Treatment Of Gynecologic Malignancies Research Articles

A Review of Nuclear Medicine Approaches in the Diagnosis and the Treatment of Gynecological Malignancies.

Simple SummaryIn this literature review, we will provide a short overview of the role of nuclear medicine in the diagnosis of obstetric and gynecological cancers.Nuclear medicine is defined as the diagnosis and the treatment of disease using radiolabeled compounds known as radiopharmaceuticals. Single-photon emission computed tomography/computed tomography (SPECT/CT) and positron emission tomography/computer tomography (PET/CT) based radiopharmaceuticals have proven reliable in diagnostic imaging in nuclear medicine and cancer treatment. One of the most critical cancers that also relies on an early diagnosis is gynecological cancer. Given that approximately 25% of all cancers in developing countries are a subset of gynecological cancer, investigating this cancer subtype is of significant clinical worth, particularly in light of its high rate of mortality. With accurate identification of high grade distant abdominal endometrial cancer as well as extra abdominal metastases, 18F-Fluorodeoxyglucose ([18F]FDG) PET/CT imaging is considered a valuable step forward in the investigation of gynecological cancer. Considering these factors, [18F]FDG PET/CT imaging can assist in making management of patient therapy more feasible. In this literature review, we will provide a short overview of the role of nuclear medicine in the diagnosis of obstetric and gynecological cancers.

Pelvic Sidewall Anatomy in Gynecologic Oncology-New Insights into a Potential Avascular Space.

The surgical treatment of gynecological malignancies is, except for tumors diagnosed at the earliest stages and patients’ desire for fertility preservation, not limited to only the affected organ. In cases of metastatic iliac lymph nodes, gynecological tumors or recurrences located near the pelvic sidewall, oncogynecologists should dissect tissues in that region. Moreover, surgery of deep infiltrating endometriosis, e.g., within the sacral plexus, or oncological procedures, such as a laterally extended endoplevic resection or a laterally extended parametrectomy, often require a dissection of the pelvic sidewall. Dissection should be meticulous, and detailed knowledge of anatomy is mandatory. There are many controversies among authors regarding the terminology in the pelvic sidewall. In particular, several imprecise or confusing definitions exist in regard to the region located medially to the psoas major muscle. Therefore, after discussing the anatomy of the pelvic sidewall and the commonly used terminology, we define a new term and boundaries of a potential avascular space, the medial psoas space. Contrary to the variety of earlier definitions, the proposed boundaries relate to a truly avascular space and could help surgeons to avoid complications resulting from misleading anatomical descriptions. Additionally, describing the clear boundaries of and possible anatomical variations in the medial psoas space may urge oncogynecologists to consider different approaches during surgery. The purpose of the present study is to describe the anatomy of the pelvic sidewall and the applications of the medial psoas space in gynecologic oncology.

Vaginal mucositis in patients with gynaecological cancer undergoing (chemo-)radiotherapy: a retrospective analysis

The objective of this retrospective analysis was to determine the incidence and extent of vaginal mucositis (VM) in women with gynaecological cancer undergoing external (chemo)radiation therapy (CRT). A retrospective analysis was set up to collect data on the incidence and severity of VM in women treated with external pelvic RT for gynaecological cancer at the Jessa Hospital, Hasselt and ZOL, Genk, BE between January 2017 and June 2018. At the start and end of their external (C)RT, they rated the frequency and intensity of five common symptoms of VM. Thirty-three patients treated with RT for gynaecological cancer met the inclusion criteria. A non-negligible proportion of patients already experienced at least one VM symptom to any degree before the start of RT, a proportion that further increased towards the end of the RT (73%). At the end of RT, on average, about 25% of these patients reported moderate-to-severe symptoms (against about 7% before the (C)RT). These results suggest that VM is a rather frequent side effect in gynaecological cancer patients that aggravates during treatment up to a moderate severity level. Although the small sample size, these data highlight the need for attention to VM. Impact Statement What is already known about this topic? Radiotherapy plays an important role in the treatment of gynaecological malignancies. A debilitating complication in patients undergoing pelvic radiotherapy is vaginal mucositis, an inflammation of the vaginal mucosal lining. To date, the incidence of vaginal mucositis is still not well documented. What this paper adds? A non-negligible proportion of patients already experienced at least one symptom related to vaginal mucositis before the start of radiotherapy. Most patients presented mild to moderate vaginal mucositis symptoms at the end of external pelvic radiotherapy. Burning sensation, pruritus, and pain were the most frequently documented radiotherapy-induced complications. The implications of this paper: Vaginal mucositis is an underrated side effect of pelvic radiotherapy that needs to be tackled multidisciplinary by a team of nurses, radiotherapists, oncologists, and gynaecologists. The team should tackle the complication from the start of radiotherapy by using the most appropriate measures. Due to a possible link between acute vaginal mucositis and late vaginal toxicity, the team needs to follow-up patient’s post-radiotherapy to support patients in late complications and advise/encourage patients in performing vaginal dilatation to prevent vaginal stenosis.

Immunotherapy and Systemic Therapy in Metastatic/Recurrent Endometrial and Cervical Cancers

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.

PLEN01 Presentation Time: 1:15 PM: Virtual Reality-Based Simulation Improves Gynecologic Brachytherapy Proficiency, Engagement, and Trainee Self-Confidence

Purpose: Brachytherapy is an integral component in treatment of gynecologic malignancies. Intracavitary brachytherapy has the highest rates of local control and survival in cervical cancer. Classical brachytherapy training requires 1-on-1 instruction during patient encounters. This training is resource intensive and variable based on the type/frequency of the procedures performed by the attending physician/facility. Consequently, exposure to brachytherapy varies among residency programs. Even with Accreditation Council for Graduate Medical Education mandated requirements, only about 50% of graduating residents express confidence to develop a brachytherapy practice with caseload as the greatest barrier. The use of simulation-based education has been shown to increase confidence, applicator placement quality, and decrease implant time and errors.

A Prospective Single-Arm Study Evaluating the Effects of a Multimodal Physical Therapy Intervention on Psychosexual Outcomes in Women With Dyspareunia After Gynecologic Cancer

Dyspareunia affects most women after treatment for gynecologic malignancies. However, to date, evidence-based interventions remain limited and no study has examined the effects of multimodal physical therapy on psychosexual outcomes in these patients. To assess the effects of multimodal physical therapy on psychosexual outcomes including sexual distress, body image concerns, pain anxiety, pain catastrophizing, pain self-efficacy and depressive symptoms in women with dyspareunia after treatment for gynecologic malignancies. Thirty-one gynecologic cancer survivors with dyspareunia enrolled in this prospective single-arm interventional study. The participants undertook 12 weekly sessions of physical therapy incorporating education, pelvic floor muscle exercises with biofeedback, manual therapy and home exercises. Outcome measures were evaluated pre- and post-treatment. Paired t-tests were conducted to investigate the changes from pre-treatment (P-value˂0.05) while effect sizes (Cohen's d) were calculated to measure the magnitude of the change. Sexual distress (Female Sexual Distress Scale-Revised), body image concerns (Body Image Scale), pain anxiety (Pain Anxiety Symptoms Scale), pain catastrophizing (Pain Catastrophizing Scale), pain self-efficacy (Painful Intercourse Self-Efficacy Scale) and depressive symptoms (Beck Depression Inventory-II). Significant changes were found from pre- to post-treatment for all psychosexual outcomes. Women reported reductions in sexual distress (P˂0.001, d=1.108), body image concerns (P˂0.001, d=0.829), pain anxiety (P˂0.001, d=0.980), pain catastrophizing (P˂0.001, d=0.968) and depression symptoms (P=0.002, d=0.636) with an increase in pain self-efficacy (P˂0.001, d≥0.938) following the intervention. The results suggest that multimodal physical therapy significantly improves sexual distress, body image concerns, pain anxiety, pain catastrophizing, pain self-efficacy and depressive symptoms in our sample of women with dyspareunia after treatment for gynecologic malignancies. The medium to large effect sizes obtained with the high proportion of women presenting meaningful changes according to the known minimal clinically important difference or clinical cut-off underlines the significance of these effects. The current study used validated questionnaires to assess the psychosexual outcomes of a well-designed physical therapy intervention using multiple modalities to address the multifaceted aspect of dyspareunia in cancer survivors. This study did not include a control group, which may limit drawing definitive conclusions. Findings showed that multimodal physical therapy yielded significant improvements in psychosexual outcomes in gynecologic cancer survivors with dyspareunia. A randomized controlled trial is indicated to confirm these results. Cyr M-P, Dumoulin C, Bessette P, etal. A Prospective Single-Arm Study Evaluating the Effects of a Multimodal Physical Therapy Intervention on Psychosexual Outcomes in Women With Dyspareunia After Gynecologic Cancer. J Sex Med 2021;18:946-954.

The gut microbiome and cancer immunotherapeutics: A review of emerging data and implications for future gynecologic cancer research.

Investigation of the gynecologic tract microbial milieu has revealed potential new biomarkers. Simultaneously, immunotherapeutics are establishing their place in the treatment of gynecologic malignancies. The interplay between the microbiome, the tumor micro-environment and response to therapy is a burgeoning area of interest. There is evidence to support that microbes, through their genetic make-up, gene products, and metabolites affect human physiology, metabolism, immunity, disease susceptibility, response to pharmacotherapy, and the severity of disease-related side effects. Specifically, the richness and diversity of the gut microbiome appears to affect carcinogenesis, response to immunotherapy, and modulate severity of immune-mediated adverse effects. These effects have best been described in other tumor types and these have shown compelling results. This review summarizes the current understanding and scope of the interplay between the human microbiome, host factors, cancer, and response to treatments. These findings support further exploring whether these associations exist for gynecologic malignancies.

Non-invasive Technology Advances in Cancer-A Review of the Advances in the Liquid Biopsy for Endometrial and Ovarian Cancers.

Improving cancer survival rates globally requires improvements in disease detection and monitoring, with the aim of improving early diagnosis and prediction of disease relapse. Traditional means of detecting and monitoring cancers rely largely on imaging and, where possible, blood-based protein biomarkers, many of which are non-specific. Treatments are being improved by identification of inherited and acquired genomic aberrations in tumors, some of which can be targeted by newly developed therapeutic interventions. Treatment of gynecological malignancy is progressively moving toward personalized therapy, as exemplified by application of PARP-inhibition for patients with BRCA-deficient tubo-ovarian cancers, or checkpoint inhibition in patients with mismatch repair-deficient disease. However, the more recent discovery of a group of biomarkers described under the umbrella term of “liquid biopsy” promises significant improvement in our ability to detect and monitor cancers. The term “liquid biopsy” is used to describe an array of tumor-derived material found in blood plasma and other bodily fluids such as ascites, pleural fluid, saliva, and urine. It includes circulating tumors cells (CTCs), circulating nucleic acids including DNA, messenger RNA and micro RNAs, and extracellular vesicles (EVs). In this review, we discuss recent advancements in liquid biopsy for biomarker detection to help in diagnosis, prognosis, and planning of treatment of ovarian and endometrial cancer.

Utilization and prognostic impact of somatic tumor testing in ovarian cancer: A single-institution experience

Objective: Comprehensive genomic profiling (CGP) to identify potential therapeutic targets in treatment of ovarian cancer has allowed for individualized treatment approaches in a new era of personalized medicine. This analysis reflects the application of CGP in the treatment of gynecologic malignancies at our institution and reveals novel mutation patterns that may reflect differential survival outcomes in women with ovarian cancer.

PARP Inhibitors in Endometrial Cancer: Current Status and Perspectives.

Advanced, recurrent and metastatic endometrial cancer (EC) has a dismal prognosis due to poor response rates to conventional treatments. In the era of precision medicine, the improved understanding of cancer genetics and molecular biology has led to the development of targeted therapies, such as poly (ADP-ribose) polymerase (PARP) inhibitors. This class of drugs that inhibit PARP enzymes has been investigated in many different types of tumors and its use in the treatment of gynecological malignancies has rapidly increased over the past few years. Data from several clinical trials showed that PARP inhibitors have a beneficial role in cancers with a defect in the homologous DNA recombination system, regardless of the BRCA mutational status. Since EC frequently shows mutations in PTEN and TP53 genes, indirectly involved in the homologous DNA recombination pathway, several in vivo and in vitro studies investigated the efficacy of PARP inhibitors in EC, showing promising results. This review will discuss the use of PARP inhibitors in endometrial cancer, summarizing data from preclinical studies and providing an overview of the ongoing trials, with a special focus on the development of combined treatment strategies with PARP inhibitors and immune checkpoint inhibitors.

Wnt Signaling in Gynecologic Malignancies.

Gynecologic malignancies, including ovarian cancer, endometrial cancer, and cervical cancer, affect hundreds of thousands of women worldwide every year. Wnt signaling, specifically Wnt/β-catenin signaling, has been found to play an essential role in many oncogenic processes in gynecologic malignancies, including tumorigenesis, metastasis, recurrence, and chemotherapy resistance. As such, the Wnt/β-catenin signaling pathway has the potential to be a target for effective treatment, improving patient outcomes. In this review, we discuss the evidence supporting the importance of the Wnt signaling pathways in the development, progression, and treatment of gynecologic malignancies.

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.

Targeting cervical cancer: Is there a role for poly (ADP-ribose) polymerase inhibition?

Patients with metastatic and recurrent cervical cancer (CC) have a poor prognosis with limited palliative treatment options. Increasing understanding of the cellular aberrations inherent to cancer cells has allowed the development of therapies to target biological pathways, an important step toward the individualization of cancer therapy. The poly (ADP-ribose) polymerase (PARP) family of enzymes is important in several DNA repair pathways. Drugs that inhibit these PARP enzymes have been investigated in many types of cancer and their application in the treatment of gynecologic malignancies has rapidly evolved. Although the majority of data for PARPi in gynecologic malignancies has been specifically regarding ovarian cancer, their role in the treatment of uterine and CC is currently being investigated. This review will examine PARP inhibitors in CC, summarizes the critical clinical trials of PARP inhibitors that have been completed, provides an overview of the on-going trials, presents the confirmed conclusions and notes the issues that need to be addressed in future studies.

Management of cancer during the COVID pandemic: Treatment of gynecological malignancies

Management of cancer during the COVID pandemic: Treatment of gynecological malignancies

Pazopanib for the treatment of gynecological malignancies

Pazopanib for the treatment of gynecological malignancies

Hormone replacement therapy following treatment of gynaecological malignancies

Key content Approximately 21 000 women in the UK were diagnosed with a gynaecological malignancy in 2015; although most of these malignancies occurred in postmenopausal women, 30–40% present in premenopausal or perimenopausal women. Management typically involves surgery and/or chemotherapy and/or radiotherapy, which in younger women may result in an induced menopause. Many women struggle with both the immediate symptoms and the long‐term consequences of estrogen deficiency, all of which are debilitating and compromise the quality and quantity of life, in addition to the cancer diagnosis and treatment. These patients represent a complex group and most units in the UK do not have easy access to menopause specialists. Gynaecologists may be reluctant to prescribe hormone replacement therapy (HRT) to these women; clinicians involved in the care of these women must appreciate when HRT is and is not contraindicated. Learning objectives To understand the safety of HRT in women who have undergone treatment for endometrial, ovarian, cervical, vulval or vaginal malignancies, with particular emphasis on the type, stage and grade of cancer. To establish an evidence‐based approach to the management of menopausal symptoms using HRT in women who have previously been treated for a gynaecological malignancy. To appreciate the role of non‐hormonal alternatives to HRT in these women. Ethical issues How to balance the known benefits of HRT against the potential risks, when evidence is limited in women who have undergone treatment for a gynaecological malignancy.

Lymphovenous anastomosis: A reasonable treatment of secondary lower extremity lymphedema arising from the treatment of gynecologic malignancies

Lymphovenous anastomosis: A reasonable treatment of secondary lower extremity lymphedema arising from the treatment of gynecologic malignancies

Sexual quality of life after the treatment of gynecologic cancer: what women want.

While the incidence of sexual dysfunction after treatment for gynecologic malignancies is well documented, few studies describe how patients want healthcare providers to address these concerns. The objective of this study was to evaluate changes in sexual function and describe patient preferences regarding healthcare provider roles in addressing and treating sexual dysfunction in gynecologic cancer survivors. Patients undergoing gynecologic cancer treatment from 2013 to 2014 at a single University-based Gynecologic Cancer clinic were surveyed using a modified Changes in Sexual Function Questionnaire (CSFQ), along with questions relating to healthcare provider interactions and preferences. Among 277 eligible patients approached to participate, 85 (30.7%) completed the survey. The mean age was 52.2 ± 12.3years; most were non-Hispanic White (78.8%), partnered (73.2%), had endometrial or ovarian cancer (30.6% and 44.7%, respectively), and were in surveillance (57.3%). Most women (64.7%) reported much or great sexual enjoyment 1year prior to cancer treatment which decreased to 27.4% currently; 33.3% report only rare sexual activity. There were no statistically significant differences in mean total CSFQ scores by treatment modality. A minority wanted healthcare providers to initiate sexual health discussions (25.3%); the remaining reported not wanting sexual health addressed or preferred raising the issue themselves. The most commonly cited barrier to communication was the feeling that there are more important issues to discuss with their oncology providers (46.2%). While gynecologic cancer patients report changes in sexual function following cancer therapy, many believe there are other issues more paramount to be addressed. Further studies are warranted to develop better strategies for addressing sexual health in women receiving treatment for gynecologic cancers.

Treatment of gynecological malignancies: long-term follow-up of health-related quality of life and healthcare costs.

Aim: To assess long-term health-related quality of life (HRQoL) and treatment-related costs in gynecological cancer patients, and to compare HRQoL between cancer types and to age-standardized general female population. Materials & methods: A prospective 8-10-year follow-up of 218 patients treated in Helsinki University Hospital in 2002-2004. Results: The most common malignancies were uterine, ovarian and cervical cancers. The mean HRQoL scores were 0.880 (baseline), 0.885 (6 months) and 0.884 for survivors in the end of the study. Depression, vitality and sexual activity were impaired at baseline but improved during follow-up. Total secondary healthcare costs during the follow-up averaged EUR 41342. Conclusion: The long-term HRQoL of surviving gynecological cancer patients was good and similar to that of age-standardized general female population.

Novel Surgical Strategies in the Treatment of Gynecological Malignancies.

The main advancement in the surgical treatment of early cervical cancer has been a de-escalation in the radical surgical approach of early stage disease. Similarly, sentinel lymph node detection with cervical tracer injection can be performed alone in microscopic tumors (stage IA) while additional lymphadenectomy is still performed in macroscopic tumors (IB1 and IIA). Parametrial resection has been progressively reduced in tumors less than 2cm, and simple procedures, conservative (trachelectomy) or not (simple hysterectomy), are currently being evaluated in several phase III trials. Since the preliminary results of the LACC (locally advanced cervical cancer) trial, the value of minimally invasive surgery as the standard approach for the treatment of early stage cervical cancer has been questioned and patients should be aware when discussing the approach for radical hysterectomy. While awaiting the results of ongoing clinical trials comparing radiological and surgical staging in locally advanced cervical cancer patients, surgical staging with paraaortic lymphadenectomy remains the standard of care before definitive chemoradiotherapy in patients with negative aortic PET/TDM. Patients undergoing salvage surgeries for isolated pelvic recurrences of cervical cancer benefit from advanced reconstructive techniques as DIEP flaps and continent reconstructive urinary techniques. In selected patients, a minimally invasive approach can be considered. Surgery is the mainstay of the treatment of endometrial cancer. The major evolution in surgical strategy has occurred in lymph node staging. The standard surgical staging includes pelvic and paraaortic lymph node dissection to the level of the left renal vein. Sentinel lymph node dissection has been validated as a less morbid alternative of systematic lymphadenectomy, indicated in patients with low and intermediate risk of lymph node involvement. In advanced ovarian cancer, complete cytoreduction is the main objective of surgery. To achieve this goal, upper abdominal complex procedures have been developed. Best survival rates are obtained with primary debulking surgery. Exploratory laparoscopy may be performed before cytoreduction to evaluate resectability and thus avoid unnecessary laparotomy. Although systematic pelvic and paraaortic lymphadenectomy is being questioned in patients with advanced ovarian cancer and clinically negative lymph nodes undergoing complete primary debulking surgery, this procedure is still recommended. While waiting publication of the GOG 252 trial, IP chemotherapy after complete CRS is under debate. HIPEC after interval debulking surgery in patients undergoing complete cytoreduction is an intriguing new option. Patients within the first recurrence of ovarian cancer, with score AGO-positive, benefit from a second complete cytoreductive surgery followed by chemotherapy. Ovarian cancer survival rates are higher in specialized high-volume centers, and thus cases should be centralized and quality indicators used.