BackgroundImmune checkpoint inhibitors (ICIs) have modest activity in ovarian cancer (OC). To augment their activity, we used priming with the hypomethylating agent guadecitabine in a phase II study.MethodsEligible patients had platinum-resistant OC, normal organ function, measurable disease, and received up to 5 prior regimens.
View Article and Find Full Text PDFBackground: Blocking the PI3K/AKT/mTOR pathway decreases resistance to hormonal therapy in endometrial carcinoma (EC).
Objective: In this study, the aim was to assess the efficacy and tolerability of everolimus(E)/letrozole (L) or medroxyprogesterone acetate(M)/tamoxifen(T) in the treatment of metastatic EC.
Study Design: This single stage, open-label two arm randomized phase II trial accrued women with advanced/persistent/recurrent EC.
Purpose: CD137 agonism and CSF1R blockade augment stereotactic body radiotherapy (SBRT) and anti-programmed death-1 in preclinical models. We evaluated the safety and efficacy of SBRT with nivolumab+urelumab (CD137 agonist) or nivolumab+cabiralizumab (CSF1R inhibitor).
Patients And Methods: This phase I clinical trial enrolled patients with advanced solid tumors that had progressed on standard therapies.
Purpose: Multisite stereotactic body radiotherapy followed by pembrolizumab (SBRT+P) has demonstrated safety in advanced solid tumors (ASTs). However, no studies have examined the relationships between irradiated tumor response, SBRT-induced tumor gene expression, and overall survival (OS).
Patients And Methods: Patients with AST received SBRT (30-50 Gy in 3-5 fractions) to two to four metastases followed by pembrolizumab (200 mg i.
Purpose: Atezolizumab has shown antitumor activity in patients with ovarian cancer. Dual blockade of programmed death-ligand 1 (PD-L1) and VEGF enhances anticancer immunity and augments antitumor activity in several cancers. The safety and efficacy of atezolizumab plus bevacizumab were evaluated in patients with ovarian cancer.
View Article and Find Full Text PDFImmune checkpoint inhibitors are an exciting new class of cancer therapeutics. Recently, a PD-1 inhibitor has been approved by the Food and Drug Administration for several indications that are relevant to patients with gynecologic malignancies. In this review, we explore the clinical considerations for the use of checkpoint inhibitor therapy in this population.
View Article and Find Full Text PDFImportance: Patients with recurrent ovarian carcinoma frequently develop resistance to platinum-based chemotherapy, at which time treatment options become limited.
Objective: To evaluate the poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor niraparib combined with pembrolizumab in patients with recurrent ovarian carcinoma.
Design, Setting, And Participants: The TOPACIO/KEYNOTE-162 (Niraparib in Combination With Pembrolizumab in Patients With Triple-Negative Breast Cancer or Ovarian Cancer) trial, an open-label, single-arm phases 1 and 2 study enrolled women with advanced or metastatic triple-negative breast cancer (TNBC) or recurrent ovarian carcinoma, irrespective of BRCA mutation status.
Endometrial cancer is the most common gynecologic cancer in the United States, and its incidence is rising. Although there have been significant recent advances in our understanding of endometrial cancer biology, many aspects of treatment remain mired in controversy, including the role of surgical lymph node assessment and the selection of patients for adjuvant radiation or chemotherapy. For the subset of women with microsatellite-instable, metastatic disease, anti- programmed cell death protein 1 immunotherapy (pembrolizumab) is now approved by the US Food and Drug Administration, and numerous trials are attempting to build on this early success.
View Article and Find Full Text PDFImmune checkpoint inhibitors have become an area of intense interest in oncology and are actively being studied in a variety of cancer types with a wide range of success. In vitro data suggest mechanisms by which radiation can activate the immune system, and ongoing studies are exploring the potential interaction of checkpoint inhibitors with radiotherapy in both preclinical and clinical settings. Gynecologic malignancies are a heterogeneous group of tumors with varying prognoses, intrinsic immunogenicity, and potential for response to immune-based therapies.
View Article and Find Full Text PDFBackground: Ovarian tumors, although uncommon in children, can retain endocrine function that disrupts normal feedback mechanisms leading to amenorrhea. Inheritance of germline DICER1 mutations can lead to increased risk for development of ovarian Sertoli-Leydig cell tumors (SLCTs).
Case: We report, to our knowledge, the first case of secondary amenorrhea due to elevated inhibin B levels in a female adolescent with an ovarian SLCT.
Gynecol Oncol Case Rep
December 2013
•Definitive treatment of cervical cancer in pregnancy poses a dilemma for patients desiring to continue gestation.•Robotic surgical staging of cervical cancer diagnosed during pregnancy is feasible.•Robotic surgical staging improves the prognostic assessment for pregnant patients when making a decision between immediate versus delayed treatment.
View Article and Find Full Text PDFPurpose: Liposomal doxorubicin (D) and bevacizumab (A) are active single agents in gynecologic and breast malignancies which share a resistance mechanism: upregulation of hypoxia inducible factor (HIF-1α). We, therefore, added temsirolimus (T), which inhibits HIF-1α, to D and A (DAT). Trial objectives were assessment of safety, preliminary efficacy, and identification of biological response correlates.
View Article and Find Full Text PDFPreclinical data suggest that PIK3CA mutations predict response to PI3K/AKT/mTOR inhibitors. Concomitant KRAS or BRAF mutations may mediate resistance. Therefore, tumors from patients referred to the phase I program for targeted therapy starting in October 2008 were analyzed for PIK3CA mutations using PCR-based DNA sequencing of exons 9 and 20.
View Article and Find Full Text PDFAngiogenesis is a hallmark of malignant transformation. With improved understanding of angiogenic signaling in both the normal and malignant state, there have been a number of agents developed that target VEGF signaling. These targeted agents can affect downstream VEGF signal transduction via unique mechanisms at different cellular and extracellular locations.
View Article and Find Full Text PDFGynecologic concerns in postmenopausal women are common. Although various conditions may affect all women in this age group, the prevalence of certain disorders, and also diagnostic approaches and treatment options, may vary significantly when considering very elderly women compared with those early in the sixth decade. The focus of this chapter is to address several commonly encountered gynecologic issues in postmenopausal women, with particular attention given to aspects that must be considered when caring for women in the geriatric age group.
View Article and Find Full Text PDFIn thalassemia, deficient globin-chain production during erythropoiesis results in anemia. Thalassemia may be further complicated by iron overload (frequently exacerbated by blood transfusion), which induces numerous endocrine diseases, hepatic cirrhosis, cardiac failure and even death. Accumulation of iron in the absence of blood transfusions may result from inappropriate suppression of the iron-regulating peptide hepcidin by an erythropoietic mechanism.
View Article and Find Full Text PDFObjective: The 2001 Bethesda System consensus statement directs the reporting of endometrial cells on cervical cytologic preparations in women aged 40 years or older. Our objective was to assess the significance of endometrial cells on cervical liquid-based cytology (LBC) specimens in this population.
Methods: The population included women aged 40 years or older in whom endometrial cells were identified in otherwise normal LBC specimens from December 2001 through June 2005, and who subsequently underwent endometrial sampling within a 12-month period.
Interruption of the normal fetal-to-adult transition of hemoglobin expression should largely ameliorate sickle cell and beta-thalassemia syndromes. Achievement of this clinical goal requires a robust understanding of gamma-globin gene and protein silencing during human development. For this purpose, age-related changes in globin phenotypes of circulating human erythroid cells were examined from 5 umbilical cords, 99 infants, and 5 adult donors.
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