Long-term follow-up of efficacy and safety of selinexor maintenance treatment in patients with TP53wt advanced or recurrent endometrial cancer: A subgroup analysis of the ENGOT-EN5/GOG-3055/SIENDO study.

OBJECTIVE: To report long-term efficacy and safety of selinexor maintenance therapy in adults with TP53 wild-type (TP53wt) stage IV or recurrent endometrial cancer (EC) who achieved partial remission (PR) or complete remission (CR) following chemotherapy. METHODS: Analysis of the prespecified, exploratory subgroup of patients with TP53wt EC from the phase 3 SIENDO study was performed. Progression-free survival (PFS) benefit in patients with TP53wt EC and across other patient subgroups were exploratory endpoints. Safety and tolerability were also assessed. RESULTS: Of the 263 patients enrolled in the SIENDO trial, 113 patients had TP53wt EC; 70/113 (61.9%) had TP53wt/proficient mismatch repair (pMMR) EC, and 29/113 (25.7%) had TP53wt/deficient mismatch repair (dMMR) EC. As of April 1, 2024, the median PFS (mPFS) for TP53wt patients who received selinexor compared with placebo was 28.4 versus 5.2 months (36.8-month follow-up, HR 0.44; 95% CI 0.27-0.73). A benefit in mPFS was seen with selinexor versus placebo regardless of MMR status (patients with TP53wt/pMMR EC: 39.5 vs 4.9 months, HR 0.36; 95% CI 0.19-0.71; patients with TP53wt/dMMR EC: 13.1 vs 3.7 months, HR 0.49; 95% CI 0.18-1.34). Selinexor treatment was generally manageable, with no new safety signals identified. CONCLUSION: In the phase 3 SIENDO study, selinexor maintenance therapy showed a promising efficacy signal and a manageable safety profile in the prespecified subgroup of patients with TP53wt EC who achieved a PR or CR following chemotherapy. These results are being further evaluated in an ongoing randomized phase 3 trial (NCT05611931).

Vulvar Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Vulvar cancer is annually diagnosed in an estimated 6,470 individuals and the vast majority are histologically squamous cell carcinomas. Vulvar cancer accounts for 5% to 8% of gynecologic malignancies. Known risk factors for vulvar cancer include increasing age, infection with human papillomavirus, cigarette smoking, inflammatory conditions affecting the vulva, and immunodeficiency. Most vulvar neoplasias are diagnosed at early stages. Rarer histologies exist and include melanoma, extramammary Paget's disease, Bartholin gland adenocarcinoma, verrucous carcinoma, basal cell carcinoma, and sarcoma. This manuscript discusses recommendations outlined in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for treatments, surveillance, systemic therapy options, and gynecologic survivorship.

Niraparib and dostarlimab for the treatment of recurrent platinum-resistant ovarian cancer: results of a Phase II study (MOONSTONE/GOG-3032).

OBJECTIVE: This study assessed the efficacy, safety, and health-related quality of life (HRQoL) of the treatment regimen of dostarlimab, a programmed death-1 inhibitor, combined with niraparib, a poly (ADP-ribose) polymerase inhibitor, in patients with BRCA wild type (BRCAwt) recurrent platinum-resistant ovarian cancer (PROC) who had previously received bevacizumab treatment. METHODS: This Phase II, open-label, single-arm, multicenter study, conducted in the USA, enrolled patients with recurrent PROC to receive niraparib and dostarlimab until disease progression or unacceptable toxicity (up to 3 years). A preplanned interim futility analysis was performed after the first 41 patients had undergone ≥1 radiographic evaluation (approximately 9 weeks from the first treatment). RESULTS: The prespecified interim futility criterion was met and the study was therefore terminated. For the 41 patients assessed, the objective response rate (ORR) was 7.3% (95% confidence interval: 1.5-19.9); no patients achieved a complete response, 3 patients (7.3%) achieved a partial response (duration of response; 3.0, 3.8, and 9.2 months, respectively), and 9 patients (22.0%) had stable disease. In total, 39 patients (95.1%) experienced a treatment-related adverse event, but no new safety issues were observed. HRQoL, assessed using FOSI, or Functional Assessment of Cancer Therapy - Ovarian Symptom Index scores, worsened over time compared with baseline scores. CONCLUSIONS: The study was terminated due to the observed ORR at the interim futility analysis. This highlights a need for effective therapies in treating patients with recurrent BRCAwt PROC.

NCCN Guidelines® Insights: Cervical Cancer, Version 1.2024.

The NCCN Guidelines for Cervical Cancer provide recommendations for all aspects of management for cervical cancer, including the diagnostic workup, staging, pathology, and treatment. The guidelines also include details on histopathologic classification of cervical cancer regarding diagnostic features, molecular profiles, and clinical outcomes. The treatment landscape of advanced cervical cancer is evolving constantly. These NCCN Guidelines Insights provide a summary of recent updates regarding the systemic therapy recommendations for recurrent or metastatic disease.

Uterine Neoplasms, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology.

Adenocarcinoma of the endometrium (also known as endometrial cancer, or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. It is estimated that 65,950 new uterine cancer cases will have occurred in 2022, with 12,550 deaths resulting from the disease. Endometrial carcinoma includes pure endometrioid cancer and carcinomas with high-risk endometrial histology (including uterine serous carcinoma, clear cell carcinoma, carcinosarcoma [also known as malignant mixed Müllerian tumor], and undifferentiated/dedifferentiated carcinoma). Stromal or mesenchymal sarcomas are uncommon subtypes accounting for approximately 3% of all uterine cancers. This selection from the NCCN Guidelines for Uterine Neoplasms focuses on the diagnosis, staging, and management of pure endometrioid carcinoma. The complete version of the NCCN Guidelines for Uterine Neoplasms is available online at NCCN.org.

The impact of distance to closest negative margin on survival after pelvic exenteration.

OBJECTIVE: To determine the effect of distance to closest negative margin on survival after pelvic exenteration (PE). METHODS: In this retrospective analysis of PE at Moffitt Cancer Center from 2000 to 2019, baseline characteristics, clinical details, and outcomes were ascertained. Distance to closest negative margin was measured. Close and distant negative margins were defined as <3 mm and ≥3 mm from malignancy to nearest surgical margin, respectively. Overall survival (OS) and progression-free survival (PFS) were determined, and Kaplan-Meier curves were compared. Cox proportional hazards regression was used to examine the association of margin status with OS and PFS. RESULTS: Of 124 PEs with malignancy, 80 (64.5%) had negative margins. Median survival was 62 (95% confidence interval [CI] 27-70) months for negative and 21 (95% CI 15-29) months for positive margins. Of 76 with negative margins and documented margin length, 26 had close and 50 had distant margins. Median survival was 32 (95% CI 14-62) months for close and 111 (95% CI 42-166) months for distant margins. Distant margins were associated with improved OS (p = 0.0054) and PFS (p = 0.0099) compared to close margins. After adjusting for other prognostic factors, patients with distant margins had significantly decreased risk of all-cause mortality (HR 0.39, 95% CI 0.19-0.78; p = 0.008) and progression (HR 0.48, 95% CI 0.23-0.99; p = 0.04) compared to positive margins. No significant differences in OS or PFS were observed between close and positive margins. This survival benefit remained among those with cervical cancer. Median survival in this cohort was 34.1 (95% CI 2.0-69.8) months for close and 165.7 (95% CI 24.5-165.7) for distant margins. CONCLUSIONS: Distant margins following PE are associated with improved OS and PFS compared to close margins.

Impact of age, comorbidity, and treatment characteristics on survival in older women with advanced high grade epithelial ovarian cancer.

OBJECTIVES: Older women have a worse prognosis with advanced epithelial ovarian cancer (EOC) and comorbidities likely contribute to poor outcomes. We sought to identify comorbid conditions and treatment-related factors in older women. METHODS: A retrospective chart review identified 351 patients who underwent cytoreductive surgery (CRS). 100/351 (28.5%) were ≥ 70 years old. Demographic and clinicopathologic information was collected. Crude progression-free (PFS) and overall survival (OS) estimates were calculated using Kaplan-Meier method. Cox proportional hazards regression model was used to estimate hazard ratios and adjustments for confounders. RESULTS: Study subjects ≥70 years old had significantly: higher Cumulative Illness Rating Scale-Geriatric (CIRS-G) score (5.9 vs 4.3; p = 0.0001), less completion of adjuvant chemotherapy (24% vs 15.1%; p = 0.049), less intraperitoneal (IP) therapy (18.2% vs 35.5%; p = 0.002), less clinical trial participation (16% vs 26.3%; p = 0.040), decreased platinum sensitivity (60% vs 73.7%; p = 0.012) and lacked BRCA mutations (0% vs 12%; p = 0.0006). They were less likely to have optimal CRS (75% vs 86.9%; p = 0.007) with same surgical complexity (p = 0.89). Patients ≥70 had significantly worse PFS and OS. In a multivariate analysis, better OS was associated with younger age (<70 years old), any IP therapy, completion of adjuvant chemotherapy, and platinum sensitivity. CONCLUSION: The older cohort had worse CIRS-G scores (5.9 vs 4.3; p = 0.0001), but no strong associations between comorbidities and treatment characteristics, but less optimal CRS rates (75% vs 86.9%; p = 0.007) with similar surgical complexity and less platinum sensitivity. Our results show comorbid conditions in older patients with advanced EOC may have less impact than tumor biology.

NCCN Guidelines® Insights: Uterine Neoplasms, Version 3.2021.

The NCCN Guidelines for Uterine Neoplasms provide recommendations for diagnostic workup, clinical staging, and treatment options for patients with endometrial cancer or uterine sarcoma. These NCCN Guidelines Insights focus on the recent addition of molecular profiling information to aid in accurate diagnosis, classification, and treatment of uterine sarcomas.

High-dose intensity-modulated chemoradiotherapy in vulvar squamous cell carcinoma: Outcome and toxicity.

INTRODUCTION: To evaluate clinical outcomes, pattern of failure, and toxicity after high-dose intensity-modulated radiation therapy (IMRT) for advanced vulvar cancer. METHODS: In this IRB approved retrospective study, the charts of women with histologically confirmed, non-metastatic vulvar cancer consecutively treated at our institution from 2012 to 2018 were reviewed to identify patients that received high-dose IMRT with curative intent. The treatment compliance, toxicities, and patterns of failure were investigated. Actuarial local, regional and distant recurrence and survival were estimated using Kaplan-Meier method and compared using log rank test. RESULTS: Twenty-six patients were identified, 23 were unresectable, and 3 refused surgery. Fifteen patients (58%) had inguinal node metastases; 10(38%) had pelvic node metastases. Elective surgical staging of groins was performed in 9-patients. Median tumor dose was 65.4Gy. Concurrent platinum-based chemotherapy was administered in 22(84.6%) patients. Complete response (CR) was achieved in 21/26 (80.7%) patients. Five patients had persistent disease following treatment and one sustained recurrence 5-months following radiotherapy. All persistent or recurrent disease occurred inside the irradiated volume. Median follow-up was 19 months (3-52 months). Actuarial 1-year local, regional and distant controls were 72.4%, 85.4%, and 86%, respectively. One and 2-year overall survivals were 91% and 62%, respectively. Complete response at 3-months was a strong predictor for overall survival (1-yr OS 73% vs 27%, HR 7.1 (95% CI 1.2-44); p = 0.01). Lymph node metastases adversely affected overall survival (2-yr OS 49% vs. 83%, p = 0.09). Grade 3-4 late urinary and soft-tissue toxicity was seen in 5 patients. Tumor doses >66 Gy (p = 0.03) and prior pelvic radiotherapy (p = 0.002) predicted grade 3-4 toxicity. CONCLUSION: High-dose IMRT for vulvar cancer achieves high rates of local control with acceptable dose dependent long-term toxicity.

NCCN Guidelines Insights: Cervical Cancer, Version 1.2020.

The NCCN Guidelines for Cervical Cancer provide recommendations for diagnostic workup, staging, and treatment of patients with the disease. These NCCN Guidelines Insights focus on recent updates to the guidelines, including changes to first- and second-line systemic therapy recommendations for patients with recurrent or metastatic disease, and emerging evidence on a new histopathologic classification system for HPV-related endocervical adenocarcinoma.

A longitudinal examination of associations between age and chemotherapy-induced peripheral neuropathy in patients with gynecologic cancer.

OBJECTIVE: Increasing age has been associated with higher risk of chemotherapy-related toxicities, often resulting in treatment disruptions or discontinuations. Age has also been evaluated as a potential risk factor for chemotherapy-induced peripheral neuropathy (CIPN), but current understanding of recovery from CIPN in older adults after treatment is limited. The goal of the current study was to: 1) evaluate longitudinal change in patient-reported CIPN symptoms from the start of chemotherapy to one year post-chemotherapy; and 2) examine treatment modifications in older (≥65 years) and younger patients (<65 years). METHODS: As part of a larger ongoing study, gynecologic cancer patients (n = 90) treated with cytoxic chemotherapy reported their CIPN symptoms via the EORTC-CIPN20 three times during active treatment and at 6 and 12 months post-treatment. Medical record reviews were conducted to abstract clinical information during active treatment. RESULTS: Piecewise mixed models revealed that older and younger patients reported similar increases in CIPN during the active treatment phase. However, older patients did not recover from CIPN after treatment completion, whereas younger patients exhibited significant declines in CIPN symptoms post-treatment. No age differences were observed in the presence of provider-recorded sensory neuropathy and pain; neuropathy-related treatment delays, changes in chemotherapy dose, regimen, or discontinuations; or falls (all p-values > 0.05). CONCLUSIONS: Results from the current study indicate that older adults are at higher risk for chronic CIPN. Older survivors may require additional education and treatment for chronic CIPN symptoms. Additional studies are needed to explore novel interventions to manage chronic CIPN in older cancer survivors.

Gestational Trophoblastic Neoplasia, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.

Gestational trophoblastic neoplasia (GTN), a subset of gestational trophoblastic disease (GTD), occurs when tumors develop in the cells that would normally form the placenta during pregnancy. The NCCN Guidelines for Gestational Trophoblastic Neoplasia provides treatment recommendations for various types of GTD including hydatidiform mole, persistent post-molar GTN, low-risk GTN, high-risk GTN, and intermediate trophoblastic tumor.

Cervical Cancer, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology.

Cervical cancer is a malignant epithelial tumor that forms in the uterine cervix. Most cases of cervical cancer are preventable through human papilloma virus (HPV) vaccination, routine screening, and treatment of precancerous lesions. However, due to inadequate screening protocols in many regions of the world, cervical cancer remains the fourth-most common cancer in women globally. The complete NCCN Guidelines for Cervical Cancer provide recommendations for the diagnosis, evaluation, and treatment of cervical cancer. This manuscript discusses guiding principles for the workup, staging, and treatment of early stage and locally advanced cervical cancer, as well as evidence for these recommendations. For recommendations regarding treatment of recurrent or metastatic disease, please see the full guidelines on NCCN.org.

Adherence to practice guidelines is associated with reduced referral times for patients with ovarian cancer.

BACKGROUND: Patients with ovarian cancer tend to receive the highest quality of care at high-volume cancer centers with gynecological oncologists. However, the care that they receive prior to gynecological oncology consult has not been examined. We investigated the quantity and quality of care given to patients with ovarian cancer before being seen by a gynecological oncologist. OBJECTIVE: We evaluated the variability, quantity, and quality of diagnostic testing and physician-referral patterns prior to consultation with a gynecological oncologist, in women with suspicious pelvic masses seen on imaging. STUDY DESIGN: A chart review was performed on patients treated for ovarian cancer at a single institution from 2001 to 2014. We evaluated their workup in 4 categories, drawn from National Comprehensive Care Network guidelines: provider visits, abdominal/pelvic imaging, chest imaging, and tumor markers. Workup was classified as guideline adherent or guideline nonadherent. RESULTS: We identified 335 cases that met our criteria. In the provider visit category, 83.9% of patients received guideline-adherent workup: 77% in the abdominal/pelvic imaging, 98.2% in the chest imaging, and 95.2% in the tumor marker categories. Each patient's workup was assessed as a compilation of the 4 categories, yielding 65.7% patients as having received an adherent workup and 34.3% of workup as nonadherent to guidelines. The timeframe to see a gynecological oncologist for patients with guideline-adherent workup was significantly shorter than for those whose workup was nonadherant (20 vs 86 days, P < .001). A suspicious pelvic mass was identified by obstetrics-gynecology in only 23.9% of patients; 42.7% of patients did not have tumor marker testing before a gynecological oncologist consult. When an obstetrics-gynecology specialist discovered the suspicious pelvic mass, the remaining workup was more likely to be guideline adherent prior to gynecological oncologist referral than when initial imaging was not ordered by an obstetrics-gynecology specialist (P = .18). Survival was not significantly different (P = .103). CONCLUSION: With a guideline-adherent workup, including tumor marker testing, gynecological oncologist referral times can be shortened, minimizing cost inefficiencies and delays that can compromise the effectiveness of downstream care for patients with ovarian cancer. Guidelines should be disseminated beyond the obstetrics-gynecology field.

Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology.

Endometrial carcinoma is a malignant epithelial tumor that forms in the inner lining, or endometrium, of the uterus. Endometrial carcinoma is the most common gynecologic malignancy. Approximately two-thirds of endometrial carcinoma cases are diagnosed with disease confined to the uterus. The complete NCCN Guidelines for Uterine Neoplasms provide recommendations for the diagnosis, evaluation, and treatment of endometrial cancer and uterine sarcoma. This manuscript discusses guiding principles for the diagnosis, staging, and treatment of early-stage endometrial carcinoma as well as evidence for these recommendations.

Quality of life after pelvic exenteration for gynecologic cancer: Findings from a qualitative study.

OBJECTIVE: Pelvic exenteration (PE) in carefully selected gynecologic cancer patients has a 5-year survival rate as high as 60%. Thus, there is a growing number of PE survivors dealing with the effects of this radical surgery. The current study sought to explore women's physical, psychological, and social quality of life (QOL) after PE. METHODS: Fourteen women who had undergone PE for recurrent gynecologic cancer at least 1 year previously completed semistructured qualitative interviews designed to elicit expectations and experiences of QOL following PE. Thematic analysis was used to code transcripts for both a priori and emergent themes. RESULTS: Themes included PE versus palliative care, preparedness, persistent symptoms, the not so normal new normal, new rules of social engagement, support, emotional diversity, and bouncing back through adaptive coping. Key differences with previous studies include the explicit acknowledgement of the need for palliative care, the chronic nature of multiple, seemingly unaddressed physical symptoms in survivorship, and the predominance of positive psychological symptoms. While a minority expressed emotional distress and regret for undergoing PE, most articulated a sense of resilience gained through a variety of adaptive coping strategies. CONCLUSIONS: Findings underscore the persistent physical, psychological, and social effects of PE on QOL and the need for comprehensive, multidisciplinary patient care before and long after surgery. Findings should promote development of a best practice clinical pathway for the care and education of women who undergo PE with curative intent for gynecologic cancer.

Gene Expression Signature-Based Prediction of Lymph Node Metastasis in Patients With Endometrioid Endometrial Cancer.

OBJECTIVE: This study aimed to develop a prediction model for lymph node metastasis using a gene expression signature in patients with endometrioid-type endometrial cancer. METHODS: Newly diagnosed endometrioid-type endometrial cancer cases in which the patients had undergone lymphadenectomy during a surgical staging procedure were identified from a national dataset (N = 330). Clinical and pathologic data were extracted from patient medical records, and gene expression datasets of their tumors were used to create a 12-gene predictive model for lymph node metastasis. We used principal components analysis on a training set (n = 110) to develop multivariate logistic models to predict low-risk patients having a probability of lymph node metastasis of less than 4%. The model with the highest prediction performance was selected for an evaluation set (n = 112), which, in turn, was validated in an independent validation set (n = 108). RESULTS: The model applied to the evaluation set showed 100% sensitivity (90% confidence interval [CI], 74%-100%) and 42% specificity (90% CI, 34%-51%), which resulted in 100% negative predictive value (90% CI, 89%-100%). In the validation set, we confirmed that the model consistently showed 100% sensitivity (90% CI, 88%-100%), 42% specificity (90% CI, 32%-50%), and 100% negative predictive value (90% CI, 88%-100%). CONCLUSIONS: Our 12-gene signature model is a useful tool for the identification of patients with endometrioid-type endometrial cancer at low risk of lymph node metastasis, particularly given that it can be used to analyze histologic tissue before surgery and used to tailor surgical options.

Phase I study of oral ridaforolimus in combination with paclitaxel and carboplatin in patients with solid tumor cancers.

BACKGROUND: Ridaforolimus is a mammalian target of rapamycin inhibitor that has activity in solid tumors. Paclitaxel and carboplatin have broad antineoplastic activity in many cancers. This phase I trial was conducted to determine the safety profile, maximal tolerated dose, and recommended phase II dose and schedule of oral ridaforolimus combined with paclitaxel and carboplatin in patients with solid tumor cancers. METHODS: Eligible patients with advanced solid tumor cancers received oral 10 to 30 mg ridaforolimus daily for 5 consecutive days per week combined with intravenous paclitaxel (175 mg/m2) and carboplatin (area under the curve [AUC] 5-6 mg/mL/min) in 3-week cycles. A standard 3 + 3 design was used to escalate doses, with predefined changes to an alternate dosing schedule and/or changes in carboplatin AUC doses based on dose-limiting toxicity (DLT). Secondary information was collected regarding response and time to progression. Patients were continued on treatment if therapy was tolerated and if stable disease or better was demonstrated. RESULTS: Thirty-one patients were consented, 28 patients were screened, and 24 patients met eligibility requirements and received treatment. Two patients were replaced for events unrelated to drug-related toxicity, resulting in 22 DLT-evaluable patients. Two grade 4 DLTs due to neutropenia were observed at dose level 1. The next cohort was changed to a predefined alternate dosing schedule (days 1-5 and 8-12). DLTs were neutropenia, sepsis, mucositis, and thrombocytopenia. The most common adverse events were neutropenia, anemia, thrombocytopenia, fatigue, alopecia, nausea, pain, and leukopenia. Twenty-four patients received a median of 4 cycles (range, 1-12). Evaluable patients for response (n = 18) demonstrated a median tumor measurement decrease of 25%. The best response in these 18 patients included 9 patients with partial response (50%), 6 with stable disease (33%), and 3 with progressive disease (17%). Thirteen of these patients received treatment for 4 or more cycles. CONCLUSIONS: Treatment with ridaforolimus combined with paclitaxel and carboplatin had no unanticipated toxicities and showed antineoplastic activity. The recommended phase II dose and schedule is ridaforolimus 30 mg (days 1-5 and 8-12) plus day 1 paclitaxel (175 mg/m2) and carboplatin (AUC 5 mg/mL/min) on a 21-day cycle. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01256268 (trial registration date: December 1, 2010).

Vulvar Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology.

Vulvar cancer is a rare gynecologic malignancy. Ninety percent of vulvar cancers are predominantly squamous cell carcinomas (SCCs), which can arise through human papilloma virus (HPV)-dependent and HPV-independent pathways. The NCCN Vulvar Cancer panel is an interdisciplinary group of representatives from NCCN Member Institutions consisting of specialists in gynecological oncology, medical oncology, radiation oncology, and pathology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Vulvar Cancer provide an evidence- and consensus-based approach for the management of patients with vulvar SCC. This manuscript discusses the recommendations outlined in the NCCN Guidelines for diagnosis, staging, treatment, and follow-up.

Micro-RNAs associated with the evolution of ovarian cancer cisplatin resistance.

OBJECTIVES: Ovarian cancer (OVCA) is the leading cause of mortality among women with gynecologic malignancy, in part due to the development of chemoresistance. We sought to identify micro-RNAs (miRNAs) associated with in vitro development of OVCA chemoresistance that may also represent potential targets for therapy. METHODS: In this study, four OVCA cell lines (A2780CP, A2780S, IGROV1, and OVCAR5) were serially treated with cisplatin in parallel with measurements of miRNA expression changes. RESULTS: Nine miRNAs were found to be associated with increasing cisplatin resistance (IC50) (p<0.01); however, only 5 of these miRNAs have publically available information. Pathway analysis identified 15 molecular signaling pathways that were represented by genes predicted to be targets of the 5 miRNAs (false discovery rate<0.05), 11 of which are associated with the epithelial-mesenchymal transition (EMT). Further analysis identified 2 of those pathways as being associated with overall survival in 218 patients with OVCA. CONCLUSIONS: Collectively, this panel of miRNAs associated with in vitro evolution of OVCA cisplatin resistance and the pathways identified to be associated with EMT and overall patient survival provide a framework for further investigations into EMT as a therapeutic target in patients with OVCA.