Treatment Of Gynecologic Cancers Research Articles

WEE1i-ATRi combination therapy: a promising low-dose treatment for CCNE1-amplified gynecologic cancers

CCNE1 amplification is an oncogenic driver for many gynecologic cancers and is associated with poor patient outcomes. In this issue, Xu et al.1 identify a combination therapy that is responsive to high CCNE1-copy number ovarian and endometrial cancers using PDX models.

Impact of COVID-19 on medical treatment patterns in gynecologic oncology: a MITO group survey

ObjectiveCOVID-19 is a global public health emergency. The increasing spread of COVID-19 presents challenges for the clinical care of patients with gynecological tumors. The Multicenter Italian Trials in Ovarian cancer...

Functional effects of chemotherapy in patients with gynecological cancer

Background: The pelvic floor is responsible for urinary, sexual and anorectal functions, but its soft tissues are negatively impacted by radiotherapy and surgery for gynecological cancers. It is not clear, however, whether chemotherapy alone is responsible for sequelae on the pelvic floor. Aims: To discuss the kineciologic-functional effects of chemotherapy in the treatment of gynecological cancers. Method: electronic review using the terms chemotherapy, women, genital, physiotherapy and their variants in portuguese, including studies that address the functional effects of radiotherapy, chemotherapy and surgery for gynecological cancers. Results: Six studies were considered eligible. The most prevalent dysfunctions were urinary incontinence, chronic pelvic pain, pelvic organ prolapse and sexual dysfunctions, especially vaginal lubrication. All three treatments for cancer were responsible for functional sequelae. Conclusion: Not only radiotherapy and surgery, but chemotherapy, even when isolated, is likely to cause kinesiological-functional sequelae on the female pelvis, and for these, pelvic physiotherapy should be the first option of treatment.

Development of a Framework and the Content for a Psychoeducational Internet-Delivered Intervention for Women after Treatment for Gynecological Cancer.

The number of women treated for gynecological cancer is increasing. At the same time, the duration of in-patient hospitalization has decreased, and follow-up with its primary focus on early recognition of recurrence does not meet all patients’ needs. One method of follow-up may be digital intervention. This study describes the development of a psychoeducational Internet-delivered intervention targeting women’s psychosocial needs during the follow-up period after treatment for gynecological cancer. The project consisted of three phases following the UK Medical Research Council Framework guidelines for the development of complex interventions. Phase one identified the evidence in the field, phase two identified the relevant theoretical framework, and phase three included a two-year work process including focus group interviews and think aloud interviews with users. Through the steps of literature review, theoretical framework, and an iterative development process with users and other stakeholders, a six-week program was developed. The program included psychoeducational information, multimedia, exercises, and weekly telephone follow-up with a dedicated nurse. This Internet-delivered intervention can be a novel method for addressing the gap in the provision of follow-up for women after treatment for gynecological cancer.

Factors associated with increased financial toxicity after the completion of radiation treatment for gynecologic cancer

<h3>Objectives:</h3> Financial toxicity is estimated to impact up to 50% of patients with gynecologic malignancies, but little is known about the factors that may predispose patients receiving radiation treatment for gynecologic cancer to increased financial distress. <h3>Methods:</h3> Patients from an urban academic gynecologic radiation oncology practice completed a financial toxicity survey at their 1-month follow-up visit after completion of radiation treatment from August 2019-March 2020. The survey was modified from our prior study and included basic demographic questions, the Comprehensive Score for Financial Toxicity (COST) tool and the EQ-5D to measure quality of life. Consistent with our prior work, high financial toxicity was defined as COST score ≤23. We assessed correlation of COST scores with QOL. Demographic and disease characteristics between high and low financial toxicity groups were compared using Chi-square or Fisher's exact test for categorical variables and Wilcoxon rank sum test for continuous variables. We used log-binomial regression to examine associations between high financial toxicity and cost-coping strategies. <h3>Results:</h3> The response rate was 88%. Of the 49 patients surveyed, 71% were White, 14% Black and 10% Asian. The majority of patients had uterine cancer (65%), followed by cervical (23%) and vaginal (8%) cancer. Two-thirds (63%) received external beam radiation with or without brachytherapy; the remaining (37%) received brachytherapy alone. Median COST score was 13 (IQR 5-19) in the high financial toxicity group (n=18) and 32 (IQR 27-36) in the low toxicity group (n=31). Greater financial toxicity was significantly correlated with worse QOL (R=-0.36, P=0.02). No demographic, disease or treatment characteristics were associated with high financial toxicity aside from employment status (p=0.03), though income was borderline significant (p=0.053). Compared with the low financial toxicity group, patients with high financial toxicity were more likely to move from full-time to part-time employment since diagnosis (22% vs 0%, p=0.01) and reported that difficulty paying for transportation or parking was a consideration in making medical decisions (33.3 vs 3.2%, p=0.01). Patients with high financial toxicity were more likely to report delaying or avoiding medical care (22% vs 0%, P=0.01), 13.8 (95% CI 1.9-101.4, P<0.001) times more likely to borrow money, and 10.3 (95% CI 1.3-79.1, p=0.01) times more likely to report reduced spending on basic goods. <h3>Conclusions:</h3> Financial toxicity correlated with worse quality of life in patients who received radiation for their gynecologic cancer diagnosis and was associated with delays or avoidance of medical care and use of economic cost-coping strategies. A larger survey cohort may improve our ability to meaningfully detect other associations with high financial toxicity. Moreover, transportation and parking costs should be considered in the design of any future intervention study in this population.

The clinical utility of the Khorana score in determining risk for venous thromboembolism in patients with gynecologic cancer

Objectives: Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in patients with gynecologic cancer. The Khorana Score (KS) is a risk stratification tool for VTE that has been validated across multiple cancer types and ASCO recommends consideration of VTE chemoprophylaxis among cancer patients with KS of 2 or above. The best KS for initiating VTE chemoprophylaxis among gynecologic oncology patients has not previously been evaluated. The purpose of this study was to evaluate the clinical utility of the KS among patients with gynecologic cancer. Methods: A retrospective review was completed of all chemotherapy-naive patients who initiated treatment for gynecologic cancer at our institution between December 2019 and December 2020. Demographic, oncologic, clinical and laboratory data was collected. KS was calculated for all patients using previously specified parameters of cancer type, pre-chemotherapy leukocyte count >11, pre-chemotherapy hemoglobin 300 and BMI >35. Patients were also assessed for history of VTE during treatment and history of inpatient admission for therapeutic anticoagulation. Multivariate logistic regression analyses were completed to assess risk factors for VTE. Results: A total of 62 patients met inclusion criteria. Median age was 64 years. The majority of patients reported White race (82%), had ovarian cancer (39%), and advanced stage disease (57%). The majority of patients had a KS of 2 or above (52%). Median KS was 2 (Range= 1-4). During treatment, 7 (11.3%) of patients were diagnosed with VTE. The majority of VTE occurred in patients with KS of 3 or above (n=4, 57%). A logistic regression was performed to evaluate associations between age, stage, race, and KS on VTE diagnosis. Increasing KS was noted to be associated with increased risk of VTE (OR 4.9, p=0.01). When using a cut-off KS of 2 or greater, no significant increase in VTE was noted. However, when using a cut-off KS of 3 or greater, patients were 15 times more likely to have VTE (OR 15.2, p=0.04). Conclusions: Previous studies have reported that cancer patients with KS of ≥ 2 are at high risk for VTE with incidence as high as 10.2% within 6 months of starting chemotherapy. Clinical practice guidelines recommend consideration of VTE chemoprophylaxis for patients with KS ≥2 who are starting chemotherapy in the outpatient setting. In our gynecologic oncology population, KS ≥2 was not associated with increased VTE risk. The most notable increase was found in those with KS ≥3. These results suggest that KS of 3 may be a more appropriate cutoff to determine risk for VTE and guide clinical management regarding VTE prophylaxis in patients with gynecologic cancer.

Integration of survivorship program into outpatient gynecologic oncology office setting

<h3>Objectives:</h3> To determine the proportion of women with a gynecologic malignancy that complete a survivorship visit when integrating the survivorship program into a routine outpatient gynecologic oncology office visit. <h3>Methods:</h3> In 2017, in an effort to improve the survivorship care for women with gynecologic malignancies, the Program in Women's Oncology at Women and Infants Hospital in Providence, RI instituted a survivorship visit for all patients one month after completion of upfront treatment. This visit took place in the outpatient clinic with the primary gynecologic oncologist present and the nurse practitioner completing the visit. Patients were then referred to subspecialities (nutrition, physical therapy, genetics, urogynecology) for consultation based on needs identified during their survivorship review. We performed a retrospective review of patients completing upfront treatment for gynecologic cancers at our institution. Eligible patients had uterine, ovarian, cervical, or vulvar cancer, and completed treatment with surgery, chemotherapy, radiation, or a combination of these modalities. Records were reviewed to ascertain percentage of patients referred for survivorship visit and the number of patients completing the visit. In addition, we collected information on cancer type and stage, treatment, age, race, and ethnicity. <h3>Results:</h3> 1072 patients with new diagnoses of primary gynecologic cancers were treated between 2017 and 2019 at Women and Infants Hospital. Of these, 30% of patients were referred for survivorship visit. Patients with ovarian cancer had the highest rate of referral for survivorship visit with 51% referred, while patients with vulvar cancer had the lowest rates of referral with 10% referred. 9% of all patients self-identified as race other than White, and of these, 32% were referred for survivorship visit, compared to 30% of patients identifying as White. During the study period, there was an increase in proportion of referrals across all gynecologic cancers from 16% to 39%. <h3>Conclusions:</h3> Survivorship review can be integrated into primary gynecologic oncology office setting to streamline care for patients completing upfront therapy. Further analysis evaluating the impact of stage and specific modality of therapy is warranted to clarify barriers that affect emphasis on transition to survivorship in patients with gynecologic cancers.

The impact of the SARS-COV2 pandemic on the delivery of chemotherapy for gynecologic cancer at a tertiary care institution in the United States epicenter

Objectives:In New York City, the SARS-CoV2 pandemic epicenter of the United States, the surge of cases predated much of the country by several weeks, leading to changes in practice patterns that have informed decisions made by other medical institutions. As the SARS-CoV2 pandemic unfolded, many professional subspecialty organizations released practice guidelines in order to minimize transmission of COVID-19 and protect vulnerable populations. The impact of modifications to traditional gynecologic cancer treatment is not known. Here, we describe the impact of the SARS-COV2 pandemic on chemotherapy practices for gynecologic cancer during the pandemic surge.Methods:We identified patients age 18 or older at Montefiore Medical Center who had a confirmed or suspected diagnosis of gynecologic cancer and received care between March 16, 2020 and June 7, 2020; these dates reflect a series of executive orders issued by the Governor of New York allowing the State Commissioner of Health to cancel elective procedures at hospitals and ambulatory surgery centers. Clinical data were abstracted from patients’ charts. Patients with incomplete treatment records were excluded.Results:A total of 146 women who were included to whom 169 cycles of cytotoxic chemotherapy were delivered during the study period and 68 women (46.6%) received at least one cycle of chemotherapy. Nine patients screened positive for symptoms of COVID or active infection during the study period. Among patients receiving chemotherapy, 52.9% (n=36) had modifications to traditional cancer treatment as a result of state and institutional regulations. Dose reduction was the leading pandemic-related treatment modification and occurred in 69.4% of patients (n=25). Other treatment modifications included prophylactic use of pegfilgrastim (n=1), and treatment deferral or delay (n=7). Women receiving a platinum-based doublet (n=36) during the study period were more likely to sustain dose reduction in chemotherapy (25%) compared to patients undergoing other regimens (0%). A total of 111 women received at least one dose of disease-modifying therapy during the cohort period including chemotherapy, immunotherapy, anti-angiogenesis agents, hormonal therapy, PARP inhibitors, or investigational agents. Treatments were most often discontinued due to completion of adjuvant therapy (n=5), progression of disease (n=4), or toxicity (n=5). Notably 5 patients chose to defer therapy in the setting of the pandemic surge. Only one patient was identified as receiving neoadjuvant chemotherapy specifically due to COVID pandemic-related restrictions.Conclusions:The SARS-COV2 pandemic has led to modification of current standard chemotherapy delivery for gynecologic malignancies with the shared goal of protecting the most vulnerable populations from COVID infection. The impact of these modifications on cancer specific outcomes is not yet known. Future investigation will focus on identifying whether treatment modification to circumvent iatrogenic immunosuppression compromises oncologic outcomes.

Gynecologic cancer treatment toxicities and relationships with the vaginal microbiome

<h3>Objectives:</h3> Gynecologic cancer survivors may live for decades with clinically significant, often persistent symptoms/toxicities including pain, dyspareunia, sexual dysfunction and fatigue. The vaginal microbiome (VM) plays a crucial role in women's health and has been previously associated with vaginal symptoms related to menopause (ie dryness). Our previous work showed that gynecologic cancer patients exhibit distinct VM profiles from healthy women with low abundance of lactobacilli and prevalence of multiple opportunistic pathogenic bacteria. Here we explore the association of the vaginal microbiome with the persistence of vaginal toxicities, one year upon completion of cancer therapies while controlling for clinical and sociodemographic factors. <h3>Methods:</h3> We studied 20 women that received pelvic radiation therapy in parallel with a group of 27 age and race matched healthy women. We obtained VM data during 4 sampling times (pre-therapy, after 2, 6, and 12 months post-therapy) by amplicon 16S rRNA gene sequencing. For each sampling we recorded vaginal toxicities as measured by clinician/patient-reported validated instruments, including PRO-CTCAE, CTCAE, and FSFI, as well as lifestyle behaviors (use of estrogen, sexual activity, etc). <h3>Results:</h3> We observed differences among the VM profiles of cancer and healthy women at all time points assessed, but differences were further exacerbated with the progression of time. Cancer patients exhibit higher diversity VMs and a variety of vaginal community state types (CST) that are not dominated by <i>Lactobacilli,</i> with extensive VM variation -between individuals. Additionally, cancer patients exhibit highly unstable VMs (average Bray-Curtis distances) compared to healthy controls (Kruskal-Wallis, p=0.004). Vaginal symptoms prevalent in cancer patients included vaginal pain (40%), hemorrhage (35%), vaginismus (28%), and inflammation (20%), while symptoms such as dryness (45%), lack of lubrication (33%), and dyspareunia (32%) were equally or more prominent in healthy women. However, among the symptomatic subjects, 24% of cancer patients experienced persistent symptoms at all time points, as opposed to 12% of healthy women. Symptom persistence was strongly inversely correlated with VM stability, for example, patients with persistent dryness and/or abnormally high pH have the most unstable microbiomes (Fisher's exact test, p=0.014 and 0.002). Associations were identified between vaginal symptoms and individual bacterial taxa, including <i>Prevotella</i> with vaginal dryness (p=0.0004), <i>Delftia</i> with pain following vaginal intercourse (p=0.0006), and <i>Gemillaceaea</i> with low levels of lubrication during intercourse (p=0.0002). <h3>Conclusions:</h3> Differences in the VM among healthy and gynecologic cancer patients are more prominent a year after completion of cancer therapies, including enrichment of opportunistic bacterial pathogens. Highly unstable microbiomes are typical in cancer patients and were associated with symptom persistence which warrants further attention.

Impact of education on the expanding treatment armamentarium in gynecologic cancers for oncologists

<h3>Objectives:</h3> Chemotherapy was a mainstay of advanced gynecologic cancer treatment but recently, novel therapies are offering expanded treatment options for patients with cervical (CC) and endometrial (EC) cancers. As the treatment paradigm evolves and becomes increasingly nuanced, oncologists, including gynecologic oncologists, can benefit from continuing medical education (CME) to offer their patients the most optimal care. <h3>Methods:</h3> Two CME-certified activities were launched to educate oncologists with one developed in partnership with the Society for Immunotherapy of Cancer. Effectiveness was analyzed using 3 multiple-choice questions measuring knowledge and competence and 1 self-efficacy question measuring confidence, presented as pre/post-CME repeated pairs for each of the activities. Oncologists who completed both the pre- and post-CME questions were included in the analysis and McNemar's tests were conducted to assess statistical significance of the results with p<.05 being considered significant for knowledge and competence. A 2-tailed paired t-test was used to analyze confidence and determine p-values. The CME activities launched from 12/14/19 and data are collected and reported as of 10/2/2020. <h3>Results:</h3> As of 10/2/20, 4833 learners participated in the activities, including 760 oncologists. Those who answered all of the assessment questions within the study period were included in the analyses. Analyses from the activities found significant improvements in knowledge and competence measured as relative changes in % of correct responses from pre- to post-CME for all oncologists (n=85-276) and those in the community setting (n=55-197) as indicated in sub-bullets: <ul><li>•Knowledge regarding biomarkers for immunotherapy use in EC and CC (19% pre, 34% post, p<.01) <li>○Community practitioners: 22% pre, 38% post, p<.05</li></li><li>•Knowledge regarding clinical trial data in CC (55% pre, 67% post, p<.001) <li>○Community practitioners: 58% pre, 72% post, p<.001</li></li><li>•Knowledge regarding clinical trial data in EC (45% pre, 59% post, p<.001) <li>○Community practitioners: 47% pre, 62% post, p<.001</li></li><li>•Knowledge regarding current treatment of EC and CC (24% pre, 36% post, p<.01) <li>○Community practitioners: 25% pre, 37% post, p<.05</li></li><li>•Competence regarding selection of immunotherapy for patients with EC and CC (42% pre, 51% post, p<.05).</li></ul>Additionally, the activities found significant improvement in confidence represented as % confidence shifts pre- to post-CME for allcomers (n=85-276) and those in the community setting (n=55-197) as indicated in sub-bullets: <ul><li>•Confidence optimizing immunotherapy in EC and CC (D 23%, p<.001) <li>○Community practitioners: 20% D (p<.001)</li></li><li>•Confidence regarding potential impact of novel agents and clinical trial data in EC and CC (25% D, p<.001) <li>○Community practitioners: 27% D (p<.001)</li></li></ul> <h3>Conclusions:</h3> These 2 online, CME-certified educational activities resulted in statistically significant gains in oncologist knowledge, competence, and confidence surrounding emerging treatment paradigms in EC and CC. These results demonstrate the effectiveness of on-demand and timely education as new data emerge and indications expand to reinforce existing knowledge, close persistent gaps, and increase confidence in managing these patients.

Sexual and Psychosexual Consequences of Treatment for Gynaecological Cancers

Modern multimodality cancer treatment has led to a rise in cancer survivors, and by 2030 the survival rate is estimated to increase by 31.4%. This is an impressive survival statistic on which clinicians and services continue to build. One of the less well-acknowledged consequences of survivorship among health professionals and patients alike is female sexual dysfunction, despite it occurring in more than 60% of women diagnosed with cancer. The systematic assessment and management of late effects from cancer lack integration within current models of oncology follow-up. Although highly prevalent, issues linked to sexual health are often not addressed among survivors. This overview aims to focus on the sexual impact of gynaecological cancer treatment. Clinicians should raise the topic of the sexual consequences of cancer treatment as a legitimate aspect of survivorship and service provision. Increased focus on the sexual consequences of treatment and cancer survivorship may in time lead to greater clinical recognition, service development and, most importantly, increase research focused on the effective management of what remains a neglected aspect of cancer care.

Stress Hormones: Emerging Targets in Gynecological Cancers.

In the past decade, several discoveries have documented the existence of innervation in ovarian cancer and cervical cancer. Notably, various neurotransmitters released by the activation of the sympathetic nervous system can promote the proliferation and metastasis of tumor cells and regulate immune cells in the tumor microenvironment. Therefore, a better understanding of the mechanisms involving neurotransmitters in the occurrence and development of gynecological cancers will be beneficial for exploring the feasibility of using inexpensive β-blockers and dopamine agonists in the clinical treatment of gynecological cancers. Additionally, this article provides some new insights into targeting tumor innervation and neurotransmitters in the tumor microenvironment.

Abstract 899: Sexual dysfunction among gynecologic cancer survivors in a population-based cohort study

Abstract Background: Treatment for gynecologic cancer is associated with side effects including sexual dysfunction, that present during and after treatment, and can be long lasting. The aim of this study was to investigate the frequency and the risk of sexual dysfunction among gynecologic cancer survivors compared to cancer-free women in a population-based cohort study. Methods: We identified a cohort of 4,889 endometrial, ovarian and cervical cancer survivors diagnosed between 1997-2012 in the Utah Cancer Registry. Up to five cancer-free women were matched to cancer survivors on birth year and birth state from the Utah Population Database (N=22,809). We used ICD-9 codes to identify sexual dysfunction including dyspareunia, vaginal dryness/atrophic vaginitis, decreased libido, and lack of arousal/orgasm. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for sexual dysfunction with adjustment for potential confounders, including race/ethnicity, baseline body mass index (BMI), and baseline Charlson Comorbidity Index (CCI). Results: Gynecologic cancer survivors had higher risks of sexual dysfunction (HR: 2.52, 95% CI: 2.16, 2.93) compared to a general population of women 1-5 years after cancer diagnosis. Sexual dysfunction was associated with advance cancer stage (HRRegional vs. Localized: 1.59, 95% CI:1.19, 2.12), radiation therapy (HR: 1.65, 95% CI: 1.26, 2.16), and chemotherapy (HR: 1.53, 95% CI: 1.17, 2.01). Conclusions: Although this large cohort study confirms an increased risk of sexual dysfunction among gynecologic cancer survivors, the proportion of cases documented with diagnosis codes was lower than those commonly reported by gynecologic cancer survivors (6% vs. 10-85%). Further investigation into this discrepancy is important in improving survivorship issues for gynecological cancer patients. Sexual dysfunction among gynecologic cancer survivors and women from the general population**Gynecologic cancer survivorsOvarian cancer survivorsEndometrial cancer survivorsCervical cancer survivorsHR (95% CI)bHR (95% CI)bHR (95% CI)bHR (95% CI)bSexual dysfunctiona2.52 (2.16, 2.93)*2.76 (2.02, 3.76)*2.35 (1.88, 2.92)2.62 (1.83, 3.74)*Dyspareunia3.25 (2.62, 4.04)*3.20 (2.10, 4.88)*3.03 (2.16, 4.24)3.24 (2.04, 5.14)*Vaginal Dryness/Atrophic Vaginitis2.62 (2.21, 3.11)*3.43 (2.26, 5.22)2.49 (2.00, 3.09)*2.90 (1.77, 4.76)Abbreviation: HR, hazard ratio; CI, confidence interval. a. Sexual dysfunction included dyspareunia, vaginal dryness/atrophic vaginitis, decreased libido, lack of arousal/orgasm. b. Models adjusted for matching factors (birth year and birth state), race/ethnicity, baseline body mass index, baseline Charlson Comorbidity Index.*Proportional hazards assumption not met; flexible model was used.**1 to 5 years after cancer diagnosis Citation Format: Chun-Pin Chang, Christina M. Wilson, Kerry Rowe, John Snyder, Mark Dodson, Vikrant Deshmukh, Michael Newman, Alison Fraser, Ken Smith, Ankita Date, Joseph B. Stanford, David Gaffney, Kathi Mooney, Mia Hashibe. Sexual dysfunction among gynecologic cancer survivors in a population-based cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 899.

Chemotherapy-induced neurotoxicity in the treatment of gynecological cancers: State of art and an innovative approach for prevention.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect that occurs in 20% of ovarian cancer patients treated with the combination of carboplatin/paclitaxel (CP). This toxicity is directly correlated with the dose of paclitaxel administered. Several studies have investigated whether different formulations of taxane can induce this side effect at a lower rate, but, unfortunately, no significant improvement was obtained. CIPN can be disabling in the daily lives of patients and can cause dose reduction or early termination of the treatment. Neuropathy can last for months and even years after its onset. Moreover, patients responsive to CP treatment are candidates for a reintroduction of the same drugs when disease relapse occurs, and residual neuropathy can affect the continuation of treatment. There are no approved drugs that mitigate or prevent the onset of CIPN. In this review, we summarize the evidence regarding the incidence of CIPN with different taxane formulations, regimen schedules and prevention systems. In particular, the Hilotherm® Chemo care device is a regional cooling system that lowers the temperature of the hands and feet to reduce the flow of chemotherapy into the capillaries. We used hilotherapy during chemotherapy infusion to prevent the onset of CIPN. Updated data from 44 ovarian cancer patients treated with 6 cycle of CP show that hilotherapy was well tolerated; only two patients (4.5%) stopped hilotherapy because of cold intolerance, and only one patient (2.2%) experienced grade ≥ 2 CIPN.

Importance of guidelines and networking for the management of rare gynecological cancers.

Guidelines are essential to support appropriate medical management. The objective of our paper is to highlight the need for such recommendations, to reinforce strategies in place and to promote the creation of multidisciplinary networks to provide the most appropriate care to patients and to improve it. Gynecological rare cancers are not that rare since they represent around 50% of all gynecological cancers. Surgery remains the cornerstone of management for all subtypes. Apart from malignant ovarian germ-cell tumors for which conventional chemotherapy was proven to be efficient, response to standard systemic treatment for other gynecological cancers are disappointing. Better understanding of these pathologies is needed and requires more adapted management. Rare cancers are substantially heterogeneous but raise the need of integrating new cases in dedicated networks to enhance and homogenize medical practices. Centralized diagnosis, improved medical practice based on regularly updated international guidelines, and inclusion in innovative clinical trials linked to preclinical studies are essential to contribute to the promotion of improvement in patient care.

Association between Ultra-Processed Food Consumption and Excess of Weight in Women with Endometrial Cancer

Obesity is one of major risk factor for endometrial cancer, which is the eighth most incident cancer among women in Brazil. The present study aimed to assess any possible associations between ultra-processed food (UPF) consumption and clinical or sociodemographic characteristics of women diagnosed with endometrial cancer. This is a cross-sectional study with women newly diagnosed with endometrial cancer (EC). The study was conducted between December 2016 and January 2020, at a reference center for gynecological cancer treatment. The nutritional status was assessed by measuring anthropometric parameters and food consumption by the food frequency questionnaire. Multiple logistic regression was performed for the dependent variables overweight and obesity. The analyses were considered statistically significant when p < 0,05. The study population consisted of 318 women, with a mean age of 59.1 ± 6.9 years. The average daily energy intake was 2365.13 kcal/day, with 70.48% of energy consumption from fresh or minimally processed foods and 16.95% from UPF. Women above the highest tertile of UPF intake (19.27%) were more likely to be obese (OR: 1.95; 95% CI: 1.12; 3.41, p < 0.01). Having a partner and systemic arterial hypertension was associated with the outcome. The high intake of UPF was associated with obesity, which indicates the need for nutritional intervention in this population.

Recommendations for Physiotherapy in Breast and Gynecological Cancer during COVID-19 Pandemic: Literature Review

Introduction: Considering COVID-19 pandemic, physiotherapeutic care for breast and gynecological cancer has the challenge of continuing or beginning the treatment, preventing or treating complications. Objective: To offer guidance about physiotherapy for breast and gynecological cancer during and after the COVID-19 pandemic. Method: Descriptive study produced after a public consultation about the theme and based on literature review and opinions of a group of experts. To classify the strength of the recommendations of the outcomes included, the GRADE system was used. Results: 82 Brazilian physiotherapists responded the online survey. Most of the professionals (36.6%) reported they needed information about the use of personal protective equipment and its hygiene, 18.3%, control and prevention of lymphedema, bandaging and skin care and 17.1%, pelvic floor dysfunction. The analysis of the public consultation, literature review and expert’s consensus resulted in recommendations related to the impact of the COVID-19 pandemic over the care to women undergoing breast or gynecological cancer treatment and on physiotherapy follow-up; on telephysiotherapy follow-up of the most prevalent complications; on women in palliative care and safety after resuming in-person consultation. Aspects of the decision making in relation to the format of the sessions were discussed and the criteria to return to in-person routine. Conclusion: This manuscript recommends the continuation of the physiotherapy services during and after the COVID-19 pandemic highlighting the educative and self-applied components of the sessions, prioritizing a physical activity plan and specific exercises to contribute for better quality of life of the women.

Management of Long-Term Toxicity From Pelvic Radiation Therapy.

Pelvic radiation therapy is an integral component in the treatment of various gastrointestinal, gynecologic, and genitourinary cancers. As survival rates from these malignancies improve, the prevalence of toxicity secondary to pelvic radiation has increased. Gastrointestinal toxicities are the most common complications and greatly impact quality of life. Toxicities can present in acute or late stages; although symptoms may be similar during both, the management may differ. Acute toxicities represent an inflammatory reaction in response to the radiation exposure, whereas late toxicities may arise as a result of small vessel disease, ischemia, and fibrosis. Currently, there are no large clinical trials and only limited guidelines on the management of late gastrointestinal radiation toxicities. Therapy is generally approached in a stepwise manner from medical to endoscopic to surgical methods. Several endoscopic therapies, such as the treatment of radiation proctitis with argon plasma coagulation and dilation of radiation bowel strictures, may prevent the need for surgical intervention, which may be associated with high morbidity and mortality. Given that late toxicities can occur years after radiation therapy, they are often difficult to recognize and diagnose. Successful management of late toxicities requires recognition, an understanding of the underlying pathophysiology, and a multidisciplinary approach. More dedicated research could clarify the prevalence of gastrointestinal pelvic radiation toxicities, permit a better understanding of the efficacy and safety profile of current therapies, and allow for the development of novel therapeutic approaches.

Molecular and Cellular Mechanisms of Metformin in Cervical Cancer.

Simple SummaryThe potential effects of metformin in terms of cancer prevention and therapy have been widely studied, and a number of studies have indicated its potential role in cancer treatment. Metformin exerts anticancer effects, alone or in combination with other agents, on cervical cancer in vitro and in vivo. Metformin might thus serve as an adjunct therapeutic agent for cervical cancer.Cervical cancer is one of the major gynecologic malignancies worldwide. Treatment options include chemotherapy, surgical resection, radiotherapy, or a combination of these treatments; however, relapse and recurrence may occur, and the outcome may not be favorable. Metformin is an established, safe, well-tolerated drug used in the treatment of type 2 diabetes; it can be safely combined with other antidiabetic agents. Diabetes, possibly associated with an increased site-specific cancer risk, may relate to the progression or initiation of specific types of cancer. The potential effects of metformin in terms of cancer prevention and therapy have been widely studied, and a number of studies have indicated its potential role in cancer treatment. The most frequently proposed mechanism underlying the diabetes–cancer association is insulin resistance, which leads to secondary hyperinsulinemia; furthermore, insulin may exert mitogenic effects through the insulin-like growth factor 1 (IGF-1) receptor, and hyperglycemia may worsen carcinogenesis through the induction of oxidative stress. Evidence has suggested clinical benefits of metformin in the treatment of gynecologic cancers. Combining current anticancer drugs with metformin may increase their efficacy and diminish adverse drug reactions. Accumulating evidence is indicating that metformin exerts anticancer effects alone or in combination with other agents in cervical cancer in vitro and in vivo. Metformin might thus serve as an adjunct therapeutic agent for cervical cancer. Here, we reviewed the potential anticancer effects of metformin against cervical cancer and discussed possible underlying mechanisms.

Far Infrared Radiation Therapy for Gynecological Cancer-Related Lymphedema Is an Effective and Oncologically Safe Treatment: A Randomized-Controlled Trial.

Background: Gynecological cancer-related lymphedema (GCRL) is a devastating condition that adversely influences function, health, and quality of life. We conducted a randomized-controlled clinical study as well as in vitro experiments to investigate the efficacy and safety of far infrared radiation (FIR) to treat lymphedema in patients having previously undergone surgery for gynecological tumors. Materials and Methods: Seventy-four women with GCRL, cancer free for 5 years or more, were randomly allocated into two treatment groups: standard of care with bandage treatment and treatment with FIR plus bandage. Variations of fluid, circumference of lymphedematous limbs, serum tumor markers (cancer antigen 125 [CA125]), inguinal-pelvic lymph nodes, vagina, lungs, and adverse reactions were assessed after 1 year. In vitro experiments examined the effects on cell viability, proliferation, apoptosis, and the cell cycle of fibroblast, A2780, SKOV-3, HELA, and Ishikawa cells. Results: The FIR+bandage group showed significantly decreased tissue fluid and reduced limb circumference (p < 0.05) in comparison with the control group at 1 year. There was no increase of serum CA125 in both groups, and no recurrence of neoplasia or lymphadenopathy was detected. No adverse reactions were recorded. In addition, no changes were detected after FIR treatment for fibroblast, A2780, SKOV-3, HELA, and Ishikawa cells in cell viability, proliferation, apoptosis, and cell cycle. Conclusion: FIR can be used to treat patients with GCRL following gynecological cancer treatment. Following clinical and experimental studies, we confirm that FIR is an oncologically safe treatment for lymphedema in gynecological tumor patients.