Federal Ministry of Education & Research (BMBF), Fondazione AIRC per la ricerca sul cancro Compagnia di San Paolo Consiglio Nazionale delle Ricerche (CNR), Netherlands Government Netherlands Government, World Cancer Research Fund International (WCRF), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII) (Spain), Junta de Andalucia, Regional Government of Asturias (Spain), Regional Government of Basque Country (Spain), Regional Government of Murcia (Spain), Regional Government of Navarra (Spain), Catalan Institute of Oncology-ICO (Spain), Swedish Cancer Society, Swedish Research Council, County Council of Skkne (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK 14136 C8221/A29017, UK Research & Innovation (UKRI), Medical Research Council UK (MRC) 1000143 MR/M012190/1

Objectives: Investigate the average facility volume of minimally invasive radical hysterectomy (MIRH) and the impact of facility volume on the outcomes of patients with apparent early-stage cervical carcinoma. Methods: The National Cancer Database was accessed and patients with a cervical malignancy who underwent MIRH between 2010 and 2016 were identified. Annual facility volume was calculated, and high-volume centers were defined as those who performed at least 6 procedures per year. Impact of facility volume on inpatient stay, readmission rate and overall survival (OS) was evaluated for patients with apparent early-stage disease and no history of another tumor with available survival data. OS was compared with the log-rank test while a multivariate Cox model was constructed to control for confounders. Results: A total of 5806 patients with cervical cancer underwent MIRH between 2010-2016 in 669 facilities. Median facility volume was 1.5 cases per year; only 19 facilities performed at least 6 MIRH per year. A total of 3529 patients with apparent early-stage disease who underwent MIRH were selected; 16.7% were managed at a high-volume center. Patient age, race, and presence of co-morbidities and tumor extension was comparable between high and low-volume centers. Rate of robotic-assisted surgery was 22.7% and 20.9% for patients undergoing surgery at high and low-volume centers, p=0.33. Conversion to open surgery (2% vs 2.9%, p=0.24), and 30-day readmission (5.4% vs 4%, p=0.12) rates were comparable between high and low-volume centers. Patients at high-volume centers were more likely to be discharged within 1 day (65.6% vs 60.5%, p=0.022). There was no difference in the OS between patients who had MIRH at a high or low- volume centers, p=0.14; 3-year OS rates were 92.5% and 94.2% respectively. After controlling for confounders, patients who had MIRH at a high-volume center did not have better survival (HR: 1.32, 95% CI: 0.96, 1.33). Conclusions: Given the rarity of cervical cancer, MIRH was a highly de-centralized procedure with the vast majority of centers not achieving a large annual surgical volume. However, we could not observe a direct impact of hospital volume on outcomes for patients with apparent early stage disease.

Objectives: Uterine sarcomas frequently harbor non-actionable oncogenic mutations, limiting the use of targeted therapies. Alterations in the potentially targetable CDK4/6 pathway have recently been described. We explored clinicopathologic differences between uterine sarcomas with CDKN2A loss-of-function genetic alterations and TP53 loss-of-function mutations and sought to determine whether these molecularly defined uterine sarcomas differ in prognosis among early stage patients. Methods: Patients with uterine sarcoma were consented to a prospective study of tumor-normal targeted massively parallel sequencing of up to 468 cancer-related genes. Clinicopathologic data were abstracted from the medical record. Fisher's exact tests and Mann-Whitney-U tests were employed to compare categorical and continuous variables, respectively. Kaplan-Meier curves were used to estimate survival, compared using log-rank test. Results: A total of 229 patients with uterine leiomyosarcoma (LMS; n=191) or undifferentiated uterine sarcoma (UUS; n=38) were identified. The most common genomic alterations were TP53 (62%, n=142) and RB1 (41%, n=94) mutations/homozygous deletions. Furthermore, 10% (n=23) harbored CDKN2A loss-of-function mutations or homozygous deletions, which were mutually exclusive with both TP53 and RB1 alterations (p Download : Download high-res image (93KB) Download : Download full-size image Conclusions: CDKN2A loss-of-function alterations, found in 10% of uterine sarcomas, are mutually exclusive with TP53 and RB1 alterations commonly present in this malignancy. CDKN2A altered uterine sarcoma may be a genomically and morphologically distinct tumor. We demonstrate poor survival outcomes for patients with early stage disease harboring these CDKN2A alterations. Identifying uterine sarcomas with CDKN2A loss-of-function alterations provides rationale for testing cyclin-dependent kinase inhibitors in this molecular subset.

Objectives: To evaluate the perioperative outcomes and oncologic outcomes of patients undergoing pelvic exenteration, first described by Alexander Brunschwig in 1948, for non-ovarian gynecologic malignancies at a comprehensive cancer center. Methods: All patients who underwent exenteration at our institution from 1/2010-12/2019 were identified. Patients with non-ovarian gynecologic malignancies were included. Patients undergoing palliative exenteration were included for perioperative outcomes but excluded from the survival analysis. Post-operative complications were defined as early (≤30 days) and delayed (31-180 days). Complications were graded using a validated institutional secondary surgical events system. Major complications were defined as Grade 3 or above which would, at minimum, require surgical, endoscopic, or radiological intervention. Appropriate statistical analyses were performed. Results: One-hundred patients were identified. Eighty-nine (89%) received treatment for recurrent disease, 5 (5%) for primary disease, 1 (1%) for persistent disease, and 5 (5%) received palliative treatment. The most common cancer type was cervical (n=30, 30%), followed by vulvar (n=27, 27%), uterine (n=24, 24%), and vaginal (n=19, 19%). The most common histologies were squamous cell carcinoma (n=61, 61%), endometrioid carcinoma (n=18, 18%), and adenocarcinoma (n=13, 13%). Sixty-two (62%) patients had total exenteration, 30 (30%) anterior exenteration, 8 (8%) posterior exenteration. The median age at time of surgery was 61.3 years (range, 28-86 years). There were no intraoperative deaths or deaths within 30 days of surgery. Six patients expired within the delayed time frame, including 1 (16.7%) from respiratory failure and 5 (83.3%) from aggressive progression of disease. Ninety-seven (97%) patients experienced a perioperative complication: 49 (50%) early, 1 (1%) delayed, 47 (48%) both early and delayed. Fifty/100 patients (50%) had a major complication: 22/50 (44%) early, 19/50 (38%) delayed, 9/50 (18%) both early and delayed. We did not identify any variables statistically associated with the development of a complication, including exenteration type, initial malignancy type, conduit type, operative time, estimated blood loss, or tumor volume. The median follow-up time for the entire cohort was 27.6 months (range, 1.0-117.5). The median follow-up time for survivors was 38.0 months (range, 1.0-117.5). The 3-year PFS was 61.0%, and the 3-year OS was 61.6%. There are 58 total survivors (58%), of whom 16 (28%) and 4 (7%) remain alive after 5 and 10 years, respectively. Conclusions: The complication rate for pelvic exenteration remains high, although we identified no variables showing association with the development of a complication. However, the lack of perioperative mortality, and improved oncologic outcomes, exemplify the advancements of this surgical approach since its inception.

Objectives: The goal of this study was to compare the number of new, solid malignancy diagnoses at a single, public safety-net referral institution before and after the issuance of a statewide COVID-19 stay-at-home order. Methods: Patients with a new diagnosis of solid malignancy between 9/25/2019 and 9/9/2020 were identified by querying pathology reports for ‘carcinoma,’ ‘sarcoma,’ or ‘lymphoma.’ Patients under 18 years and those with recurrent cancers were excluded. New cancer diagnoses were then compared in two cohorts. The exposure cohort (‘Post-COVID-19’) included all patients with new, solid malignancy diagnoses from the first day of the mandated stay-at-home order in California, 3/19/2020, until 9/9/2020 (175 days). The control cohort (‘Pre-COVID-19’) included all patients with new, solid malignancy diagnoses during an equivalent time period before the statewide order, from 9/25/2019 until 3/18/2020 (175 days). Results: A total of 718 patients were found to have new histologic diagnoses of carcinoma, sarcoma, or lymphoma between 9/25/2019 and 9/9/2020. There were 409 patients diagnosed Pre-COVID-19 and 309 patients diagnosed Post-COVID-19, for an overall 24.44% decrease in the number of new, solid malignancy diagnoses (Table 1). There were 51 patients diagnosed with a new gynecologic malignancy Pre-COVID-19 compared to 37 patients Post-COVID-19, representing a 27.45% relative decrease in new diagnoses. Subgroup analysis of gynecologic malignancies revealed a 29.62 to 57.14% decrease in the number of new uterine, cervical and vaginal cancer diagnoses, while the number of new ovarian cancer diagnoses remained relatively stable. Download : Download high-res image (57KB) Download : Download full-size image Conclusions: In our public safety net institution, which serves a largely non-White, 70% Latinx patient population, there has been a significant decrease in the total number of new, solid malignancy diagnoses since the start of COVID-19 pandemic. Of gynecologic malignancies, the impact has been most pronounced in uterine, cervical and vaginal cancer diagnoses. In contrast, new ovarian cancer diagnoses have remained relatively stable. This may be explained by the different ways each of these cancers presents. Uterine cancers typically present with abnormal bleeding, a symptom often perceived as tolerable and shared with many benign conditions, and may be missed if patients defer outpatient or emergency encounters. Cervical and vaginal cancers are most often identified through outpatient screening practices, and may be missed if in-person clinic encounters are deferred. The relatively stable number of ovarian cancer diagnoses likely reflects the lack of screening and the significant symptom burden common at time of diagnosis, leading patients to seek care even during the pandemic. The results of this study indicate that delaying routine cancer screening and work-up for potential early cancer symptoms, as a result of the COVID-19 pandemic, is diminishing our ability to presciently diagnose cancer.

Objectives: NCCN recommends testing for BRCA based on personal and family history of cancer and known mutations. BRCA testing can have preventative implications with increased screening and risk-reducing surgery if a mutation is diagnosed. The objective of this study was to determine the number of patients meeting BRCA testing criteria prior to a personal diagnosis of a BRCA related-cancer (BRC) and reasons for genetic testing in those without a BRC among a cohort of BRCA carriers. Methods: This was a retrospective cohort study at three satellite sites within one institution from 2014 to 2018. Patients were identified by ICD-10 codes associated with hereditary disposition of malignancy (Z15.01, Z15.02, Z15.09, Z15.89, C50.919, Q99.8, C54.1). Patients with BRCA1 and BRCA2 pathogenic mutations with and without a personal history of cancer were included in this study; BRCA1/2 not specified, variants of uncertain significance, and unknown dates of testing and cancer diagnosis were excluded. NCCN testing criteria were applied to those who underwent testing with and without a diagnosis of a BRCA-related cancer (BRC). Outcomes of interest were the number of patients meeting NCCN criteria for BRCA testing and reasons for testing in those without a BRC. Chi-square and Mann-Whitney U tests were performed with significance at p Download : Download high-res image (129KB) Download : Download full-size image Results: Six hundred thirty-eight patients met inclusion criteria; 331 (51.9%) had a BRCA1 mutation and 312 (48.9%) a BRCA2 mutation. The median age of genetic testing was 40 (range 19-90). Of 281 patients with a personal history of a BRC, 193 (68.7%) underwent genetic testing after a diagnosis of cancer. The majority (205/281, 73.0%) of these patients with a cancer diagnosis met NCCN criteria for testing by either family history of mutation or family history of cancer. Patients with a family history of known mutation were more likely to be tested prior to their cancer diagnosis (44/88, 50.0% vs 49/193, 25.4%, p Conclusions: Almost 70% of patients with BRCA mutations and BRC undergo genetic testing after a personal cancer diagnosis; approximately 75% of these patients met criteria for testing based on family history of cancer or family history of mutation. Those with a family history of a mutation were twice as likely to be tested before their cancer diagnosis. Identification of these mutations prior to development of cancer is critical to improve screening and preventative measures. Increased education of genetic testing criteria and methods to improve identification and cascade testing with outreach efforts are desperately needed.

Objective Women with gynecologic malignancies will be cured or may become long-term survivors. Management of menopausal symptoms is important in addressing their quality of life. We review the benefit and safety of hormone therapy use in these patients. Methods MEDLINE was searched for studies on menopause management published in English through December of 2016. Results Available data suggest that short-term use of hormone therapy in gynecologic cancer patients who do not have an estrogen-dependent malignancy do not adversely impact oncologic outcome and results in improvement of menopausal vasomotor and genitourinary symptoms. Evidence regarding safety of hormone therapy use in women with estrogen-dependent gynecologic malignances is currently lacking. Conclusions Candidates for hormone therapy in gynecologic oncology include women with menopausal symptoms diagnosed with low-grade, early-stage endometrial cancer, cervical, vulvar and vaginal cancer, and ovarian cancer.