Clinical Utility of Molecular Tumor Board Review for Identification of Possible Germline Pathogenic Variants on Tumor Next-Generation Sequencing Reports.

Purpose: Tumor next-generation sequencing (NGS) testing identifies possible germline pathogenic variants (PGPVs), creating a dilemma for appropriate recognition, triage, and management. The objective of this study was to determine the clinical utility of an institutional molecular tumor board (MTB) in assessing tumor NGS reports for PGPVs.

Methods: Our institutional MTB reviews all NGS reports to provide treatment and further testing recommendations, including genetic counseling referral and consideration of genetic testing (GC/GT).

Feasibility and Clinical Utility of Reporting Hereditary Cancer Predisposition Pathogenic Variants Identified in Research Germline Sequencing: A Prospective Interventional Study.

Purpose: Patients with cancer frequently undergo research-grade germline sequencing but clinically actionable results are not routinely disclosed. The objective of this study is to evaluate the feasibility of reporting clinically relevant secondary findings (SF) identified in germline research sequencing using the institutional molecular tumor board (MTB) and the treating oncology physician.

Methods: This prospective, interventional cohort study enrolled Total Cancer Care participants with any cancer diagnosis at a single institution.

A phase I study of the Wee1 kinase inhibitor adavosertib (AZD1775) in combination with chemoradiation in cervical, upper vaginal, and uterine cancers.

Objective: Wee1 kinase is a crucial regulator of the G2/M checkpoint which prevents entry of damaged DNA into mitosis. Adavosertib (AZD1775), a selective inhibitor of Wee1, induces G2 escape and increases cytotoxicity when combined with DNA damaging agents. We aimed to evaluate the safety and efficacy of adavosertib in combination with definitive pelvic radiotherapy and concurrent cisplatin in patients with gynecological cancers.

Implementation of Nurse Navigation Improves Rate of Molecular Tumor Testing for Ovarian Cancer in a Gynecologic Oncology Practice.

Purpose: The purpose of this study was to assess the impact of implementing a Nurse Navigator (NN) to improve the rate and timeliness of molecular tumor testing.

Methods: This is an evaluation of the impact of education sessions, consensus building, and NN implementation for molecular tumor testing in patients with epithelial ovarian cancer. The NNs' responsibilities included attending tumor boards and ensuring Next Generation Sequencing (NGS) is ordered, reviewed, and coordinated for appropriate patients.

Bleeding from Gynecologic Malignancies.

Initial assessment of vaginal bleeding in gynecologic malignancies includes a thorough history and physical examination, identification of site and extent of disease, and patient goals of care. Patients who are initially hemodynamically unstable may require critical care services. Choice of treatment is disease site specific.

Significance of Pelvic Fluid Observed during Ovarian Cancer Screening with Transvaginal Sonogram.

The primary objective was to examine the role of pelvic fluid observed during transvaginal ultrasonography (TVS) in identifying ovarian malignancy. A single-institution, observational study was conducted within the University of Kentucky Ovarian Cancer Screening trial from January 1987 to September 2019. We analyzed true-positive (TP), false-positive (FP), true-negative (TN), and false-negative (FN) groups for the presence of pelvic fluid during screening encounters.

Clinical Outcomes of Molecular Tumor Boards: A Systematic Review.

Unlabelled: We conducted this systematic review to evaluate the clinical outcomes associated with molecular tumor board (MTB) review in patients with cancer.

Methods: A systematic search of PubMed was performed to identify studies reporting clinical outcomes in patients with cancer who were reviewed by an MTB. To be included, studies had to report clinical outcomes, including clinical benefit, response, progression-free survival, or overall survival.

Molecular Tumor Board Review and Improved Overall Survival in Non-Small-Cell Lung Cancer.

Unlabelled: With the introduction of precision medicine, treatment options for non-small-cell lung cancer have improved dramatically; however, underutilization, especially in disadvantaged patients, like those living in rural Appalachian regions, is associated with poorer survival. Molecular tumor boards (MTBs) represent a strategy to increase precision medicine use. UK HealthCare at the University of Kentucky (UK) implemented a statewide MTB in January 2017.

Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids to Predict Carboplatin Resistance.

The development of patient-derived tumor organoids (TOs) from an epithelial ovarian cancer tumor obtained at the time of primary or interval debulking surgery has the potential to play an important role in precision medicine. Here, we utilized TOs to test front-line chemotherapy sensitivity and to investigate genomic drivers of carboplatin resistance. We developed six high-grade, serous epithelial ovarian cancer tumor organoid lines from tissue obtained during debulking surgery (two neoadjuvant-carboplatin-exposed and four chemo-naïve).

DACH1 mutation frequency in endometrial cancer is associated with high tumor mutation burden.

Objective: DACH1 is a transcriptional repressor and tumor suppressor gene frequently mutated in melanoma, bladder, and prostate cancer. Loss of DACH1 expression is associated with poor prognostic features and reduced overall survival in uterine cancer. In this study, we utilized the Oncology Research Information Exchange Network (ORIEN) Avatar database to determine the frequency of DACH1 mutations in patients with endometrial cancer in our Kentucky population.

Factors Predicting Participation in the Prospective Genomic Sequencing Study, Total Cancer Care (TCC), in Kentucky.

Purpose: Large-scale genomic sequencing studies are driving oncology drug development. However, rural populations, like those residing in Appalachian Kentucky, are underrepresented in these efforts. In this study, we determined the frequency of participation, reasons for nonparticipation, and factors predicting the decision to participate in the Total Cancer Care (TCC) prospective genomic cohort study.

Disease-Specific Survival of Type I and Type II Epithelial Ovarian Cancers-Stage Challenges Categorical Assignments of Indolence & Aggressiveness.

Epithelial ovarian cancers (EOC) consist of several sub-types based on histology, clinical, molecular and epidemiological features that are termed "histo-types", which can be categorized into less aggressive Type I and more aggressive Type II malignancies. This investigation evaluated the disease-specific survival (DSS) of women with Type I and II EOC using histo-type, grade, and stage. A total of 200,658 EOC cases were identified in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) data.

Uterine Corpus Malignancies in Appalachia Kentucky: Incidence, Survival, and Related Health Disparities.

Objectives: Uterine cancer is the nation's most common gynecologic malignancy, but it is understudied in the geographically and socioeconomically diverse state of Kentucky (KY). Our aim was to assess the frequency, distribution, and survival of uterine corpus malignancies in KY, and specifically the differences between Appalachia (AP) and non-Appalachia (NAP) KY.

Methods: This population-based cohort study used Surveillance, Epidemiology, and End Results data and the Kentucky Cancer Registry to study uterine corpus malignancy between January 1, 2000 and December 31, 2014.

Clinical Factors Associated with Longer Hospital Stay Following Ovarian Cancer Surgery.

: Ovarian cancer (OC) is the leading cause of death from gynecologic malignancy and is treated with a combination of cytoreductive surgery and platinum-based chemotherapy. Extended length of stay (LOS) after surgery can affect patient morbidity, overall costs, and hospital resource utilization. The primary objective of this study was to identify factors contributing to prolonged LOS for women undergoing surgery for ovarian cancer.

Phase II trial design with growth modulation index as the primary endpoint.

Molecularly targeted, genomic-driven, and immunotherapy-based clinical trials continue to be advanced for the treatment of relapse or refractory cancer patients, where the growth modulation index (GMI) is often considered a primary endpoint of treatment efficacy. However, there little literature is available that considers the trial design with GMI as the primary endpoint. In this article, we derived a sample size formula for the score test under a log-linear model of the GMI.

Survival of Women With Type I and II Epithelial Ovarian Cancer Detected by Ultrasound Screening.

Objective: To estimate the effect of ultrasound screening on stage at detection and long-term disease-specific survival of at-risk women with epithelial ovarian cancer.

Methods: Eligibility included all asymptomatic women 50 years of age or older and women 25 years of age or older with a documented family history of ovarian cancer. From 1987 to 2017, 46,101 women received annual ultrasound screening in a prospective cohort trial.

Population-Based Analysis of Patient Age and Other Disparities in the Treatment of Ovarian Cancer in Central Appalachia and Kentucky.

Objectives: Adherence to National Comprehensive Cancer Network (NCCN) guidelines for ovarian cancer treatment improves patient outcomes. The aim of this study was to assess disparities associated with ovarian cancer treatment in the state of Kentucky and central Appalachia.

Methods: Data on patients diagnosed as having ovarian cancer from 2007 through 2011 were extracted from administrative claims-linked Kentucky Cancer Registry data.

Symptoms Relevant to Surveillance for Ovarian Cancer.

To examine how frequently and confidently healthy women report symptoms during surveillance for ovarian cancer. A symptoms questionnaire was administered to 24,526 women over multiple visits accounting for 70,734 reports. A query of reported confidence was included as a confidence score (CS).

Complications from Surgeries Related to Ovarian Cancer Screening.

The aim of this study was to evaluate complications of surgical intervention for participants in the Kentucky Ovarian Cancer Screening Program and compare results to those of the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial. A retrospective database review included 657 patients who underwent surgery for a positive screen in the Kentucky Ovarian Cancer Screening Program from 1988-2014. Data were abstracted from operative reports, discharge summaries, and office notes for 406 patients.

Prospective validation of an intraoperative algorithm to guide surgical staging in early endometrial cancer.

Objectives: Prospectively validate an intraoperative surgical staging algorithm to stratify patients with early endometrial cancer by risk of lymph node metastasis.

Methods: Subjects with endometrial cancer clinically confined to the uterus were prospectively enrolled at an academic cancer center between Jan 2012 and Jun 2015. Study participants were stratified intraoperatively into two groups based on risk of nodal involvement using cell type, tumor grade, myometrial invasion, and tumor size in accordance with an established protocol from the Mayo Clinic.