Gynecologic oncology research and practice最新文献

Background: After platinum and taxane chemotherapy, with or without bevacizumab, active regimens for advanced or recurrent cervical cancer are lacking. Our objective was to review a single institution experience in treating recurrent, refractory cervical cancer with nano-particle albumin bound (NAB) paclitaxel with or without bevacizumab.

Methods: This retrospective case series was conducted in accordance with the regulations set forth by the Institutional Review Board at St. Joseph's Hospital and Medical center. The chemotherapy log at the outpatient infusion center at the University of Arizona Cancer Center was reviewed to identify all advanced cervical cancer patients treated with NAB-paclitaxel from November 2011 until February 2015. The following data points were extracted from patient charts: demographic information, number of cycles, progression free survival (PFS), overall survival (OS), dose reductions and dose-limiting toxicities. In addition the average number of treatment cycles and age at recurrence were calculated.

Results: A total of 12 subjects were identified as receiving treatment with NAB-paclitaxel. Mean age at time of recurrence was 47.2 years (36-55). Nine subjects had squamous cell histology and three subjects had adenocarcinoma histology. All subjects had failed treatment with platinum and taxane, or platinum and topotecan chemotherapy. Two subjects were lost to follow up. The Median number of cycles of NAB-paclitaxel was 6.5 (2-19). The total number of cycles of NAB-paclitaxel in the study population was 65. Seven subjects were treated in combination with bevacizumab. Of these, three subjects are still alive and one subject is currently receiving active treatment with NAB-paclitaxel. The median PFS and OS for all subjects that met mortality endpoint was 4.8 months and 8.9 months (n = 7), respectively. One subject discontinued NAB-paclitaxel secondary to peripheral neuropathy, and one subject developed a vesicovaginal fistula while obtaining combination NAB-paclitaxel and bevacizumab therapy.

Conclusions: NAB-paclitaxel with or without bevacizumab is tolerable and potentially active in treating recurrent cervical cancer after failing platinum-taxane or topotecan chemotherapy. This small case series deserves confirmation through prospective clinical trials.

Poly(ADP-ribose) polymerase (PARP), which was first described over 50 years ago by Mandel, are a family of protein enzymes involved in DNA damage response and works by recognizing the single-strand DNA break (ssDNA) and then effecting DNA repair. A double-strand DNA (dsDNA) break can be repaired by one of two different pathways: homologous recombination (HR) or non-homologous end joining (NHEJ). Homologous recombination occurs in the G2 or M phase of the cell cycle when a sister chromatid is available to use as a template for repair. Because a template is available, HR is a high fidelity, error-free form of DNA repair. With NHEJ there is not a template and the DNA is trimmed and ligated which is a very error-prone process of repair which can lead to genetic instability. Exploiting these mechanism led to development of PARP inhibitors with the idea of utilizing synthetic lethality, where two deficiencies each having no effect on the cellular outcome become lethal when combined, as single agent in BRCA deficient patients or as chemotherapy/radiotherapy combinations to inhibit ssDNA repair. The recent approval of olaparib in BRCA deficient ovarian cancer patients in US and Europe has opened up a whole new treatment option for ovarian cancer patients. This review will discuss the different PARP inhibitors in development and the potential use of this class of agents in the future.

[This corrects the article DOI: 10.1186/s40661-015-0020-3.].

Background: Many women who develop endometrial cancer (EC) or endometrial hyperplasia with atypia are obese and therefore at high risk of surgical complications. Recently clinical trials have been initiated offering non-surgical treatment to these women, but not all may agree to participate in such trials. This paper aims to describe the patient characteristics, and surgical outcomes of women with suspected early stage endometrial cancer and body mass index (BMI) of 30 or greater, who declined enrolment in the feMMe trial, which offers non-surgical hormonal treatment, hormonal plus metformin or hormonal plus weight loss as primary treatment.

Methods: Consecutive case series from a tertiary gynaecological oncology unit. Over the course of the first 2 years of the feMMe trial, 27 patients met the initial eligibility screening, but declined enrolment in the feMMe trial and opted for upfront surgery. The main surgical outcome measures were type of surgical approach, need for conversion from laparoscopic to open approach, length of stay in hospital and adverse events.

Results: Patients' median age was 63 years (range 40 to 86); median BMI was 37.3 kg/m2 (range 30.7 to 54.7); median medical co-morbidities were six (range 3-10). Of the 26/27 surgeries planned to be undertaken laparoscopically, 2/26 patients had to be converted (7 %). Overall, the average hospital stay was 4.5 days, and 11/27 (41 %) of the patients developed one or more adverse events grade 2+ rated according to the Common Toxicity Criteria Version 3.

Conclusions: Adverse surgical outcomes are common in multi-morbid, obese or morbidly obese patients diagnosed with early stage EC or endometrial hyperplasia with atypia and who have a hysterectomy.

Radiation induced Lumbosacral plexophaty (RILP) is a rare but severe complication that has a considerable impact on quality of life. Its occurrence is rare but increasing with improved long-term cancer survival. This entity commonly results in different degrees of sensory and motor deficits. The pathophysiological mechanisms are not yet fully understood. Diagnosis of radiation myelopathy in women with gynecologic malignancies may increase with the use of concomitant chemo-radiation. This report describes the effect of this combination therapy in a 64-year-old woman with cervical carcinoma.

Endometrial cancer is the only gynecologic malignancy with a rising incidence and mortality. While cure is routinely achieved with surgery alone or in combination with adjuvant pelvic radiotherapy when disease is confined to the uterus, patients with metastatic or recurrent disease exhibit limited response rates to cytotoxic chemotherapy, targeted agents, or hormonal therapy. Given the unmet clinical need in this patient population, exploration of novel therapeutic approaches is warranted, and attention is turning to immunomodulation of the tumor microenvironment. Existing evidence suggests that endometrial cancer is sufficiently immunogenic to be a reasonable candidate for active and/or passive immunotherapy. In this review, we critically examine what is known about the microenvironment in endometrial cancer and what has been learned from preliminary immunotherapy trials that enrolled endometrial cancer patients, encouraging further attempts at immunomodulation in the treatment of aggressive forms of this disease.

Background: Early-stage vaginal and vulvar cancer can be cured. But outcomes of patients with metastatic disease are poor. Thus, new therapeutic strategies are urgently required.

Methods: In this retrospective study, we analyzed the clinical outcomes of consecutive patients with metastatic vaginal or vulvar cancer who were referred to a phase I trial clinic between January 2006 and December 2013. Demographic and clinical data were obtained from patients' electronic medical records.

Results: Patients with metastatic vaginal (n = 16) and vulvar (n = 20) cancer who were referred for phase I trial therapy had median overall survival durations of 6.2 and 4.6 months, respectively. Among those who underwent therapy (n = 27), one experienced a partial response and three experienced stable disease for at least 6 months. Patients with a body mass index ≥30 had a significantly longer median overall survival duration than did those with a body mass index <30 (13.2 months versus 4.4 months, p = 0.04). Preliminary data revealed differences in molecular profiling between patients with advanced vaginal cancer and those with advanced vaginal cancer.

Conclusions: Metastatic vaginal and vulvar cancers remain to be difficult-to-treat diseases with poor clinical outcomes. The currently available phase I trial agents provided little meaningful clinical benefits. Understanding these tumors' molecular mechanisms may allow us to develop more effective therapeutic strategies than are currently available regimens.

Background: The incidence of molar pregnancy has demonstrated marked geographic and ethnic differences. The reported data in Nepal is inconsistent with minimal published literature. Thus, we designed a study to determine prevalence of molar pregnancies and demonstrate clinical and epidemiological characteristics of the patients attending a tertiary care center in eastern Nepal.

Methods: A retrospective review of medical records was conducted to determine the prevalence of molar pregnancies at the B.P. Koirala Institute of Health Sciences (BPKIHS) from the year 2008 to 2012. Secondary data from the medical records were analyzed. Annual and 5-year prevalence of molar pregnancy per 1000 live births was calculated. Demographic characteristics, clinical presentation, management methods and complications of molar pregnancy were studied.

Results: The 5- year prevalence of molar pregnancy at BPKIHS is 4.17 per 1000 live births with annual prevalence ranging 3.8-4.5 per 1000 live births. More than one third of the patients were in the age group of 20-35 years and majority of them were of Hindu religion. For more than one third (41.7 %) of the patients, it was their first pregnancy while about 10 % gave a positive past history of molar pregnancy. Abnormal uterine bleeding (86.3 %) was the most frequent complaint, suction evacuation was the most common method of treatment and more than half of the patients required prolonged care after initial management.

Conclusion: There is a need for studies at country level which will give us a national figure on molar pregnancies. Thus, a standardized clinic-epidemiological profile of molar pregnancy in Nepal can be created.

Despite the introduction of screening and, latterly, vaccination programs in the developed world, globally cervical cancer remains a significant health problem. For those diagnosed with advanced or recurrent disease even within resource rich communities, prognosis remains poor with an overall survival (OS) of just over 12 months. New therapeutic interventions are urgently required. Advances in our understanding of the mechanisms underlying tumor growth and the downstream effects of human papilloma virus (HPV) infection identified angiogenesis as a rational target for therapeutic intervention in cervical cancer. Anti-angiogenic agents showed promising activity in early phase clinical trials culminating in a randomized phase III study of the humanized monoclonal antibody to vascular endothelial growth factor (VEGF), bevacizumab, in combination with chemotherapy. This pivotal study, the Gynecologic Oncology Group protocol 240, met its primary endpoint demonstrating a significant improvement in OS. Bevacizumab became the first targeted agent to be granted regulatory approval by the United States Food and Drug Administration for use alongside chemotherapy in adults with persistent, recurrent or metastatic carcinoma of the cervix. This review outlines the rationale for targeting angiogenesis in cervical cancer focusing on the current indications for the use of bevacizumab in this disease and future directions.

Background: Cervical cancer (CC) is one of the most widespread gynecological malignancies in women worldwide. Treatment strategies and screening modalities have largely evolved these past years resulting in an improvement of survival. However, treatment modalities are associated with long term side effects that significantly impacts quality of life (QOL) in cervical cancer survivors. The aim of this study is to evaluate QOL (General and sexual QOL) in cervical cancer survivors up to 10 years after the diagnosis.

Material and methods: In a cross-sectional descriptive study design, 110 cervical cancer survivors (CCS) and 80 healthy controls completed questionnaires assessing QOL.

Results: Participants were Arabic White, sexually active. The mean age at diagnosis was 34 years and was 43 years at the time of the interview. In our series long term CCS have generally a good global QOL comparable with healthy controls. However, issues concerning emotional functioning were over expressed by CCS. As to the sexual impact of cervical cancer; CCS experienced less sexual functioning and enjoyment and less satisfaction with their body image when compared to healthy controls. In a multivariate analysis, spiritual well-being and social support were the predictor factors that statistically affected QOL among the studied cohort, it accounted for 81 % of the variance in QOL scores.

Conclusions: A better understanding of the complexity of the relationship between QOL and cervical cancer sequelae in one hand and socio-demographic factors in the other hand is necessary to improve QOL among cervical cancer survivors. More efforts should make to inform disease free patients about expected side effects and symptoms to face the physical changes that would affect their QOL and sexual activity.