Gynecologic Cancer Therapy Research Articles

Cytomegalovirus (CMV) colitis associated with chemotherapy and molecular targeted therapy for gynecologic cancer: A case report of ovarian cancer

Cytomegalovirus (CMV) colitis associated with chemotherapy and molecular targeted therapy for gynecologic cancer: A case report of ovarian cancer

Higher distress scores associated with reduced ability to complete prescribed gynecologic cancer therapy

Objective: The association of social determinants of health with oncologic outcome is extensively described in the literature. The mechanism by which these social determinants have a direct impact on oncologic outcome is not clearly known. The aim of this study is to investigate whether a priori patient-reported distress levels, as measured by validated toolkits, correlate with treatment interruption and nonadherence to care.

Aromatase inhibitor use, side effects and discontinuation rates in gynecologic oncology patients

ObjectiveAromatase inhibitors (AI) are frequently prescribed in gynecologic oncology. We sought to define the frequency and duration of AI use, characterize AI side effects and determine the reasons for discontinuation in these patients. MethodsUterine and ovarian cancer patients with AI use for gynecologic cancer therapy were identified retrospectively. Data were abstracted from the electronic medical record, including cancer type, stage, prior cancer treatments, body mass index, concurrent medications, prevalence of AI side effects before and during AI therapy, length of AI treatment and reason for AI discontinuation. Results146 women received AI therapy, with 68 for ovarian cancer (46.6%) and 78 for uterine cancer (53.4%). The majority (71.9%) had advanced stage disease at diagnosis. 54.1% noted AI-associated side effects within the first three visits after starting AI therapy. The most common side effects were arthralgias (29.5%), hot flashes (25.3%), new/worsening fatigue (16.4%), muscle or joint stiffness (8.2%) and myalgias (6.8%). The mean duration of therapy was 14.7 months. Gabapentin or selective serotonin reuptake inhibitor (SSRI) use was associated with decreased musculoskeletal side effects (gabapentin: p < .001, OR 0.88, 95% CI 0.83–0.94; SSRI: p < .001, OR 0.82, 95% CI 0.77–0.89). The most common reason for AI discontinuation was disease progression (87.9%), with 5.0% discontinuing due to side effects and 7.1% for other reasons. ConclusionAI therapy for gynecologic cancers is frequently associated with musculoskeletal side effects, but rarely leads to treatment discontinuation. Thus, AI side effects should be assessed in gynecologic cancer patients to allow potential mitigation of symptoms through adjunct therapies.

Roles of Medicinal Plants and Constituents in Gynecological Cancer Therapy: Current Literature and Future Directions.

Gynecologic cancers, including cervical, primary peritoneal, ovarian, uterine/endometrial, vaginal and vulvar cancers and gestational trophoblastic disease, are characterized by abnormal cell proliferation in female reproductive cells. Due to the variable pathology of these cancers and the lack of appropriate screening tests in developing countries, cancer diagnosis can be reported in advanced stages in most women and this situation adversely affects prognosis and clinical outcomes of illness. For this reason, many researchers in the field of gynecological oncology have carried out many studies. The treatment of various gynecological problems, which cause physical, biological and psychosocial conditions such as fear, shame, blame and anger, has been important throughout the history. Treatment with herbs has become popular nowadays due to the serious side effects of the synthetic drugs used in treatment and the medical and economical problems caused by them. Many scientists have identified various active drug substances through in vivo and in vitro biological activity studies on medicinal plants from the past to the present. While the intrinsic complexity of natural product-based drug discoveries requires highly integrated interdisciplinary approaches, scientific and technological advances and research trends clearly show that natural products will be among the most important new drug sources in the future. In this review, an overview of the studies conducted for the discovery of multitargeted drug molecules in the rational treatment of gynecological cancers is presented.

Identification of hub genes and key pathways associated with the progression of gynecological cancer.

Gynecological cancer is the leading cause of cancer mortality in women. However, the mechanisms underlying gynecological cancer progression have remained largely unclear. In the present study, 799 dysregulated genes were identified in ovarian serous cystadenocarcinoma (OV), 488 dysregulated genes in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), and 621 dysregulated genes in uterine corpus endometrial carcinoma (UCEC). Bioinformatics analysis revealed that mRNA splicing and cell proliferation-associated biological processes served important roles in OV progression. Metabolism-associated biological processes played important roles in CESC progression, and protein phosphorylation and small GTPase-mediated signal transduction served important roles in UCEC progression. The present study also constructed OV, CESC and UCEC progression-associated protein-protein interaction networks to reveal the associations among these genes. Furthermore, Kaplan-Meier curve analysis showed that progression-related genes were associated with the duration of overall survival. Finally, NARS2 and TPT1 in OV, SMYD2, EGLN1, TNFRSF10D, FUT11, SYTL3, MMP8 and EREG in CESC, and SLC5A1, TXN, KDM4B, TXNDC11, HSDL2, COX16, MGAT4A, DAGLA, ELOVL7, THRB and PCOLCE2 in UCEC were identified as hub genes in cancer progression. Therefore, this study may assist in the identification of novel mechanisms underlying cancer progression and new biomarkers for gynecological cancer prognosis and therapy.

Pelvic Insufficiency Fractures After External Beam Radiation Therapy for Gynecologic Cancers: A Meta-analysis and Meta-regression of 3929 Patients

To estimate the overall rate, symptomatic proportion, and most common sites of pelvic insufficiency fracture (PIF) after external beam radiation therapy for gynecologic cancers based on posttreatment computed tomography, magnetic resonance imaging, positron emission tomography, or bone scintigraphy. A systematic search of databases (PubMed and EMBASE) was performed (CRD42019125679). The pooled summary of overall PIF and the proportion of symptomatic cases were calculated using the random-effects model weighted by the inverse variance. A multivariate meta-regression was performed to evaluate potential sources of heterogeneity regarding PIF fractures. Twenty-one studies met the inclusion criteria (total 3929 patients). Five hundred four patients developed PIF, translating to an overall rate of 14% (95% confidence interval, 10%-18%, based on 21 studies). Among these cases with PIF, the proportion of symptomatic patients was 61% (95% confidence interval, 52%-69%, based on 14 studies). The total number of PIFs was 704 (mean, 1.72 PIFs per each patient to develop PIF, based on 14 studies). More recent series (P = .0074) and the use of intensity modulated radiation therapy (P = .0299) were associated with lower fracture rates. The most common fracture sites were sacroiliac joint (39.7%), body of the sacrum (33.9%), pubis (13%), lumbar vertebra (7%), iliac bone (2.8%), acetabulum (2.1%), and femoral head/neck (1.5%). The median time to fracture was 7.1 to 19 months after radiation therapy. The incidence of PIF after radiation therapy for gynecologic cancers is high (14%), with the majority affecting the sacral bone or joint (73.6%), although this risk appears to be lower with intensity modulated radiation therapy. Posttreatment bone surveillance is warranted in this population because nearly 40% of patients were asymptomatic at the time of PIF diagnosis.

Comparison of Vaginal Microbiota in Gynecologic Cancer Patients Pre- and Post-Radiation Therapy and Healthy Women

Importance of microbes in vaginal health well appreciated, yet little is known about effects of gynecological cancer (GynCa) and radiation therapy (RT) vaginal microbiome (VM). Pilot study conducted to establish rigorous methods in bacterial vs human DNA extraction, quality assurance (Q/A), VM sequencing and beginning assessment of differences in VM among women with GynCa pre & post RT compared to healthy controls. Women with GynCa (cervical or endometrial) treated for RT curative intent, had vaginal swabs collected according Human Microbiome Project protocol (T0) pre-RT and 1-2 mo post-RT (T1). Controls were sampled (T0) routine gyn visit. Quality assurance (QA) conducted on first 7 cancer pts. VM sequencing assessed V3-V4 region of 16S rRNA gene. Cohorts compared in pairwise mode of 3 groups: healthy, pre- and post-RT, accounting for potential confounders (e.g., age & ethnicity) in ADONIS analysis. Alpha/beta diversity estimates computed in non-rarefied OTU libraries. Chao-Shen correction for alpha-diversity applied to account for differences in library size, and beta-diversity was computed in CSS-normalized OTU matrix. OTU richness estimated using Chao-1 index; diversity calculated as Shannon Index. Alpha diversity metric was statistically compared between GynCa and control groups using the Wilcoxon test. Beta-diversity analyses included Bray-Curtis and Jaccard. Final study included 69 VM samples obtained from 27 cancer patients (cervical n=13; endometrial n=14) and 30 healthy controls. QA showed high reproducibility of VM data. While some pre-RT communities overlapped with healthy, most post-RT VM communities did not overlap with the healthy, especially when dichotomized as “presence/absence”- distance metric (Jaccard), indicating RT as important factor contributing to differences. Trend toward lower microbial richness observed in healthy samples relative to GynCa. Characterization at genus level revealed 13 phylogroups differentially abundant between pre-RT and healthy groups: of note are- Streptococcus anginosus (p=0.01), Corynebacterium spp (p=0.01), Actinomyces spp (p=0.005), Faecalibacterium prausnitzii (p=0.04), and Bacteroides ovatus (p=0.02) significantly higher in relative abundance in healthy vs. cancer: opposite pattern or only present in the cancer seen in Sneathia spp (p<0.001), Methylobacterium adhaesivum (p<0.001), Bacillus spp (p<0.001), Ruminococcus spp (p=0.02), Clostridium spp (p=0.02), Peptostretococcus anaerobius (p=0.006), Moryella spp (p=0.01), and Shuttleworthia spp (p=0.02). Note: Sneathia, potential female reproductive tract pathogen enriched (>10% relative abundance) in the GynCa vs healthy group (<1% relative abundance). Analysis showed rigorous methods and trends in detecting RT as significant determinant of the variation observed between post-RT and control samples. Patients treated by RT likely experience vaginal injuries that may be related to changes in VM.

Development and Themes of Diagnostic and Treatment Procedures for Secondary Leg Lymphedema in Patients with Gynecologic Cancers.

Patients with leg lymphedema sometimes suffer under constraint feeling leg heaviness and pain, requiring lifelong treatment and psychosocial support after surgeries or radiation therapies for gynecologic cancers. We herein review the current issues (a review of the relevant literature) associated with recently developed diagnostic procedures and treatments for secondary leg lymphedema, and discuss how to better manage leg lymphedema. Among the currently available diagnostic tools, indocyanine green lymphography (ICG-LG) can detect dermal lymph backflow in asymptomatic legs at stage 0. Therefore, ICG-LG is considered the most sensitive and useful tool. At symptomatic stage ≥1, ultrasonography, magnetic resonance imaging-lymphography/computed tomography-lymphography (MRI-LG/CT-LG) and lymphosintiography are also useful. For the treatment of lymphedema, complex decongestive physiotherapy (CDP) including manual lymphatic drainage (MLD), compression therapy, exercise and skin care, is generally performed. In recent years, CDP has often required effective multi-layer lymph edema bandaging (MLLB) or advanced pneumatic compression devices (APCDs). If CDP is not effective, microsurgical procedures can be performed. At stage 1–2, when lymphaticovenous anastomosis (LVA) is performed, lymphaticovenous side-to-side anastomosis (LVSEA) is principally recommended. At stage 2–3, vascularized lymph node transfer (VLNT) is useful. These ingenious procedures can help maintain the patient’s quality of life (QOL) but unfortunately cannot cure lymphedema. The most important concern is the prevention of secondary lymphedema, which is achieved through approaches such as skin care, weight control, gentle limb exercises, avoiding sun and heat, and elevation of the affected leg.

Immunotherapy: Checkpoint Inhibitors in Lynch-Associated Gynecologic Cancers.

Research into novel therapies for gynecologic cancers is underfunded, and as a result, we are still playing catchup with other solid tumors in the realm of immune checkpoint inhibition. This is despite the fact that two of the most common gynecologic cancers in the USA have strong biologic rationales for response to these agents. Work is now underway to demonstrate safe and effective therapies for our patients. As we better understand the immune system, and more specifically the tumor microenvironment, we will be able to achieve complete responses. The immune system can learn, adapt, and provide ongoing surveillance; if only we could mimic its abilities.

Adjuvant Radiation for Gynecologic Cancers

Radiation therapy plays a significant role in the treatment of nearly all gynecologic cancers, including endometrial cancer, cervical cancer, vaginal cancer, and vulvar cancer. Radiotherapy can be given as the primary modality for curative treatment of gynecologic cancers, most often for cervical, vaginal, and vulvar cancers, but can also be used adjuvantly in the postoperative setting. Radiation can be delivered in the form of external beam radiation therapy or as gynecologic implants for brachytherapy, which is radiation that is delivered internally. This review highlights the data supporting radiation therapy for gynecologic cancers and explains the different methods of radiation delivery. This review contains 5 figures, and 4 tables, and 40 references. Key Words: adjuvant treatment, brachytherapy, cervical cancer, endometrial cancer, IMRT, ovarian cancer, radiation therapy, vaginal cancer, vulvar cancer

The Impact of Molecular Testing and Therapy for Gynecologic Cancers in Low Resource Environments [31D

INTRODUCTION: Targeted cancer therapies based on tumor molecular analysis have grown exponentially in the last 5 years. Multiple gynecologic tumors can express markers that predict response to specific treatments. However not all insurance covers costly testing for every tumor marker, which can prevent un- or under-insured women from receiving optimal treatment. We worked with independent laboratories to provide free or cost-reduced testing. This study's aim is to demonstrate the impact of a universal molecular-based therapeutic program for gynecologic cancers in a low-resource environment. METHODS: Women with new gynecologic cancers presenting to an inner-city academic facility were identified between 1/1/18 and 6/30/18. Pedigree analysis and molecular testing of tumor specimens were done in all subjects. Data collected includes: demographics (including insurance status), tumor type and stage, and initial treatments. RESULTS: 45 women with gynecologic cancer were identified. (Cervix-18, Ovary-7, Uterus-10, Vulva/vagina-10). 5/18 cervix cancers showed Combined Predictive Score &gt;1.0; 3/10 uterine cancers showed mismatch repair (MMR) deficiencies; 3/10 vulva/vagina showed MMR deficiencies; and 2/7 ovarian cancers showed somatic BRCA mutations. In this 6-month period, 13/45 (29%) of gynecologic malignancies diagnosed had molecular markers associated with targeted therapies, and 7/13 (53%) patients with predictive molecular markers accepted a targeted therapy. CONCLUSION: Molecular analysis of cancer with therapy based on molecular markers is the gold standard for gynecologic cancers. 29% of the subjects had molecular markers associated with targeted therapies. While molecular testing and targeted therapies may be expensive, many laboratories and pharmaceutical companies are willing to work with patients with limited resources.

The role of artificial nutrition in gynecological cancer therapy.

Cancer patients are at risk of developing malnutrition from underlying disease as well as from cancer treatment. Moreover, weight loss is considered as a predictive factor for disease progression and shorter survival time. As many as 10-20% of patients with cancer die from the results of malnutrition, instead of from the cancer itself. In the case of cancer-related malnutrition, it is necessary to quickly implement individualized nutritional support depending on the type and stage of the disease, metabolic changes, the patient's condition, expected survival and the function of the gastrointestinal tract. Artificial nutrition reduces the side effects of chemotherapy and improves immunity. Perioperatively it reduces the risk of infection, facilitates wound healing and shortens the length of hospitalization, thereby reducing the costs of the treat- ment. Initially, a malnourished patient, without gastrointestinal dysfunction, qualifies for nutritional counseling. When the energy needs cannot be met by normal feeding, nutritional supplements, taken orally, are recommended. The next step is to feed the patient by nasogastric tube or percutaneous endoscopic gastrostomy. Parenteral nutrition, which results in more side effects, is only started when enteral nutrition is insufficient to ensure adequate nutritional status or in cases of gastrointestinal tract obstruction. The benefit of parenteral nutrition is that it especially provides for those patients with gynaecological cancer who have radiation-induced intestinal damage and post-surgical complications such as short bowel syndrome. Palliative nutrition must to relieve hunger and thirst. Nutritional interventions should be individualized and focused on the changing nutrient needs of the patient and should be supported by physical activity. Regular assessment of the nutritional status of the patient should be an inherent element of the oncological treatment.

New and Novel Therapies for Gynecologic Cancers.

To review recent therapies approved by the US Food and Drug Administration for the treatment of gynecologic malignancies. PubMed, FDA.gov, ASCO.org. The landscape for treating gynecologic malignancies is rapidly changing. Maintenance therapy now exists for women with advanced ovarian cancer after completing chemotherapy for both newly diagnosed and platinum-sensitive recurrent ovarian cancer. Anti-angiogenic therapy has many applications in gynecologic malignancies. Immunotherapy can be used in certain situations for women with gynecologic malignancies. Biologic agents and immunotherapy have distinct side-effect profiles that nurses need to be aware of to optimize patient care and outcomes.

Development and Evaluation of a New In Vivo Volume Measuring System in Mouse Tail Lymphedema Model.

Backgrounds: Secondary lymphedema is a common complication of parasitization and breast or gynecologic cancer therapy; however, options for the treatment of lymphedema are ineffective and limited. A mouse tail model is one of the most successful animal models for a lymphatic study. Lymphedema of the mouse tail is characterized by increases in the volume of the extremity caused by accumulation of tissue fluid, proliferation of fibroblasts and adipocytes, and excessive production of collagen. However, the study of lymphedema using mouse has been plagued with difficulty in directly assessing physiologic changes owing to limitations in the measurement of the mouse tail volume. Furthermore, the mouse tail volume cannot be obtained using the general in vivo measurement method such as volumetric water displacement. Methods and Results: Lymphatic researchers have used the truncated cone formula to approximate the volume as used in the numerical approximation of a cylindrical figure. Although this formula is simple and easy to use, it has difficulties of repeatability and accuracy because the measurement procedure is highly subjective and the accuracy depends on the number of divided segments on the tail. In this article, two novel volumetric measurement methods for the mouse tail model were introduced. The methods were evaluated and compared using three mice with surgically created lymphedema on the tails. Conclusions: The two continuous measuring methods showed a possibility to improve the conventional method by continuous measurement using visual and physical detecting methods. The proposed methods facilitate the extraction of longitudinal section-specific information, which can be an important clue in a lymphatic study.

Targeted therapy for gynecologic cancers: Toward the era of precision medicine.

Recent advances in molecular biology of cancer have led to the development of targeted agents, mainly of monoclonal antibodies and small-molecule compounds. Unlike traditional drugs that inhibit DNA synthesis and mitosis, these agents target the signaling pathways of cancer cells, stroma, and vasculature in tumor tissues. For gynecologic cancers, drugs targeting angiogenesis such as anti-VEGF antibody have been used in the treatment of advanced or recurrent ovarian and cervical cancers, and the drugs targeting homologous recombination deficiency such as PARP inhibitors have been approved for maintenance after chemotherapy in platinum-sensitive ovarian cancer. In addition, novel immunotherapy using the immune checkpoint inhibitors such as anti-PD-1 antibody has received much attention for modulation of local immunity, resulting in the durable response of platinum-resistant ovarian cancer. In the precision medicine era, further understanding of cancer genomics and identification of predictive biomarkers are essential to ensure better health for women with gynecologic cancer.

Cancer survivorship issues with radiation and hemorrhagic cystitis in gynecological malignancies.

Given that more cancers are being diagnosed earlier and that treatment of cancer is improving, health issues of cancer survivors are becoming more common and apparent. Pelvic radiation therapy for the treatment of gynecological cancers can lead to long-term collateral damage to the bladder, a condition termed radiation cystitis (RC). Late sequelae may take many years to develop and include incontinence and pain as well as hematuria. RC is a rare but potentially life-threatening condition for which there are few management and treatment options. There are limited data in the literature regarding the effects of radiation on the bladder after gynecological cancer therapy and we hereby review the literature on cancer survivorship issues of pelvic radiation for gynecology literature. Treatment options are available for patients with radiation-induced hemorrhagic cystitis. However, most treatments are risky or only effective for a short timeframe and no therapy is currently available to reverse the disease progress. Furthermore, no standardized guidelines exist describing preferred management options. Common therapies include hyperbaric oxygen therapy, clot evacuation, fulguration, intravesical instillation of astringent agents, and surgery. Novel developing strategies include Botulinum Toxin injections and liposomal-tacrolimus instillations. These treatments and strategies are discussed. In this review, we will present current and advanced therapeutic strategies for RC to help cancer survivors deal with long-term bladder health issues.

Progress in record numbers of approved therapies for gynecologic cancers: The lack of upfront approval for newly diagnosed cases.

e14551Background: To determine progress in FDA approved drugs for cancer therapies in over the past 12 years. Methods: Data from all approved oncologic or malignant hematologic indications were obt...

Feasibility of a sexual health program for women receiving pelvic radiation therapy for gynecologic and lower GI cancers.

135 Background: Long term effects of pelvic radiation for women include vaginal stenosis, leading to distress regarding sexual function. The NCCN guidelines recommend asking patients about sexual function at frequent intervals. NCCN recommends the use of vaginal dilators for women who have had pelvic radiation. Vaginal dilators have been widely recommended to minimize these long term effects. However, current evidence demonstrates poor adherence (less than 50%) of vaginal dilator use. Methods: A sexual health clinic was implemented at the radiation oncology department of a large academic medical center. This initiative consisted of three visits with a nurse practitioner over a twelve week period. The first visit was completed prior to the start of radiation, consisted of sexual history, completion of the PROMIS sexual health survey, and education regarding vaginal stenosis. The importance of the use of vaginal dilators following the completion of radiation was emphasized.. The second visit occurred at the completion of radiation and consisted of the PROMIS sexual health survey, and reinforcement of the use of vaginal dilators. Patients were instructed to begin use of vaginal dilators two weeks later. Each patient was given a set of four vaginal dilators, and a vaginal dilator diary. The third visit was completed six to eight weeks post treatment and consisted of completion of the PROMIS sexual health survey, review of the vaginal dilator diary, discussion of patient progress, and reinforcement of education. Results: From August 2016 to September 2017, 38 patients were approached and all completed the first visit (100%). Twenty-three patients completed the second visit (61%). Thirteen patients have completed all three visits (35%). At the end of three visits 11 (85%) of 13 patients were using vaginal dilators, and three had become sexually active. Conclusions: This program demonstrates a high enrollment and completion rate, as well as an important survivorship issue for women undergoing pelvic radiation. The reinforcement of long term effects of radiation enabled patients to understand the importance of using vaginal dilators in to maintain vaginal health and maintain sexual function.

The Role of Secondary Metabolites on Gynecologic Cancer Therapy: Some Pathways and Mechanisms.

Gynecologic cancers are among the most common cancers in humans and animals. Treatment success depends on several factors including stage at diagnosis, tumor type, origin and metastasis. Currently, surgery, chemotherapy, and radiotherapy are preferred in the treatment of these cancers. However, many anticarcinogenic drugs can cause severe adverse effects and also the expected response to treatment may not be obtained. In recent studies, the importance of the relationship between cancer and inflammation has been emphasized. Therefore, several phytochemicals that exhibit beneficial bioactive effects towards inflammatory pathways were proven to have anticarcinogenic potential for gynecologic cancer therapy. This review summarizes the role of inflammatory pathways in gynecologic cancers and effective secondary metabolites for cancer therapy.

Absence of cardiotoxicity with prolonged treatment and large accumulating doses of pegylated liposomal doxorubicin.

Pegylated liposomal doxorubicin (PLD) is used as a second-line therapy for gynecologic cancers, with a better short-term toxicity profile compared to doxorubicin or other anthracyclines. We screened 14 patients with recurrent gynecologic cancers, who underwent prolonged treatment with large cumulative doses of PLD for overt or subtle signs of cardiotoxicity (CTX) using standard and advanced echocardiography techniques [3D volumetric method for left ventricular ejection fraction (LVEF) and left ventricular/right ventricular global longitudinal strain]. Half the patients had previous echocardiographic studies available for comparison. The average PLD treatment duration was 23.6±10.8months (range 13-57), accumulating dose of 1387±483mg (range 780-2538mg). The study group had a normal LVEF both by 2D-echo (60±5%, range 50-67) and 3D echo (58±5%, range 46-63). Two patients (14%) were found to have minimally reduced ejection fraction by 2D and 3D echo (50%/46% and 51%/49%, respectively) that did not meet the current definition of CTX. For the seven patients who had consecutive echocardiography studies, the average LVEF remained stable between studies (59±7, 60±9 and 58±10.5% for the latest study, previous, p<0.79, and most remote study p<0.9); No change was found in average left ventricular/right ventricular global longitudinal strain as well: -20.8±4.6% at the latest study and -19.3±2.6% for the previous (p<0.51). No prevalent or incident cases of cardiotoxicity were found despite prolonged treatment with large cumulative doses of PLD, adding to previous reports on shorter treatment duration.