Gynecologic oncology research and practice最新文献

Background: 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.

Case presentation: 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.

Conclusion: 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.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Background: 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.

Methods: A retrospective single-institution descriptive cohort study was conducted from 2003 to 2014. Patients with leiomyoma and/or uterine malignancy who underwent minimally invasive surgery with contained uterine manual morcellation were identified from surgical logs. Demographic data, pathology results, operative details and adjuvant treatments were abstracted.

Results: Eighty-eight patients were identified; 35 with leiomyoma and 53 with endometrial cancer. The mean age was 48 and 60, respectively. Uterine size/weight was greater in women with leiomyoma compared to those with cancer (15.1 weeks/448 g vs. 10.7 weeks/322 g). Mean operative time was 206 min (range 115-391) for leiomyoma cases and 238 min (range 131-399) for cancer cases. Median length of stay was 1 day (range 0-3 days). There were no cases of occult leiomyosarcoma and all specimens were successfully manually morcellated within a bag. There were no intraoperative complications. Thirty-day postoperative complications occurred in 7 patients, including one readmission for grade (G) 1 vaginal cuff separation after intercourse, G1 port-site hematoma (1), G2 port-site cellulitis (1), G2 vaginal cuff cellulitis (2), G2 bladder infection (2), G2 pulmonary edema (1), and G1 musculoskeletal injury (1).

Conclusions: Contained uterine hand morcellation is a feasible procedure with low peri-operative complication rates that allows for minimally invasive surgical procedures for women with large uterine neoplasms. Further evaluation is needed to assess survival outcomes for uterine malignancies.

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.

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.

Background: 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.

Methods: A cross-sectional survey was conducted among English speaking women with gynecologic malignancies at the University of Arizona Cancer Centers in Phoenix and Tucson from April 2012 to July 2015. The survey was a paper packet of questions that was distributed to cancer patients at the time of their clinic visit. The packet contained questions on demographic information, treatment, lifestyle characteristics, pelvic pain and Health-related quality of life (HRQoL). Measures included the generic and cancer-specific scores on the Functional Assessment of Cancer Therapy-General (FACT-G) and the Female Genitourinary Pain Index (GUPI). The total scores and subdomains were compared with descriptive variables (age, body mass index (BMI), diet, exercise, disease status, treatment and support group attendance) using Cronbach alpha (α), Spearman rank correlations (ρ), and Holm's Bonferroni method.

Results: One-hundred and forty-nine women completed the survey; 55% (N = 81) were older than 60 years, 38% (N = 45) were obese (BMI > 30), 46% (N = 66) exercised daily, and 84% (N = 111) ate one or more daily serving of fruit and vegetables. Women in remission, those who exercised daily and ate fruits/vegetables were less likely to have their symptoms impact their QoL. Younger women were more likely to report genitourinary issues (p = - 0.22) and overall problems with QoL (p = - 0.29) than older women. Among FACT-G support group responses, we found those that did not attend support groups had a significantly higher emotional wellbeing (p = 0.05).

Conclusions: This study identified potential areas of clinical focus, which aid in understanding our approach to caring for gynecologic cancer patients and improvement of their HRQoL. We identified that age, pelvic pain, and lifestyle characteristics have indicators to poor QoL in women with gynecologic cancers. In this population, younger women and those with pelvic pain complaints, poor diet and exercise habits should be targeted early for supportive care interventions to improve QoL throughout both treatment and survivorship.

Background: 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.

Methods: A descriptive cross-sectional study involving a convenience sample of 660 HIV-positive women aged 20 to 65 years receiving antiretroviral therapy in HIV care centres in the Central Region of Ghana was conducted using an interviewer-administered questionnaire. The data were summarised and analysed using frequencies, percentages and binary logistic regression.

Results: The study revealed that 82.0% of HIV-positive women intended to obtain cervical cancer screening. Level of education was a determinant of cervical cancer screening intention. HIV-positive women with low levels of education were 2.67 times (95% CI, 1.61-4.42) more likely to have intention to screen than those with no formal education. Those with high levels of education were 3.16 times (95% CI, 1.42-7.02) more likely to have intention to screen than those with no formal education. However, age, religion, marital status, employment status, and ability to afford the cost of cervical cancer screening were not determinants of intention to screen.

Conclusions: Education of women of all ages needs to be a priority, as it could enable them to adopt appropriate health behaviours and engage in cervical cancer screening. Additionally, interventions to improve understanding of cervical cancer screening among HIV-positive women are highly recommended. These include health education about the disease and availability of screening options in HIV/AIDS care centres.

Background: 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.

Methods: Women newly diagnosed with gynaecological cancer at the Royal Hospital for Women between 2010 and 2014 (cohort1) and 2015-2016 (cohort 2) who were identified as suitable for genetics assessment were checked against the New South Wales/Australian Capital Territory genetic database. The doctors of non-attenders were contacted regarding suitability for re-referral, and patients who were still suitable for genetics assessment were contacted by mail. Attendance was again checked against the genetics database.

Results: Among 462 patients in cohort 1, flagged for genetic assessment, 167 had not consulted a genetic service at initial audit conducted in 2014. 86 (18.6%) women whose referral was pending clarification of family history and/or immunohistochemistry did not require further genetic assessment. Letters were sent to 40 women. 7 women (1.5%) attended hereditary cancer clinic in the following 6 months.The audit conducted in 2016 identified 148 patients (cohort 2) appropriate for genetic assessment at diagnosis. 66 (44.6%) had been seen by a genetics service, 51 (34.5%) whose referral was pending additional information did not require further genetic assessment. Letters were sent to 15 women, of whom 9 (6.1%) attended genetics within 6 months.

Conclusions: To improve the effectiveness of guidelines for the genetic referral of women newly diagnosed with ovarian cancer, clinicians need to obtain a thorough family history at diagnosis; arrange for reflex MMR IHC according to guidelines; offer BRCA or panel testing to all women with non-mucinous ovarian cancer prior to discharge and systematically follow up all women referred to genetics at the post-op visit.

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.