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Objective: To examine hospital-based specialist palliative care (SPC) utilisation among patients with gynaecological cancer, including temporal trends, predictors and associations with high-intensity end-of-life care.Methods: We conducted a nationwide registry-based study for all patients dying from gynaecological cancer in Denmark during 2010-2016. We estimated the proportions of patients receiving SPC by year of death and used regression analyses to examine predictors of SPC utilisation. Use of high-intensity end-of-life care according to SPC utilisation was compared by regression analyses adjusting for type of gynaecological cancer, year of death, age, comorbidities, residential region, marital/cohabitation status, income level and migrant status.Results: Among 4502 patients dying from gynaecological cancer, the proportion of patients receiving SPC increased from 24.2% in 2010 to 50.7% in 2016. Young age, three or more comorbidities, residence outside the Capital Region and being immigrant/descendant were associated with increased SPC utilisation, whereas income, cancer type and stage were not. SPC was associated with lower high-intensity end-of-life care utilisation. Particularly, when compared with patients not receiving SPC, patients who accessed SPC >30 days before death had 88% lower risk of intensive care unit admissions within 30 days before death (adjusted relative risk: 0.12 (95% CI: 0.06; 0.24)) and 96% lower risk of surgery within 14 days before death (adjusted relative risk: 0.04 (95% CI: 0.01; 0.31)).Conclusions: Among patients dying from gynaecological cancer, SPC utilisation increased over time and age, comorbidities, residential region and migrant status were associated with access to SPC. Furthermore, SPC was associated with lower use of high-intensity end-of-life care. Objective: To examine hospital-based specialist palliative care (SPC) utilisation among patients with gynaecological cancer, including temporal trends, predictors and associations with high-intensity end-of-life care. Methods: We conducted a nationwide registry-based study for all patients dying from gynaecological cancer in Denmark during 2010–2016. We estimated the proportions of patients receiving SPC by year of death and used regression analyses to examine predictors of SPC utilisation. Use of high-intensity end-of-life care according to SPC utilisation was compared by regression analyses adjusting for type of gynaecological cancer, year of death, age, comorbidities, residential region, marital/cohabitation status, income level and migrant status. Results: Among 4502 patients dying from gynaecological cancer, the proportion of patients receiving SPC increased from 24.2% in 2010 to 50.7% in 2016. Young age, three or more comorbidities, residence outside the Capital Region and being immigrant/descendant were associated with increased SPC utilisation, whereas income, cancer type and stage were not. SPC was associated with lower high-intensity end-of-life care utilisation. Particularly, when compared with patients not receiving SPC, patients who accessed SPC >30 days before death had 88% lower risk of intensive care unit admissions within 30 days before death (adjusted relative risk: 0.12 (95% CI: 0.06; 0.24)) and 96% lower risk of surgery within 14 days before death (adjusted relative risk: 0.04 (95% CI: 0.01; 0.31)). Conclusions: Among patients dying from gynaecological cancer, SPC utilisation increased over time and age, comorbidities, residential region and migrant status were associated with access to SPC. Furthermore, SPC was associated with lower use of high-intensity end-of-life care.

This study investigated whether there are pharmacogenomic markers predictive of chemotherapy induced peripheral neuropathy (CIPN) as a result of taxane-based chemotherapy.Patients were enrolled from August 2020 to November 2020 in a prospective, case-control trial evaluating pharmacogenetic predictors of CIPN. All women were treated with at least 3 cycles of taxane-based chemotherapy for histologically confirmed gynecologic malignancies. Buccal saliva samples were used to test for 32 drug metabolism variations. All testing was performed by ⍺LPHA-GENOMIX laboratories. Fisher's Exact test was used to assess for event differences of categorical variables.Of 102 enrolled patients, 58%, 28%, and 14% had ovarian, endometrial, or cervical cancers, respectively. The median age was 67, 72% were Caucasian and 25% were African American. 16% of patients were treated with 3-4 cycles, 57% received 5-7 cycles, and 27% received 8 or more cycles of chemotherapy that included paclitaxel. Grade 2 CIPN was experienced by 51 patients. There was no difference in age, race, disease site, or number of chemotherapy cycles (p0.05) between those who did or did not develop CIPN. CYP2D6 genotype (p = 0.009) and CYP3A5 genotype (p = 0.023) had different frequencies among those with and without CIPN. Patients classified as having poor or intermediate function of CYP2D6 had increased risk of CIPN (OR 1.63, 95% CI 1.04-2.57, p = 0.026). There was no difference in CYP2D6 phenotype by race (p = 0.29). No patients with normal function of CYP3A5 developed CIPN. There were no Caucasians with normal function of CYP3A5, but 28% of African Americans had normal CYP3A5 function (p0.001).Pharmacogenomics appear associated with the development of CIPN and may be able to help personalize treatment decision making.

Rhabdomyomas are benign tumors with skeletal muscle differentiation that are broadly divided into cardiac and extracardiac types. The latter demonstrate a predilection for head and neck and genital locations and are further subclassified into adult-type rhabdomyoma (ATRM), fetal-type rhabdomyoma (FTRM) and genital rhabdomyoma (GRM). Most extracardiac rhabdomyomas that arise in paratesticular tissues have a somewhat distinctive morphology and have been termed sclerosing rhabdomyomas (SRM). Therefore, we hypothesized that these tumors may harbor recurrent genetic alterations. In this study, we assessed 15 paratesticular rhabdomyomas (11 initially classified as SRM, 2 cellular FTRM and 2 ATRM) using massively parallel DNA and RNA sequencing. Five of 14 successfully sequenced cases harbored a novel H3C2 p.K37I mutation (4 SRM and 1 ATRM). This mutation replaced a highly conserved lysine residue that is a target for epigenetic modifications and plays a role in regulation of DNA replication. Moreover, 4 tumors (2 cellular FTRM, 1 case initially diagnosed as SRM and 1 ATRM) had complex copy number profiles characterized by numerous chromosome-level and arm-level copy number gains, consistent with a ploidy shift. Rereview of the SRM with copy number gains demonstrated that it was significantly more cellular and had a more prominent fascicular architecture than the rest of the SRMs included in this series. Therefore, it was retrospectively reclassified as a cellular FTRM. In conclusion, this study demonstrated that paratesticular rhabdomyomas harbor recurrent somatic H3C2 p.K37I mutations and ploidy shifts.

Pelvic exenteration, first described in 1948 and subsequently refined, may be offered as a last hope of cure to patients with recurrent or locally advanced pelvic tumours, where radiotherapy is not an option. It is a complex, morbid, ultra-radical procedure involving en-bloc resection of the female reproductive organs, lower urinary tract, and a portion of the rectosigmoid. This article discusses the evolution of and current indications for pelvic exenteration in gynaecologic oncology as well as the reasons for its decline: primary and secondary prevention of cervical cancer (the recurrence of which is the most common indication for exenteration); improvements in treatment of cervical, endometrial, vaginal and vulvar cancer in the primary and recurrent setting; and the advent of novel therapies.

We report the feasibility, experience, and early outcomes of the combined intracavitary and interstitial dedicated applicator using the Kelowna GYN template (Varian, Palo Alto, CA).The Kelowna GYN template is CT compatible and used for the treatment of gynecologic cancers. In cases with patients that have an intact uterus, a modified applicator system using the Kelowna GYN template and a 3D printed adapter piece allows for compatibility with an intrautaerine tandem.We reviewed the treatment course of 23 patients comprising of 86 fractions of HDR treatment. Median D90 for cervical tumors (n = 7) was 82.4 Gy (range 77.7-92.6); for postoperative cervical tumors (n = 2) was 73.9 Gy (range 72.0-5.8); for vaginal tumors (n = 4) was 85.8 Gy (range 79.8-88.1); for recurrent endometrial (n = 10) was 86.9 Gy (range 74.8-103.2). Median EQD2 D2cc for bladder was 72.4 Gy (range 47.7-99.4), for rectum was 61.2 Gy (range 52.4-80.6), and for sigmoid colon of 50.5 Gy (44.3-66.9). At a median follow-up of 12 months, 2 patients had a local recurrence. Two patients had distant recurrence: one with carcinomatosis at 6 months, and one with pulmonary metastases at 3 months. No patients had late grade three toxicities.Our single institutional experience supports the use of the Kelowna template as a robust system as a combined IC-IS applicator resulting in versatile and reproducible implants for a variety of gynecologic malignancies.

Same-day discharge (SDD) in patients with endometrial cancer undergoing minimally invasive surgery (MIS) is safe and feasible, with multiple patient and healthcare system benefits. Despite this, our local rate of SDD was only 29.4%. Several studies have suggested methods to improve rates of SDD but few have evaluated the application of such methods. The objectives of our quality improvement (QI) initiative were 2-fold: (1) to increase the rate of SDD in eligible patients with endometrial cancer undergoing MIS to 70% and (2) to evaluate the implementation of methods to improve rates of SDD.At our center, QI diagnostics were conducted, and root causes were identified. Four interventions were introduced: (1) setting SDD as the default discharge plan, (2) ensuring that a physician order for discharge was on the chart, (3) removing the Foley catheter in the operating room, and (4) introducing pre- and postoperative patient education documents. A time-series design was used; rate of SDD was tracked using baseline data and continuous post-intervention monitoring. Process measures (for each intervention) and balancing measures were defined and tracked.At the conclusion of our QI initiative, the average rate of SDD was 78.3%-exceeding our aim of 70%. This was achieved without compromising patient satisfaction (98.2%) or significantly impacting rates of readmission or presentations to the emergency department.Our initiative demonstrated the application of simple interventions that resulted in a substantial increase in our rate of SDD in the population of interest, without causing negative impacts on the defined balancing measures. These interventions were nonspecific to gynecologic oncology and could easily be applied across other surgical disciplines.

To better serve women with gynaecological cancers, we need a sound understanding of their health, wellbeing and needs. This study sought to explore these issues in a sample of Australian women before commencing curative radiotherapy.We undertook a secondary analysis of baseline data from a supportive care trial (n = 311). Descriptive statistics were used to summarise responses to measures of wellbeing, general psychological distress, symptom distress, sexual function and vaginal changes, and supportive care needs. Pre-specified regression models were used to examine sources of variation in wellbeing and sexual function.Women reported lower emotional, functional and physical wellbeing than population norms (all p0.001). The prevalence of general psychological distress was 31% (95% CI 26-36%). Distress caused by physical symptoms was typically low. Health system and information needs comprised eight of the top ten moderate-to-high supportive care needs. Most women reported no change in interest for physical contact or sex compared to pre-diagnosis, but some sexually active women (16-24%) reported smaller vaginal size, increased dryness, and more pain on intercourse. General psychological distress was a robust marker of poorer wellbeing and sexual function.Before radiotherapy, a substantial minority of women with gynaecological cancers experience general psychological distress, reduced wellbeing and moderate-to-high health system and information needs. A model of comprehensive care incorporating assessment of unmet needs, general psychological distress, and sexual issues is recommended. Healthcare providers may require training to elicit and respond to a constellation of interrelated issues and access relevant services for women requiring additional support.

Endosalpingiosis is a poorly understood condition of ectopic epithelium resembling the fallopian tubes. It has been described as an incidental pathology finding, a disease similar to endometriosis, and in association with malignancy. The objective of this study is to determine if endosalpingiosis (ES) has an increased association with gynecologic malignancy when compared to endometriosis (EM).This is a retrospective case-control analysis of patients with a histologic diagnosis of endosalpingiosis or endometriosis at three affiliated academic hospitals between 2000 and 2020. All ES patients were included, and 1:1 matching was attempted to obtain a comparable cohort of EM patients. Demographic and clinical data were obtained, and statistical analysis was performed.A total of 967 patients (515 ES and 452 EM) were included. ES patients were significantly older than EM patients (median age 52 vs 48 years, p0.001). The ES group had significantly more cancer diagnoses at surgery than the EM group (40.1% vs 18.1%, p0.001); this difference persisted in a sub-analysis excluding patients with known or suspected malignancy (20.9% vs 5.6%, p0.001). ES patients had lower overall survival (10-year freedom from death: 77.0% vs 90.5%, p0.001). After adjusting for confounders, multivariable analysis showed that ES patients had increased cancer diagnosed at surgery (OR = 2.48, p0.001) and greater risk of death (OR = 1.69, p = 0.017).Endosalpingiosis was found concurrently with malignancy in 40% of cases, and this effect was preserved in multi-variable and sub-group analyses. Further research consisting of longer follow-up and exploration of molecular relationships between ES and cancer are forthcoming.

Metastatic and incurable cancers of the gynaecological tract (FGTC) represent a major global health burden. Systemic treatment has modest efficacy and radiotherapy is often used for local symptoms. This study combines experience from two large UK centres in palliative radiotherapy for gynaecological cancers.Pooled data from two major centres was analysed. Advanced FGTC patients who received at least one fraction of palliative radiotherapy to the pelvis between 2013 and 2018 were included. Data collected included demographic and tumour details, radiotherapy dose fractionation and details of previous and subsequent treatment. Response was defined in terms of toxicity, symptomatic response and survival. Comorbidities were recorded using a modified ACE 27 score which is adjusted for the presence of uncontrolled FGTC in all the patients.A total of 184 patients were included for treatment response and toxicity; survival data was available for 165 patients. Subjective response in pre-radiotherapy symptoms was documented in 80.4%. Grade 3 or worse gastrointestinal, urinary and other (vomiting, fatigue, pain) toxicity incidence was 2.2%, 3.8%, and 2.7% respectively. No statistically significant correlation between the prescribed EQD2Palliative radiotherapy is effective for symptoms of advanced FGTC with low toxicity. The absence of a dose response argues for short low dose palliative radiotherapy schedules to be used.

Mounting evidence has demonstrated that a myriad of developmental signaling pathways, such as the Wnt, Notch, Hedgehog and Hippo, are frequently deregulated and play a critical role in regulating cancer stem cell (CSC) activity in human cancers, including gynecologic malignancies. In this review article, we describe an overview of various signaling pathways in human cancers. We further discuss the developmental roles how these pathways regulate CSCs from experimental evidences in gynecologic cancers. Moreover, we mention several compounds targeting CSCs in gynecologic cancers to enhance the treatment outcomes. Therefore, these signaling pathways might be the potential targets for developing targeted therapy in gynecologic cancers.

To evaluate if the 5-factor modified frailty index (mFI) is associated with postoperative complications, readmissions or non-home discharge in gynecologic cancer patients undergoing surgery.Patients with a diagnosis of gynecologic cancer (cervical, uterine, or ovarian cancer) who underwent surgery between 2014 and 2018 were identified through the National Surgical Quality Improvement Program (NSQIP) database. The 5-factor mFI was applied and patients classified into 6 categories (mFI groups 0,1,2, 3, 4 and 5). The incidence of 30-day complications, readmissions and non-home discharge was evaluated. Multivariable logistic regression models were used to determine the association between mFI category and readmissions/ complications. Adjusted probabilities of events were calculated based on patient characteristics.At total of 31,181 gynecologic cancer cases were included in the analysis: N = 2968 (9.4%) cervical, N = 20,862 (66.4%) uterine, and N = 7351 (23.4%) ovarian cancers. Of all patients, 46.1% were in category 0, 36.5% category 1, and 1% category 3-5. Factors associated with increased mFI included older age, African American race, laparoscopic surgery and obesity. A significant dose-response relationship between higher mFI and readmission and 30-day complications was noted on adjusted multivariable analysis (adjusted OR 2.37 (1.65-3.45) and 2.10 (1.59-2.75) for readmissions and complications, respectively, in mFI category 3-5). These associations were consistent within each cancer type.The 5-factor mFI universally predicts postoperative readmissions, 30-day complications and non-home discharge in patients with gynecologic cancer. Incorporation of mFI into routine preoperative assessment can identify patients for non-surgical treatments, prehabiliatation and short term home assessments.

Resection of bulky lymph nodes in gynecologic oncology is a challenging procedure. Considering the risk of intraoperative vascular injury, a technique to avoid severe complications is mandatory. In this study, we aimed to analyze the feasibility of laparoscopic ultraradical lymph node debulking using Yasargil clamps in patients with gynecologic cancer with bulky lymph node metastases.Multicenter retrospective case series (ClinicalTrialg.gov ID: NCT05318170), between September 2010 and April 2020.Units of Gynecologic Oncology.Patients with gynecologic cancer with bulky lymph node metastases.Laparoscopic ultraradical lymph node debulking using Yasargil clamps.Forty-three patients with gynecologic cancer with bulky pelvic and/or aortic lymph nodes metastases undergoing laparoscopic lymph node debulking surgery using Yasargil clamps were included. Median surgical time was 300 minutes (range, 120-550 minutes); median estimated blood loss was 170 mL (range, 0-700 mL). Median size of lymph nodes was 50 mm (range, 25-100). R0 resection was achieved in all cases. Four intraoperative complications (9.3%) occurred. No conversion to open surgery was required. There were 8 postoperative complications, classified grade 2 or worse. There were no cases with intra- or postoperative mortality.In our experience, in carefully selected patients with gynecologic cancer with bulky lymph nodes, laparoscopic lymph node debulking using Yasargil clamps could be considered a valid option to avoid potential severe vascular intraoperative complications.

To evaluate the risk of financial toxicity (FT) among inpatients undergoing gynecologic cancer resections and the association of insurance status with clinical and financial outcomes.Using the 2008-2019 National Inpatient Sample, we identified adult hospitalizations for hysterectomy or oophorectomy with a diagnosis of cancer. Hospitalization costs, length of stay (LOS), mortality, and complications were assessed by insurance status. Risk of FT was defined as health expenditure exceeding 40% of post-subsistence income. Multivariable regressions were used to analyze costs and factors associated with FT risk.Of 462,529 patients, 49.4% had government-funded insurance, 44.3% private, and 3.2% were uninsured. Compared to insured, uninsured patients were more commonly Black and Hispanic, admitted emergently, and underwent open operations. Uninsured patients experienced similar mortality but greater rates of complications, LOS, and costs. Overall, ovarian cancer resections had the highest median costs of $17,258 (interquartile range: 12,187-25,491) compared to cervical and uterine. Approximately 52.8% of uninsured and 15.4% of insured patients were at risk of FT. As costs increased across both cohorts over the 12-year study period, the disparity in FT risk by payer status broadened. After risk adjustment, perioperative complications were associated with nearly 2-fold increased risk of FT among uninsured (adjusted odds ratio 1.75, 95% confidence interval 1.46-2.09, p0.001). Among the insured, Black and Hispanic race, public insurance, and open operative approach exhibited greater odds of FT.Patients undergoing gynecologic cancer operations are at substantial risk of FT, particularly those uninsured. Targeted cost-mitigation strategies are warranted to minimize financial burden.

OBJECTIVE. Physical activity is associated with improved cancer outcomes; however, it is unclear which patients may benefit most from increased physical activity. We evaluated whether associations between meeting the American Cancer Society (ACS) physical activity recommendations and psychosocial outcomes in gynecologic cancer survivors varied by type of treatments received. METHODS. We recruited English-speaking adult gynecologic cancer patients from an academic gynecologic oncology practice to participate in a prospective cohort study. Participants completed a survey at study entry regarding their psychosocial health—including distress, depression, anxiety, post-traumatic stress disorder, and quality of life (QoL)—and physical activity. Multivariate linear regression models for each psychosocial outcome tested for interactions between physical activity and each effect modifier (receipt of chemotherapy, radiation therapy, and/or minimally invasive surgery), adjusted for age, pain, body mass index, primary cancer diagnosis, cancer stage, time since diagnosis, and annual household income. RESULTS. Among a total of 362 participants, 213 (59%) met ACS physical activity recommendations. We found evidence of interactions between physical activity and receipt of chemotherapy for depression, anxiety, and QoL scores; those who had received chemotherapy had a stronger association between physical activity and these psychosocial outcomes, compared to those who had not. We found no evidence of interactions between physical activity and receipt of radiation therapy or minimally invasive surgery for any of the outcomes. CONCLUSIONS. Gynecologic cancer survivors who received chemotherapy had significant associations between psychosocial health and physical activity, suggesting they may derive greatest benefit from prescribed exercise.

With the increasing prevalence of gynecologic cancer and obesity, there is a growing population living with cardiovascular disease, obesity and gynecologic cancer concurrently or at risk of developing these disease states.We examined cardiovascular (CV) conditions and obesity among 1824 gynecologic cancer survivors in a cross-sectional analysis, using data from the 2020 Behavioral Risk Factor Surveillance System (BRFSS). Univariate and multivariable logistic regression methods were used in the analysis.The prevalence of heart attack, CHD, and stroke were significantly higher (p0.001) among survivors of gynecologic and other cancer survivors compared to women with no history of cancer. However, no statistically significant differences were observed across gynecologic and other cancer survivors. The prevalence of obesity among gynecologic cancer survivors was significantly higher (p0.001) than that in the other two groups. While around one-third of the women with no history of cancer and survivors of other types of cancer were obese, obesity prevalence was nearly 13%-points higher among survivors of gynecologic cancer. In multivariate analysis, gynecologic cancer survivors were 2.7 times more likely to have a heart attack compared to those without any history of cancer. The odds of CHD and stroke among survivors of gynecologic cancer were respectively 3.4 and 2.7 times that of those with no history of cancer. The adjusted odds were also similar, though smaller in magnitude. Gynecologic cancer survivors were also more likely to be obese -1.8 times that of those with no cancer.Gynecologic cancer survivors are more likely than persons without a cancer history to have cardiovascular disease and other chronic illnesses, and they have a higher prevalence of heart attack, stroke, and obesity. These results underscore the sizeable opportunities for primary, secondary, and tertiary prevention of cardiovascular health conditions among gynecologic cancer survivors.

To report long-term results of an outpatient template-based high-dose-rate interstitial brachytherapy (HDR ISBT) program for the treatment of gynecologic malignancies.Patients treated between 2006 and 2020 at an academic hospital with outpatient template based HDR ISBT without spinal or general anesthesia were reviewed. Patients who had previously received HDR ISBT were excluded. Baseline patient, tumor, and treatment characteristics, such as tumor size, histology, and/or total EQD2 including prior external beam radiation therapy (EBRT) were recorded. Local control and overall survival were estimated using the Kaplan-Meier method, and factors associated with local control and overall survival were evaluated using Cox regression analyses.150 patients received HDR ISBT for a gynecologic tumor and the median follow-up time was 2.98 years (0.89-4.82). Of those, 74/150 (49%) were treated definitively, 69/150 (46%) were treated for tumor recurrence/persistence, and 7/150 (5%) were treated for durable palliation. Median tumor size was 3.00 cm (1.50-4.00). 124/150 (83%) patients received EBRT prior to HDR ISBT. Median HDR ISBT dose was 18 Gy delivered in eight fractions. Local control was 71% (64%-79%), 58% (50%-68%), and 57% (48%-67%) at one, three, and five years, respectively. On multivariate analysis, non-endometrial adenocarcinoma histology (HR = 2.423, 95% CI = 1.011-5.808, p = 0.047) and tumor size ≥ 3 cm (HR = 2.903, 95% CI 1.053-3.441, p = 0.033) were associated with lower local control.The majority of patients who received outpatient-based twice daily HDR ISBT had long-term local control. Larger tumor size and non-endometrial adenocarcinoma histology were detrimental to local control.

The term 'out-of-the-box surgery' in gynecologic oncology was recently coined to describe the resection of tumor growing out of the endopelvic cavity. In the specific case of pelvic sidewall involvement, a laterally extended pelvic resection may be required. As previously defined by Höckel, this resection requires the en bloc removal of structures including the pelvic sidewall muscles, bones, nerves, and/or major vessels. This complex radical procedure leads to tumor-free margins in more than 75% of the patients, with reliable functional results. The rate of recurrence and overall survival are directly correlated with clear resection margins. Progress in imaging, surgical techniques, and perioperative care currently offer the opportunity to attempt surgical curative resection in selected patients for whom palliative therapy was the only alternative. However, the procedure is associated with a high rate of major postoperative complications affecting up to 60% of patients. Multidisciplinary expert centers are the most likely to achieve this complex surgery with favorable oncological outcomes. The aim of this review is to summarize the key issues of out-of-the-box surgery in gynecologic cancer.

Sexual dysfunction has been reported after gynecologic cancer treatment but few studies have examined sexual function during treatment. Our objectives were to describe sexual function among women receiving systemic therapy for gynecologic cancers and to compare sexual function between women receiving upfront treatment versus treatment for cancer recurrence.We conducted a prospective study of women 18yo and older receiving systemic therapy for gynecologic cancer in the upfront or recurrent setting. Patients receiving radiation were excluded. Participants completed a survey with questions from the Patient Reported Outcome Measurement Information System (PROMIS) SexFS and Female Sexual Function Index (FSFI). Clinical information was collected from chart review. Statistical analysis included t-test, Wilcoxon rank sum test, and Fisher's exact test.Of 145 patients approached, 100 (69%) enrolled and 97 (67%) completed the survey. Median age was 65yo. Most patients had ovarian cancer (58%), then endometrial cancer (34%) and cervical cancer (8%). Fifty-two (54%) were receiving recurrent treatment and 45 (46%) upfront treatment. Thirty-eight (76%) in the recurrent group and 34 (75%) in the upfront group hadn't been sexually active in the last month (p = 1.0); however, 61 (67%) participants reported a desire for future sexual activity. Of the 31 patients who completed all FSFI questions, the median FSFI score was 24.0 and 21 (68%) had sexual dysfunction. Vaginal dryness was more common among patients receiving recurrent treatment (p = 0.09) while a "health condition" was a more common reason for sexual inactivity in the upfront setting (p = 0.07).Many patients receiving systemic therapy for gynecologic cancers are willing to discuss sexual function. Most patients reported sexual dysfunction and weren't currently sexually active. Understanding patients' sexual function concerns will allow providers to intervene.

To assess, using a national surgical outcomes database, the association of various malnutrition definitions with post-operative morbidity in three gynecologic malignancies.Patients undergoing resection of ovarian, uterine, or cervical cancer between 2005 and 2019 were identified using the National Surgical Quality Improvement Program (NSQIP) database. Patients were classified based on specific, pre-defined malnutrition criteria: severe malnutrition (Body Mass Index (BMI)18.5 + 10% weight loss), European Society for Clinical Nutrition and Metabolism ((ESPEN1); BMI 18.5-22 + 10% weight loss), ESPEN2 (BMI18.5), American Cancer Society ((ACS); normal/overweight BMI + 10% weight loss), mild malnutrition (BMI 18.5-22), or albumin (3.5 g/dL). Outcomes included 30-day major complications, readmission, reoperation. Modified Poisson regression estimated associations between definitions and outcomes.Of 76,290 total patients undergoing surgery, those meeting malnutrition definitions were: severe-98 (0.1%), ESPEN1-148 (0.2%), ESPEN2-877 (1.1%), ACS-1028 (1.3%), mild-2853 (3.7%), and albumin (11.1%). Complication rates were: unplanned readmission-5.5%, reoperation-1.7%, major complications-13.5%. For ovarian cancer, ESPEN2 malnutrition was associated with higher readmissions (risk ratio 1.69; 95% confidence interval 1.29-2.20), reoperations (2.53; 1.70-3.77), and complications (1.36; 1.20-1.54). For uterine cancer, ACS malnutrition was associated with readmissions (2.74; 2.09-3.59), reoperations (3.61; 2.29-5.71) and complications (3.92; 3.40-4.53). For cervical cancer, albumin3.5 g/dL was associated with readmissions (1.48; 1.01-2.19), reoperations (2.25; 1.17-4.34), and complications (2.59; 2.11-3.17). Albumin3.5 was associated with adverse outcomes in ovarian and uterine cancer.Preoperative risk assessments might be tailored using cancer-specific malnutrition criteria. Major complications, readmissions, and reoperations are all associated with the ESPEN2 definition for ovarian cancer, the ACS definition for uterine cancer, and with albumin3.5 for all cancers.

The demand for outpatient hospital appointments has risen steadily over recent years, almost doubling since 2008; now standing at 120 million appointments per year. Initiatives to reduce unnecessary appointments are a key area of interest, as they can be an effective way of both improving patient care and satisfaction, as well as reducing NHS costs. Patient Initiated Follow-Up (PIFU) provides an alternative to traditional hospital instigated follow-up, by which patients have autonomy in their future care, allowing them to make appointments based on their own perception of need. PIFU has proved successful when implemented in Rheumatology, Inflammatory Bowel Disease and Oncology, with trends towards reduced burden on outpatient appointments, improved patient satisfaction and lower costs. To-date, the use of PIFU in women's health has been limited to gynaecological oncology, where observations include high patient satisfaction and fewer appointments than traditional follow-up. This study aims to undertake a systematic review of the literature relating to PIFU in Obstetrics and Gynaecology in order to identify evidence-based indications for PIFU in the specialty, as well as form a foundation for a subsequent service evaluation.The project was registered with Prospero, University of York. Using the OVID platform, a literature search was conducted using the terms "patient initiated follow up", "gynaecology", "women's health", and "follow up care". Papers were then screened in accordance with the PRISMA protocol, and relevant articles identified based on our inclusion criteria. The quality of the studies was assessed using the Newcastle-Ottawa Scale, and data from the studies were extracted and compared.Eight papers were identified as relevant, two were randomised controlled trials, three were retrospective cohort studies, and the remaining three were prospective cohort studies. The majority of these studies (5/8) were of good quality, scoring 6 or more points on the Newcastle-Ottawa Scale. Four of the eight studies examined cost-effectives; all reported cost-savings relating to PIFU. Seven of the eight studies also reported an association between PIFU and greater patient satisfaction, fewer overall appointments and reduced non-attendance. One study reported no effect on patient satisfaction. Five studies related to gynaecological oncology, two were obstetric and one urogynaecology. The studies which investigated PIFU use in selected gynaecological oncology patients reported that PIFU did not have a negative impact on detection of cancer recurrence, but evidence regarding the psychological impact of PIFU on cancer survivors was conflicting.PIFU was received largely positively and was well accepted by women across these studies. It was also shown to be cost-effective, without a negative impact on health outcomes. PIFU also has the potential to offer additional benefits including reducing diagnostic delay and increasing patient engagement with their own health status. This review found a paucity of data for PIFU in Obstetrics and Gynaecology, with the exception of gynaecological oncology, and further evaluation is required before more widespread implementation.

Lower limb lymphedema (LLL) is a common postoperative complication among gynecological oncology patients following lymph node resection. In the absence of a screening strategy, LLL is frequently diagnosed only through patient's self-reported symptoms. This study investigated the prevalence of undiagnosed postoperative LLL among gynecological oncology patients and identified the associated risk factors.This was a cross-sectional postal questionnaire survey at a tertiary gynecological oncology center. Women with gynecological malignancies who underwent lymph node (inguinal/pelvic/para-aortic) resection between 2010 and 2017 were eligible. The Gynecological Cancer Lymphedema Questionnaire (GCLQ) was used and those with a score of ≥4 were referred to a lymphedema specialist for clinical confirmation.Among 376 eligible women, postoperative LLL was already diagnosed in 45/376 (12%) women. In the remaining women, 117/331 (35.3%) completed the GCLQ, of which 67/117 (57.3%) scored ≥4. Fifty-five women (55/67, 82.1%) were assessed by a lymphedema specialist and eight cases of postoperative LLL were confirmed. In the 12/67 who declined a clinical assessment, they reported no evidence of LLL. The prevalence of undiagnosed postoperative LLL in our study was 8/117 (6.8%, 95% C.I. 2.3-11.4). On univariate analysis, older women were more likely to have undiagnosed postoperative LLL.Undiagnosed postoperative LLL is not uncommon among gynecological oncology patients, especially in older patients. No vulvar cancer patient had undiagnosed LLL. Increased awareness and improved strategies for lymphedema screening are required after lymph node surgery in gynecological oncology.

To assess the effects of a quality improvement (QI) initiative designed to reduce non-surgical readmissions on a gynecologic oncology service.A two-phase QI initiative was implemented on an inpatient gynecologic oncology service to reduce non-surgical 30-day readmissions. Phase 1, from July 2018 to June 2020, included trainee education, frequent physical therapy consultation, pharmacy discharge medication review, 72-h post-discharge telephone call, and standardized 10-day clinic follow-up after discharge. Phase 2, from July 2020 to December 2020, incorporated a nurse practitioner to perform discharge navigation and arrange outpatient follow-up. The incidence of non-surgical readmissions during these phases was compared to that of a baseline period (July 2017-June 2018). We also assessed readmissions to identify common indications and evaluate potential demographic and clinical risk factors.Of 390 total non-surgical gynecologic oncology admissions, 100 were readmitted within 30 days (25.6%). Gastrointestinal tract (GI) obstruction, malignancy-associated pain and infection were the most common symptomatic diagnoses at the index admission, and 30% of readmitted patients had an identical indication for readmission. Compared to the baseline period, we observed a reduction in non-surgical readmissions from 34.1% to 22.6% in Phase 1 and to 18.9% in Phase 2 (p0.03) based on internal review, and a reduction from 13.9% to 11.9% in Phase 1 and to 4.7% in Phase 2 (p = 0.04) based on healthcare performance tracking data.30-day hospital readmission among non-surgical gynecologic oncology patients is common. Implementation of a multifaceted readmissions reduction QI initiative significantly improved readmission rates.

INTRODUCTION. Women with gynecologic cancers may face geographic barriers to standard-of-care consultation with a gynecologic oncologist. While telemedicine may help overcome these geographic barriers, there are no qualitative data exploring gynecologic cancer patients’ attitudes towards telemedicine for cancer care. Patients with gynecologic malignancies may have preferences distinct from general oncology populations due to the sensitive nature of the diseases and anatomy involved. METHODS. Semi-structured interviews were conducted with 15 patients with gynecologic cancers to identify perceived advantages and disadvantages of telemedicine use for gynecologic cancer care. Past experience with telemedicine was elicited as were suggestions for cancer care encounters most compatible with telemedicine. Interviews were transcribed, coded, and analyzed for emergent themes. RESULTS. All patients interviewed were open to the use of telemedicine. Emergent themes regarding advantages of telemedicine included convenience, cost savings, reduced travel, avoidance of infectious disease, and availability of care for those too unwell for in-person visits. Themes regarding disadvantages of telemedical care included technical difficulties, perceived need for examination or testing, and potential compromise of therapeutic relationship. Patients were particularly concerned that difficulty in establishing a therapeutic relationship would compromise initial consultations with gynecologic oncologists via telemedicine. CONCLUSION. Patients with gynecologic cancer are open to use of telemedicine for their care. Particular attention should be paid to overcoming patients’ hesitancy to have initial visits with gynecologic oncologists, as these consultations have the greatest potential to improve access to high-quality gynecologic cancer care.

Pulmonary lymphangitic carcinomatosis (PLC) is a rare event of metastatic lung disease in advanced gynecologic malignancy. Nonspecific symptoms of patients and difficulties in detection of PLC often result in a delayed diagnosis. In this study, we evaluated the clinical outcomes of PLC in patients with gynecologic cancer.We retrospectively reviewed electronic medical records of patients with gynecologic cancer who received care from January 1, 2008 through December 31, 2018 in Samsung Medical Center, Seoul, Republic of Korea. We based diagnosis of PLC on chest CT scan and analyzed clinical parameters of cancer type, International Federation of Gynecology and Obstetrics (FIGO) stage, histology, and patient survival.During the study period, 27 cases of PLC in patients with gynecologic malignancy were identified, including 11 cervical, 12 ovarian, and four uterine cancers. The most common histologic type at initial diagnosis was squamous cell in cervical (6/11, 55%), serous in ovarian (1/11, 92%), and serous in endometrial (2/4, 50%) cancer. The average survival time from diagnosis of PLC to death was a mean of 5.7 months (0.7-23.6 months) in all patients and 6.3, 6.6, and 3.6 months for cervical, endometrial, and ovarian cancer, respectively.This study showed that PLC results in extremely poor survival, from several days to a few months, in patients with gynecologic cancer. Clinicians must be aware of these clinical characteristics and consider other novel therapeutic strategies in the future.

Objective Knowledge of factors associated with intervention non-adherence may provide insights into the clinical utility of non-pharmacologic interventions. Methods This study compared complete and incomplete adherers to two separate components of a novel intervention package for women undergoing curative intent radiotherapy for gynaecological cancer on socio-demographic, clinical and pre-radiotherapy patient-reported outcomes data. Results Adherence to the tailored specialist nurse consultations was satisfactory (71% participated in all available sessions, 19% participated in all but one). Adherence to the telephone peer support sessions was less satisfactory (47% participated in all available sessions, 24% participated in all but one session). Complete adherers to the peer sessions reported significantly lower levels of psychological distress and significantly higher levels of physical, emotional and functional wellbeing before radiotherapy. No other statistically significant differences were observed between complete and incomplete adherers to the nurse- or peer-led sessions. Conclusion Women’s ability or motivation to engage with peer support may be influenced by their health and psychological status. Further, the extent of intervention non-adherence to the peer-led component may have compromised the assessment of its efficacy. Practice implications Peer support may be less acceptable or appropriate for women with more complex care needs. Such women may prefer specialised care from trained professionals.

The adjuvant and post-surgical treatment of gynaecological cancers has historically been guided by the estimation of relapse risk based on clinicopathological factors determined at the time of cancer diagnosis. The recent advancement of genomic and molecular characterisation of gynaecological cancers has begun to shift paradigms in the selection of adjuvant treatment strategy. Recent data regarding the predictive and/or prognostic value of molecular tests in the treatment of advanced ovarian cancer as well as early stage endometrial cancer have been the first such examples to enter adjuvant treatment guidelines for these diseases. In this article, we discuss the current state and future development of molecular assays for gynaecological cancers and how they impact upon treatment selection for ovarian, endometrial and cervical cancers in the post-surgical setting.

This review provides an update on immunohistochemistry applications-diagnostic, prognostic, and predictive-in the pathology evaluation of gynecologic carcinomas. The 5th edition of the WHO Classification of Female Genital Tumors introduced important changes in the diagnostic classification of lower genital tract, endometrial, and ovarian carcinomas, with major influence on the routine pathology practice. Lower genital tract carcinomas and their precursor lesions are now classified based on their human papillomavirus (HPV)-associated and HPV-independent pathogenesis, reflecting the clinically significant prognostic differences and impacting the therapeutic decision-making. Immunohistochemical markers have an increasing role in the pathology evaluation of endometrial carcinomas: in addition to their traditional use in the differential diagnosis and histologic subtyping, they have also been recently advocated for prognostic classification as surrogates for the TCGA (The Cancer Genome Atlas) molecular groups. New entities - mesonephric-like adenocarcinoma and gastric (gastrointestinal)-type mucinous adenocarcinoma of the endometrium - have also been added and often require immunostains for diagnostic confirmation. Ovarian carcinomas frequently show overlapping morphologic patterns and heterogeneous appearance within the same tumor, necessitating immunohistochemical work-up. Beyond diagnostic applications, there is increasing clinical demand for screening of inherited cancer syndromes, prediction of prognosis and guiding targeted therapy. Practical issues and pitfalls related to mismatch repair protein immunohistochemistry, HER2, and PD-L1 testing are also discussed.

STUDY OBJECTIVE To identify factors associated with same day discharge (SDD) after laparoscopic surgery in gynecologic oncology. DESIGN Retrospective cohort. SETTING Teaching hospital. PATIENTS Total of 800 patients having minimally invasive surgery in the division of gynecologic oncology during a 20-month period. INTERVENTION Minimally invasive surgery cases were reviewed for determinants of SDD to identify factors that could improve the SDD rate. MEASUREMENTS AND MAIN RESULTS During the study period, 800 minimally invasive procedures were performed with a 43.0% SDD rate. Patients who had SDD were younger (52.3 years vs 58.0 years; p

Angiomyofibroblastoma and superficial myofibroblastoma are distinctive benign mesenchymal tumors occurring in the female lower genital tract. Despite their significant overlapping clinicopathologic features, including the presence of bland-looking spindle or oval cells with myofibroblastic or myoid differentiation, the tumors have been regarded as separate entities. Although subepithelial, hormone-sensitive mesenchymal cells of the female lower genital tract are considered as their potential common progenitor cells, their potential kinship or pathogenetic similarities remain elusive. Based on the identification of a novel RNA sequencing-based MTG1-CYP2E1 fusion transcript in an angiomyofibroblastoma index case, we investigated an additional ten samples of the tumor and its site-specific histological mimics, including eight superficial myofibroblastomas, four deep angiomyxomas, four cellular angiofibromas, three fibroepithelial stromal polyps, and eight non-site-specific mesenchymal tumors occurring in the female lower genital tract. Using reverse transcription-polymerase chain reaction, we showed that the MTG1-CYP2E1 fusion transcripts were consistently detectable in angiomyofibroblastomas (5/5, 100%) and often in superficial myofibroblastomas (3/5, 60%) but were not detected in the other examined site-specific or non-site-specific mesenchymal tumors. Our immunohistochemical experiments showed that CYP2E1, an isoenzyme belonging to the cytochrome P450 superfamily, exhibited increased positivity in tumors with MTG1-CYP2E1 than was observed in fusion-negative tumors (RR = 6.56, p = 0.001). The results of our study provide further evidence supporting the assertion that angiomyofibroblastoma and superficial myofibroblastoma represent phenotypic variants of site-specific mesenchymal tumors and share a common oncogenic mechanism.

Objective To describe the incidence, complications, and trends associated with ureteral surgeries on a gynecologic oncology service in the context of a fellowship training program over a 24-year period. Methods We conducted a retrospective cohort analysis of ureteral surgeries by gynecologic oncologists at either Moffitt Cancer Center or Tampa General Hospital from 1997 to 2020. Patient characteristics, predisposing factors, location and type of injury, repair method, postoperative management and complications were abstracted from the medical record. The recent cohort (2005–2020) was compared to our prior series (1997–2004). Results Eighty-eight cases were included. The average number of ureteral surgeries per year decreased from 5.75 (1997–2004) to 2.63 (2005–2020). Of 46 iatrogenic injuries, 45 were recognized and repaired intraoperatively. Ureteral transection was the most common type (85% [39 of 46]) and the distal 5 cm was the most common location of injury (63% [29 of 46]). Ureteroneocystostomy was the most common method of repair (83% [73 of 88]). Postoperative management, including stenting and imaging, has not changed significantly. Length of urinary catheter usage decreased in the recent cohort without associated complications. Five patients had major postoperative complications and 4 involved the urinary tract. Of those with follow-up, 96% (66 of 69) of ureteroneocystostomies and 75% (9 of 12) of ureteroureterostomies had radiologically normal urinary tracts. Conclusions Ureteral surgery is necessary in the case of injury or involvement with invasive disease. There has been a decrease in number of procedures. Ureteroneocystostomy has remained the most common method of reconstruction for both injury and resection with acceptable postoperative complication rates.

Gynecologic cancers contribute to a significant portion of cancer morbidity and mortality among women in the United States and across the globe. This article provides a comprehensive review of current screening guidelines and novel techniques that have promise in the prevention and early detection of gynecologic cancers in the future. The authors anticipate a move toward less invasive testing modalities, use of cancer biomarkers, and the prevention and treatment of high-risk factors such as human papilloma virus infection and obesity.

Objective To evaluate trends in the incidence and survival of gynecologic carcinosarcoma over the last 35 years and to explore ethnic disparities. Study design Using the Israeli National Cancer Registry database, all cases of gynecologic carcinosarcoma were included (1980-2014). Age at diagnosis, patient's ethnicity and anatomical site were extracted. Age-standardized incidence rates (ASRs) were calculated for 3 time periods (1980-1994, 1995-2004 and 2005-2014). Relative survival was calculated using the Pohar-Perme method. Results Overall, 935 cases of gynecologic carcinosarcomas were diagnosed during 1980-2014. The most common gynecologic anatomical site was the uterus (83.4%). Most cases (66%) were diagnosed at ages 60-80, with median age of 69 years. There was a steady increase in ASRs from 5.6 to 8.2 per million women. Throughout 1980-1994 and 2005-2014, ASRs were significantly higher in the Jewish compared to the Arab population (5.8 vs. 3.1, p = 0.02 and 8.5 vs. 5.2, p = 0.002, respectively). Relative survival rates increased throughout the study period. No significant differences were noted in relative survival between the Jewish and Arab populations (p = 0.18). Conclusion The incidence of gynecologic carcinosarcoma increased significantly from 1980 through 2014. Nevertheless, survival rates increased during this time, with no difference in survival between the Jewish and Arab populations.

Objective to examine the geographic distribution of gynecologic oncologists (GO) and assess if the GO workforce is meeting the demand for oncology services for patients with gynecologic cancers. Methods We identified GO by National Provider Identifiers (NPI) and calculated county-level density of GO. County-level gynecologic cancer rates were derived from the U.S. Cancer Statistics to represent demand for GO services. A spatial data plot compared GO workforce to gynecologic cancer service demand. U.S. census county-level demographic information was collected and compared. Results In 2019, 1527 GO had a registered NPI. Of 3142 counties in the US, 2864 (91.2%) counties had no GO in their local county and 1943 (61.8%) counties had no GO in local or adjacent (neighboring) counties. As the gynecologic cancer rate increases (described in quintiles) in counties, there are fewer counties without a GO or adjacent GO. However, county-level GO density (number of GO per 100,000 women) did not significantly increase as the county-level incidence of gynecologic cancer increased (r = −0.12, p = 0.06)… Women living in counties with the highest gynecologic cancer rates and without access to a GO were more likely to reside in a rural area where residents had a lower median income and were predominately of White race.. Conclusion There are a significant number of counties in the U.S. without a GO. As county-level gynecologic cancer incidence increased, the proportion of counties without a GO decreased; GO density did not increase with increasing cancer rates. Rural counties with high gynecologic incidence rates are underserved by GO. This information can inform initiatives to improve outreach and collaboration to better meet the needs of patients in different geographic areas.

This review article summarizes the clinical applications of established and emerging PET tracers in the evaluation of the 5 most common gynecologic malignancies: endometrial, ovarian, cervical, vaginal, and vulvar cancers. Emphasis is given to 2-deoxy-2-[18F]fluoro-d-glucose as the most widely used and studied tracer, with additional clinical tracers also explored. The common imaging protocols are discussed, including standard dose ranges and uptake times, established roles, as well as the challenges and future directions of these imaging techniques. The key points are emphasized with images from selected cases.

Cervical cancer is the fourth most common female malignancy worldwide. As the focus of treatment is shifting towards balancing oncological outcomes with reproductive benefit, women are becoming increasingly aware of their fertility options. Cervical cancer is one of the primary malignancies where transposition of the ovaries may be indicated. Ovarian transposition should be performed in pre-menopausal women, undergoing pelvic irradiation to preserve ovarian function and prevent early menopause. The review discusses the available literature and synthesises a concise summary for gynaecologic oncology surgeons to counsel affected women. The paradoxical controversy, leading to its under use is acknowledged, due to the scarcity of published data with regard to functional outcomes, and the lack of clinical trials. In cervical cancer, ovarian transposition remains a safe fertility preservation (FP) option, which is associated with high ovarian function preservation, an acceptable rate of ovarian cysts and a negligible risk for metastases in the transposed ovaries.

From both a disease and management perspective, locally advanced gynecologic cancers present a significant challenge. Dose escalation with brachytherapy serves as a key treatment, providing conformal radiation while sparing at-risk organs. Intracavitary brachytherapy techniques have been shown to be effective, with improving tumor control and toxicity profiles with the advent of three-dimensional image planning. Despite this, the variations in tumor size, location, and pelvic anatomy may lead to suboptimal dosimetry with standard intracavitary applicators in some clinical scenarios. The addition of interstitial needles (interstitial brachytherapy (interstitial brachytherapy) can improve the conformality of brachytherapy treatments by adding needles to peripheral (and central) regions of the target volume, improving the ability to escalate doses in these undercovered regions while sparing organs at risk. Interstitial brachytherapy can be delivered by intracavitary and interstitial hybrid applicators (ICBT/ISBT), perineal template (P-ISBT), or by free-hand technique. ISBT has however yet to be widely available because of concerns of complications and toxicities from this specialized treatment. However, with the increasing use of three-dimensional image-guided brachytherapy, there is an opportunity to increase the level of expertise in the gynecologic radiation oncology community with an improved understanding of the potential complications and morbidity. In this article, we review the acute and long-term toxicity in both ICBT/ISBT and P-ISBT using image-guided brachytherapy.

Intracavitary gynecologic brachytherapy in the form of tandem-based brachytherapy and vaginal cylinder-based brachytherapy represents a fundamental component of the treatment of women with cervical or uterine cancer due to the ability to deliver a therapeutic dose of radiation with sharp dose falloff. This results in highly effective treatment in terms of oncologic outcomes with an overall favorable toxicity profile. Still, complications and side effects of brachytherapy do exist. While advances in brachytherapy techniques have led to a significant decrease in the rates of toxicity, a thorough understanding of the potential complications is crucial to ensuring optimal outcomes for women with gynecologic cancer undergoing brachytherapy. Use of equivalent dose at 2 Gy per fraction (EQD2) models has allowed incorporation of external beam radiotherapy dose to the brachytherapy dose leading to development of consolidated dose constraints for organs-at-risk in the modern era. This manuscript offers a comprehensive review of potential complications associated with intracavitary brachytherapy for gynecologic cancer including predictive factors, mitigation tactics, and management strategies.

Despite advances in the treatment of gynaecological malignancies, both recurrent endometrial and cervical cancers when not amenable to localised therapy (surgery or radiotherapy), remain incurable with limited prognosis and effective treatment options. Chemotherapy remains the standard of care for women with metastatic endometrial or cervical cancers. The addition of bevacizumab to first-line chemotherapy for metastatic cervical cancer patients represents a significant step forward in improving survival. More recently, immunotherapeutic strategies targeting the PD-1/-L1 pathway have shown clinical activity in both endometrial and cervical cancers. The increased understanding of the molecular biology of these cancers is shaping target-specific treatments. Here we summarise current treatment options and results from clinical trials of immunotherapy and other targeted therapies that have already changed, or have the potential to change, clinical practice in metastatic/recurrent endometrial and cervical cancer.

Objective Previous studies have reported low incidence of carboplatin-related drug fever in early cancer treatment cycles. This study describes and analyzes relatively higher incidence rate of carboplatin-related drug fever associated with gynecologic cancer chemotherapy in order to allay anxiety in patients and avoid unnecessary interventions. Materials and methods All gynecologic cancer cases treated with carboplatin in a women's hospital in 2017 and 2018 were retrospectively reviewed and analyzed. Data for patients who experienced carboplatin-induced drug fever and those who received the same treatment but did not experience drug fever were compared for statistical significance. Risk factors for drug fever were identified by logistic regression analysis. Results In total, 318 females with a mean age of 52 years were included in the analysis. Drug fever was observed in 25 patients (7.86%) in 45 cycles of total 1605 carboplatin-containing infusions. Fever occurred at a median of the third (range: 1–7) cycle, starting at 10.62 h (range: 1.18–50.35 h) after carboplatin infusion, and was generally controlled within 3 days. After chemotherapy rechallenge, the mean frequency of drug fever was 2 times per patient (range: 1–4 times). There were 35/45 drug fever incidents (77.78%) that were classified as grade II; in 15/45 cases (33.33%), antibiotic treatment was immediately initiated to prevent infection. Younger age was found to be a risk factor for drug fever following carboplatin treatment (odds ratio = 0.126, 95% confidence interval: 0.025–0.628; p Conclusions The retrospective analysis demonstrated that carboplatin-induced drug fever, which occurred on post treatment 3 days, was a type of delayed hypersensitivity reaction with an incidence rate of 7.86% in gynecologic cancer. Younger age was identified as a risk factor. Drug fever is generally tolerated by patients, who insist on chemotherapy. Knowledge of carboplatin-induced drug fever may help physicians reach timely recognition for appropriate interventions.

To evaluate the impact of frailty on postoperative complications following cytoreductive surgery (CRS) with hyperthermic intra-peritoneal chemotherapy (HIPEC) in women with advanced or recurrent gynecologic cancer.An IRB-approved single-institution prospective registry was queried for women who underwent CRS with HIPEC for advanced or recurrent gynecologic cancer from 1/1/2014-12/31/2020. Frailty was defined as a modified Frailty Index (mFI) score of ≥2. Logistic regression was used to assess the impact of mFI upon the rate of moderate or higher (≥ grade 2) Accordion postoperative complications.Of 141 women, 81.6% (n = 115) were non-frail with mFI of 0-1 and 18.4% (n = 26) were frail with mFI ≥2. The incidence of ≥ grade 2 complications was 21.2% (n = 14) for mFI = 0, 26.5% (n = 13) for mFI = 1, 64.7% (n = 11) for mFI = 2 and 100.0% (n = 9) for patients with mFI ≥3. The incidence of re-operation (1.7% vs. 11.5%, p = 0.044), ICU admission (13.2% vs. 34.6%, p = 0.018), acute kidney injury (6.3% vs. 30.8%, p = 0.001), and respiratory failure (0.9% vs. 19.2%, p0.001) were significantly lower amongst non-frail vs. frail women. On multivariable analysis, mFI ≥2 was associated with significantly increased ≥ grade 2 complications versus mFI of 0-1 (OR 9.4, 95% CI 3.3, 26.4, p0.001). Age (OR 1.04, 95% CI 1.00, 1.09, p = 0.07), surgical indication (recurrent vs. primary) (OR 0.71, 95% CI 0.30, 1.7, p = 0.44) and Surgical Complexity Score of Intermediate or High vs. Low (OR 1.5, 95% CI 0.67, 3.5, p = 0.31) were not associated with ≥grade 2 complications.Frailty, defined by the modified frailty index, is predictive of ≥grade 2 postoperative complications following CRS with HIPEC in women with gynecologic cancer. Frailty screening before CRS with HIPEC may assist patient selection and improve postoperative outcomes.

Mesonephric carcinoma of the cervix is a rare tumor derived from Wolffian remnants. Mesonephric-like carcinomas of the ovary and endometrium, while morphologically similar, do not have obvious Wolffian derivation. Here, we sought to characterize the repertoire of genetic alterations in primary mesonephric and mesonephric-like carcinomas, in the distinct histologic components of mixed cases, as well as in matched primary tumors and metastases. DNA from microdissected tumor and normal tissue from mesonephric carcinomas (cervix, n = 8) and mesonephric-like carcinomas (ovarian n = 15, endometrial n = 13) were subjected to sequencing targeting 468 cancer-related genes. The histologically distinct components of four cases with mixed histology and four primary tumors and their matched metastases were microdissected and analyzed separately. Mesonephric-like carcinomas were underpinned by somatic KRAS mutations (25/28, 89%) akin to mesonephric carcinomas (8/8, 100%), but also harbored genetic alterations more frequently reported in Müllerian tumors. Mesonephric-like carcinomas that lacked KRAS mutations harbored NRAS (n = 2, ovary) or BRAF (n = 1, endometrium) hotspot mutations. PIK3CA mutations were identified in both mesonephric-like (8/28, 28%) and mesonephric carcinomas (2/8, 25%). Only mesonephric-like tumors harbored CTNNB1 hotspot (4/28, 14%) and PTEN (3/13, 23%) mutations. Copy number analysis revealed frequent gains of chromosomes 1q and 10 in both mesonephric (87% 1q; 50% chromosome 10) and mesonephric-like tumors (89% 1q; 43% chromosome 10). Chromosome 12 gains were more frequent in ovarian mesonephric-like carcinomas, and losses of chromosome 9 were more frequent in mesonephric than in mesonephric-like carcinomas (both p = 0.01, Fisher’s exact test). The histologically distinct components of four mixed cases were molecularly related and shared similar patterns of genetic alterations. The progression from primary to metastatic lesions involved the acquisition of additional mutations, and/or shifts from subclonal to clonal mutations. Our findings suggest that mesonephric-like carcinomas are derived from a Müllerian substrate with differentiation along Wolffian/mesonephric lines.

PURPOSE Implanted fiducial markers are a commonly used tool in delineating the CTV in high-dose-rate interstitial brachytherapy (HDR-ISBT) for gynecologic malignancy, but their reliability in gynacological sites is not well understood. These markers and interstitial applicators can experience interfractional motion due to organ swelling or other anatomical changes. The purpose of this study was to evaluate the spatial variation of these features. METHODS AND MATERIALS The spatial positions of 50 implanted markers and 202 needles were tracked in 15 patients treated over 70 fractions of HDR brachytherapy. Marker and/or needle coordinates were extracted from CT images with contours and dose distributions. Automated analysis determined marker self-consistency and displacements between various elements of the implant. RESULTS From start to end fraction, the relative positions of the markers experienced an average magnitude displacement of 4.5 ± 3.0 mm while the average displacement of the applicator tips was 11 ± 8 mm, relative to their respective centers of mass (CM). CONCLUSIONS Markers implanted lateral and superior to the CTV experience greater drift than other implant locations.

The GOG Foundation, Inc. (GOG-F) is a non-profit 501(c)(3) organization with the purpose of promoting excellence in the quality and integrity of clinical and basic scientific research in the field of gynecologic malignancies. GOG Partners (GOG-P) is a program of the GOG-F and is positioned alongside NRG Oncology under the GOG-F organizational umbrella. GOG-P operates outside of the federally funded NCI NRG Oncology, a key distinguishing feature. By functioning as a site management organization (SMO), GOG-P provides an additional platform for clinical trial development, mentorship opportunities, patient accrual, and site infrastructure support yielding an expanded gynecologic oncology clinical trials infrastructure in the US. GOG-P has a consistent track record of conducting high quality clinical trials that lead to bringing novel FDA approved treatments for gynecologic cancer. This manuscript summarizes the history and organizational structure of the GOG-P. In addition, we outline the other key supportive programs within the GOG-F that help support the GOG-P effort to perform transformative gynecologic cancer research.

Gynecological cancer affects the female reproductive system, including ovarian, uterine, endometrial, cervical, vulvar, and vaginal tumors. Non-coding RNAs (ncRNAs), and in particular microRNAs, function as regulatory molecules, which can control gene expression in a post-transcriptional manner. Normal physiological processes like cellular proliferation, differentiation, and apoptosis, and pathological processes such as oncogenesis and metastasis are regulated by microRNAs. Numerous reports have shown a direct role of microRNAs in the modulation of angiogenesis in gynecological cancer, via targeting pro-angiogenic factors and signaling pathways. Understanding the molecular mechanism involved in the regulation of angiogenesis by microRNAs may lead to new treatment options. Recently the regulatory role of some long non-coding RNAs in gynecological cancer has also been explored, but the information on this function is more limited. The aim of this article is to explore the pathways responsible for angiogenesis, and to what extent ncRNAs may be employed as biomarkers or therapeutic targets in gynecological cancer.

OBJECTIVE. To determine the association between scores from a 25-item patient-reported Rockwood Accumulation of Deficits Frailty Index (DAFI) and survival outcomes in gynecologic cancer patients. METHODS. A frailty index was constructed from the SEER-MHOS database. The DAFI was applied to women age ≥ 65 diagnosed with all types of gynecologic cancers between 1998 and 2015. The impact of frailty status at cancer diagnosis on overall survival (OS) was analyzed using Kaplan-Meier curves and Cox proportional hazards regression. RESULTS. In this cohort (n = 1336) the median age at diagnosis was 74 (range 65–97). Nine hundred sixty-two (72%) women were Caucasian and 132 (10%) were African-American. Overall, 651(49%) of patients were considered frail. On multivariate analysis, frail patients had a 48% increased risk for death (aHR 1.48; 95% CI 1.29–1.69; P < 0.0001). Each 10% increase in frailty index was associated with a 16% increased risk of death (aHR, 1.16; 95% CI, 1.11 to 1.21; P < 0.0001). In subgroup analyses of the varying cancer types, the association of frailty status with prognosis was fairly consistent (aHR 1.15–2.24). The DAFI was more prognostic in endometrial (aHR 1.76; 95% CI 1.41–2.18, P < 0.0001) and vaginal/vulvar (aHR 1.94; 95% CI 1.34–2.81, P = 0.0005) cancers as well as patients with loco-regional disease (aHR 1.94; 95% CI 1.62–2.33, P < 0.0001). CONCLUSIONS. Frailty appears to be a significant predictor of mortality in gynecologic cancer patients regardless of chronological age. This measure of functional age may be of particular utility in women with loco-regional disease only who otherwise would have a favorable prognosis.

Circular RNAs (CircRNAs) are a class of single-stranded noncoding RNAs that are formed in a circular conformation via non-canonical splicing or back-splicing events. Aberrant expressions of many circRNAs are observed in diverse cancers, indicating their crucial roles in tumorigenesis and tumor development. Recently, several pieces of evidence have revealed that many circRNAs are involved in the promotion or suppression of cancers to varying degrees via different molecular mechanisms. Here in this review, we present a summary of the characteristics, types, biogenesis, and functions of circRNAs, and outline a series of the most recently studied circRNAs and their functional mechanisms in multiple cancer types with future perspectives. With great advances in nucleic acid-based therapeutic tools, circRNAs could be further explored as targetable molecules in future cancer treatments.0.

Psychosocial determinants can affect the mental health of women who have been diagnosed with gynecological cancer. The aim of this study was to examine how social support and self-esteem are associated with anxiety and depression symptoms in women with gynecological cancer, and who are treated by radical surgery.A cross-sectional study was performed, within the oncology department of Ibn Rochd University Hospital, Casablanca, on 100 Moroccan women. They all had undergone radical surgery for gynecological cancer, hysterectomy and/or oophorectomy.Our results showed that patients with gynecological cancer treated by radical surgery exhibited high prevalence rates of anxiety (66%) and depression symptoms (59%). Associations showed that age, having children, medical coverage system, area of residence, working status and socioeconomic status were significantly related to the prevalence of anxiety and depression symptoms (P0.05). The general social support, family support and significant other support besides high self-esteem reduce significantly the risk of getting anxiety and depression symptoms (P-values0.05).Among patients with gynecological cancer treated by radical surgery, high prevalence of anxiety and depression symptoms was found. Social support and high self-esteem could help improve mental health issues related to this type of cancer.

Purpose To assess the safety, feasibility, and efficacy of percutaneous thermal ablation (TA) in the treatment of metastatic gynecologic (GYN) tumors. Materials and Methods A study cohort of 42 consecutive women (mean age, 59. years; range, 25–78 years) with metastatic GYN tumors (119 metastatic tumors) treated with radiofrequency (n = 47 tumors), microwave (n = 47 tumors), or cryogenic (n = 30 tumors) ablation from over 2,800 ablations performed from January 2001 to January 2019 was identified. The primary GYN neoplasms consisted of ovarian (27 patients; 77 tumors; mean tumor diameter [MTD], 2.50 cm), uterine (7 patients; 26 tumors; MTD, 1.89 cm), endometrial (5 patients; 10 tumors; MTD, 2.8 cm), vaginal (2 patients; 5 tumors; MTD, 2.40 cm), and cervical (1 patient; 1 tumor; MTD, 1.90 cm) cancers. In order of descending frequency, metastatic tumors treated by TA were located in the liver or liver capsule (74%), lungs (13%), and peritoneal implants (9%). Single tumors were also treated in the kidneys, rectus muscle, perirectal soft tissue (2.5%), and retroperitoneal lymph nodes (1.6%). All efficacy parameters of TA and definitions of major and minor adverse events are categorized by the latest Society of Interventional Radiology reporting standards. Results The median follow-up of treated patients was 10 months. After the initial ablation, 95.6% of the patients achieved a complete tumor response confirmed by contrast-enhanced magnetic resonance imaging or computed tomography. On surveillance imaging, 8.5% of the ablated tumors developed local progression over a median follow-up period of 4.1 months. Five of 8 tumors with local recurrence underwent repeated treatment over a mean follow-up period of 18 months, and 4 of 5 tumors achieved complete eradication after 1 additional treatment session that resulted in a secondary efficacy of 80%. The overall technique efficacy of TA was 96.2% over a median follow-up period of 10 months. Conclusions TA was safe and effective for the local control of metastatic GYN tumors in the lungs, abdomen, and pelvis, with an overall survival rate of 37.5 months and a local progression-free survival rate of 16.5 months, with only 4.8% of treated patients experiencing a major adverse event.