Treatment Of Gynecologic Cancers Research Articles

Repurposing Kir6/SUR2 Channel Activator Minoxidil to Arrests Growth of Gynecologic Cancers.

Gynecologic cancers are among the most lethal cancers found in women, and, advanced stage cancers are still a treatment challenge. Ion channels are known to contribute to cellular homeostasis in all cells and mounting evidence indicates that ion channels could be considered potential therapeutic targets against cancer. Nevertheless, the pharmacologic effect of targeting ion channels in cancer is still understudied. We found that the expression of Kir6.2/SUR2 potassium channel is a potential favorable prognostic factor in gynecologic cancers. Also, pharmacological stimulation of the Kir6.2/SUR2 channel activity with the selective activator molecule minoxidil arrests tumor growth in a xenograft model of ovarian cancer. Investigation on the mechanism linking the Kir6.2/SUR2 to tumor growth revealed that minoxidil alters the metabolic and oxidative state of cancer cells by producing mitochondrial disruption and extensive DNA damage. Consequently, application of minoxidil results in activation of a caspase-3 independent cell death pathway. Our data show that repurposing of FDA approved K+ channel activators may represent a novel, safe adjuvant therapeutic approach to traditional chemotherapy for the treatment of gynecologic cancers.

Fertility preservation in women affected by gynaecological cancer: the importance of an integrated gynaecological and psychological approach.

Gynaecological cancer treatment significantly affects the fertility of women in reproductive age. Surgery, chemotherapy and radiotherapy are the mainstays of ovarian, cervical and endometrial cancers and anatomically or functionally impact the uterus and ovaries. Moreover, the sexual function and psychological wellbeing of patients are highly weakened after a cancer diagnosis: depression, anxiety and impairment of quality of life represent a relevant concern for patient care. The potential loss of fertility could be more distressing than cancer itself. For this reason, it is of paramount importance to try to preserve fertility in women affected by gynaecological cancers. Recently, tailored fertility preservation therapies have been developed to meet the childbearing demand from more than half of women between 18 and 40 years with a diagnosis of cancer. Currently, fertility preservation techniques play a significant role in improving the quality of life of women with gynaecological cancer. In this scenario, we propose a narrative overview of the recent literature about the importance of a multidisciplinary approach in the management of fertility preservation in the case of gynaecological cancers.

The Effect of Pelvic Floor Muscle Interventions on Pelvic Floor Dysfunction After Gynecological Cancer Treatment: A Systematic Review.

The aim of this systematic review was to identify, evaluate, and synthesize the evidence from studies that have investigated the effect of nonsurgical, nonpharmacological, pelvic floor muscle interventions on any type of pelvic floor dysfunction or health-related quality of life in patients after any type of treatment for gynecological cancer. Six electronic databases (Cochrane Library 2018, CINAHL 1982-2018, MEDLINE 1950-2018, EMBASE 1980-2018, PsycINFO 1806-2018, and EMCARE 1995-2018) were systematically searched in June 2018. Reference lists of identified articles were hand searched. Randomized controlled trials (RCTs), cohort studies, and case series were included if they investigated the effects of conservative treatments, including pelvic floor muscle training or dilator training, on bladder, bowel, or sexual function in patients who had received treatment for gynecological cancer. Risk of bias was assessed using the Physiotherapy Evidence Database scale for RCTs and the Newcastle-Ottawa scale for cohort studies. Five RCTs and 2 retrospective cohort studies were included (n=886). The results provided moderate-level evidence that pelvic floor muscle training with counseling and yoga or core exercises were beneficial for sexual function (standardized mean difference=-0.96, 95% CI=-1.22 to -0.70, I2=0%) and health-related quality of life (standardized mean difference=0.63, 95% CI=0.38 to 0.88, I2=0%) in survivors of cervical cancer and very low-level evidence that dilator therapy reduced vaginal complications in survivors of cervical and uterine cancer (odds ratio=0.37, 95% CI=0.17 to 0.80, I2=54%). There were insufficient data for meta-analysis of bladder or bowel function. Conservative pelvic floor muscle interventions may be beneficial for improving sexual function and health-related quality of life in survivors of gynecological cancer. Given the levels of evidence reported in this review, further high-quality studies are needed, especially to investigate effects on bladder and bowel function. This review provides moderate-level evidence for the role of pelvic floor rehabilitation to improve health outcomes in the gynecological cancer survivorship journey. Clinicians and health service providers should consider how to provide cancer survivors the opportunity to participate in supervised pelvic floor rehabilitation programs.

Associations between metabolic syndrome and gynecologic cancer.

Metabolic syndrome (MetS) is a group of risk factors that causes cardiovascular and diabetic morbidity and mortality, which is diagnosed by central obesity, dyslipidemia, hyperglycemia, and hypertension. Increasing epidemiological data and experimental results indicate that the presence of MetS increases the incidence of common malignancies and related mortality. Epidemiological studies have previously reported an association of endometrial cancer occurrence with MetS. Aromatization of androstenedione to estrogen, insulin resistance, and diabetes can cause increased levels of free estrogen, and the detrimental effect of elevated estrogen as a carcinogen is well studied in endometrial cancer. Medications used to manage MetS such as metformin and statins are suggested to reduce endometrial cancer risk and improve survival. Some large population-based epidemiological studies have suggested that the MetS is related to an increased risk of cervical carcinoma. MetS may contribute to viral-host interactions, which lead to persistent human papilloma virus (HPV) infection, although limited epidemiological data are available. Specific effects of obesity and diabetes on the occurrence of ovarian cancer have been suggested. However, the direct correlation between MetS and ovarian cancer is still lacking. Previous retrospective studies reported that the use of metformin, statins, and beta-blockers could be associated with cancer prevention or better prognosis. Proper diagnosis and management of the MetS should be a part of the strategies undertaken to prevent and treat gynecologic cancer. So far, only limited data is available on this subject, and further clinical and fundamental research is required to further clarify the effect of these therapies on gynecologic cancer treatment.

IGCS Intraoperative Technology Taskforce. Update on near infrared imaging technology: beyond white light and the naked eye, indocyanine green and near infrared technology in the treatment of gynecologic cancers

Surgery, by its very nature, relies on the ability of the surgeon to visualize and distinguish healthy and non-healthy tissue or structures. Without advanced technology, surgeons can visualize only that...

Incidence of postoperative shivering decreased with the use of acetaminophen: a propensity score matching analysis.

The incidence of postoperative shivering is known to be inversely associated with core body temperature. However, previous studies have pointed out that the threshold of shivering could be affected by peripheral temperature or anesthetic agents. These reports pointed specific drugs, though, anesthesia techniques have since advanced considerably. This study aimed to investigate factors associated with postoperative shivering in the context of the current body warming practice. The institutional clinical research ethics committee of Kyushu University approved the study protocol (IRB Clinical Research number 2019-233). This retrospective study involved 340 patients who had undergone radical surgery for gynecological cancer treatment under general anesthesia at our center from December 2012 to June 2019. Logistic regression analysis was performed to estimate the odds ratio (OR) for the incidence of postoperative shivering. Postoperative shivering developed in 109 out of 340 patients. After multivariate-adjusted logistic regression, the incidences of postoperative shivering decreased significantly with increasing patient age (OR = 0.96; 95%CI: 0.93-0.98; p = 0.0004). Volatile anesthesia technique was less inclined to shiver after surgery than TIVA (OR = 0.55; 95%CI: 0.30-0.99; p = 0.04). Acetaminophen was much less used in the shivering group than in the non-shivering group (OR = 0.49; 95%CI: 0.25-0.94; p = 0.03). This study indicated that the development of shivering in patients receiving the anesthetic technique currently used in our hospital was associated with use of acetaminophen or volatile agents, and patient age.

Bowel dysfunction in survivors of gynaecologic malignancies.

To assess the prevalence of bowel dysfunctions after treatment for gynaecological cancer and the impact on the quality of life. We identified a cohort of 217 eligible women treated with radiotherapy (RT) with curative intention, alone or as combined treatment, for gynaecological malignancies at three institutions in Catalonia (Spain). Demographic, diagnosis and treatment modality were reviewed. Patients were sent validated questionnaires to assess bowel function and a set of questions asking on the changes after RT in bowel function, urinary function, sexuality, pain and lymphoedema. Questionnaires were returned by 109 patients (50.2%) with a mean age of 65 ± 11years. Of them, 71.8% had been treated for endometrial cancer and 28.2% for cervical cancer. Overall, 42.7% of patients reported bowel dysfunction, affecting their quality of life in 36% of cases. Symptoms were more frequent in patients who had undergone external beam RT compared to brachytherapy. The most common symptom was defecatory urgency which was reported by more than 40% of patients according to the St Mark's score, although it was less common in other questionnaires. Overall, faecal incontinence ranged between 10 and 15%, and usual loose stools and diarrhoea were reported by 13.5% and 5.1%, respectively. Prevalence of bowel symptoms after treatment of gynaecological malignancies is high. A systematic evaluation using validated questionnaires should be performed in order to allow the decision-making process and also because there are a number of treatments available to improve the quality of life of cancer survivors.

Noninvasive prediction of lymph node status for patients with early-stage cervical cancer based on radiomics features from ultrasound images.

To investigate the feasibility of a noninvasive detection of lymph node metastasis (LNM) for early-stage cervical cancer (ECC) patients with radiomics methods based on the textural features from ultrasound images. One hundred seventy-two ECC patients between January 2014 and September 2018 with pathologically confirmed lymph node status (LNS) and preoperative ultrasound images were retrospectively reviewed. Regions of interest (ROIs) were delineated by a senior radiologist in the ultrasound images. LIFEx was applied to extract textural features for radiomics study. Least absolute shrinkage and selection operator (LASSO) regression was applied for dimension reduction and for selection of key features. A multivariable logistic regression analysis was adopted to build the radiomics signature. The Mann-Whitney U test was applied to investigate the correlation between radiomics and LNS for both training and validation cohorts. Receiver operating characteristic (ROC) curves were applied to evaluate the accuracy of the radiomics prediction models. A total of 152 radiomics features were extracted from ultrasound images, in which 6 features were significantly associated with LNS (p< 0.05). The radiomics signatures demonstrated a good discrimination between patients with LNM and non-LNM groups. The best radiomics performance model achieved an area under the curve (AUC) of 0.79 (95% confidence interval (CI), 0.71-0.88) in the training cohort and 0.77 (95% CI, 0.65-0.88) in the validation cohort. The feasibility of radiomics features from ultrasound images for the prediction of LNM in ECC was investigated. This noninvasive prediction method may be used to facilitate preoperative identification of LNS in patients with ECC. • Few studied had investigated the feasibility of radiomics based on ultrasound images for cervical cancer, even though it is the most common practice for gynecological cancer diagnosis and treatment. • The radiomics signatures based on ultrasound images demonstrated a good discrimination between patients with and without lymph node metastasis with an area under the curve (AUC) of 0.79 and 0.77 in the training and validation cohorts, respectively. • The radiomics model based on preoperative ultrasound images has the potential ability to predict lymph node status noninvasively in patients with early-state cervical cancer, so as to reduce the impact of invasive examination and to optimize the treatment choices.

Applications of CRISPR-Cas9 in gynecological cancer research.

Gynecological cancers pose a significant threat to women's health worldwide, with cervical cancer, ovarian cancer, and endometrial cancer having high incidences. Current gynecological cancer treatment methods mainly include surgery, chemotherapy, radiotherapy, and chemoradiotherapy. The CRISPR-Cas9 gene editing technology as a new therapeutic method has shown tremendous effect in the treatment of other cancers, promoting research on its potential therapeutic effect in gynecological cancer. In this article, we reviewed the current research status of CRISPR-Cas9 technology in gynecological cancer, focusing on the importance of studying the mechanism of CRISPR-Cas9 in gynecological cancer treatment, thereby laying a foundation for further research on its clinical application.

Hormone therapy (HT) in women with gynecologic cancers and in women at high risk for developing a gynecologic cancer: A Society of Gynecologic Oncology (SGO) clinical practice statement: This practice statement has been endorsed by The North American Menopause Society

•Treatment or prevention of gynecologic cancer often results in induced menopause significantly impacting quality of life. •Hormone therapy is underutilized in in these settings despite more severe symptoms with induced menopause. •The risk/benefit profile of HT is favorable in most EOC, early stage endometrial, and cervical cancer. •HT is not recommended in women with advanced EC, uterine sarcoma, endometrioid or low grade serous ovarian cancer. •Lynch syndrome patients and BRCA mutation carriers without history of breast cancer may also use HT to improve QOL.

Initial Clinical Experience Treating Patients With Gynecologic Cancers on a 6MV Flattening Filter Free O-Ring Linear Accelerator

PurposeRadiation therapy (RT) is commonly used in the treatment of gynecologic cancers. Intensity-modulated RT (IMRT) has been shown to reduce gastrointestinal toxicity compared with 2-dimensional and 3-dimensional RT modalities. We report the initial clinical experience using IMRT for gynecologic cancers with a novel 6MV flattening filter free O-ring linear accelerator (6X-FFF ORL). Methods and MaterialsWe retrospectively identified consecutive women with uterine or cervical cancer who received pelvic RT on Halcyon (Varian Medical Systems, Palo Alto, CA), a novel 6X-FFF ORL. We report their clinicopathologic data, RT details, early disease-control outcomes, acute toxicities, dose-volume histogram data, couch corrections, and treatment times. ResultsSeventeen women received RT on a 6X-FFF ORL for uterine cancer (76%) or cervical cancer (24%) between January 2017 and September 2019. RT was delivered postoperatively (82%) or to intact disease (18%), to a median dose of 50.4 Gy (range, 19.8-55.0 Gy) in 25 fractions (range, 11-28), with 12% receiving extended-field RT and 65% receiving chemotherapy. Target and organ-at-risk constraints were met in all plans. The 3-dimensional vector couch correction average was 0.90 ± 0.37 cm. The mean beam-on time was 2.9 ± 0.4 min and mean treatment time, from imaging start to beam-off, was 3.6 ± 0.4 min. Grade 2 fatigue, anorexia, diarrhea, bloating, and nausea occurred in 41%, 12%, 12%, 6%, and 6% of patients, respectively. There were no grade ≥3 toxicities. ConclusionsIn the initial clinical report of pelvic RT for gynecologic cancers using a 6X-FFF ORL, the linac showed versatility in treatment; comparability to flattening-filtered IMRT for early disease-control, toxicity, and dosimetry; and treatment speed that compared favorably to IMRT on a C-arm gantry. Accordingly, a 6X-FFF ORL may increase throughput or reduce day length in departments with high gynecologic cancer volumes, without compromising clinical outcomes.

Developing an Australian multi-module clinical quality registry for gynaecological cancers: a protocol paper

IntroductionGynaecological cancers collectively account for almost 10% of cancer diagnoses made in Australian women. The extent of variation in gynaecological cancer survival rates and treatment outcomes across Australia is not...

Repurposing the Kir6.2/SUR2 Channel Activator Minoxidil to Treat Gynecological Cancers

Gynecologic cancers, are among the most lethal cancers (more than 70% of patients dying in the 5-years period after diagnosis) because the treatments can be toxic, cost-prohibitive, and eventually, all ovarian cancer patients relapse with a tumor that has developed resistance to chemotherapy (e.g., cisplatin, carboplatin). Ion channels are known to contribute to cellular homeostasis in all cells and mounting evidence indicates that ion channels could be considered potential therapeutic targets against the cancer. Nevertheless, the pharmacologic effect of targeting ion channels in this cancer is still understudied. Our meta-analysis revealed that patients affected by ovarian or endometrial cancers (gynecological cancers) that express high level of the Kir6.2/SUR2 potassium channel complex present better survival rate when compared to patients with low expression. Therefore, we conclude that expression of Kir6.2/SUR2 potassium channel is a potential favorable prognostic factor in gynecologic cancers. We tested the effect of pharmacological stimulation of the Kir6.2/SUR2 channel activity by using the selective activator, FDA approved molecule, minoxidil (Rogaine ®; Loniten ®) on ovarian cancer growth. We found that minoxidil arrested tumor growth in a xenograft model of cisplatin-resistant ovarian cancer. Analysis of the mechanism underlying the anticancer effect of minoxidil revealed that Kir6.2/SUR2 activator inhibit proliferation of cancer cells by arresting the cell cycle. Also, minoxidil alters the cellular metabolic and oxidative state resulting in mitochondrial disruption, production of reactive oxygen species (ROS) and extensive DNA damage. Consequently, these events activate a caspase-3 independent cell death pathway. Our data indicate that repurposing of FDA approved K+ channel activators may represent a novel, safe adjuvant therapeutic approach to traditional chemotherapy for the treatment of gynecologic cancers.

Risk factors for late-onset lower limb lymphedema after gynecological cancer treatment: A multi-institutional retrospective study

IntroductionLate-onset lower limb lymphedema (LLL) is a significant clinical challenge for physicians dealing with patients that undergo treatment involving the pelvic cavity. We aimed to clarify the prevalence of and risk factors for late-onset LLL after treatment for gynecological cancer. MethodsWe conducted a multicenter retrospective study using records of cases in which LLL diagnosed by physical findings and measurement of limbs girths. Patients with LLL after treatment for uterine cervical, endometrial, and ovarian cancer were sequentially enrolled. We examined the timing of LLL onset and the associations between the time to onset and clinical characteristics, including age, type of cancer, lymphadenectomy sites, and performance of radiotherapy. We also investigated the risk factors for late-onset LLL and their effects on the cumulative incidence of late-onset LLL. ResultsIn total, 711 patients fulfilled the required criteria. Mean age of was 50.2 years old and median follow-up period was 5.05 years. More than half of them (50.5%) presented with LLL ≥5 years after undergoing treatment for gynecological cancer. A substantial number of patients (29.4%) developed LLL ≥10 years after undergoing treatment for gynecological cancer. Being aged <50 years [(odds ratio (OR): 1.919, P = 0.001), cervical cancer (OR: 1.912, P = 0.001), and radiotherapy (OR: 1.664, P = 0.017) were identified as significant risk factors for late-onset LLL in multivariate logistic regression analysis. ConclusionsA substantial number of patients present with LLL ≥5 years after receiving treatment for gynecological malignancies. Clinicians are required to identify high-risk patients and inform them of the risk of late-onset LLL.

Improving gynecologic brachytherapy patient experience by optimizing MRI, anesthesia, and scheduling to decrease the length of time tandem and ovoid applicators are in place

PurposeBrachytherapy requires multiple different steps and plays a critical role in treatment for gynecological cancer. In an effort to improve gynecologic patient experience, we investigated how different aspects of the procedure influence how long the patient has the brachytherapy applicator in place. Methods and MaterialsWe prospectively recorded 145 consecutive tandem and ovoid treatments for 33 patients and determined how anesthesia vs. conscious sedation, MRI or not, and the number of procedures in the day impact applicator in time. The data were analyzed in a mixed effects linear regression model to account for the within-patient correlation. ResultsWe found average applicator in place time was 179 minutes (range: 87–311 minutes). Patients who received anesthesia had a significant increase in length of applicator in patient time by an average of 42 minutes compared with those who received conscious sedation. Undergoing an MRI increased length of applicator in time by an average of 66 minutes, although the actual MRI performed generally took less than 30 minutes. Having three or more procedures scheduled for 1 day increased the length of time the tandem and ovoid was inserted by an average of 35 minutes. ConclusionThe use of anesthesia vs. conscious sedation, MRI scans for treatment planning, and number of procedures scheduled per day have significant influence on the duration of brachytherapy treatments. This information can help us work to optimize scheduling and thereby improve patient brachytherapy experience.

Precise Personalized Medicine in Gynecology Cancer and Infertility.

Since the conception of precision medicine has been put forward in oncology, this idea has been popularized and applied in many specialties. Significant progress has been made toward personalizing the entire process, including diagnosis, treatment planning, and embryo identification, and combining large-scale genetic information data and knowledge discovery can offer better prospects in reproductive medicine. This work reviews the application of precision medicine and possibilities in reproductive medicine and gynecologic cancer diagnosis and treatment. The limitations and challenges of precision medicine in this area remain to be discussed.

The Communication Between the PI3K/AKT/mTOR Pathway and Y-box Binding Protein-1 in Gynecological Cancer.

Studies of the mechanistic (mammalian) target of rapamycin inhibitors (mTOR) represent a step towards the targeted treatment of gynecological cancers. It has been shown that women with increased levels of mTOR signaling pathway targets have worse prognosis compared to women with normal mTOR levels. Yet, targeting mTOR alone has led to unsatisfactory outcomes in gynecological cancer. The aim of our review was therefore to provide an overview of the most recent clinical results and basic findings on the interplay of mTOR signaling and cold shock proteins in gynecological malignancies. Due to their oncogenic activity, there are promising data showing that mTOR and Y-box-protein 1 (YB-1) dual targeting improves the inhibition of carcinogenic activity. Although several components differentially expressed in patients with ovarian, endometrial, and cervical cancer of the mTOR were identified, there are only a few investigated downstream actors in gynecological cancer connecting them with YB-1. Our analysis shows that YB-1 is an important player impacting AKT as well as the downstream actors interacting with mTOR such as epidermal growth factor receptor (EGFR), Snail or E-cadherin.

Challenges in the diagnosis and treatment of gynecological cancers during the COVID-19 pandemic

Challenges in the diagnosis and treatment of gynecological cancers during the COVID-19 pandemic

CÂNCER GINECOLÓGICO E SUAS POLÍTICAS PÚBLICAS SOB A PERSPECTIVA DE PEPLAU

When paralleling the Interpersonal Theory with public health policies in Brazil and the assistance to women in health promotion, prevention or treatment of gynecological cancer, it is reflected that gynecological cancer in women is seen by the woman herself as a part of your self, is your femininity, your identity; concepts which are deeply crushed by the news of a cancer diagnosis. In view of the exchange of experiences at the time of assistance, Peplau states that the assistance and the relationship of those involved are influenced by the external environment (environment), internal environment (personality, lived experiences, religion, culture) and the professional's posture. In this scenario of a fragile and frightened woman, often without due privacy or attention due to the lack of inputs, structure and high demand from the public health service in Brazil, her assistance can be compromised, precisely because she does not have interpersonal skills, either in promotion health, prevention or treatment. It can be said that information is a precious asset when it comes to health care. In addition to the correct information, the nursing professional and the others who form the multidisciplinary team need to have an empathetic, humanized, welcoming attitude, based on science, ethics and respect for the woman's life, in order to pass the correct information in the correct way for greater adherence. Given “golden assistance”, it is only possible based on public training policies for its employees, which certainly not only update and train professionals, they save lives.

GIM During Active Treatment for Cancer: Considerations for Clinical Practice

Some attempts have been made to use modifications of GIM in various stages of cancer care for individuals or groups. No attempt has been made so far to use the classical model of Guided Imagery and Music (GIM) by Helen Bonny involving spontaneous imagery and interactive dialogue during the music in individual sessions concurrent with active treatment of cancer, mainly chemotherapy or radiotherapy treatment. This paper describes the process and aspects of working with GIM with patients during the period of active treatment for gynecologic and breast cancer. This paper is based on qualitative results of a research study at Aalborg University, combined with the author’s experience as a clinician in cancer care over the years.