Safety of Fezolinetant for Vasomotor Symptoms Associated With Menopause: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the safety, tolerability, and effect of fezolinetant on endometrial health over 52 weeks. METHODS: We conducted a phase 3, randomized, double-blind, 52-week safety study (SKYLIGHT 4 [Study to Find Out How Safe Long-term Treatment With Fezolinetant is in Women With Hot Flashes Going Through Menopause]) of placebo, fezolinetant 30 mg, and fezolinetant 45 mg once daily (1:1:1). Participants were postmenopausal and seeking treatment for vasomotor symptoms associated with menopause. Primary endpoints were treatment-emergent adverse events, percentage of participants with endometrial hyperplasia, and percentage with endometrial malignancy. Endometrial hyperplasia or malignancy was evaluated according to U.S. Food and Drug Administration guidance (point estimate of 1% or less with an upper bound of one-sided 95% CI of 4% or less). Secondary endpoints included change in bone mineral density (BMD) and trabecular bone score. A sample size of 1,740 was calculated to enable observation of one or more events (≈80% probability for events with background rate of less than 1%). RESULTS: A total of 1,830 participants were randomized and took one or more medication dose (July 2019-January 2022). Treatment-emergent adverse events occurred in 64.1% (391/610) of the placebo group, 67.9% (415/611) of the fezolinetant 30-mg group, and 63.9% (389/609) of the fezolinetant 45-mg group. Treatment-emergent adverse events leading to discontinuation were similar across groups (placebo, 26/610 [4.3%]; fezolinetant 30 mg, 34/611 [5.6%]; fezolinetant 45 mg, 28/609 [4.6%]). Endometrial safety was assessed in 599 participants. In the fezolinetant 45-mg group, 1 of 203 participants had endometrial hyperplasia (0.5%; upper limit of one-sided 95% CI 2.3%); there were no cases in the placebo (0/186) or fezolinetant 30 mg (0/210) group. Endometrial malignancy occurred in 1 of 210 in the fezolinetant 30-mg group (0.5%; 95% CI 2.2%) with no cases in the other groups. Liver enzyme elevations more than three times the upper limit of normal occurred in 6 of 583 placebo, 8 of 590 fezolinetant 30 mg, and 12 of 589 fezolinetant 45 mg participants; no Hy's law cases were reported (ie, no severe drug-induced liver injury with alanine aminotransferase or aspartate aminotransferase more than three times the upper limit of normal and total bilirubin more than two times the upper limit of normal, with no elevation of alkaline phosphatase and no other reason to explain the combination). Changes in BMD and trabecular bone score were similar across groups. CONCLUSION: Results from SKYLIGHT 4 confirm the 52-week safety and tolerability of fezolinetant and support its continued development. FUNDING SOURCE: Astellas Pharma Inc. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT04003389.

Radical abdomino-pelvic surgery in the management of uterine carcinosarcoma with concomitant para-aortic lymphadenopathy metastasising from anal carcinoma.

Uterine carcinosarcomas are aggressive gynaecological cancers comprising less than 5% of uterine malignancies. We present the case of a woman in her 70s with a complicated history of advanced anal carcinoma treated with pelvic radiotherapy and multiple laparotomies, who was referred to gynae-oncology following MRI surveillance imaging showing evidence of endometrial carcinoma and para-aortic lymphadenopathy. Successful surgical excision required multidisciplinary teamwork between gynae-oncology, colorectal and urology surgeons. The patient underwent midline laparotomy, with adhesiolysis, ileum resection and side to side anastomosis, posterior exenteration, left kidney mobilisation and suspension, para-aortic lymph node debulking and left ureteric stent insertion. Significant challenge was posed by the extensive adhesions from previous laparotomies and the debulking of the para-aortic lymph nodes around the renal vessels. This case demonstrates the importance of a multidisciplinary approach in complex pelvic surgery and the vitality of good communication between colleagues in achieving effective patient care.

Is advanced bipolar v anced bipolar vessel sealing de essel sealing device really eff eally effective in decreasing the pelvic lymphocele ratio in open surgery for endometrial cancer?

BACKGROUND: We aim to show pelvic lymphocele (PL) rates in patients who were operated for endometrial cancer (EC) and underwent systematic paraaortic bilateral pelvic lymph node dissection (PABPLND) with advanced bipolar vessel sealing device (ABVSD). METHODS: The medical files of all patients who underwent open surgery for EC between January 2017 and December 2021 were retrospectively analyzed. One hundred three patients who operated with the diagnosis of high-intermediate and high-risk endometrial cancer were included. Systematic PABPLND was performed with total abdominal hysterectomy with or without bilateral salpingo-oophorectomy during surgery to all patients. All operations were performed by same three surgeons who were expert in their field. While the lymph packages were removed during surgical dissection, the distal afferent and proximal efferent lymphatic channels were sealed with LigaSure™ blunt tip sealer/divider (Medtronic, Covidien, USA). The patients were scanned with computed tomography (CT) between 8 and 12 weeks postoperatively. Lymphocele diagnosis was confirmed by radiologists and largest diameter was recorded. Clinical-pathological findings of all patients were recorded. RESULTS: Mean age and body mass index (BMI) of all participants were 58.6 ±10.2 years and 28.1± 5.6 kg/m2 . The most histopathological findings were endometrioid type (84.5%) and grade 2 (44.2%) ECs. The pelvic lymphocele (PL) was detected with CT in 24 of 103 patients at 8 to 12 weeks postoperatively. Only two PL patients were symptomatic. The first patient had symptoms of pelvic fullness and compression while the second patient had infected image. PL was located to right pelvic area in first case while the second was located on the vaginal cuff. DISCUSSION: The dissection and sealing of major lymph vessels were achieved during the removal of all lymph packages with LigaSure™ blunt tip laparoscopic sealer/divider. The use of advanced bipolar systems can reduce the formation of PL in lymph node dissection in endometrial cancer.

Prehabilitation in an ERAS program for endometrial cancer patients: impact on post-operative recovery.

OBJECTIVES: Enhanced recovery after surgery (ERAS) and prehabilitation programs are multidisciplinary care pathways that aim to reduce stress response and improve perioperative outcomes. However, literature is limited regarding the impact of ERAS and prehabilitation in gynecologic oncology surgery. The aim of this study was to assess the impact of implementing an ERAS and prehabilitation program on post-operative outcomes of endometrial cancer patients undergoing laparoscopic surgery. METHODS: We evaluated consecutive patients undergoing laparoscopy for endometrial cancer that followed ERAS and the prehabilitation program at a single center. A pre-intervention cohort that followed the ERAS program alone was identified. The primary outcome was length of stay, and secondary outcomes were normal oral diet restart, post-operative complications and readmissions. RESULTS: A total of 128 patients were included: 60 patients in the ERAS group and 68 patients in the prehabilitation group. The prehabilitation group had a shorter length of hospital stay of 1 day (p<0.001) and earlier normal oral diet restart of 3.6 hours (p=0.005) in comparison with the ERAS group. The rate of post-operative complications (5% in the ERAS group and 7.4% in the prehabilitation group, p=0.58) and readmissions (1.7% in the ERAS group and 2.9% in the prehabilitation group, p=0.63) were similar between groups. CONCLUSIONS: The integration of ERAS and a prehabilitation program in endometrial cancer patients undergoing laparoscopy significantly reduced hospital stay and time to first oral diet as compared with ERAS alone, without increasing overall complications or the readmissions rate.

Interventions for weight reduction in obesity to improve survival in women with endometrial cancer.

BACKGROUND: This is an updated version of the original Cochrane Review published in Issue 2, 2018. Diagnoses of endometrial cancer are increasing secondary to the rising prevalence of obesity. Obesity plays an important role in promoting the development of endometrial cancer, by inducing a state of unopposed oestrogen excess, insulin resistance and inflammation. It also affects treatment, increasing the risk of surgical complications and the complexity of radiotherapy planning, and may additionally impact on subsequent survival. Weight-loss interventions have been associated with improvements in breast and colorectal cancer-specific survival, as well as a reduction in the risk of cardiovascular disease, which is a frequent cause of death in endometrial cancer survivors. OBJECTIVES: To evaluate the benefits and harm of weight-loss interventions, in addition to standard management, on overall survival and the frequency of adverse events in women with endometrial cancer who are overweight or obese compared with any other intervention, usual care, or placebo. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was from January 2018 to June 2022 (original review searched from inception to January 2018). SELECTION CRITERIA: We included randomised controlled trials (RCTs) of interventions to facilitate weight loss in women with endometrial cancer who are overweight or obese undergoing treatment for, or previously treated for, endometrial cancer compared with any other intervention, usual care, or placebo.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. overall survival and 2. frequency of adverse events. Our secondary outcomes were 3. recurrence-free survival, 4. cancer-specific survival, 5. weight loss, 6. cardiovascular and metabolic event frequency and 7. quality of Life. We used GRADE to assess certainty of evidence. We contacted study authors to obtain missing data, including details of any adverse events. MAIN RESULTS: We identified nine new RCTs and combined these with the three RCTs identified in the original review. Seven studies are ongoing.  The 12 RCTs randomised 610 women with endometrial cancer who were overweight or obese. All studies compared combined behavioural and lifestyle interventions designed to facilitate weight loss through dietary modification and increased physical activity with usual care. Included RCTs were of low or very low quality, due to high risk of bias by failing to blind participants, personnel and outcome assessors, and significant loss to follow-up (withdrawal rate up to 28% and missing data up to 65%, largely due to the effects of the COVID-19 pandemic). Importantly, the short duration of follow-up limits the directness of the evidence in evaluating the impact of these interventions on any of the survival and other longer-term outcomes.  Combined behaviour and lifestyle interventions were not associated with improved overall survival compared with usual care at 24 months (risk ratio (RR) mortality, 0.23, 95% confidence interval (CI) 0.01 to 4.55, P = 0.34; 1 RCT, 37 participants; very low-certainty evidence). There was no evidence that such interventions were associated with improvements in cancer-specific survival or cardiovascular event frequency as the studies reported no cancer-related deaths, myocardial infarctions or strokes, and there was only one episode of congestive heart failure at six months (RR 3.47, 95% CI 0.15 to 82.21; P = 0.44, 5 RCTs, 211 participants; low-certainty evidence). Only one RCT reported recurrence-free survival; however, there were no events. Combined behaviour and lifestyle interventions were not associated with significant weight loss at either six or 12 months compared with usual care (at six months: mean difference (MD) -1.39 kg, 95% CI -4.04 to 1.26; P = 0.30, I2 = 32%; 5 RCTs, 209 participants; low-certainty evidence). Combined behaviour and lifestyle interventions were not associated with increased quality of life, when measured using 12-item Short Form (SF-12) Physical Health questionnaire, SF-12 Mental Health questionnaire, Cancer-Related Body Image Scale, Patient Health Questionnaire 9-Item Version or Functional Assessment of Cancer Therapy - General (FACT-G) at 12 months when compared with usual care (FACT-G: MD 2.77, 95% CI -0.65 to 6.20; P = 0.11, I2 = 0%; 2 RCTs, 89 participants; very low-certainty evidence). The trials reported no serious adverse events related to weight loss interventions, for example hospitalisation or deaths. It is uncertain whether lifestyle and behavioural interventions were associated with a higher or lower risk of musculoskeletal symptoms (RR 19.03, 95% CI 1.17 to 310.52; P = 0.04; 8 RCTs, 315 participants; very low-certainty evidence; note: 7 studies reported musculoskeletal symptoms but recorded 0 events in both groups. Thus, the RR and CIs were calculated from 1 study rather than 8).  AUTHORS' CONCLUSIONS: The inclusion of new relevant studies has not changed the conclusions of this review. There is currently insufficient high-quality evidence to determine the effect of combined lifestyle and behavioural interventions on survival, quality of life or significant weight loss in women with a history of endometrial cancer who are overweight or obese compared to those receiving usual care. The limited evidence suggests that there is little or no serious or life-threatening adverse effects due to these interventions, and it is uncertain if musculoskeletal problems were increased, as only one out of eight studies reporting this outcome had any events. Our conclusion is based on low- and very low-certainty evidence from a small number of trials and few women. Therefore, we have very little confidence in the evidence: the true effect of weight-loss interventions in women with endometrial cancer and obesity is currently unknown. Further methodologically rigorous, adequately powered RCTs are required with follow-up of five to 10 years of duration. These should focus on the effects of varying dietary modification regimens, and pharmacological treatments associated with weight loss and bariatric surgery on survival, quality of life, weight loss and adverse events.

Risk Stratified Follow-Up for Endometrial Cancer: The Clinicians' Perspective.

Risk-stratified follow-up for endometrial cancer (EC) is being introduced in many cancer centres; however, there appears to be diversity in the structure and availability of schemes across the UK. This study aimed to investigate clinicians' and clinical specialist nurses' (CNS) experiences of follow-up schemes for EC, including patient-initiated follow-up (PIFU), telephone follow-up (TFU) and clinician-led hospital follow-up (HFU). A mixed-methods study was conducted, consisting of an online questionnaire to CNSs, an audience survey of participants attending a national "Personalising Endometrial Cancer Follow-up" educational meeting, and qualitative semi-structured telephone interviews with clinicians involved in the follow-up of EC. Thematic analysis identified three main themes to describe clinicians' views: appropriate patient selection; changing from HFU to PIFU schemes; and the future of EC follow-up schemes. Many participants reported that the COVID-19 pandemic impacted EC follow-up by accelerating the transition to PIFU/TFU. Overall, there was increasing support for non-HFU schemes for patients who have completed primary treatment of EC; however, barriers were identified for non-English-speaking patients and those who had communication challenges. Given the good long-term outcome associated with EC, greater focus is needed to develop resources to support patients post-treatment and individualise follow-up according to patients' personal needs and preferences.

Comprehensive Bioinformatics analysis of angiotensin-converting enzyme 2 (ACE2) (preprint)

ACE2, a member of the angiotensin converting enzyme family, plays an irreplaceable role in the renin-angiotensin system. And the variations of ACE2 are regarded as the key factor to human diseases such as the novel coronavirus pneumonia, cardiovascular disease, and tumors. Here, we summarized the mutation, expression, modification and function of the human ACE2 based on comprehensive bioinformatics analysis. Especially, the relationship between ACE2 expression and diseases, especially tumor was further discussed. ACE2 is highly conserved in different genera and families. We explored the correlation between ACE2 and disease based on the datasets of GCBI and GEO (Gene expression omnibus), and found the expression of ACE2 is related to heart failure. High prevalence of ACE2 mutations is observed in diffuse large B-cell lymphoma, uterine carcinosarcoma (UCS), and stomach adenocarcinoma (STAD). We first identified that highly expressed of ACE2 was linked to poor prognosis of overall survival for tumors of brain lower grade glioma (LGG). Specially, the expression level of ACE2 in kidney-related tumor tissues is much higher than that of normal kidney tissues. ACE2 is negatively correlated with the infiltration level of cancer-associated fibroblasts in most kinds of cancers, such as uterine corpus endometrial carcinoma (UCEC), esophageal carcinoma (ESCA), ovarian serous cystadenocarcinoma (OV) and kidney renal clear cell carcinoma (KIRC); positively correlation in testicular germ cell tumors (TGCT). The different phosphorylation sites of ACE2 were analyzed in CPTAC dataset, and the DNA methylation of ACE2 in colon adenocarcinoma (COAD), kidney renal papillary cell carcinoma (KIRP), and rectum adenocarcinoma (READ) was lower than that of normal control by using SMART database. Moreover, we summarized the interaction proteins and targeted miRNAs of ACE2 through bioinformatics. Then we found the endocrine process and the regulation of systemic arterial blood pressure were involved in the functional mechanisms of ACE2 by using KEGG and GO analysis. Our study offers a relatively comprehensive understanding of ACE2.

Genome tumor profiling in endometrial cancer and clinical relevance in endometrial cancer management: a retrospective single-center experience.

OBJECTIVE: Next-generation sequencing (NGS) analysis has become an essential tool for endometrial carcinoma management. Moreover, molecular-driven therapies play an increasingly remarkable role in the era of precision oncology. This study aims to determine the clinical relevance of NGS testing in endometrial carcinoma management by analyzing the clinical benefit of NGS-driven targeted therapies. METHODS: A single-center retrospective study was conducted on 25 endometrial carcinoma patients who underwent Foundation Medicine CDx assay at Fondazione Policlinico Universitario Agostino Gemelli, IRCCS (Rome, Italy). Tumor samples were analyzed by Foundation One CDx. A descriptive analysis of tumor genome profiles was performed. Assessment of clinical benefit according to RECIST 1.1 criteria was analyzed for patients who received a tailored treatment according to actionable targets identified by NGS testing. RESULTS: Out of 25 endometrial carcinoma patients, 11 received targeted therapy. One patient was excluded from the clinical benefit assessment because of COVID-19-related death 1 month after starting the treatment. Eight of the remaining 10 patients benefited from targeted therapies, with an overall clinical benefit rate of 80%. A targeted agent belonging to the PI3K pathway was given to seven patients, with evidence of three partial responses (42.9%), three stable diseases (42.9%), and one progressive disease (14.2%) according to RECIST 1.1 criteria. One complete response (33.3%), one stable disease (33.3%), and one progressive disease (33.3%) were observed in the three patients treated with poly(ADP-ribose) polymerase (PARP) inhibitors according to their homologous recombination deficiency (HRD) status. CONCLUSION: This study highlights the importance of characterizing the mutation profile of patient tumors through NGS. Our findings suggest a clinical benefit of using NGS-driven targeted therapies in endometrial carcinoma patients. However, this personalized approach could benefit the health system in terms of cost-effectiveness by reducing the costs of inappropriate, ineffective, and often expensive treatments.

Assessment of Hospital Volume in the Surgical Management of Endometrial and Ovarian Cancer: A Polish Population-Based Study.

BACKGROUND Surgery is a cornerstone in management of ovarian and endometrial cancer. The European Society of Gynecological Oncology introduced quality indicators to improve management of these cancers. The optimal annual number of surgeries per unit was established for high-quality surgical treatment. MATERIAL AND METHODS The database of the National Health Fund on surgical management of endometrial and ovarian cancer was analyzed. Patients treated between 2017 and 2020 were included. Departments where patients underwent surgery were divided according to number of surgeries performed per year in endometrial cancer: ≥80, 79-50, 49-20, 19-0; and ovarian cancer: ≥100, 99-50, 49-20, 19-0. Optimal number of surgeries per center was defined as at least 100 and 80 surgeries per year in ovarian and endometrial cancer, respectively. RESULTS Totally, there were 22 325 surgeries in 316 units and 10 381 surgeries in 251 units due to endometrial and ovarian cancer, respectively. Most surgeries in endometrial cancer (n=15 077; 67.5%) and ovarian cancer (n=9642; 92.88%) were performed in departments that did not meet optimal criteria in number of surgeries. Between 2017 and 2019, an increasing trend in number of surgeries per year in endometrial and ovarian cancer was found. In 2020, there was a decrease in the number of surgeries by 7.8% (n=453) and 8.6% (n=234) in endometrial and ovarian cancer, respectively. CONCLUSIONS In Poland, surgical treatment of ovarian and endometrial cancer is decentralized. Most cancer patients underwent surgery in low-volume general gynecologic departments. The COVID-19 pandemic impaired cancer management, leading to a decreased number of surgeries.

Impact of the COVID-19 Pandemic on Diagnosis and Management of Gynecological Cancer: A Single-Center Analysis.

Background and Objectives: The COVID-19 pandemic impacted health systems worldwide, particularly cancer care. Because the actual implications of these changes on gynecological oncology healthcare are still unclear, we aim to evaluate the impact of this pandemic on the diagnosis and management of gynecological cancer. Materials and Methods: This is a single-center retrospective observational study, including patients diagnosed with gynecological malignancies between January 2019 and December 2021. Patients were included into three groups based on the timing of cancer diagnosis: pre-pandemic (2019), pandemic with high restrictions (2020) and pandemic recovery (2021). Results: Overall, 234 patients were diagnosed with gynecological cancer during the period of study. A decrease in the number of newly diagnosed cervical cancers and other rare tumors (leiomyosarcoma, invasive hydatidiform mole) was apparent in 2020. Some aggressive histological types of endometrial and ovarian cancer were more commonly diagnosed in the pandemic recovery group (p < 0.05), although no differences were demonstrated concerning tumor staging in all gynecological cancers. The median time between the first multidisciplinary team meeting and the treatment initiation was higher after the COVID-19 pandemic in endometrial cancer (23.0 vs. 34.0 vs. 36.0 days, p < 0.05). Patients with ovarian cancer were more frequently proposed for neoadjuvant therapy in 2020 compared to the other periods (33.3% vs. 55.0% vs. 10.0% p < 0.05). A significant reduction in the laparoscopic approach was observed during 2020 in endometrial cancer (32.1% vs. 14.3% vs. 36.4%, p < 0.05). No significant differences were registered regarding median hospitalization days or intra- and post-operative complications between these periods. Conclusions: The COVID-19 pandemic had a significant impact on the diagnosis and management of most gynecological malignancies, namely, on time to first treatment, chosen oncological therapies and surgical approaches. These results suggest important clinical and healthcare implications that should be addressed in future prospective studies.

Improved Rates of Same-day Discharge in Patients Undergoing Surgery for Endometrial Cancer Following the COVID-19 Pandemic.

STUDY OBJECTIVE: To determine the effect of the coronavirus disease 2019 (COVID-19) pandemic on the rate of same-day discharge (SDD) after minimally invasive surgery for endometrial cancer. DESIGN: Retrospective cohort. SETTING: Teaching hospital. PATIENTS: A total of 166 patients underwent a minimally invasive surgery procedure for the indication of endometrial cancer at a large academic institution from September 1, 2019, to October 1, 2020-80 patients before the implementation of the COVID-19 restrictions and 86 patients after. INTERVENTIONS: COVID-19 pandemic with visitor restrictions and hospital policy changes placed on March 17, 2020. MEASUREMENTS AND MAIN RESULTS: SDD rate was increased by 18% after the start of the COVID-19 pandemic (40% vs 58%, p = .02). There were no differences between the 2 groups with regard to operative time (p = .07), estimated blood loss (p = .21), uterine weight (p = .12), age (p = .06), body mass index (p = .42), or surgery start time (p = .15). In a multivariable logistic regression model, subjects in the COVID-19 group had 3.08 times (95% confidence interval, 1.40-6.74; p = .01) higher odds of SDD than those in the pre-COVID-19 group. There was no difference in 30-day readmission rates (7.5% vs 5.8%, p = .66). CONCLUSION: There was a significant increase in the SDD of patients with endometrial cancer since the start of the COVID-19 pandemic. The pandemic has strained hospital resources and motivated patients and physicians to avoid hospitalization. This shows that with proper motivation, an increase in SDD rates is possible without an increase in complications or rehospitalization.

Are female-specific cancers long-term sequelae of COVID-19? Evidence from a large-scale genome-wide cross-trait analysis (preprint)

ABSTRACT Background Little is known regarding the long-term adverse effects of COVID-19 on female-specific cancers due to the restricted length of observational time, nor the shared genetic influences underlying these conditions. Methods Leveraging summary statistics from the hitherto largest genome-wide association studies conducted in each trait, we performed a comprehensive genome-wide cross-trait analysis to investigate the shared genetic architecture and the putative genetic associations between COVID-19 with three main female-specific cancers: breast cancer (BC), epithelial ovarian cancer (EOC), and endometrial cancer (EC). Three phenotypes were selected to represent COVID-19 susceptibility (SARS-CoV-2 infection) and severity (COVID-19 hospitalization, COVID-19 critical illness). Results For COVID-19 susceptibility, we found no evidence of a genetic correlation with any of the female-specific cancers. For COVID-19 severity, we identified a significant genome-wide genetic correlation with EC for both hospitalization ( r g =0.19, P =0.01) and critical illness ( r g =0.29, P =3.00×10 −4 ). Mendelian randomization demonstrated no valid association of COVID-19 with any cancer of interest, except for suggestive associations of genetically predicted hospitalization (OR IVW =1.09, 95%CI=1.01-1.18, P =0.04) and critical illness (OR IVW =1.06, 95%CI=1.00-1.11, P =0.04) with EC risk, none withstanding multiple correction. No reverse association was found. Cross-trait meta-analysis identified multiple pleiotropic SNPs between COVID-19 and female-specific cancers, including 20 for BC, 15 for EOC, and 5 for EC. Transcriptome-wide association studies revealed shared genes, mostly enriched in the hematologic, cardiovascular, and nervous systems. Conclusions Our genetic analysis highlights an intrinsic link underlying female-specific cancers and COVID-19 - while COVID-19 is not likely to elevate the immediate risk of the examined female-specific cancers, it appears to share mechanistic pathways with these conditions. These findings may provide implications for future therapeutic strategies and public health actions.

A pan-cancer analysis of the oncogenic role of COVID-19 risk gene Leucine Zipper Transcription Factor-Like Protein 1 (LZTFL1) in human tumors (preprint)

Population-based studies showed that COVID-19 infection causes higher death rate in cancer patients. However, the molecular mechanism of COVID-19 with cancer is still largely unknown. Here we analyzed the Leucine Zipper Transcription Factor-Like Protein 1 (LZTFL1) which is the most significant gene associated with COVID-19. First, we explored the potential oncogenic roles of LZTFL1 through transcriptome data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. LZTFL1 is significantly low expressed in 11 of 34 kinds of cancers we analyzed. Consistent with the mRNA expression data, the protein expression of LZTFL1 in lung adenocarcinoma (LUAD), clear cell renal cell carcinoma (ccRCC), Uterine corpus endometrial carcinoma (UCEC), and ovarian cancer (OV) patients are significantly decreased compared to healthy tissues. The survival analysis from the Kidney renal clear cell carcinoma (KIRC), Rectum adenocarcinoma (READ), and Uveal Melanoma (UVM), the LZTFL1 high expression group have a significantly higher survival rate compared to the low expression group. Taken together, LZTFL1 acts as a cancer suppressor gene for several cancers. Moreover, LZTFL1 expression was associated with the cancer-associated fibroblast infiltration in several tumors including Bladder Urothelial Carcinoma (BLCA), Breast invasive carcinoma (BRCA), Esophageal carcinoma (ESCA), Head and Neck squamous cell carcinoma (HNSC), Lung squamous cell carcinoma (LUSC), and Pancreatic adenocarcinoma (PAAD). Gene ontology analysis showed that cilium organization, positive regulation of establishment of protein localization to telomere and SRP-dependent cotranslational protein targeting to the membrane were involved in the function mechanisms related to LZTFL1. Our studies offer a relatively comprehensive understanding of the oncogenic roles of LZTFL1 across different kinds of tumors.

The socioeconomic gradient in mortality from ovarian, cervical, and endometrial cancer in Australian women, 2001-2018: A population-based study.

BACKGROUND: Socio-economic (SE) status is closely linked to health status and the mechanisms of this association are complex. One important adverse effect of SE disadvantage is vulnerability to cancer and cancer is a major cause of morbidity and mortality in Australia. AIMS: We aimed to estimate the effect of SE status on mortality rates from ovarian, cervical, and endometrial cancer. MATERIALS AND METHODS: National mortality data were obtained from the Australian Bureau of Statistics (ABS) for the calendar years from 2001 to 2018, inclusive. Individual deaths were grouped by the ABS Index of Relative Socio-economic Advantage and Disadvantage. Population data were obtained to provided denominators allowing calculation of mortality rates (deaths per 100 000 women aged 30-79 years). Statistical analyses performed included tabulating point-estimates of mortality rates and their changes over time and modelling the trends of rates using maximum likelihood method. RESULTS: Age-standardised mortality rates for ovarian and cervical cancer fell over the study period but increased for endometrial cancer. There was clear evidence of a SE gradient in the mortality rate for all three cancers. This SE gradient increased over the study period for ovarian and cervical cancer but remained unchanged for endometrial cancer. CONCLUSIONS: Women at greater SE disadvantage have higher rates of death from the commonest gynaecological cancers and this gradient has not reduced over the last two decades. After the COVID-19 pandemic efforts must be redoubled to ensure that Australians already at risk of ill health do not face even greater risks because of their circumstances.

Maintenance therapy for long-term control of high-grade endometrial stromal sarcoma.

High-grade endometrial stromal sarcoma (HG-ESS) is a malignant uterine tumour with a poor prognosis. This study aimed to demonstrate the usefulness of maintenance chemotherapy with paclitaxel (PTX) and carboplatin (CBDCA) for HG-ESS recurrence, by examining a case of HG-ESS tumour progression as a result of maintenance therapy interruption because of the COVID-19 pandemic. The patient was a woman in her 60s who presented with lower abdominal pain, nausea and a pelvic tumour, which was diagnosed as HG-ESS. Chemotherapy with PTX (175 mg/m2 day 1) + CBDCA (area under the concentration-time curve 5 day 1) every 21-28 days (TC therapy) was administered for long-term maintenance of HG-ESS. After 26 cycles, chemotherapy had to be postponed because of the COVID-19 pandemic, thus leading to disease progression and eventually death. In conclusion, TC therapy can prolong survival in patients with HG-ESS, and maintenance chemotherapy should not be postponed.

Impact of the COVID-19-pandemic on patients with gynecological malignancies undergoing surgery: A Dutch population-based study using data from the 'Dutch Gynecological Oncology Audit'.

OBJECTIVE: The COVID-19-pandemic caused drastic healthcare changes worldwide. To date, the impact of these changes on gynecological cancer healthcare is relatively unknown. This study aimed to assess the impact of the COVID-19-pandemic on surgical gynecological-oncology healthcare. METHODS: This population-based cohort study included all surgical procedures with curative intent for gynecological malignancies, registered in the Dutch Gynecological Oncology Audit, in 2018-2020. Four periods were identified based on COVID-19 hospital admission rates: 'Pre-COVID-19', 'First wave', 'Interim period', and 'Second wave'. Surgical volume, perioperative care processes, and postoperative outcomes from 2020 were compared with 2018-2019. RESULTS: A total of 11,488 surgical procedures were analyzed. For cervical cancer, surgical volume decreased by 17.2% in 2020 compared to 2018-2019 (mean 2018-2019: n = 542.5, 2020: n = 449). At nadir (interim period), only 51% of the expected cervical cancer procedures were performed. For ovarian, vulvar, and endometrial cancer, volumes remained stable. Patients with advanced-stage ovarian cancer more frequently received neoadjuvant chemotherapy in 2020 compared to 2018-2019 (67.7% (n = 432) vs. 61.8% (n = 783), p = 0.011). Median time to first treatment was significantly shorter in all four malignancies in 2020. For vulvar and endometrial cancer, the length of hospital stay was significantly shorter in 2020. No significant differences in complicated course and 30-day-mortality were observed. CONCLUSIONS: The COVID-19-pandemic impacted surgical gynecological-oncology healthcare: in 2020, surgical volume for cervical cancer dropped considerably, waiting time was significantly shorter for all malignancies, while neoadjuvant chemotherapy administration for advanced-stage ovarian cancer increased. The safety of perioperative healthcare was not negatively impacted by the pandemic, as complications and 30-day-mortality remained stable.