Gynecologic oncology research and practice最新文献

Background: In Ethiopia, cervical cancer is ranked as the second most common type of cancer in women and it is about 8 times more common in HIV infected women. However, data on knowledge of HIV infected women regarding cervical cancer and acceptability of screening is scarce in Ethiopia. Hence, the present study was aimed at assessing the level of knowledge of about cervical cancer and uptake of screening among HIV infected women in Gondar, northwest Ethiopia.

Methods: A cross sectional, questionnaire based survey was conducted on 302 HIV infected women attending the outpatient clinic of University of Gondar referral and teaching hospital from March 1 to 30, 2017. Descriptive statistics, univariate and multivariate logistic regression analysis were also performed to examine factors associated with uptake of cervical cancer screening service.

Results: Overall, only 64 (21.2%) of respondent were knowledgeable about cervical cancer and screening and only 71 (23.5%) of respondents were ever screened in their life time. Age between 21 and 29 years old (AOR = 2.78, 95% CI = 1.71-7.29), perceived susceptibility to develop cervical cancer (AOR =2.85, 95% CI = 1.89-6.16) and comprehensive knowledge of cervical cancer (AOR = 3.02, 95% CI = 2.31-7.15) were found to be strong predictors of cervical cancer screening service uptake.

Conclusion: The knowledge and uptake of cervical cancer screening among HIV infected women was found to be very poor. Taking into consideration the heightened importance of comprehensive knowledge in boosting up the number of participants towards cervical cancer screening services, different stakeholders working on cancer and HIV/AIDS should provide a customized health promotion intervention and awareness creation to HIV-infected women, along with improving accessibility of cervical cancer screening services in rural areas.

Endometrial cancer is the most common gynecologic malignancy in the United States, accounting for 6% of cancers in women. In 2017, an estimated 61,380 women were diagnosed with endometrial cancer, and approximately 11,000 died from this disease. From 1987 to 2008, there was a 50% increase in the incidence of endometrial cancer, with an approximate 300% increase in the number of associated deaths. Although there are many chemotherapeutic and targeted therapy agents approved for ovarian, fallopian tube and primary peritoneal cancers, since the 1971 approval of megestrol acetate for the palliative treatment of advanced endometrial cancer, only pembrolizumab has been Food and Drug Administration (FDA)-approved for high microsatellite instability (MSI-H) or mismatch repair deficient (dMMR) endometrial cancer; this highlights the need for new therapies to treat advanced, recurrent, metastatic endometrial cancer. In this review, we discuss current and emerging treatment options for endometrial cancer, including chemotherapy, targeted therapy, and immunotherapy. The National Cancer Institute (NCI) and others are now focusing their efforts on the design of scientifically rational targeted therapy and immunotherapy trials for specific molecular phenotypes of endometrial cancer. This is essential for the advancement of cancer care for women, which is threatened by a severe enrollment decline of approximately 80% for gynecologic oncology clinical trials.

Poly (ADP-ribose) polymerases (PARPs) are an important family of nucleoproteins highly implicated in DNA damage repair. Among the PARP families, the most studied are PARP1, PARP2 and PARP 3. PARP1 is found to be the most abundant nuclear enzyme under the PARP series. These enzymes are primarily involved in base excision repair as one of the major single strand break (SSB) repair mechanisms. Being double stranded, DNA engages itself in reparation of a sub-lethal SSB with the aid of PARP. Moreover, by having a sister chromatid, DNA can also repair double strand breaks with either error-free homologous recombination or error-prone non-homologous end-joining. For effective homologous recombination repair, DNA requires functional heterozygous breast cancer genes (BRCA) which encode BRCA1/2. Currently, the development of PARP inhibitors has been one of the promising breakthroughs for cancer chemotherapy. In March 2017, the United States Food and Drug Administration (FDA) approved niraparib for maintenance therapy of recurrent gynecologic cancers (epithelial ovarian, primary peritoneal and fallopian tube carcinomas) which are sensitive to previous platinum based chemotherapy irrespective of BRCA mutation and homologous recombination deficiency status. It is the third drug in this class to receive FDA approval, following olaparib and rucaparib and is the first global approval for maintenance therapy of the aforementioned cancers. Niraparib preferentially blocks both PARP1 and PARP2 enzymes. The daily tolerated dose of niraparib is 300 mg, above which dose limiting grade 3 and 4 toxicities were observed. In combination with humanized antibody, pembrolizumab, it is also under investigation for those patients who have triple negative breast cancer. By and large, there are several clinical trials that are underway investigating clinical efficacy and safety, as well as other pharmacokinetic and pharmacodynamic profiles of this drug for various malignancies.

Background: While many of these agents have been compared in prospective clinical trials, the gemcitabine/platinumbased regimens have not been compared in a prospective, randomized clinical trial. While bothgemcitabine/carboplatin and gemcitabine/cisplatin have a similar ORR in separate clinical trials, the tworegimens have never been directly been compared. With overlapping dose-limiting toxicity of thrombocytopenia, the gemcitabine/carboplatin regimen has been challenging to employ in the clinical setting in previously treated ovarian cancer patients and is often associated with treatment delays and/or dose reductions. Gemcitabine/cisplatin can also be a challenge due to its dose limiting neuropathy and renal toxicity, especially in previously treated patients. In the absence of any prospective, head to head comparison this retrospective study was embarked upon to compare the response rate and toxicity profiles of gemcitabine/cisplatin verses gemcitabine/carboplatin for the treatment of platinum-sensitive verses platinum-resistant recurrent ovarian cancer.

Methods: This was a retrospective chart review study that identified patients that had received either gemcitabine/cisplatin or gemcitabine/carboplatin for treatment of recurrent ovarian cancer and compared documented hematological and non-hematological toxicity and response based on RECIST (v1.1). Data was evaluated based upon platinum sensitivity/resistance as well.

Results: A total of 93 patients were identified that had received a gemcitabine/platinum regimen with 48 with recurrent ovarian cancer that were included in the study. There were 21 patients in the gemcitabine/cisplatin arm and 27 patients identified in the gemcitabine/carboplatin arm. Objective response rate (ORR) was greater in platinum-sensitive patients that received gemcitabine/carboplatin compared to gemcitabine/cisplatin (8 (67%) vs 2 (25%), p < 0.05). Conversely, ORR was greater in platinum-resistant patients treated with gemcitabine/cisplatin (4 (57%) vs 1 (25%), NS). Mean time to progression was greater in gemcitabine/cisplatin patients (7.2 vs 5.1 months, p < 0.03). Patients treated with gemcitabine/carboplatin discontinued due to toxicity at a greater rate (8 (33%) vs 5 (24%)). Specifically gemcitabine/carboplatin had a greater incidence (85%) of grade 2 or greater leukopenia, thrombocytopenia, and neutropenia compared to gemcitabine/cisplatin (19%) However, there was no significant difference in dose reductions, treatment delays, or granulocyte-colony stimulating factor (G-CSF) administration between regimens.

Conclusions: Gemcitabine/cisplatin appears to have greater efficacy in platinum-resistant patients, while gemcitabine/carboplatin seems to have greater efficacy in platinum-sensitive patients. Overall, gemcitabine/carboplatin was associated with a greater incidence of myelosuppression and discontinuation due

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.

Background: Although cervical cancer is preventable, it is still the second leading cause of cancer deaths among women in the world. Further, it is estimated that around 5-10% of hospital admissions are due to drug related problems (DRPs), of which 50% are avoidable. In cancer therapy, there is an immense potential for DRPs due to the high toxicity of most chemotherapeutic regimens. Hence, this study sought to assess DRPs among patients with cervical cancer at Kenyatta National Hospital (KNH).

Methods: A cross-sectional study was conducted at the oncology units of KNH. A total of 81 study participants were recruited through simple random sampling. Data were collected from medical records and interviewing patients. The appropriateness of medical therapy was evaluated by comparing with National Compressive Cancer Network and European Society for Medical Oncology practice guideline of cervical cancer treatment protocol. The degree of adherence was determined using eight-item Morisky medication adherence scale. The likelihood of drug interaction was assessed using Medscape, Micromedex and Epocrates drug interaction checkers. The data were entered in Microsoft Excel and analysed using statistical software STATA version 13.0. Descriptive statistics such as mean, percent and frequency were used to summarise patients' characteristics. Univariable and multivariable binary logistic regression were used to investigate the potential predictors of DRPs.

Result: A total of 215 DRPs were identified from 76 patients, translating to a prevalence of 93.8% and a mean of 2.65 ± 1.22 DRPs. The predominant proportion of DRPs (48.2%) was identified in patients who had been treated with chemoradiation regimens. Adverse drug reactions 56(69.1%) and drug interactions 38(46.9%) were the most prevalent DRPs. Majority (67.9%) of the study population were adherent to their treatment regimens. Forgetfulness 18(69.2%), expensive medications 4(15.4%) and side effects of medications 4(15.4%) were the main reasons for medication non-adherence. Patients with advanced stage cervical cancer were 15.4 times (AOR = 15.4, 95% CI = 1.3-185.87, p = 0.031) more likely to have DRPs as compared to patients with early stage disease.

Conclusion: Adverse drug reactions, drug interactions, and need of additional drug therapy were the most common DRPs identified among cervical cancer patients. Advanced stage cervical cancer was the only predictor of DRPs.

Background: Preparation in the business of medicine is reported to be poor across a number of specialties. No data exist about such preparation in gynecologic oncology training programs. Our objectives were to evaluate current time dedicated to these initiatives, report recent graduate perceptions about personal preparedness, and assess areas where improvements in training can occur.

Methods: Two separate surveys were created and distributed, one to 183 Society of Gynecologic Oncology candidate members and the other to 48 gynecologic oncology fellowship program directors. Candidate member surveys included questions about perceived preparedness for independent research, teaching, job-hunting, insurance, and billing. Program director surveys assessed current and desired time dedicated to the topics asked concurrently on the candidate survey. Statistical analysis was performed using Chi-squared (or Fisher's exact test if appropriate) and logistic regression.

Results: Survey response rates of candidate members and program directors were 28% and 40%, respectively. Candidate members wanted increased training in all measures except retrospective protocol writing. Female candidates wanted more training on writing letters of intent (LOI) (p = 0.01) and billing (p < 0.01). Compared to their current schedules, program directors desired more time to teach how to write an investigator initiated trial (p = 0.01). 94% of program directors reported having career goal discussions with their fellows, while only 72% of candidate members reported that this occurred (p = 0.05).

Conclusion: Recent graduates want more preparation in the non-clinical aspects of their careers. Reconciling program director and fellow desires and increasing communication between the two may serve to achieve the educational goals of each.

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.

Background: 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.

Methods: From 2005 to 2014, a retrospective cohort study of patients with suspected placenta percreta at an academic tertiary care institution was performed. Treatment modalities included immediate hysterectomy at the time of cesarean section (CHYS), planned delayed hysterectomy (interval hysterectomy 6 weeks after delivery) (DH), and fertility sparing (uterine conservation) (FS). Prognostic factors of maternal morbidity were identified from medical records. Complications directly related to interventional procedures and DH was recorded. Descriptive statistics were utilized.

Results: Of the 21 patients with suspected placenta percreta, 7 underwent CHYS, 13 underwent DH, and 1 had FS with uterine preservation. Of the 20 cases that underwent hysterectomy, final pathology showed 11 increta, 7 percreta, and 2 inconclusive. 19/20 cases underwent interventional radiology (IR) procedures. Selective embolization was utilized in 14 cases (2/7 CHYS; 12/13 DH). The median time from cesarean section (CS) to DH was 41 [26-68] days. There were no cases of emergent hysterectomy, delayed hemorrhage, or sepsis in the DH group. Both estimated blood loss and number of packed red blood cell transfusions were significantly higher in the CHYS group. 3/21 cases required massive transfusion (2 CHYS, 1 FS) with median total blood product transfusion of 13 units [12-15]. The four IR-related complications occurred in the DH group. Incidence of postoperative complications was similar between both groups. Median hospital length of stay (LOS) after CHYS was 4 days [3-8] compared to DH cohort: 7 days [3-33] after CS and 4 days [1 -10] after DH. The DH cohort had a higher rate of hospital readmission of 54% (7/13) compared to 14% (1/7) CHYS, most commonly due to pain. There were no maternal deaths.

Conclusion: This multidisciplinary strategy may appear feasible; however, further investigation is warranted to evaluate the effectiveness of alternative approaches to cesarean hysterectomy in cases of morbidly adherent placenta.

Background: 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.

Methods: A cost-effectiveness analysis using a decision tree structure with a 30.5 day time-horizon was used to calculate incremental cost-effectiveness ratio (ICER) values per quality-adjusted life-year (QALY). Base-case costs, probabilities, and QALY values were identified from recently published all-payer national database studies, 2017 Medicare fee-schedules, randomized trials, institutional case series, or assumed, when published values were not available. One-way, two-way and multiple probabilistic sensitivity analyses were performed.

Results: The TAP strategy dominated the oral opioid-only strategy, with decreased costs and increased effectiveness. Specifically, the TAP strategy saved $235.90 under the base-case assumptions. Threshold analyses demonstrated that if the relative same-day discharge probability was ≥ 12% higher in the TAP group, then TAP was cost-saving over oral opioids-alone. Similarly, TAP was cost-saving whenever the costs saved by same-day discharge compared to admission were ≥ $1115.22. Cost-effectiveness of the TAP strategy was highly robust of a variety of sensitivity analyses.

Conclusions: TAP with liposomal bupivacaine was robustly cost-effective at conventional willingness-to-pay thresholds. Further, TAP was cost-saving compared to opioids-only when the same-day discharge rate among TAP users was greater than among opioid-only users.