Although genetic testing is recommended for women with epithelial ovarian cancer (EOC), little is known about patient preferences for various testing options. We measured relative preferences for attributes of testing in women with EOC referred for genetic counseling. Subjects were recruited to participate in a discrete-choice-experiment survey to elicit preferences for attributes of genetic testing: out-of-pocket cost ($0, $100, $250, or $1000), probability of a deleterious mutation (60, 80%, or 88%), probability of a variant of uncertain significance (VUS) result (5, 20%, or 40%), sample requirements (blood or saliva), and turn-around time (1, 2 or 4 weeks). Subjects viewed educational videos followed by a series of choices between pairs of constructed genetic tests with varying attribute levels. Random-parameters logit was used to estimate preference weights for attribute levels. Relative importance weights and money-equivalent values were calculated. Ninety-four patients were enrolled; 68 (76.4%) presented for genetic counseling. Test cost was the most important attribute to subjects (importance weight = 41 out of 100) followed by probability to detect deleterious mutations (36) and probability of a VUS result (20). Sample requirements and turnaround time did not drive test choices. Subjects were willing to pay an additional $155 and $70 for incremental 5% improvements in the probability to detect deleterious mutations and probability of a VUS result. At genetics consultation, 55/68 (80.9%) subjects chose multigene testing. Low out-of-pocket cost, high probability of detecting deleterious mutations and high probability of a VUS result are preferred by patients with EOC considering genetic testing.
Endometrial stromal sarcoma (ESS) is a rare neoplasm accounting for only 0.2% of female genital tract tumors. The primary extra-uterine location of ESS is an extremely uncommon occurrence. We present a case of a 64-year-old woman presenting with abdominopelvic and bilateral ovarian tumors with misleading clinical presentation and diagnostic challenge. The histopathological examination of the resected specimens disclosed the diagnosis of primary extra-uterine ESS arising from ovarian endometriosis. Adjuvant therapy with an aromatase inhibitor drug was prescribed for the patient, and she is still alive with no evidence of disease 7 months after surgery. The awareness of the potential extra-uterine location of ESS should lead to correct diagnosis as this tumor has histopathological features and clinical behavior similar to its uterine counterpart.
Measuring QoL is essential to the field of gynecologic oncology but there seems to be limited standardized data regarding collecting QoL assessments throughout a patient’s cancer treatment especially in non-clinical trial patients. The aim of this study is to explore patient characteristics that may be associated with poor quality of life (QoL) in women with gynecologic cancers at two University of Arizona Cancer Center (UACC) sites.
In India, cervical cancer accounts for almost 14% of all female cancer cases. Although poverty continues to cast a wide net over the Indian subcontinent, the preceding three decades have borne witness to improvements in nutrition and sanitation for many citizens. However, due to an absence of a national immunization program to cover human papillomavirus (HPV) vaccination and lack of accessible cervical cancer screening, the disease is characterized by late detection, lack of access to affordable and quality health care, and high mortality rates. Treatment of cervical cancer is stage-specific and depends on the patient’s age, desire to preserve fertility, overall health, the clinician’s expertise, and accessibility to resources. There is a paucity of uniform treatment protocols for various stages of cervical cancer in India. Considering all these parameters, a need to optimize treatment paradigms for the Indian population emerged.
Background Ovarian cancer remains a major health problem for women as it is often diagnosed at a late stage with metastatic disease. There are limited therapeutic agents and survival rates remain poor. The perinucleolar compartment (PNC) has been shown to be associated with malignancy and is considered a surrogate phenotypic marker for metastatic cancer cells. A small molecule, ML246, was derived from a screen against PNCs. In this study, the effect of ML246 on ovarian cancer growth and spread was investigated. Methods SKOV3 or OVCAR3 cells were treated with ML246 in vitro and PNC was visualized with immunofluorescent staining. Cell invasion was assessed using Matrigel-coated transwell systems. SKOV3 cells were xenografted orthotopically under the ovarian bursa of immunocompromised mice. Additionally, a patient derived ovarian cancer cell line was grafted subcutaneously. Mice were treated with ML246 and tumor growth and spread was assessed. Results PNCs were prevalent in the ovarian cancer cell lines OVCAR3 and SKOV3 with higher prevalence in OVCAR3 cells. Treatment with ML246 significantly reduced PNC prevalence in OVCAR3 and SKOV3 cells. Moreover, the invasive activity of both cell lines was significantly inhibited in vitro. Orthotopic implantation of SKOV3 cells resulted in growth of the tumor on the ovary as well as spread of tumor tissues outside of the primary site on organs into the abdominal cavity. Treatment with ML246 decreased the incidence of tumors outside of the ovary. In addition, a patient-derived xenograft (PDX) line was grafted subcutaneously to monitor tumor growth. ML246 significantly attenuated growth of tumors over a 5-week treatment period. Conclusions PNC’s are present in ovarian cancer cells and treatment with ML246 decreases invasion in vitro and tumor growth and spread in vivo. Additional studies are warranted to determine the efficacy of ML246 as an inhibitor of metastatic disease in ovarian cancer and to determine its precise mechanism of action.
Widespread concerns have been raised regarding the safety of power morcellation of uterine specimens because of the potential to disseminate occult malignancy. We sought to assess the safety and feasibility of contained manual uterine morcellation within a plastic specimen bag among women with uterine neoplasms.
Combretastatin A4-phosphate (CA4P) is a vascular-disrupting agent (VDA) in clinical development for the treatment of ovarian and other cancers. In contrast to antiangiogenic agents, such as bevacizumab, which suppress the development of new tumor vasculature, VDAs target established tumor vasculature. These differing but complementary mechanisms of action are currently being explored in clinical trials combining CA4P and bevacizumab. Clinical experience to date has highlighted an important need to better understand the cardiovascular adverse events of CA4P, both alone and in combination with antiangiogenic agents, which can also be associated with cardiovascular adverse events. An acute but transient increase in blood pressure is often the most clinically relevant toxicity associated with CA4P. Increases in CA4P-related blood pressure typically occur 0.5 to 1 h after initiation of the 10-min infusion, peak by 2 h, and return to baseline 3 to 4 h after the infusion. Post-infusion increases in blood pressure are likely to recur in subsequent treatment cycles; however, the severity does not appear to increase with successive cycles. Other cardiovascular adverse events, such as transient, predominantly grade 1–2 tachycardia, bradycardia, QTc prolongation, and in rare cases myocardial ischemia, have also been observed with CA4P but at markedly lower frequencies than hypertension. The clinical trial experience with CA4P suggests that cardiovascular assessment of patients prior to CA4P treatment and careful management of blood pressure during CA4P treatment can largely mitigate the risk of cardiovascular adverse events. Accordingly, we have developed a blood pressure management algorithm for use in the ongoing phase II/III FOCUS study of the triple combination of CA4P with physician’s choice chemotherapy and bevacizumab.
BACKGROUND:Ovarian carcinosarcoma is a rare malignancy associated with a high rate of cancer-related mortality even at early stages. Guidelines for systemic treatment have been difficult to establish because the disease is commonly excluded from prospective clinical trials. Ovarian carcinosarcoma is usually managed as high-grade epithelial ovarian cancer despite major histologic differences. Owing to the rarity and poor prognosis of ovarian carcinosarcoma, salvage treatments and their efficacy have been poorly described.CASE PRESENTATION:A patient heavily treated for ovarian carcinosarcoma showed an objective response to an immune checkpoint inhibitor, pembrolizumab. Pembrolizumab in this patient appeared to provide tumor control in multifocal metastatic sites.CONCLUSIONS:Pembrolizumab should be evaluated in prospective trials for the treatment of ovarian carcinosarcoma and further work is needed to identify patients most likely to respond to this type of intervention.
The burden of HIV and cervical cancer is concentrated in sub-Saharan Africa. Women with HIV are more likely to have persistent HPV infection leading to cervical abnormalities and cancer. Cervical cancer screening seems to be the single most critical intervention in any efforts to prevent cervical cancer. The purpose of this study was to determine the socio-demographic factors influencing intention to seek cervical cancer screening by HIV-positive women in the Central Region of Ghana.
Gynaecological cancers may be the sentinel malignancy in women who carry a mutation in BRCA1 or 2, a mis-match repair gene causing Lynch Syndrome or other genes. Despite published guidelines for referral to a genetics service, a substantial number of women do not attend for the recommended genetic assessment. The study aims to determine the outcomes of systematic follow-up of patients diagnosed with ovarian or endometrial cancer from Gynaecologic-oncology multidisciplinary meetings who were deemed appropriate for genetics assessment.
OBJECTIVE:Bevacizumab is an important component in the treatment of various cancers, and despite guidelines recommending its use in both ovarian and cervical cancer, patient access to bevacizumab and other angiogenesis inhibitors is limited. Biosimilars are large, structurally complex molecules that are intended to be highly similar to, and treat the same condition(s) as, an existing licensed or approved (reference) biologic, with no clinically meaningful differences in purity, potency and safety. This article summarizes the role of bevacizumab in the treatment paradigm of ovarian and cervical cancer. We also discuss the potential role of biosimilars to bevacizumab, which may offer more affordable options in the future treatment of gynecologic cancers.METHODS:Literature searches of PubMed and ClinicalTrials.gov databases were conducted. Regulatory and individual pharmaceutical company web pages were also reviewed. Search terms included "biosimilar" and "bevacizumab," and these were used to identify information regarding biosimilar development, reporting results of biosimilar studies or biosimilars in development.RESULTS:At present, four bevacizumab biosimilar candidates are undergoing comparative clinical assessment, with the potential to increase access and offer efficiencies across healthcare systems.CONCLUSIONS:It is anticipated that biologics such as bevacizumab will continue to play a key role in the treatment of an array of gynecologic cancers. Biosimilars to bevacizumab are currently in development and have the potential to increase access to medicines in a variety of settings, including gynecologic cancers.
Clear cell carcinoma and endometrioid adenocarcinoma are histologic subtypes of ovarian and uterine cancer that demonstrate unique clinical behavior but share common underlying genomic aberrations and oncogenic pathways. ARID1A mutations are more frequently identified in these tumors, in comparison to other gynecologic histologies, and loss of ARID1A tumor suppressor function is thought to be an essential component of carcinogenic transformation. Several therapeutic targets in ARID1A mutated cancers are in development, including EZH2 inhibitors. EZH2 facilitates epigenetic methylation to modulate gene expression, and both uterine and ovarian cancers show evidence of EZH2 over expression. EZH2 inhibition in ARID1A mutated tumors acts in a synthetically lethal manner to suppress cell growth and promote apoptosis, revealing a unique new therapeutic opportunity. Several phase 1 and 2 clinical trials of EZH2 inhibitors are ongoing currently and there is considerable promise in translational trials for utilization of this new targeted therapy, both to capitalize on ARID1A loss of function and to increase sensitivity to platinum-based adjuvant chemotherapies. This review will synthesize the molecular carcinogenesis of these malignancies and their unique clinical behavior, as a foundation for an emerging frontier of targeted therapeutics – the synergistic inhibition of EZH2 in ARID1A mutated cancers.
Due to the significant morbidity and mortality associated with placenta percreta, alternative management options are needed. Beginning in 2005, our institution implemented a multidisciplinary strategy to patients with suspected placenta percreta. The purpose of this study is to present our current strategy, maternal morbidity and outcomes of patients treated by our approach.
Survival of patients with advanced, recurrent, or metastatic human papillomavirus (HPV)-associated cancer is suboptimal despite the availability of various treatment modalities. The recently developed bacterial vector Listeria monocytogenes ( Lm ) activates innate and adaptive immune responses and is expected to offer immunologic advantages. Axalimogene filolisbac (AXAL or ADXS11–001) is a novel immunotherapeutic based on the live, irreversibly attenuated Lm fused to the nonhemolytic fragment of listeriolysin O ( Lm -LLO) and secretes the Lm -LLO-HPV E7 fusion protein targeting HPV-positive tumors. Herein are reported the development and recent results of various clinical trials in patients with HPV-associated cervical, head and neck, and anal cancers.
To determine the cost-effectiveness of transversus abdominis plane block with liposomal bupivacaine (TAP) compared to oral opioids alone for acute postoperative pain after laparoscopic hysterectomy for early endometrial cancer.
The National Comprehensive Cancer Network (NCCN) and the Society of Gynecologic Oncology (SGO) recommend lymph node sampling (LNS) as a key component in the surgical staging of high-grade endometrial cancer. Our goal was to examine surgical staging patterns for high-grade endometrial cancer in the United States.
Merkel cell carcinoma is a rare and aggressive neoplasm originating from mechanoreceptor Merkel cells of the stratum basale of the epidermis. Cases affecting the vulva are exceedingly rare, with the currently available literature primarily in case report form.
Until recently our knowledge of a genetic contribution to ovarian cancer focused almost exclusively on mutations in the BRCA1/2 genes. However, through germline and tumor sequencing an understanding of the larger phenomenon of homologous recombination deficiency (HRD) has emerged. HRD impairs normal DNA damage repair which results in loss or duplication of chromosomal regions, termed genomic loss of heterozygosity (LOH). The list of inherited mutations associated with ovarian cancer continues to grow with the literature currently suggesting that up to one in four cases will have germline mutations, the majority of which result in HRD. Furthermore, an additional 5–7% of ovarian cancer cases will have somatic HRD. In the near future, patients with germline or somatic HRD will likely be candidates for a growing list of targeted therapies in addition to poly (ADP-ribose) polymerase (PARP) inhibitors, and, as a result, establishing an infrastructure for widespread HRD testing is imperative. The objective of this review article is to focus on the current germline and somatic contributors to ovarian cancer and the state of both germline and somatic HRD testing. For now, germline and somatic tumor testing provide important and non-overlapping clinical information. We will explore a proposed testing strategy using somatic tumor testing as an initial triage whereby those patients found with somatic testing to have HRD gene mutations are referred to genetics to determine if the mutation is germline. This strategy allows for rapid access to genomic information that can guide targeted treatment decisions and reduce the burden on genetic counselors, an often limited resource, who will only see patients with a positive somatic triage test.
Immune responses to the facultative intracellular bacterium Listeria monocytogenes (Lm) are robust and well characterized. Utilized for decades as a model of host-disease immunology, Lm is well suited for use as an immunotherapeutic bacterial vector for the delivery of foreign antigen. Genetic modification of Lm has been undertaken to create an attenuated organism that is deficient in its master transcriptional regulator, protein-related factor A, and incorporates a truncated, nonhemolytic version of the listeriolysin O (LLO) molecule to ensure its adjuvant properties while also preventing escape of the live organism from the phagolysosome. Delivery of a vaccine construct (Lm-LLO-E7; axalimogene filolisbac [AXAL] or ADXS11-001) in which the modified LLO molecule is fused with the E7 oncoprotein of human papillomavirus type 16 (HPV-16) consistently stimulates strong innate and E7 antigen-specific adaptive immune responses, resulting in reduction of tumor burden in animal cancer models. In the clinical setting, AXAL has shown early promise in phase I/II trials of women with cervical cancer, and several more trials are currently underway to assess the efficacy and safety of this antitumor vaccine in patients with HPV-positive head and neck and anal cancers.
BACKGROUND:Therapy for advanced epithelial ovarian cancer (OC) includes first line platinum/taxane-containing chemotherapy and re-treatment with platinum-containing regimens for disease recurrence in patients likely to respond again. Single-agent, non-platinum, cytotoxic agents are commonly used to treat patients resistant to platinum retreatment, but these agents are associated with dose-limiting toxicities and response rates below 20%.MAIN BODY:Recent advances have led to novel targeted treatments for recurrent OC that offer opportunities to improve response rates and prolong progression-free intervals. However, they also add complexity to the process of selecting treatment for individual patients at different stages of the disease process. Advanced and recurrent OC is rarely cured. Multiple lines of platinum combinations, and nonplatinum chemotherapeutics eventually fail to achieve clinical benefit, thus other active and tolerable systemic therapies are needed. Consequently, the US Food and Drug Administration has created a mechanism for "accelerated approval" of new medicines in situations of high unmet medical need.CONCLUSION:We review the clinical implications of recent key clinical studies in these settings and outline the path forward for study design and approval of novel therapeutics to treat recurrent OC.
