The prognostic value of MEK pathway-associated estrogen receptor signaling activity for female cancers.

BACKGROUND: Other than for breast cancer, endocrine therapy has not been highly effective for gynecologic cancers. Endocrine therapy resistance in estrogen receptor positive gynecologic cancers is still poorly understood. In this retrospective study, we examined the estrogen receptor (ER) signaling pathway activities of breast, ovarian, endometrial, and cervical cancers to identify those that may predict endocrine therapy responsiveness. METHODS: Clinical and genomic data of women with breast and gynecological cancers were downloaded from cBioPortal for Cancer Genomics. Estrogen receptor alpha (ESR1) expression level and sample-level pathway enrichment scores (EERES) were calculated to classify patients into four groups (low/high ESR1 and low/high EERES). Correlation between ESR1/EERES score and survival was further validated with RNAseq data from low-grade serous ovarian cancer. Pathway analyses were performed among different ESR1/EERES groups to identify genes that correlate with endocrine resistance, which are validated using Cancer Cell Line Encyclopedia gene expression and Genomics of Drug Sensitivity in Cancer data. RESULTS: We identified a novel combined prognostic value of ESR1 expression and the corresponding estrogen response signaling (EERES score) for breast cancer. The combined prognostic value (ESR1/EERES) may be applicable to other gynecologic cancers. More importantly, we discovered that ER signaling can cross-regulate MEK pathway activation. We identified downstream genes in the MEK pathway (EPHA2, INAVA, MALL, MPZL2, PCDH1, and TNFRSF21) that are potential endocrine therapy response biomarkers. CONCLUSION: This study demonstrated that targeting both the ER and the ER signaling activity related MEK pathway may aid the development of endocrine therapy strategies for personalized medicine.

A systematic review and meta-analysis on mortality rate following total pelvic exenteration in cancer patients.

BACKGROUND: Total pelvic exenteration (TPE), an en bloc resection is an ultraradical operation for malignancies, and refers to the removal of organs inside the pelvis, including female reproductive organs, lower urological organs and involved parts of the digestive system. The aim of this meta-analysis is to estimate the intra-operative mortality, in-hospital mortality, 30- and 90-day mortality rate and overall mortality rate (MR) following TPE in colorectal, gynecological, urological, and miscellaneous cancers. METHODS: This is a systematic review and meta-analysis in which three international databases including Medline through PubMed, Scopus and Web of Science on November 2023 were searched. To screen and select relevant studies, retrieved articles were entered into Endnote software. The required information was extracted from the full text of the retrieved articles by the authors. Effect measures in this study was the intra-operative, in-hospital, and 90-day and overall MR following TPE. All analyzes are performed using Stata software version 16 (Stata Corp, College Station, TX). RESULTS: In this systematic review, 1751 primary studies retrieved, of which 98 articles (5343 cases) entered into this systematic review. The overall mortality rate was 30.57% in colorectal cancers, 25.5% in gynecological cancers and 12.42% in Miscellaneous. The highest rate of mortality is related to the overall mortality rate of colorectal cancers. The MR in open surgeries was higher than in minimally invasive surgeries, and also in primary advanced cancers, it was higher than in recurrent cancers. CONCLUSION: In conclusion, it can be said that performing TPE in a specialized surgical center with careful patient eligibility evaluation is a viable option for advanced malignancies of the pelvic organs.

Superior prognostic accuracy of FIGO staging system in primary female genital tract lymphomas: A retrospective study (IELSG35).

Primary lymphoma of the female genital tract (PLFGT) is a rare type of extranodal lymphoma. In this retrospective study from the International Extranodal Lymphoma Study Group, we analyzed clinical data from 60 women diagnosed with PLFGT between 1982 and 2012. The median age was 52 years. Limited stage, as defined by the Ann Arbor and FIGO staging systems, was observed in 55% and 63% of cases, respectively. The uterus was the primary site of lymphoma in 25 cases, with the ovaries as the second most common site (n = 24). The most common histological subtype was diffuse large B-cell lymphoma (DLBCL, n = 44), followed by follicular lymphoma and marginal zone lymphoma (6 patients each). Two patients received surgery alone as first-line therapy, while 58 underwent systemic therapy, 16 following major surgery. Thirteen patients received consolidation radiotherapy and six were given central nervous system (CNS) prophylaxis. Twenty patients had disease progression or recurrence. Six patients with DLBCL (14%) experienced CNS relapse, which was the only site of recurrence in five of them. All but one patient with CNS relapse had primary ovarian involvement, and three had bulky disease; none of these patients had received CNS prophylaxis. With a median follow-up of 60 months, the median overall survival of the DLBCL cohort was approximately 13 years, with a 5-year survival rate of 77%. In multivariable analysis, advanced disease according to the FIGO system was the only parameter significantly associated with shorter overall, cause-specific, and progression-free survival in patients with DLBCL.

Clinical characteristics and outcome of early-stage diffuse large B cell lymphoma of female genital track: A retrospective study of the Hellenic cooperative lymphoma group.

Involvement of female genital track (FGT) by diffuse large B cell lymphoma (DLBCL) represents an extremely rare diagnosis. Especially data regarding early-stage disease (i.e., IE, IIE) is very limited. Importantly, previous studies showed controversial results about the risk of central nervous system (CNS) relapse in this entity. Herein, we describe one of the largest reported real-world series of patients with early-stage FGT DLBCL aiming to investigate the clinicopathological characteristics, response to therapy and survival outcomes in the era of immunochemotherapy. We analyzed 21 consecutive patients with biopsy proven DLBCL from uterus or ovary classified as stage IE or IIE out of 1905 newly diagnosed DLBCL patients (1.1%). Uterine and ovarian localization was observed in 14 and seven patients, respectively. Median age was 66 years (range 33-96); 9/21 (43%) were <55 years. Regarding Cell of Origin DLBCL subtype, Germinal Center B-cell subtype was found in seven patients, non-GCB in 10 and non-classified in 4 patients. Median follow-up was 57 months and 5-year overall survival, lymphoma specific survival and Freedom from Progression were 78%, 89% and 90%, respectively. There was no correlation of patients' characteristics with survival parameters. Interestingly, none of the patients experienced CNS relapse. Our results indicate that localized FGT DLBCL exhibits a good prognosis and may not increase the risk for secondary CNS involvement.

Associations between race and ethnicity and treatment setting among gynecologic cancer patients.

INTRODUCTION: Racial and ethnic disparities in gynecologic cancer care have been documented. Treatment at academic facilities is associated with improved survival, yet no study has examined independent associations between race and ethnicity with facility type among gynecologic cancer patients. MATERIALS & METHODS: We used the National Cancer Database and identified 484,455 gynecologic cancer (cervix, ovarian, uterine) patients diagnosed between 2004 and 2020. Facility type was dichotomized as academic vs. non-academic, and we used logistic regression to estimate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) between race and ethnicity and facility type. Secondarily, we examined joint effects of race and ethnicity and facility type on overall survival using Cox proportional hazards regression. RESULTS: We observed higher odds of treatment at academic (vs. non-academic) facilities among American Indian/Alaska Native (OR = 1.42, 95% CI = 1.28-1.57), Asian (OR = 1.64, 95% CI = 1.59-1.70), Black (OR = 1.69, 95% CI = 1.65-1.72), Hispanic (OR = 1.70, 95% CI = 1.66-1.75), Native Hawaiian/Pacific Islander (OR = 1.74, 95% CI = 1.57-1.93), and other race (OR = 1.29, 95% CI = 1.20-1.40) patients compared with White patients. In the joint effects survival analysis with White, academic facility-treated patients as the reference group, Asian, Hispanic, and other race patients treated at academic or non-academic facilities had improved overall survival. Conversely, Black patients treated at academic facilities [Hazard Ratio (HR) = 1.10, 95% CI = 1.07-1.12] or non-academic facilities (HR = 1.19, 95% CI = 1.16-1.21) had worse survival. DISCUSSION: Minoritized gynecologic cancer patients were more likely than White patients to receive treatment at academic facilities. Importantly, survival outcomes among patients receiving care at academic institutions differed by race, requiring research to investigate intra-facility survival disparities.

Racial and ethnic differences in early death among gynecologic malignancy.

BACKGROUND: Racial and ethnic differences in early death after cancer diagnosis have not been well studied in gynecologic malignancy. OBJECTIVE: This study aimed to assess population-level trends and characteristics of early death among patients with gynecologic malignancy based on race and ethnicity in the United States. STUDY DESIGN: The National Cancer Institute's Surveillance, Epidemiology, and End Results Program was queried to examine 461,300 patients with gynecologic malignancies from 2000 to 2020, including uterine (n=242,709), tubo-ovarian (n=119,989), cervical (n=68,768), vulvar (n=22,991), and vaginal (n=6843) cancers. Early death, defined as a mortality event within 2 months of the index cancer diagnosis, was evaluated per race and ethnicity. RESULTS: At the cohort level, early death occurred in 21,569 patients (4.7%), including 10.5%, 5.5%, 2.9%, 2.5%, and 2.4% for tubo-ovarian, vaginal, cervical, uterine, and vulvar cancers, respectively (P<.001). In a race- and ethnicity-specific analysis, non-Hispanic Black patients with tubo-ovarian cancer had the highest early death rate (14.5%). Early death racial and ethnic differences were the largest in tubo-ovarian cancer (6.4% for Asian vs 14.5% for non-Hispanic Black), followed by uterine (1.6% for Asian vs 4.9% for non-Hispanic Black) and cervical (1.8% for Hispanic vs 3.8% to non-Hispanic Black) cancers (all, P<.001). In tubo-ovarian cancer, the early death rate decreased over time by 33% in non-Hispanic Black patients from 17.4% to 11.8% (adjusted odds ratio, 0.67; 95% confidence interval, 0.53-0.85) and 23% in non-Hispanic White patients from 12.3% to 9.5% (adjusted odds ratio, 0.77; 95% confidence interval, 0.71-0.85), respectively. The early death between-group difference diminished only modestly (12.3% vs 17.4% for 2000-2002 [adjusted odds ratio for non-Hispanic White vs non-Hispanic Black, 0.54; 95% confidence interval, 0.45-0.65] and 9.5% vs 11.8% for 2018-2020 [adjusted odds ratio, 0.65; 95% confidence interval, 0.54-0.78]). CONCLUSION: Overall, approximately 5% of patients with gynecologic malignancy died within the first 2 months from cancer diagnosis, and the early death rate exceeded 10% in non-Hispanic Black individuals with tubo-ovarian cancer. Although improving early death rates is encouraging, the difference among racial and ethnic groups remains significant, calling for further evaluation.

Survival prediction in patients with gynecological cancer irradiated for brain metastases.

BACKGROUND AND PURPOSE: This large population-based, retrospective, single-center study aimed to identify prognostic factors in patients with brain metastases (BM) from gynecological cancers. MATERIAL AND METHODS: One hundred and forty four patients with BM from gynecological cancer treated with radiotherapy (RT) were identified. Primary cancer diagnosis, age, performance status, number of BM, presence of extracranial disease, and type of BM treatment were assessed. Overall survival (OS) was calculated using the Kaplan-Meier method and the Cox proportional hazards regression model was used for multivariable analysis. A prognostic index (PI) was developed based on scores from independent predictors of OS. RESULTS: Median OS for the entire study population was 6.2 months. Forty per cent of patients died within 3 months after start of RT. Primary cancer with the origin in cervix or vulva (p = 0.001),  Eastern Cooperative Oncology Group (ECOG) 3-4 (p < 0.001), and the presence of extracranial disease (p = 0.001) were associated with significantly shorter OS. The developed PI based on these factors, categorized patients into three risk groups with a median OS of 13.5, 4.0, and 2.4 months for the good, intermediate, and poor prognosis group, respectively. INTERPRETATION: Patients with BM from gynecological cancers carry a poor prognosis. We identified prognostic factors and developed a scoring tool to select patients with better or worse prognosis. Patients in the high-risk group have a particular poor prognosis, and omission of RT could be considered.

Obesity paradox: is a high body mass index positively influencing survival outcomes in gynecological cancers? A systematic review and meta-analysis.

OBJECTIVE: Obesity represents an exponentially growing preventable disease leading to different health complications, particularly when associated with cancer. In recent years, however, an 'obesity paradox' has been hypothesized where obese individuals affected by cancer counterintuitively show better survival rates. The aim of this systematic review and meta-analysis is to assess whether the prognosis in gynecological malignancies is positively influenced by obesity. METHODS: This study adheres to PRISMA guidelines and is registered with PROSPERO. Studies reporting the impact of a body mass index (BMI) of >30 kg/m2 compared with <30 kg/m2 in patients with gynecological cancers listed in PubMed, Google Scholar and ClinicalTrials.gov were included in the analysis. The Quality Assessment of Diagnostic Accuracy Studies 2 tool (QUADAS-2) was used for quality assessment of the selected articles. RESULTS: Twenty-one studies were identified for the meta-analysis, including 14 108 patients with cervical, ovarian, or endometrial cancer. There was no benefit in 5-year overall survival for obese patients compared with non-obese patients (OR 1.2, 95% CI 1.00 to 1.44, p=0.05; I2=71%). When pooling for cancer sub-groups, there were no statistically significant differences in 5-year overall survival in patients with cervical cancer and 5-year overall survival and progression-free survival in patients with ovarian cancer. For obese women diagnosed with endometrial cancer, a significant decrease of 44% in 5-year overall survival (p=0.01) was found, with no significant difference in 5-year disease-free survival (p=0.78). CONCLUSION: According to the results of the present meta-analysis, a BMI of ≥30 kg/m2 does not have a positive prognostic effect on survival compared with a BMI of <30 kg/m2 in women diagnosed with gynecological cancers. The existence of the 'obesity paradox' in other fields, however, suggests the importance of further investigations with prospective studies.

Assessment of secular trends of three major gynecologic cancers burden and attributable risk factors from 1990 to 2019: an age period cohort analysis.

BACKGROUND: This study aims to assess the long-term trends in the burden of three major gynecologic cancers(GCs) stratified by social-demographic status across the world from 1990 to 2019. To assess the trends of risk factor attributed mortality, and to examine the specific effects of age, period, cohort behind them in different regions. METHODS: We extracted data on the mortality, disability-adjusted life years(DALYs), and age-standardized rates(ASRs) of cervical cancer(CC), uterine cancer(UC), and ovarian cancer(OC) related to risks from 1990 to 2019, as GCs burden measures. Age-period-cohort analysis was used to analyze trends in attributable mortality rates. RESULTS: The number of deaths and DALYs for CC, UC and OC increased since 1990 worldwide, while the ASDRs decreased. Regionally, the ASDR of CC was the highest in low SDI region at 15.05(11.92, 18.46) per 100,000 in 2019, while the ASDRs of UC and OC were highest in high SDI region at 2.52(2.32,2.64), and 5.67(5.16,6.09). The risk of CC death caused by unsafe sex increased with age and then gradually stabilized, with regional differences. The period effect of CC death attributed to smoking showed a downward trend. The cohort effect of UC death attributed to high BMI decreased in each region, especially in the early period in middle, low-middle and low SDI areas. CONCLUSIONS: Global secular trends of attributed mortality for the three GCs and their age, period, and cohort effects may reflect the diagnosis and treatment progress, rapid socioeconomic transitions, concomitant changes in lifestyle and behavioral patterns in different developing regions. Prevention and controllable measures should be carried out according to the epidemic status in different countries, raising awareness of risk factors to reduce future burden.

The challenge of survivors of gynecological carcinomas: a retrospective study on occurrence of second tumors.

OBJECTIVE: To clarify the epidemiologic characteristics and risk of other tumors in survivors of gynecological tumors. MATERIALS AND METHODS: This is a retrospective study based on the Surveillance, Epidemiology, and End Results database (SEER). RESULTS: The morbidity of other malignant tumors in patients with gynecological cancer was 8.07%. The most common subsequent tumors are breast, lung, colorectal, thyroid, and bladder cancers. Taking the incidence rate of the general population as reference, the second tumor with the highest relative risk in patients with cervical cancer is vulvar cancer. Bladder cancer is the second tumor with the highest relative risk value both in patients with corpus and ovarian cancer. The median period from the diagnosis of the initial tumor to the diagnosis of the second tumor was 5 years. Most patients with other tumors following gynecological cancer showed worse prognosis than patients with gynecological tumors only. However, thyroid cancer following ovarian cancer is a protective factor in survival. CONCLUSION: Patients with gynecological tumors have a significantly higher risk of malignant tumors in other systems compared to ordinary population. It is necessary to be vigilant against subsequent high-risk tumors and tumors with poor prognosis within 5 years of initial diagnosis.

Gynaecological cancer-related deaths in a tertiary hospital: A four-year retrospective review.

The aim of this study is to describe the profile, causes of death, and associated complications among women who died with a diagnosis of gynecological cancer during a four-year period in a gynae oncology unit in a tertiary hospital. The study is based on a retrospective review of clinical records of patients. There were 368 gynecological cancer admissions during the study period and 51 gynecological cancer-related deaths (13.8%); however, only 48 (13%) of the 51 files were available for analysis. The mean age of the women who died was 52.7 years (SD ±16.92). Most of the women who died were South African citizens (41, 85%), black (44, 91.7%) and unemployed (37, 77.1%). The most common comorbidities were hypertension and HIV which occurred at similar frequencies (20, 41.7%), followed by diabetes mellitus (7, 14,6%). The three most common cancers were cervical (18, 37.5%), ovarian (13, 27.1%), and endometrial (12, 25,0%). All women who died (48, 100%) had some form of cancer-related complications on admission to the hospital. The most common complication at presentation was obstructive uropathy (16, 31.3%) followed by ascites (11, 21.6%) and pleural effusion (8, 15.8%). Just less than half of the patients (22, 45.8%) received palliative treatment due to advanced-stage disease, and the remainder, (20, 41.6%) and (5, 10.4%) surgical and radiation therapy, respectively. The surgical procedure performed was staging laparotomy for ovarian and endometrial cancer (19, 95%) and radical hysterectomy and lymph node dissection for operatable cervical cancer (01, 5%). Forty-nine complications were recorded among the 20 women who underwent surgical treatment. The most common complications were sepsis and hemorrhage followed by organ injury.

Le but de cette étude est de décrire le profil, les causes de décès et les complications associées chez les femmes décédées avec un diagnostic de cancer gynécologique au cours d'une période de quatre ans dans une unité de gynécologie-oncologie d'un hôpital tertiaire. L'étude est basée sur une revue rétrospective des dossiers cliniques des patients. Il y a eu 368 admissions pour cancer décès liés au cancer gynécologique 51 décès d'origine gynécologique (13,8 %) ; cependant, seulement 48 (13 %) des 51 dossiers étaient disponibles pour analyse. L'âge moyen des femmes décédées était de 52,7 ans (ET ± 16,92). La plupart des femmes décédées étaient des citoyennes sud-africaines (41, 85 %), noires (44, 91,7 %) et au chômage (37, 77,1 %). Les comorbidités les plus courantes étaient l'hypertension et le VIH, qui survenaient à des fréquences similaires (20, 41,7 %), suivis du diabète sucré (7, 14,6 %). Les trois cancers les plus courants étaient le cancer du col de l'utérus (18, 37,5 %), de l'ovaire (13, 27,1 %) et de l'endomètre (12, 25,0 %). Toutes les femmes décédées (48, 100 %) ont présenté une forme ou une autre de complications liées au cancer lors de leur admission à l'hôpital. La complication la plus fréquente lors de la présentation était l'uropathie obstructive (16, 31,3 %), suivie de l'ascite (11, 21,6 %) et de l'épanchement pleural (8, 15,8 %). Un peu moins de la moitié des patients (22, 45,8 %) ont reçu un traitement palliatif en raison d'un stade avancé de la maladie, et le reste (20, 41,6 %) et (5, 10,4 %), une chirurgie et une radiothérapie, respectivement. L'intervention chirurgicale réalisée était une laparotomie de stadification pour un cancer de l'ovaire et de l'endomètre (19, 95 %) et une hystérectomie radicale et un curage ganglionnaire pour un cancer du col de l'utérus opérable (01, 5 %). Quarante-neuf complications ont été enregistrées parmi les 20 femmes ayant bénéficié d'un traitement chirurgical. Les complications les plus courantes étaient la septicémie et l'hémorragie, suivies de lésions organiques.

Therapy Response and Survival among Patients with Gynecologic Tumors Treated with Transarterial Chemoperfusion and Transarterial Chemoembolization.

Background and Objectives: This study aimed to evaluate the tumor response relating to and survival benefit of transarterial chemoperfusion (TACP) and transarterial chemoembolization (TACE) in the treatment of patients with unresectable gynecologic tumors who are intolerant of or have a suboptimal response to chemotherapy and radiotherapy. Materials and Methods: Between January 2000 and October 2023, 75 patients diagnosed with gynecologic tumors underwent 213 TACP and 154 TACE procedures. Of these, 33 patients were treated with TACP, 20 were treated with TACE, and 22 received a combination of both therapies. A retrospective evaluation of local tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST) was conducted, and survival rates were determined using the Kaplan-Meier estimator. Results: Of the total 75 patients, 50 (67%) maintained a stable course of disease until the completion of therapy, 10 (13%) had a partial response, 2 (3%) had a complete response following thermal ablation, and 13 (17%) experienced progression. Furthermore, a 6% reduction in the sum of the longest diameters and an 8% reduction in tumor volume were observed. The median overall survival was 16.15 months, while the median progression-free survival was 13.19 months. Conclusions: TACP and TACE are potential treatment options for local tumor control in patients with unresectable gynecologic tumors who are intolerant of or show a poor response to chemotherapy and radiotherapy. However, further investigation and adjustment of treatment protocols are required to improve therapy response and survival outcomes.

Pelvic Exenteration - Past, Present and Future.

Background: Bearing in mind that the open procedure is already validated by multiple studies, the article aims to prove that pelvic exenteration performed in a minimally invasive fashion might offer better survival and to potentially identify prognostic factors for the outcome of these patients. Material and Methods: Data regarding past and present classifications and surgical indications are presented. Patient data were collected retrospectively. Results: The most frequent diseases treated with pelvic exenteration, in terms of the hystological type, were gynecological malignancy and squamous cell carcinoma. Recurrent pelvic disease was found in 68.2% of patients. R0 resection was achieved in 72.7% of patients in the MI group, and in 73.7% of patients in the OP group. Peri-operative morbidity was reported to be 56.6% for open surgery, and 18.1% for minimally invasive. Average DFS was 20.15 months, ranging from 1.5 to 70.3 months, while the OS was calculated to be 38.1 months (0.33 1508) up until November 2023. Conclusion: Pelvic exenteration is a continuously improving surgical procedure, open approach being favored to minimally invasive one. On the other hand, hospitalization and morbidity are reduced when choosing the latter. R0 and lymph node status are important predictors for overall survival, as well as major early postoperative complications. All in all, pelvic exenteration is still a promising surgical procedure to extend cancer patients lives.

Statin use and incidence and mortality of breast and gynecology cancer: A cohort study using the National Health Insurance claims database.

Previous studies have reported inconsistent findings concerning the impact of statin use on cancer prevention. Our study examined the association between statin use and cancer incidence and mortality related to breast and gynecologic cancers in South Korea. A population-based cohort study was conducted using the National Health Insurance claims database. Women aged 45 to 70 years old who had taken statins for at least 6 months were compared to statin non-users of the same age from January 2005 to June 2013. The primary outcomes were cancer incidence and mortality related to breast cancer, total gynecologic cancers, cervix uteri cancer and ovarian cancer. Cox proportional hazards regression was conducted to calculate the adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs). Out of 587 705 women, there were 3591 cases of breast cancer, 2239 cases of gynecologic cancers and 565 breast and total gynecologic cancer deaths during 7.6 person-years. The aHRs for the association between the risk of each cancer and statin use were 0.88 (95% CI 0.79-0.97) for breast cancer and 0.83 (95% CI 0.67-0.99) for cervix uteri cancer. Statin use was associated with decreased breast cancer mortality (HR = 0.65, 95% CI 0.43-0.99) and total gynecologic cancer mortality (HR = 0.70, 95% CI 0.50-0.98). A dose-response relationship was only found for all-cancer mortality. Statin use for at least 6 months was significantly associated with a lower risk of breast and cervix uteri cancer incidence, and with lower mortality of breast and gynecologic cancers. Further research on these associations will be needed.

How do age and social environment affect the dynamics of death hazard and survival in patients with breast or gynecological cancer in France?

Several studies have investigated the association between net survival (NS) and social inequalities in people with cancer, highlighting a varying influence of deprivation depending on the type of cancer studied. However, few of these studies have accounted for the effect of social inequalities over the follow-up period, and/or according to the age of the patients. Thus, using recent and more relevant statistical models, we investigated the effect of social environment on NS in women with breast or gynecological cancer in France. The data were derived from population-based cancer registries, and women diagnosed with breast or gynecological cancer between 2006 and 2009 were included. We used the European deprivation index (EDI), an aggregated index, to define the social environment of the women included. Multidimensional penalized splines were used to model excess mortality hazard. We observed a significant effect of the EDI on NS in women with breast cancer throughout the follow-up period, and especially at 1.5 years of follow-up in women with cervical cancer. Regarding corpus uteri and ovarian cancer patients, the effect of deprivation on NS was less pronounced. These results highlight the impact of social environment on NS in women with breast or gynecological cancer in France thanks to a relevant statistical approach, and identify the follow-up periods during which the social environment may have a particular influence. These findings could help investigate targeted actions for each cancer type, particularly in the most deprived areas, at the time of diagnosis and during follow-up.

COVID-19 outcomes of patients with gynecologic cancer in New York City: An updated analysis from the initial surge of the pandemic.

BACKGROUND: Despite significant increase in COVID-19 publications, characterization of COVID-19 infection in patients with gynecologic cancer remains limited. Here we present an update of COVID-19 outcomes among people with gynecologic cancer in New York City (NYC) during the initial surge of severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]). METHODS: Data were abstracted from gynecologic oncology patients with COVID-19 infection among 8 NYC area hospital systems between March and June 2020. Multivariable logistic regression was utilized to estimate associations between factors and COVID-19 related hospitalization and mortality. RESULTS: Of 193 patients with gynecologic cancer and COVID-19, the median age at diagnosis was 65.0 years (interquartile range (IQR), 53.0-73.0 years). One hundred six of the 193 patients (54.9%) required hospitalization; among the hospitalized patients, 13 (12.3%) required invasive mechanical ventilation, 39 (36.8%) required ICU admission. Half of the cohort (49.2%) had not received anti-cancer treatment prior to COVID-19 diagnosis. No patients requiring mechanical ventilation survived. Thirty-four of 193 (17.6%) patients died of COVID-19 complications. In multivariable analysis, hospitalization was associated with an age ≥ 65 years (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.11, 4.07), Black race (OR 2.53, CI 1.24, 5.32), performance status ≥2 (OR 3.67, CI 1.25, 13.55) and ≥ 3 comorbidities (OR 2.00, CI 1.05, 3.84). Only former or current history of smoking (OR 2.75, CI 1.21, 6.22) was associated with death due to COVID-19 in multivariable analysis. Administration of cytotoxic chemotherapy within 90 days of COVID-19 diagnosis was not predictive of COVID-19 hospitalization (OR 0.83, CI 0.41, 1.68) or mortality (OR 1.56, CI 0.67, 3.53). CONCLUSIONS: The case fatality rate among patients with gynecologic malignancy with COVID-19 infection was 17.6%. Cancer-directed therapy was not associated with an increased risk of mortality related to COVID-19 infection.

Early referral to a palliative team improves end-of-life care among gynecological cancer patients: a retrospective, population-based study.

OBJECTIVE: To assess end-of-life care among patients with gynecological cancer, and to describe the association between timing of palliative care referral and patterns of care. METHODS: All women with residence in Oslo, Norway, who died of gynecological cancer between January 1, 2015 and December 30, 2017 (36 months), were identified. Patients were primarily treated at the Norwegian Radium Hospital and clinical data on end-of-life care were retrospectively extracted from the medical records. RESULTS: We identified 163 patients with median age 70.1 years at death (range 26-100) with the following diagnoses: ovarian (n=100), uterine (n=40), cervical (n=21), and vulvar cancer (n=2). 53 (33%) of patients died in a palliative care unit, 34 patients (21%) died in nursing homes without palliative care, and 48 (29%) patients died in hospital. Only 15 (9%) patients died at home. 25 (15%) patients received chemotherapy in the last 30 days before death, especially ovarian cancer patients (n=21, 21%). 103 patients (61%) were referred to a palliative team prior to death. Referral to a palliative team was associated with a significantly reduced risk of intensive care unit admission (OR 0.11, 95% CI 0.02 to 0.62) and higher likelihood of a structured end-of-life discussion (OR 2.91, 95% CI 1.03 to 8.25). Palliative care referral also seemed to be associated with other quality indicators of end-of-life care (less chemotherapy use, more home deaths). CONCLUSIONS: End-of-life care in patients with gynecological cancer suffers from underuse of palliative care. Chemotherapy is still commonly used towards end-of-life. Early palliative care referral in the disease trajectory may be an important step towards improved end-of-life care.

Stereotactic radiosurgery for brain metastases from pelvic gynecological malignancies: oncologic outcomes, validation of prognostic scores, and dosimetric evaluation.

INTRODUCTION: Stereotactic radiosurgery is a well-established treatment option in the management of brain metastases. Multiple prognostic scores for prediction of survival following radiotherapy exist, but are not disease-specific or validated for radiosurgery in women with primary pelvic gynecologic malignancies metastatic to the brain. The aim of the present study is to evaluate the feasibility, safety, outcomes, and impact of established prognostic scores. METHODS: We retrospectively identified 52 patients treated with radiotherapy for brain metastases between 2008 and 2021. Stereotactic radiosurgery was utilized in 31 patients for an overall number of 75 lesions; the remaining 21 patients received whole-brain radiotherapy. Kaplan-Meier survival analysis and the log-rank test were used to calculate and compare survival curves and univariate and multivariate Cox regression to assess the influence of cofactors on recurrence, local control, and prognosis. RESULTS: With a median follow-up of 10.7 months, overall survival rates post radiosurgery were 65.3%, 51.3%, and 27.7% for 1, 2, and 5 years, respectively, which were significantly higher than post whole-brain radiotherapy (p=0.049). Five local failures (6.7%) were detected, resulting in 1 and 2 year local cerebral control rates of 97.4% and 94.0%, respectively. Univariate factors for prediction of superior overall survival were high performance status (p=0.030) and application of three prognostic scores, especially the Recursive Partitioning Analysis score (p=0.028). Uni- and multivariate analysis revealed that extracranial progression prior to radiosurgery was significant for inferior overall survival (p<0.0001). Radionecrosis was diagnosed in five women (16%); long-term neurotoxicity was significantly worse after whole-brain radiotherapy compared with radiosurgery (p=0.023). CONCLUSION: Stereotactic radiosurgery for brain metastases from pelvic gynecologic malignancies appears to be safe and well tolerated, achieving promising local cerebral control. Prognostic scores were shown to be transferable and radiosurgery should be recommended as primary intracranial treatment, especially in women with no prior extracranial progression and Recursive Partitioning Analysis class I.

Genomics of gynaecological carcinosarcomas and future treatment options.

Gynaecological carcinosarcomas are the most lethal gynaecological malignancies that are often highly resistant to standard chemotherapy. They are composed of both carcinomatous and sarcomatous components and are associated with high rates of metastatic disease. Due to their rarity, molecular studies have been carried out on relatively few tumours, revealing a broad spectrum of heterogeneity. In this review, we have collated the gene mutations, gene expression, epigenetic regulation and protein expression reported by a number of studies on gynaecological carcinosarcomas. Based on these results, we describe potential therapeutics that may demonstrate efficacy and present any pre-clinical studies that have been carried out. We also describe the pre-clinical models currently available for future research to assess the potential of molecularly matched therapies. Interestingly, over-expression of many biomarkers in carcinosarcoma tumours often doesn't correlate with a worse prognosis. Therefore, we propose that profiling the mutational landscape, gene expression, and gene amplification/deletion may better indicate potential treatment strategies and predict response, thus improving outcomes for women with this rare, aggressive disease.

Tumor immune microenvironment in brain metastases from gynecologic malignancies.

INTRODUCTION: The density and distribution of the tumor immune microenvironment associated with brain metastases (BM) from gynecologic malignancies are unknown and have not been previously reported. We sought to describe the clinical features of a cohort of patients with BM from gynecologic malignancies and to characterize the tumor immune microenvironment from available archival surgical specimens. METHODS: We performed a retrospective review of electronic medical records from 2002 to 2018 for patients with BM from gynecologic malignancies. Data on patient characteristics, treatment regimens, and clinical outcomes were procured. CD4, CD8, CD45RO, CD68, CD163, and FOXP3 immunohistochemistry were evaluated from available archival surgical specimens from primary disease site and neurosurgical resection. RESULTS: A cohort of 44 patients with BM from gynecologic malignancies was identified, 21 (47.7%) endometrial primaries and 23 (52.3%) ovarian primaries. Tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) were evaluated in 13 primary cases and 15 BM cases. For the 13 primary cases, CD4+ TILs were evident in 76.9% of cases, CD8+ in 92.3%, CD45RO+ in 92.3%, and FOXP3+ in 46.2%, as well as CD68+ TAMs in 100% and CD163+ in 100%. For the 15 BM cases, CD4+ TILs were evident in 60.0% of cases, CD8+ in 93.3%, CD45RO+ in 73.3%, and FOXP3+ in 35.7%, as well as CD68+ TAMs in 86.7% and CD163+ in 100%. CONCLUSION: An active tumor immune microenvironment is present with similar distribution in the primary disease site and BM from patients with gynecologic malignancies.