Circulating Tumor Cell-Free DNA Genes as Prognostic Gene Signature for Platinum Resistant Ovarian Cancer Diagnosis.

Clinical management of gynecological cancer begins by optimal debulking with first-line platinum-based chemotherapy. However, in ~80% patients, ovarian cancer will recur and is lethal. Prognostic gene signature panel identifying platinum-resistance enables better patient stratification for precision therapy.

Shifts in gut and vaginal microbiomes are associated with cancer recurrence time in women with ovarian cancer.

Many studies investigating the human microbiome-cancer interface have focused on the gut microbiome and gastrointestinal cancers. Outside of human papillomavirus driving cervical cancer, little is known about the relationship between the vaginal microbiome and other gynecological cancers, such as ovarian cancer. In this retrospective study, we investigated the relationship between ovarian cancer, platinum-free interval (PFI) length, and vaginal and gut microbiomes.

The presence of an endometrioid component does not alter the clinicopathologic profile or survival of patients with uterine serous cancer: A gynecologic oncology group (GOG/NRG) study of 934 women.

Objective: While most cases of endometrial cancer can readily be classified as pure endometrioid, pure serous, or another type, others show an apparent mixture of serous and endometrioid components, or indeterminate serous versus endometrioid features. Since serous histology carries a worse prognosis than endometrioid, Gynecologic Oncology Group protocol GOG-8032 was established to examine whether the presence of a non-serous component is a favorable feature in an otherwise serous cancer.

Methods: 934 women with serous cancer were prospectively identified among a larger group enrolled in GOG-0210.

Potential and mechanism of mebendazole for treatment and maintenance of ovarian cancer.

Objective: Mebendazole and other anti-parasitic drugs are being used off-prescription based on social media and unofficial accounts of their anti-cancer activity. The purpose of this study was to conduct a controlled evaluation of mebendazole's therapeutic efficacy in cell culture and in vivo models of ovarian cancer. The majority of ovarian cancers harbor p53 null or missense mutations, therefore the effects of p53 mutations and a mutant p53 reactivator, PRIMA-1 (APR246) on mebendazole activity were evaluated.

Developing a new radiomics-based CT image marker to detect lymph node metastasis among cervical cancer patients.

Background And Objective: In diagnosis of cervical cancer patients, lymph node (LN) metastasis is a highly important indicator for the following treatment management. Although CT/PET (i.e.

Corrigendum to "Phase II evaluation of copanlisib, a selective inhibitor of Pi3kca, in patients with persistent or recurrent endometrial carcinoma harboring PIK3CA hotspot mutations: An NRG oncology study (NRG-GY008)" [Gynecol. Oncol. Rep. 31 (2020) 100532].

[This corrects the article DOI: 10.1016/j.gore.

Randomized Phase II Trial of Nivolumab Versus Nivolumab and Ipilimumab for Recurrent or Persistent Ovarian Cancer: An NRG Oncology Study.

Purpose: Single-agent PD-1 blockade exhibits limited efficacy in epithelial ovarian cancer (EOC). We evaluated ipilimumab plus nivolumab compared with nivolumab alone in women with persistent or recurrent EOC.

Methods: Eligibility criteria included measurable disease, 1-3 prior regimens, and platinum-free interval (PFI) < 12 months.

Phase II evaluation of copanlisib, a selective inhibitor of Pi3kca, in patients with persistent or recurrent endometrial carcinoma harboring PIK3CA hotspot mutations: An NRG Oncology study (NRG-GY008).

Purpose: NRG Oncology conducted a phase II trial to assess the antitumor activity and tolerability of copanlisib, a selective inhibitor of PIK3CA, in persistent or recurrent endometrial carcinoma harboring hotspot PIK3CA mutations.

Patients And Methods: Eligible patients had endometrial cancer with endometrioid, serous or mixed histology, a somatic PIK3CA gene mutation, measurable disease, and GOG performance status ≤2. Treatment consisted of IV copanlisib (60 mg weekly, day 1, 8 and 15 of 28-day cycle) until disease progression or prohibitive toxicity.

Extending the platinum-free interval: The impact of omitting 2nd line platinum chemotherapy in intermediate platinum-sensitive ovarian cancer.

Objectives: Patients with epithelial ovarian cancer (EOC) recurring between 6 and 12 months after primary platinum chemotherapy have worse prognosis than those recurring in >12 months. Artificially prolonging the platinum-free interval (PFI) with cytotoxic chemotherapy was tested in MITO-8 with poor outcomes. This study aimed to determine the impact of using non-platinum or targeted therapy in 2nd line treatment of EOC patients recurring 6-12 months after completion of primary platinum-based chemotherapy.

A phase 1b dose escalation study of ipafricept (OMP54F28) in combination with paclitaxel and carboplatin in patients with recurrent platinum-sensitive ovarian cancer.

Objectives: The WNT pathway is an important oncologic driver of epithelial ovarian cancer (EOC). The first-in-class recombinant fusion protein ipafricept (IPA) blocks Wnt signaling through binding of Wnt ligands. This phase Ib trial was designed to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RPh2) for IPA in combination with taxane and platinum therapy (C/P).

Intellectual Equipoise and Challenges: Accruing Patients With Advanced Cancer to a Trial Randomizing to Surgical or Nonsurgical Management (SWOG S1316).

Background: Prospective, randomized trials are needed to determine optimal treatment approaches for palliative care problems such as malignant bowel obstruction (MBO). Randomization poses unique issues for such studies, especially with divergent treatment approaches and varying levels of equipoise. We report our experience accruing randomized patients to the Prospective Comparative Effectiveness Trial for Malignant Bowel Obstruction (SWOG S1316) study, comparing surgical and nonsurgical management of MBO.

Prospective Evaluation of Multinational Association of Supportive Care in Cancer Risk Index Score for Gynecologic Oncology Patients With Febrile Neutropenia.

Background: The Multinational Association of Supportive Care of Cancer (MASCC) risk-index score has been validated as a stratification tool for febrile neutropenia (FN) risk in a heterogeneous group of cancer patients; recently, it has been deemed a suitable tool in gynecologic oncology patients in a retrospective study. This is a prospective multi-institutional study wherein we sought to validate MASCC score for stratifying FN morbidity in gynecologic oncology patients.

Methods: IRB approval was obtained at 4 institutions for prospective data collection of gynecologic cancer patients admitted with FN from 3/1/2013 to 9/1/2014.

Update in the use and evaluation of poly (ADP-ribose) polymerase inhibitors in epithelial ovarian cancer: current and pending clinical research.

Purpose Of Review: This review will provide an update of recently presented clinical data as well as discuss ongoing trials focused on the incorporation of poly (ADP-ribose) polymerase inhibitors (PARPi) into the treatment paradigm for ovarian cancer.

Recent Findings: As of this publication, PARPi have indications in many parts of the globe as maintenance therapy following response to platinum-based chemotherapy in the setting of platinum-sensitive recurrence. In addition, in the United States, two PARPi have indications as monotherapy treatment for recurrent ovarian cancer in patients with a BRCA mutation and at least two prior lines of therapy.

Classification of Tumor Epithelium and Stroma by Exploiting Image Features Learned by Deep Convolutional Neural Networks.

The tumor-stroma ratio (TSR) reflected on hematoxylin and eosin (H&E)-stained histological images is a potential prognostic factor for survival. Automatic image processing techniques that allow for high-throughput and precise discrimination of tumor epithelium and stroma are required to elevate the prognostic significance of the TSR. As a variant of deep learning techniques, transfer learning leverages nature-images features learned by deep convolutional neural networks (CNNs) to relieve the requirement of deep CNNs for immense sample size when handling biomedical classification problems.

Prediction of chemotherapy response in ovarian cancer patients using a new clustered quantitative image marker.

This study aimed to investigate the feasibility of integrating image features computed from both spatial and frequency domain to better describe the tumor heterogeneity for precise prediction of tumor response to postsurgical chemotherapy in patients with advanced-stage ovarian cancer. A computer-aided scheme was applied to first compute 133 features from five categories namely, shape and density, fast Fourier transform, discrete cosine transform (DCT), wavelet, and gray level difference method. An optimal feature cluster was then determined by the scheme using the particle swarm optimization algorithm aiming to achieve an enhanced discrimination power that was unattainable with the single features.

A contemporary framework of health equity applied to gynecologic cancer care: A Society of Gynecologic Oncology evidenced-based review.

Health disparities are defined as the preventable difference in the burden of disease, injury, and violence, or opportunity to achieve optimal health that socially disadvantaged populations experience compared to the population as a whole. Disparities in incidence and cancer outcomes for women with gynecologic malignancies have been well described particularly for American women of Black race. The etiology of these disparities has been tied to socio-economics, cultural, educational and genetic factors.

Consideration of older patients for enrollment in phase 1 clinical trials: Exploring treatment related toxicities and outcomes.

Objectives: Age imposes a disparity in the treatment of and outcomes with gynecologic cancer. Older patients are underrepresented in primary treatment trials, but little is known about their ability to withstand trial-based treatment for recurrent or refractory disease. This study sought to examine treatment-related toxicities and outcomes of older versus younger patients participating in phase 1 clinical trials.

Management of the toxicities of common targeted therapeutics for gynecologic cancers.

As precision medicine has become a focus in oncology in recent years, many targeted and biologic agents are being used along with or in place of traditional cytotoxic chemotherapy. As these drugs have been developed and some have received FDA approval, we have gained substantial data about the adverse event profiles. However, the management and approach to the toxicities incurred and subsequent complications are often not well understood, especially for physicians who have a varied clinical practice.

Factors influencing clinical trial enrollment among ovarian cancer patients.

Objective: To characterize patients who did not enroll on a clinical trial and identify barriers that may limit enrollment among patients with advanced epithelial ovarian cancer (EOC) presenting for first-line chemotherapy.

Methods: We conducted a retrospective review of patients diagnosed with stage II-IV EOC from 10/2009-4/2013, a time period during which multiple trials were available to all EOC patients, including optimally debulked, suboptimally debulked, or undergoing neoadjuvant chemotherapy. Enrollment status, demographics, tumor characteristics, and treatment details were recorded.

Applying Quantitative CT Image Feature Analysis to Predict Response of Ovarian Cancer Patients to Chemotherapy.

Rationale And Objectives: The study aimed to investigate the role of applying quantitative image features computed from computed tomography (CT) images for early prediction of tumor response to chemotherapy in the clinical trials for treating ovarian cancer patients.

Materials And Methods: A dataset involving 91 patients was retrospectively assembled. Each patient had two sets of pre- and post-therapy CT images.

Contribution of age to clinical trial enrollment and tolerance with ovarian cancer.

Introduction: Increasing age has been correlated with shorter survival in ovarian cancer patients, a finding attributed to diminished tolerance of standard therapy. Elderly patients, however, are less likely to enroll on clinical trials; thus, limited data exists to evaluate their response to front line treatment. This study describes how elderly patients on trial fared, with respect to toxicity and response, compared to younger women.

Three versus six cycles of adjuvant platinum-based chemotherapy in early stage clear cell ovarian carcinoma - A multi-institutional cohort.

Objectives: To determine if 6 versus 3cycles of adjuvant platinum-based chemotherapy with or without taxane impacts survival in early stage ovarian clear cell carcinoma (OCCC).

Methods: We retrospectively identified all cases of stage I and II OCCC treated at 5 institutions from January 1994 through December 2011. Patients were divided into 2 groups: those who received 3 versus 6cycles of adjuvant chemotherapy.

Intravenous leiomyomatosis disguised as a large deep vein thrombosis.

Intravenous leiomyomatosis is a benign smooth muscle tumor which despite its histology can have devastating consequences. Furthermore, the clinical manifestations are variable and nonspecific, typically leading to delayed or missed diagnosis. Thus, it is critical for clinicians to be aware of this condition and have a high index of suspicion in a middle-aged woman with a history of uterine leiomyoma presenting with an inferior vena cava mass to enable early diagnosis and treatment.

Impact of histology and surgical approach on survival among women with early-stage, high-grade uterine cancer: An NRG Oncology/Gynecologic Oncology Group ancillary analysis.

Objectives: We sought to analyze the clinicopathologic features, recurrence patterns and survival outcomes of women with high-grade uterine cancer (UC) enrolled on The Gynecologic Oncology Group (GOG) LAP2 trial.

Methods: This is a post-hoc analysis of LAP-2 patients with grade 3 endometrioid adenocarcinoma (ENDO), uterine serous (USC), clear cell (CC) and carcinosarcoma (CS). Demographics, clinicopathologic features, and recurrence patterns, were compared by histology and surgical approach.

The pro-inflammatory effect of obesity on high grade serous ovarian cancer.

Introduction: Obesity is a known generator of chronic inflammation but has an uncertain role in ovarian carcinogenesis and survival. Pro-inflammatory cytokines have previously been associated with poor outcomes. Given the established links, we sought to determine whether obesity and pro-inflammatory cytokines affect platinum sensitivity.