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Background and Aim: The present meta-analysis aims to investigate a potential link between pelvic inflammatory disease (PID) and an increased risk of genitourinary cancers (ovarian, cervical, uterus, and vagina cancers). While previous research has hinted at a possible link, this meta-analysis seeks to delve deeper into the available evidence. Understanding this association is crucial for preventive strategies and improving clinical management practices., Methodology: A comprehensive literature search was conducted across various databases, covering studies published between 2016 and 2024. We included 13 observational studies meeting stringent criteria, followed by meticulous data extraction and quality assessment. Meta-analytical techniques were then employed to calculate pooled odds ratios (ORs), adjusted hazard ratios (HRs), and 95% confidence intervals (CIs), with heterogeneity assessed using the I 2 statistic., Results: Our analysis revealed significant findings, underscoring the association between PID and increased risks of genitourinary cancers. Specifically, individuals with a history of PID demonstrated notably higher odds of developing ovarian cancer (OR = 1.477, 95% CI 1.033-2.207), uterine cancer (OR = 1.263, 95% CI 0.827-2.143), cervical cancer (OR = 1.000, 95% CI 0.900-1.100), and vaginal cancer (OR = 2.500, 95% CI 1.400-4.000) compared to those without such a history. The overall heterogeneity across studies was high (I 2  = 82.92%), suggesting varying trends across different populations and study designs., Conclusion: This meta-analysis provides updated evidence supporting a significant association between PID and an increased risk of cervical, ovarian, and uterine cancers. Early detection and management of PID are crucial in potentially mitigating the risk of these cancers., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ovarian cancer remains a formidable challenge in oncology due to its late-stage diagnosis and limited treatment options. Recent research has revealed the intricate interplay between glycan diversity and the immune microenvironment within ovarian tumors, shedding new light on potential therapeutic strategies. This review seeks to investigate the complex role of glycans in ovarian cancer and their impact on the immune response. Glycans, complex sugar molecules decorating cell surfaces and secreted proteins, have emerged as key regulators of immune surveillance in ovarian cancer. Aberrant glycosylation patterns can promote immune evasion by shielding tumor cells from immune recognition, enabling disease progression. Conversely, certain glycan structures can modulate the immune response, leading to either antitumor immunity or immune tolerance. Understanding the intricate relationship between glycan diversity and immune interactions in ovarian cancer holds promise for the development of innovative therapeutic approaches. Immunotherapies that target glycan-mediated immune evasion, such as glycan-based vaccines or checkpoint inhibitors, are under investigation. Additionally, glycan profiling may serve as a diagnostic tool for patient stratification and treatment selection. This review underscores the emerging importance of glycan diversity in ovarian cancer, emphasizing the potential for unraveling immune interplay and advancing tailored therapeutic prospects for this devastating disease., (© 2024. The Author(s).)

The evidence from previous studies of serum 25-hydroxyvitamin D (25(OH)D) and ovarian cancer risk is not conclusive. However, the 25(OH)D levels were generally only measured in late adulthood, which may not capture the etiologically relevant exposure periods. We investigated predicted 25(OH)D over the adult lifetime in relation to ovarian cancer risk in a population-based case-control study conducted from 2011 to 2016 in Montreal, Canada (n = 490 cases and 896 controls). Predicted 25(OH)D was computed using previously validated regression models. Unconditional multivariable logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% CIs for average predicted 25(OH)D over the adult lifetime and ovarian cancer risk. In addition, the relative importance of different periods of past 25(OH)D exposure was explored using a weighted cumulative exposure (WCE) model. For each 20-nmol/L increase in average predicted 25(OH)D over the adult lifetime, the aOR (95% CI) was 0.73 (0.55-0.96). In WCE analyses, the inverse association was strongest for exposures 5 to 20 years and 35 to 55 years prior to diagnosis, with aORs (95% CIs) of 0.82 (0.69-0.94) and 0.79 (0.66-1.02), respectively, for each 20-nmol/L increase in predicted 25(OH)D. These results support an inverse association between 25(OH)D levels in adulthood and ovarian cancer risk. This article is part of a Special Collection on Gynecological Cancers., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Endometriosis is a common estrogen-dependent inflammatory disease with a chronic course and a tendency to recur. The association between endometriosis and cancer has been studied for several years. Numerous reports have demonstrated a strong association between specific ovarian malignancies and endometriotic lesions. Atypical endometriosis has been widely described as a malignant precursor to ovarian epithelial tumors, particularly clear cell carcinomas and endometrioid carcinomas. These histological types associated with endometriosis develop predominantly in the ovary rather than in extragonadal sites. The detailed molecular mechanism of etiology remains unclear. Recent studies have analyzed the genetic and molecular mechanisms involved in endometriosis-associated ovarian cancer. A critical role appears to be played by a carcinogenic model based on iron-induced oxidative stress, which is typical of the endometriosis microenvironment. It has been hypothesized that trans-tubal reflux of blood, endometrial cells and associated iron-induced oxidative stress underlie the development of endometriosis-associated ovarian cancer. However, the multifactorial mechanisms of this malignant transformation are not fully understood. The aim of this review is to summaries the current epidemiological, histopathological, genetic and molecular findings in the progression of endometriosis-associated ovarian cancer.

Objective: This study aimed to systematically examine the relationship between polycystic ovary syndrome and ovarian, endometrial, and cervical cancers using the National Inpatient Sample (NIS) database., Methods: We utilized the International Classification of Diseases (ICD-10) system to identify relevant codes from the NIS database (2016-2019). Univariate and multivariable regression analyses (adjusted age, race, hospital region, hospital teaching status, income Zip score, smoking, alcohol use, and hormonal replacement therapy) were conducted to evaluate association between PCOS and gynecologic cancers. Results were summarized as odds ratio (OR) with 95% confidence intervals (CI)., Results: Overall, 15,024,965 patients were analyzed, of whom 56,183 and 14,968,782 patients were diagnosed with and without PCOS, respectively. Among the patients diagnosed with gynecologic cancers (n = 91,599), there were 286 with PCOS and 91,313 without PCOS. Univariate analysis revealed that PCOS was significantly associated with higher risk of endometrial cancer (OR = 1.39, 95 % CI [1.18-1.63], p < 0.0001), but lower risk of ovarian cancer (OR = 0.55, 95 % CI [0.45-0.67], p < 0.0001) and cervical cancer (OR = 0.68, 95 % CI [0.51-0.91], p = 0.009). In contrast, after Bonferroni correction, multivariable analysis depicted that PCOS remained significantly associated with higher risk of endometrial cancer (OR = 3.90, 95 % CI [4.32-4.59], p < 0.0001). There was no significant correlation between PCOS and risk of ovarian cancer (OR = 1.09, 95 % CI [0.89-1.34], p = 0.409) and cervical cancer (OR = 0.83, 95 % CI [0.62-1.11], p = 0.218)., Conclusion: This first-ever NIS analysis showed that patients with PCOS exhibited unique gynecologic cancer risk profiles, with higher risk for endometrial cancer, and no significant risk for ovarian or cervical cancers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Endometriosis is a hormone-dependent, chronic inflammatory condition that affects 5-10% of reproductive-aged women. It is a complex disorder characterized by the growth of endometrial-like tissue outside the uterus, which can cause chronic pelvic pain and infertility. Despite its prevalence, the underlying molecular mechanisms of this disease remain poorly understood. Current treatment options are limited and focus mainly on suppressing lesion activity rather than eliminating it entirely. Although endometriosis is generally considered a benign condition, substantial evidence suggests that it increases the risk of developing specific subtypes of ovarian cancer. The discovery of cancer driver mutations in endometriotic lesions indicates that endometriosis may share molecular pathways with cancer. Moreover, the application of single-cell and spatial genomics, along with the development of organoid models, has started to illuminate the molecular mechanisms underlying disease etiology. This review aims to summarize the key genetic mutations and alterations that drive the development and progression of endometriosis to malignancy. We also review the significant recent advances in the understanding of the molecular basis of the disorder, as well as novel approaches and in vitro models that offer new avenues for improving our understanding of disease pathology and for developing new targeted therapies.

Estrogen plays a crucial role in ovarian tumorigenesis. Phytoestrogens (PEs) are a type of daily dietary nutrient for humans and possess a mild estrogenic characteristic. This study aimed to assess the correlation of the consumption of dietary PEs with ovarian cancer risk using data in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial. Participants were enrolled in PLCO from 1993 to 2001. Hazard ratios (HR) and 95% confidence intervals (CI) were utilized to determine the association between the intake of PEs and ovarian cancer occurrence, which were calculated by the Cox proportional hazards regression analysis. In total, 24 875 participants were identified upon completion of the initial dietary questionnaire (DQX). Furthermore, the analysis also included a total of 45 472 women who filled out the diet history questionnaire (DHQ). Overall, after adjustment for confounders, the dietary intake of total PEs was significantly associated with the risk of ovarian cancer in the DHQ group (HRQ4vsQ1 = 0.69, 95% CI: 0.50-0.95; P for trend = 0.066). Especially, individuals who consumed the highest quartile of isoflavones were found to have a decreased risk of ovarian cancer in the DHQ group (HRQ4vsQ1 = 0.68, 95% CI: 0.50-0.94; P for trend = 0.032). However, no such significant associations were observed for the DQX group. In summary, this study suggests that increased dietary intake of total PEs especially isoflavones was linked with a lower risk for developing ovarian cancer. More research is necessary to validate the findings and explore the potential mechanisms., (© The Author(s) 2024. Published by Oxford University Press.)

Endometriosis is a chronic condition affecting reproductive-aged women, characterized by the growth of ectopic endometrial tissue. Despite being benign, endometriosis is associated with an increased risk of certain cancers, including endometriosis-associated ovarian cancer (EAOC). Ovarian cancer is rare, but more common in women with endometriosis, particularly endometrioid and clear-cell carcinomas. Factors such as hormonal imbalance, reproductive history, environmental exposures, and genetic predisposition contribute to the malignant transformation of endometriosis. Thus, understanding potential risk factors causing malignancy is crucial. Over the past few decades, various genetic mutations, microRNAs, as well as tumor microenvironmental factors have been identified, impacting pathways like PI3K/AKT/mTOR, DNA repair mechanisms, oxidative stress, and inflammation. Thus, this review aims to summarize molecular studies involved in EAOC pathogenesis as potential therapeutic targets. However, further research is needed to better understand the molecular and environmental factors driving EAOC development, to target the susceptibility of endometriotic lesions to malignant progression, and to identify effective therapeutic strategies.

Background: Women's inability to recognize ovarian cancer (OC) causation myths to be incorrect may lead to behavioral changes that could distract them from actual risk factors and impact their treatment decision making. This study examined Palestinian women's recognition of OC mythical causes, and explored factors associated with good recognition., Methods: A national cross-sectional study was conducted. Adult Palestinian women were recruited from hospitals, primary healthcare facilities, and public areas in 11 governorates. The Cancer Awareness Measure-Mythical Causes Scale was modified and utilized for data collection. Awareness level was determined based on the number of myths around OC causation recognized to be incorrect: poor (0-4), fair (5-9), and good (10-13)., Results: A total of 5618 participants agreed and completed the questionnaire out of 6095 approached (response rate = 92.1%), and 5411 questionnaires were included in the final analysis. The most recognized food-related myth was 'drinking from plastic bottles' (n = 1370, 25.3%) followed by 'eating burnt food' (n = 1298, 24.0%). The least recognized food-related myth was 'eating food containing additives' (n = 611, 11.3%). The most recognized food-unrelated myth was 'having a physical trauma' (n = 2899, 53.6%), whereas the least recognized was 'using mobile phones' (n = 1347, 24.9%). Only 273 participants (5.1%) had good awareness of OC causation myths as incorrect. Earning higher monthly incomes as well as visiting governmental healthcare facilities were associated with a decrease in the likelihood of exhibiting good awareness., Conclusion: The overall recognition of OC causation myths was low. Addressing mythical beliefs should be included in OC prevention strategies and public health interventions to improve women's understanding of OC risk factors versus mythical causes., (© 2024. The Author(s).)

Objective: To investigate associations between air particulate matter of ≤2.5 μm in diameter (PM 2.5 ) and ovarian cancer., Design: County-level ecological study., Setting: Surveillance, epidemiology, and end results from a collection of state-level cancer registries across 744 counties. Data from the Environmental Protection Agency's network for PM 2.5 monitoring was used to calculate trailing 5- and 10-year PM 2.5 county-level values. County-level data on demographic characteristics were obtained from the American Community Survey., Population: A total of 98 751 patients with histologically confirmed ovarian cancer as a primary malignancy from 2000 to 2016., Methods: Generalised linear regression models were developed to estimate the association between PM 2.5 and PM 10 levels, over 5- and 10-year periods of exposure, and ovarian cancer risk, after accounting for county-level covariates., Main Outcome Measures: Risk ratios for associations between ovarian cancer (both overall and specifically epithelial ovarian cancer) and PM 2.5 levels., Results: For the 744 counties included, the average PM 2.5 level from 1990 through 2018 was 11.75 μg/m 3 (SD = 3.7) and the average PM 10 level was 22.7 μg/m 3 (SD = 5.7). After adjusting for county-level covariates, the overall annualised ovarian cancer incidence was significantly associated with increases in 5-year PM 2.5 (RR = 1.11 per 10 units (μg/m 3 ) increase, 95% CI 1.06-1.16). Similarly, when the analysis was limited to epithelial cell tumours and adjusted for county-level covariates there was a significant association with trailing 5-year PM 2.5 exposure models (RR = 1.12 per 10 units increase, 95% CI 1.08-1.17). Likewise, 10-year PM 2.5 exposure was associated with ovarian cancer overall and with epithelial ovarian cancer., Conclusions: Higher county-level ambient PM 2.5 levels are associated with 5- and 10-year incidences of ovarian cancer, as measurable in an ecological study., (© 2023 John Wiley & Sons Ltd.)

It is unclear how increasing body mass index (BMI) influences risk of cancer in young women. We used data from the Medical Birth, Patient and Cause of Death registers collected between 1982 and 2014 to determine the risk of obesity-related cancer types, breast cancer, all cancer and cancer-related death in relation to BMI in 1,386,725 women, aged between 18 and 45 years, in Sweden. During a median follow-up of 16.3 years (IQR 7.7-23.5), 9808 women developed cancer. The hazard ratio (HR) of endometrial and ovarian cancer increased with higher BMI from 1.08 (95% CI 0.93-1.24) and 1.08 (95% CI 0.96-1.21) among women with BMI 22.5-< 25 to 2.33 (95% CI 1.92-2.83) and 1.48 (95% CI 1.24-1.77), respectively, among women with BMI ≥ 30. There were linear and positive associations between BMI and incident cancer in the ovary, colon, endometrium, pancreas, rectum, gallbladder, esophageal cancer and renal cell carcinoma, as well as death from obesity-related cancer forms. In conclusion, we found that elevated BMI in young women linearly associated with several obesity-related cancer forms, including death from these cancers., (© 2024. The Author(s).)

The fear that the medical oncologist may have is that HIPEC integrated into a multidisciplinary care pathway will negatively impact the treatments that will follow. This fear is largely related to the side effects, which are themselves dependent on the medication used. Cisplatin, most frequently used for epithelial ovarian cancers, has essentially renal toxicity, which can be avoided by the use of sodium thiosulfate. Oxaliplatin induces more severe toxicities post surgery than mitomycin C in colorectal cancers. However, the data from randomized trials are reassuring for the medical oncologist concerning the course of postoperative treatment, as long as HIPEC is performed according to a standardized protocol, within trained teams, and after multidisciplinary discussion concerning its modalities., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

The association between glycemic index (GI),glycemic load (GL) and ovarian cancer risk remains unclear. Carbohydrate intake promotes insulin secretion, leading to cell proliferation and invasion. We hypothesized that high GI and GL intake may increase ovarian cancer risk. Therefore, we conducted a meta-analysis after systematically searching PubMed, Embase, Web of Science, and Cochrane Library from inception to December 2022. Fixed- or random-effect models calculated the pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs). Subgroup, sensitivity, publication bias analysis, and dose-response analysis were performed. Nine original studies were included, involving 4716 cases and 119,960 controls. No significant association was observed between GI or GL and ovarian cancer risk (GI: RR = 1.02 [95% CI, 0.83-1.26]; GL: RR = 1.11 [95% CI, 0.84-1.47]). Subgroup analysis suggested the results were not significantly modified by any group. Sensitivity analysis identified the sources of heterogeneity. No publication bias was observed. A linear positive dose-response relationship was observed between dietary GL and ovarian cancer risk after removing heterogeneous sources (RR = 1.11 [95% CI, 1.05-1.17], I 2 = 32.9%, P = .23 at 50 U/d; RR = 1.04 [95% CI, 1.02-1.07], I 2 = 19.1%, P = .29 at 20 U/d). These outcomes suggest that high dietary GL, but not GI, is associated with significantly increased ovarian cancer risk. Thus, sufficient intake of a low dietary GL is important for reducing ovarian cancer risk., Competing Interests: Declarations of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In recent years, the relationship between the microbiota and various aspects of health has become a focal point of scientific investigation. Although the most studied microbiota concern the gastrointestinal tract, recently, the interest has also been extended to other body districts. Female genital tract dysbiosis and its possible impact on pathologies such as endometriosis, polycystic ovary syndrome (PCOS), pelvic inflammatory disease (PID), and gynecological cancers have been unveiled. The incursion of pathogenic microbes alters the ecological equilibrium of the vagina, triggering inflammation and compromising immune defense, potentially fostering an environment conducive to cancer development. The most common types of gynecological cancer include cervical, endometrial, and ovarian cancer, which occur in women of any age but especially in postmenopausal women. Several studies highlighted that a low presence of lactobacilli at the vaginal level, and consequently, in related areas (such as the endometrium and ovary), correlates with a higher risk of gynecological pathology and likely contributes to increased incidence and worse prognosis of gynecological cancers. The complex interplay between microbial communities and the development, progression, and treatment of gynecologic malignancies is a burgeoning field not yet fully understood. The intricate crosstalk between the gut microbiota and systemic inflammation introduces a new dimension to our understanding of gynecologic cancers. The objective of this review is to focus attention on the association between vaginal microbiota and gynecological malignancies and provide detailed knowledge for future diagnostic and therapeutic strategies.

Opinion Statement: Homologous recombination deficiency (HRD) is an important biomarker guiding selection of ovarian cancer patients who will derive the most benefit from poly(ADP-ribose) polymerase inhibitors (PARPi). HRD prevents cells from repairing double-stranded DNA damage with high fidelity, PARPis limit single-stranded repair, and together these deficits induce synthetic lethality. Germline or somatic BRCA mutations represent the narrowest definition of HRD, but do not reflect all patients who will have a durable PARPi response. HRD can also be defined by its downstream consequences, which are measured by different metrics depending on the test used. Ideally, all patients will undergo genetic counseling and germline testing shortly after diagnosis and have somatic testing sent once an adequate tumor sample is available. Should barriers to one test be higher, pursuing germline testing with reflex to somatic testing for BRCA wildtype patients or somatic testing first strategies are both evidence-based. Ultimately both tests offer complementary information, germline testing should be pursued for any patient with a history of ovarian cancer, and somatic testing is valuable at recurrence if not performed in the upfront setting. There is a paucity of data to suggest superiority of one germline or somatic assay; therefore, selection should optimize turnaround time, cost to patients, preferred result format, and logistical burden. Each clinic should implement a standard testing strategy for all ovarian cancer patients that ensures HRD status is known at the time of upfront chemotherapy completion to facilitate comprehensive counseling about anticipated maintenance PARPi benefit., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: The benefits of exercise in reducing treatment-related morbidity and improving quality of life following a primary diagnosis of cancer have been well documented and have led to exercise being recommended by oncology societies for all people with a cancer diagnosis. However, these recommendations are derived from research typically involving cohorts with more common cancers and relatively good prognosis, such as breast and prostate. Evidence from these cancers may not apply to women with recurrent ovarian cancer. Therefore, the primary objective of this trial is to evaluate the feasibility and safety of a home-based, telephone-delivered exercise intervention for women undergoing chemotherapy for recurrent ovarian cancer., Methods and Analysis: The Exercise During Chemotherapy for Recurrent Ovarian Cancer (ECHO-R) trial is a single-arm, phase II, pre/postintervention trial of a 6-month, telephone-delivered exercise intervention (consistent with recommended exercise oncology prescription). The target sample size is 80 women who are currently undergoing (or are scheduled to receive) chemotherapy for recurrent ovarian cancer. Recruitment is through participating hospital sites in Queensland, Australia, or via self-referral. The exercise intervention comprises 12 telephone sessions over a 6-month period delivered by trial-trained exercise professionals and supplemented (where feasible) by five sessions face to face. Exercise prescription is individualised and works towards an overall goal of achieving a weekly target of 150 min of moderate-intensity, mixed-mode exercise. Assessments via self-administered survey and physical fitness and function tests occur at baseline and then at 6 and 9 months postbaseline. Data to inform feasibility and safety are recorded as case notes by the exercise professional during each session., Ethics and Dissemination: Ethics approval for the ECHO-R trial was granted by the Metro North Human Research Ethics Committee (HREC/2020/QRBW/67223) on 6 November 2020. Findings from the trial are planned to be disseminated via peer-reviewed publications and both national and international exercise and oncology conferences., Trial Registration Number: ACTRN12621000042842., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Recently, with the advancement of medical technology, the postoperative morbidity of pelvic exenteration (PE) has gradually decreased, and it has become a curative treatment option for some patients with recurrent gynecological malignancies. However, more evidence is still needed to support its efficacy. This study aimed to explore the safety and long-term survival outcome of PE and the feasibility of umbilical single-port laparoscopic PE for gynecologic malignancies in a single medical center in China., Patients and Methods: PE for gynecological cancers except for ovarian cancer conducted by a single surgical team in Sun Yat-sen University Cancer Center between July 2014 and December 2019 were included and the data were retrospectively analyzed., Results: Forty-one cases were included and median age at diagnosis was 53 years. Cervical cancer accounted for 87.8% of all cases, and most of them received prior treatment (95.1%). Sixteen procedures were performed in 2016 and before, and 25 after 2016. Three anterior PE were performed by umbilical single-site laparoscopy. The median operation time was 460 min, and the median estimated blood loss was 600 ml. There was no perioperative death. The years of the operations was significantly associated with the length of the operation time (P = 0.0018). The overall morbidity was 52.4%, while the severe complications rate was 19.0%. The most common complication was pelvic and abdominal infection. The years of surgery was also significantly associated with the occurrence of severe complication (P = 0.040). The median follow-up time was 55.8 months. The median disease-free survival (DFS) was 17.9 months, and the median overall survival (OS) was 25.3 months. The 5-year DFS was 28.5%, and the 5-year OS was 30.8%., Conclusion: PE is safe for patient who is selected by a multi-disciplinary treatment, and can be a curative treatment for some patients. PE demands a high level of experience from the surgical team. Umbilical single-port laparoscopy was a technically feasible approach for APE, meriting further investigation., (© 2024. The Author(s).)

Objective: To assess the association between childhood body fatness and epithelial ovarian cancer (EOC), and whether this association differs by type of EOC., Methods: Using data from a population-based case-control study (497 cases and 902 controls) in Montreal, Canada conducted 2011-2016, we examined the association between childhood body fatness and EOC, overall and separately for invasive vs. borderline EOCs. A figure rating scale was used to measure body fatness at ages 5 and 10. Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (95% CI). Quantitative bias analyses were conducted to assess the impact of exposure misclassification and non-participation., Results: The aOR (95% CI) of overall EOC for high vs. low body fatness was 1.07 (0.85-1.34) at age 5 and 1.28 (0.98-1.68) at age 10. The associations were stronger for invasive EOC, specifically the endometrioid histological type. For borderline cancers, the aORs were below the null value with wide confidence intervals. Bias analyses did not reveal a strong influence of non-participation. Non-differential exposure misclassification may have biased aORs towards the null for invasive cancers but did not appear to have an appreciable influence on the aORs for borderline cancers., Conclusions: Childhood body fatness may be a risk factor for invasive EOC in later adult life. Our study highlights the potential importance of examining early life factors for a comprehensive understanding of EOC development., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: The link between cruciferous vegetables (CVs) and ovarian cancer (OC) is still uncertain. This meta-analysis is intended to investigate the association between CV consumption and the risk of OC, as well as to conduct a dose-response analysis to determine the degree of correlation between them., Methods: We systematically searched PubMed, Web of Science, Embase, and Cochrane Library databases between database creation and October 2023. The present meta-analysis has been duly registered and assigned the registration number CRD42023470299. This study followed the PRISMA guidelines. The statistical analysis was performed using Stata 14.0 software., Results: There were a total of 7 cohort studies and 7 case-control studies with 7,269 cases and 742,952 subjects. The combined relative risk (RR) of the highest intake of CVs was 0.90 (95% confidence intervals [CIs]: 0.84-0.96; I2 = 54.7%; p = 0.007) compared to the lowest intake of CVs. The odds ratio (OR) was 0.97 (95% CIs: 0.86-1.08; p = 0.192) for cohort studies, and the RR was 0.79 (95% CIs: 0.67-0.91; p = 0.167) for case-control studies. The intake of CVs and the risk of OC were linearly correlated. Adding 15 g of CVs to the diet each day decreased the likelihood of developing OC by almost 4% (RR = 0.963, 95% CIs: 0.905-1.025; p = 0.235)., Conclusions: Consumption of CVs may be linked to a lower risk of OC., (© 2024 S. Karger AG, Basel.)

Polycystic ovary syndrome (PCOS) is a common hormonal disorder that affects women. It is characterized by hyperandrogenism, polycystic ovarian morphology, and other related disorders. It is associated with various health conditions, such as infertility and increased risk of heart problems. Ovarian cancer is also a significant concern, as it is the fifth leading cause of death in women. While there is evidence suggesting a potential association between PCOS and ovarian cancer, the exact nature of this relationship remains unclear. Thyroid disorders, particularly hypothyroidism and Hashimoto's thyroiditis, have also been linked to PCOS. The presence of hypothyroidism can contribute to the development of polycystic ovarian morphology, affecting ovulation and hormone balance. Many works have shown a higher ubiquity of autoimmune thyroid disease in PCOS patients, indicating a potential association between the two conditions. The occurrence of PCOS, hirsutism, and acne underscores the frequency of endocrine disorders in women. This review paper examines the present relevant work on the association between PCOS and ovarian cancer as well as PCOS and thyroid disorders. A systematic literature search was conducted on the internet, such as PubMed, Scopus, and Google Scholar database, to identify peer-reviewed publications pertaining to PCOS, ovarian cancer, and thyroid disorders. While some studies have delineated a significant link between PCOS and ovarian cancer or thyroid disorders, others have yielded inconclusive results. Further research is necessary to establish a definitive causal relationship between these conditions. Understanding the relationship between PCOS, ovarian cancer, and thyroid disorders is crucial for early detection, accurate diagnosis, and effective management of these conditions. Identifying potential risk factors and developing appropriate screening strategies can improve women's health outcomes and reduce the burden associated with these disorders., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The association between asbestos exposure and ovarian cancer has been questioned given the possible misdiagnosis of peritoneal mesothelioma as ovarian cancer., Aims: To update a systematic review on ovarian cancer risk in women occupationally exposed to asbestos, exploring the association with the time since first exposure and the duration of exposure., Methods: We searched PubMed from 2008 onwards, screened previous systematic reviews, combined standardized mortality ratios (SMR) using random effect models and quantified heterogeneity using the I2 statistic. To assess tumour misclassification, we compared the distribution of observed excess ovarian cancers (OEOC) to that expected (EEOC) from the distribution of peritoneal cancers in strata of latency and exposure duration., Results: Eighteen publications (20 populations), including a pooled analysis of 21 cohorts, were included. The pooled SMR was 1.79 (95% confidence interval 1.38-2.31), with moderate heterogeneity between studies (I2 = 42%), based on 144 ovarian cancer deaths/cases. The risk was increased for women with indirect indicators of higher exposure, longer duration and latency, and lower for chrysotile than for crocidolite exposure. The effect of duration and latency could not be completely disentangled, since no multivariate analysis was available for time-related variables. The dissimilarity index between OEOC and EEOC for the time since first exposure was small suggesting a similar pattern of risk., Conclusions: While some misclassification between ovarian and peritoneal cancers cannot be excluded, the observed excess risk of ovarian cancer should be added to the overall disease burden of asbestos., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

This study evaluated whether psychological stress increases the incidence of ovarian cancer. A literature search of the electronic databases PubMed and Web of Science from the date of inception to August 2022 was undertaken. Studies with data on psychosocial factors associated with ovarian cancer incidence were included in this study. A random-effect model meta-analysis was undertaken to estimate these data. We used subgroup analysis to adjust for heterogeneity. A total of 4 articles, 10 sets of data, 8 cohort studies, and 2 case-control studies from 682 records were included in this review. Meta-analyses of the included cohort study subgroups suggested that psychological factors increase the risk of ovarian cancer (effect size = 1.37, 95% CI: 1.20-1.53); the subgroup of case-control studies suggested that psychological factors did not increase ovarian cancer risk (effect size = 0.84, 95% CI: 0.70-0.98). These findings indicate that psychological stress is a possible new risk factor for ovarian cancer. Prospero registration number: CRD42022357983IMPACT STATEMENT What is already known on this subject? Psychological stress has been shown to increase the risk of many diseases. The relationship between psychological stress and the incidence of ovarian cancer has not been confirmed. What do the results of this study add? The effect of psychological stress on the risk of ovarian cancer was estimated using meta-analysis as an overall ratio. What are the implications of these findings for clinical practice and/or further research? Relaxing psychological stress and appropriate psychotherapy in clinical settings can help reduce the risk of ovarian cancer.

Opinion Statement: Ovarian carcinosarcoma (OCS), also known as a malignant mixed Müllerian tumour (MMMT), is a rare and aggressive form of cancer that accounts for less than 5% of ovarian cancers. It is characterized by high morbidity and mortality rates, with a median overall survival (OS) of less than 2 years. Several factors, including advancing age, nulliparity, reduced lactation rates, decreased use of oral contraceptive pills, genetic mutations in BRCA (breast cancer) genes, and the use of assisted reproductive technology, may increase the risk of OCS. Poor prognostic factors include an advanced stage at diagnosis, older age, lymph node metastasis, suboptimal surgical cytoreduction, the presence of heterologous features on histopathology, and increased expression of vascular endothelial growth factor (VEGF), tumour protein p53, and p53 alongside Wilms tumour 1 (WT1). The main treatment approach for OCS is cytoreductive surgery followed by platinum-based chemotherapy, although immunotherapy is showing promise. Homologous recombination deficiency (HRD) testing may enhance outcomes by enabling personalized immunotherapy and targeted therapies for specific patient groups, thereby reducing unnecessary side effects and healthcare costs. However, there is currently a lack of standardised treatment regimens for OCS patients, with most studies consisting of case reports and a shortage of suitable comparator groups. This article aims to provide clinicians with information on the epidemiology, risk factors, prognostic factors, and latest therapeutic advancements in OCS., (© 2023. Crown.)

Background: Testosterone plays a key role in women, but the associations of serum testosterone level with gynecological disorders risk are inconclusive in observational studies., Methods: We leveraged public genome-wide association studies to analyze the effects of four testosterone related exposure factors on nine gynecological diseases. Causal estimates were calculated by inverse variance-weighted (IVW), MR-Egger and weighted median methods. The heterogeneity test was performed on the obtained data through Cochrane's Q value, and the horizontal pleiotropy test was performed on the data through MR-Egger intercept and MR-PRESSO methods. "mRnd" online analysis tool was used to evaluate the statistical power of MR estimates., Results: The results showed that total testosterone and bioavailable testosterone were protective factors for ovarian cancer (odds ratio (OR) = 0.885, P = 0.012; OR = 0.871, P = 0.005) and endometriosis (OR = 0.805, P = 0.020; OR = 0.842, P = 0.028) but were risk factors for endometrial cancer (OR = 1.549, P < 0.001; OR = 1.499, P < 0.001) and polycystic ovary syndrome (PCOS) (OR = 1.606, P = 0.019; OR = 1.637, P = 0.017). dehydroepiandrosterone sulfate (DHEAS) is a protective factor against endometriosis (OR = 0.840, P = 0.016) and premature ovarian failure (POF) (OR = 0.461, P = 0.046) and a risk factor for endometrial cancer (OR= 1.788, P < 0.001) and PCOS (OR= 1.970, P = 0.014). sex hormone-binding globulin (SHBG) is a protective factor against endometrial cancer (OR = 0.823, P < 0.001) and PCOS (OR = 0.715, P = 0.031)., Conclusion: Our analysis suggested causal associations between serum testosterone level and ovarian cancer, endometrial cancer, endometriosis, PCOS, POF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Wang, Liu and Zhang.)

Background: Efforts have been made to investigate the role of salvage radiotherapy (RT) in treating recurrent ovarian cancer (ROC). Stereotactic ablative radiation therapy (SABR) is a state-of-the-art therapy that uses intensity modulation to increase the fractional dose, decrease the number of fractions, and target tumors with high precision., Methods: The SABR-ROC trial is a phase 3, multicenter, randomized, prospective study to evaluate whether the addition of SABR to the standard of care significantly improves the 3-year overall survival (OS) of patients with ROC. Patients who have completed the standard treatment for primary epithelial ovarian cancer are eligible. In addition, patients with number of metastases ≤ 10 and maximum diameter of each metastatic site of gross tumor ≤ 5 cm are allowed. Randomization will be stratified by (1) No. of the following clinical factors met, platinum sensitivity, absence of ascites, normal level of CA125, and ECOG performance status of 0-1; 0-3 vs. 4; (2) site of recurrence; with vs. without lymph nodes; and (3) PARP inhibitor; use vs. non-use. The target number of patients to be enrolled in this study is 270. Participants will be randomized in a 1:2 ratio. Participants in Arm 2 will receive SABR for recurrent lesions clearly identified in imaging tests as well as the standard of care (Arm 1) based on treatment guidelines and decisions made in multidisciplinary discussions. The RT fraction number can range from 1 to 10, and the accepted dose range is 16-45 Gy. The RT Quality Assurance (QA) program consists of a three-tiered system: general credentialing, trial-specific credentialing, and individual case reviews., Discussion: SABR appears to be preferable as it does not interfere with the schedule of systemic treatment by minimizing the elapsed days of RT. The synergistic effect between systemic treatment and SABR is expected to reduce the tumor burden by eradicating gross tumors identified through imaging with SABR and controlling microscopic cancer with systemic treatment. It might also be beneficial for quality-of-life preservation in older adults or heavily treated patients., Trial Registration: This trial was registered at ClinicalTrials.gov (NCT05444270) on June 29th, 2022., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: Our primary aim was to compare muscle morphology (skeletal muscle mass and density) between patients who underwent primary cytoreductive surgery versus interval cytoreductive surgery for advanced high-grade serous ovarian cancer. Secondarily, we explored the associations of muscle morphology with survival outcomes., Methods: We retrospectively analysed computed tomography (CT) images for 88 ovarian cancer patients (aged 38-89 years) to calculate skeletal muscle index (cm 2 /m 2 ) and skeletal muscle density (Hounsfield units (HU)). A skeletal muscle index of <38.5 cm 2 /m 2 and skeletal muscle density of <33.7 HU were classified as low. Analyses included repeated measures analysis of covariance and multivariable Cox proportional hazards regression., Results: At baseline, 44.3% of patients had low skeletal muscle index and 50.6% had low skeletal muscle density, with interval surgery patients having significantly lower mean skeletal muscle density than primary surgery patients (32.2±8.9 vs 37.3±8.6 HU, p=0.014). Although both groups had similar reductions in skeletal muscle index following treatment (p=0.49), primary surgery patients had a greater reduction in skeletal muscle density compared with interval surgery patients (-2.4 HU, 95% CI -4.3 to -0.5, p=0.016). Patients who experienced skeletal muscle density loss >2% during treatment (HR 5.16, 95% CI 1.33 to 20.02) and had low skeletal muscle density post-treatment (HR 58.87, 95% CI 3.70 to 935.68) had significantly worse overall survival., Conclusion: Low skeletal muscle index and skeletal muscle density were prevalent at ovarian cancer diagnosis. While both groups experienced muscle mass loss, greater reductions in skeletal muscle density occurred in patients undergoing primary surgery. In addition, skeletal muscle density loss during treatment and low skeletal muscle density post-treatment were associated with poorer overall survival. Supportive care involving resistance exercise targeting muscle hypertrophic drive, and nutrition counseling during and after ovarian cancer treatment may help preserve/enhance muscle mass and density., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Women with breast cancer have an increased risk of primary ovarian cancer (BR→OV), and women with ovarian cancer have an increased risk of primary breast cancer (OV→BR). This systematic review summarizes risk factors for developing BR→OV and OV→BR., Methods: We searched PubMed and Embase until June 2022., Results: We identified 23 articles meeting our inclusion criteria. Studies observed a lower risk of BR→OV for Black versus White women, alcohol consumption, radiotherapy and hormone therapy, BRCA2 versus BRCA1, and ER/PR positive versus negative breast tumors, and a higher risk with family history of breast/ovarian cancer, triple negative versus luminal breast cancer, and higher grade breast tumors. There was an increased risk of OV→BR with family history of cancer., Conclusions: Tumor characteristics, and genetic and familial factors are associated with risk of BR→OV and OV→BR. These results could aid clinicians in decision-making for breast and ovarian cancer patients, including risk-reducing strategies., Competing Interests: Declaration of Competing Interest Dr. Wright has received royalties from UpToDate and research support from Merck. All other authors have no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To determine the impact on overall survival (OS) and patient-reported outcomes (PROs) of combining atezolizumab with standard therapy for newly diagnosed stage III/IV ovarian cancer., Methods: The placebo-controlled double-blind randomized phase III IMagyn050/GOG 3015/ENGOT-OV39 trial (NCT03038100) assigned eligible patients to 3-weekly atezolizumab 1200 mg or placebo for 22 cycles with platinum-based chemotherapy and bevacizumab. Coprimary endpoints were progression-free survival (already reported) and OS in the PD-L1-positive and intent-to-treat (ITT) populations, tested hierarchically. Prespecified PRO analyses focused on disease-related abdominal pain and bloating symptoms (European Organisation for Research and Treatment of Cancer QLQ-OV28), functioning, and health-related quality of life (HRQoL) (QLQ-C30)., Results: After 38 months' median follow-up, the OS hazard ratio in the PD-L1-positive population was 0.83 (95% CI, 0.66-1.06; p = 0.13); median OS was not estimable with atezolizumab versus 49.2 months with placebo. The hazard ratio for OS in the ITT population was 0.92 (95% CI, 0.78-1.09; median 50.5 versus 46.6 months, respectively). At week 9, similar proportions of patients in both arms of the neoadjuvant cohort showed ≥10-point improvement from baseline in abdominal pain and bloating, functioning, and HRQoL. In the primary surgery cohort, similar proportions of patients in each arm had improved, stable, or worsened physical and role function and HRQoL from baseline over time. Neither cohort showed differences between arms in treatment-related symptoms or overall side-effect bother., Conclusions: Incorporation of atezolizumab into standard therapy for newly diagnosed ovarian cancer does not significantly improve efficacy or impose additional treatment burden for patients., Clinicaltrials: gov registration: NCT03038100., Competing Interests: Declaration of Competing Interest Sandro Pignata: Personal fees (Roche, AstraZeneca, MSD, PharmaMar, GSK, Clovis, Incyte); Research funding to institution (Roche, MSD, AstraZeneca, Clovis, GSK). Michael Bookman: Administrative and per-capita funding for conduct of the clinical trial paid to institution; Consultation fees paid to institution for ad hoc advisory boards (Merck Sharp & Dohme, AstraZeneca, Genentech/Roche, Clovis Oncology, Seattle Genetics, Aravive, AbbVie) and Data Monitoring Committee (Immunogen). Jalid Sehouli: Research funding (Roche Pharma, AstraZeneca, Bayer, Clovis Oncology, GSK, Lilly, Tesaro); Honoraria (Tesaro, GSK, PharmaMar, AstraZeneca, Clovis Oncology, Bayer, Roche, PharmaMar, Vifor Pharma, Hexal AG, Novartis Pharma); Consulting (Tesaro, Merck/Pfizer, PharmaMar, Clovis Oncology, AstraZeneca, Roche Pharma, GSK, MSD, Eisai, Novocure, Oncoinvent). Richard T. Penson: Institutional research funding as principal investigator (Array BioPharma Inc., AstraZeneca., Eisai Inc., Genentech, Inc., Regeneron, Sanofi-Aventis US LLC, Vascular Biogenics Ltd); Royalties (BMJ Publishing, UptoDate, Elsevier Ltd., Wolters Kluwer Health, Wiley Blackwell); Consulting fees for advisory boards (AstraZeneca, Eisai, GSK Inc., ImmunoGen Inc., Merck & Co., Mersana, Novacure, Roche Pharma, Sutro Biopharma, Vascular Biogenics Ltd); serves on Data and Safety Monitoring Boards (AstraZeneca, EQRx, Roche Pharma). Sakari Hietanen: Consultancy fees (AstraZeneca, Eisai, MSD, GSK); Speaker bureau (AstraZeneca, GSK). Radoslaw Madry: Licences/payments (AstraZeneca); Consulting fees (Roche, MSD, AstraZeneca); Honoraria (GSK, AstraZeneca, Roche); Support for attending meetings and/or travel (AstraZeneca, Roche); Participation on Data Safety Monitoring or Advisory Boards (GlaxoSmithKline, AstraZeneca); Receipt of equipment, materials, drugs, medical writing, gifts, or other services (AstraZeneca). Lyndsay Willmott: Honoraria for speaker bureau (AstraZeneca, Clovis, Eisai, Immunogen, GSK, Merck, Seagen); Honoraria for advisory bureau (Genentech); Participation on advisory boards (AstraZeneca, Clovis, Eisai, Genentech, GSK, Immunogen, Seagen). Tashanna Myers: Personal honorarium for lecture (Immunogen); Honorarium to institution for advisory board (Immunogen). Alain Lortholary: Personal honoraria (AstraZeneca, Clovis Oncology, Tesaro/GSK, Roche, MSD, Novartis). Jessica Thomes-Pepin: Consulting fees for advisory board (Immunogen). Carol Aghajanian: Clinical trial funding to institution (AbbVie, AstraZeneca, Clovis, Genentech/Roche); Consulting fees for advisory boards (AbbVie, Roche/Genentech, Eisai/Merck, AstraZeneca/Merck, Repare Therapeutics); Participation on an advisory board (Blueprint medicine [unrecompensed]); Membership of the Board of Directors (GOG-F [travel cost reimbursement for attending meetings], NRG Oncology [unpaid]). Carolyn McCourt: Royalties (UpToDate). Ashley Stuckey: Royalties (UpToDate). Xiaohua Wu: Honorarium for advisory board (Roche). Larry J. Copeland: DMC membership (Corcept Therapeutics, Inc.); Personal fees for advisory boards (Celsion Corporation, Corcept Therapeutics, Inc., Elevar Therapeutics, GSK Inc., Immunogen, Myriad Genetics, Inc., Rubius Therapeutics, Sorrento Therapeutics, Toray Industries, Inc., VBL Therapeutics, Inc., OncoNova, Inc., Inx Med); Research funding to institution (AbbVie, Advaxis, Agenus, Ajinomoto, Array BioPharm, AstraZeneca, Bristol Myers Squibb, Clovis Oncology, Deciphera Pharma, Eisai, EMD Serono Inc., ERGOMED Clinical Research, Exelixis, Genentech/Roche, Genmab, GSK, Inc., Hoffmann-La Roche, Immunogen, Incyte Corporation, Iovance Biotherapeutics, InVentive Health Clinical, Jansen R&D, Leap Therapetuics, Ludwig Institute for Pharmaceuticals, Merck, Mersana Therapeutics, Inc., Novocure, Novartis Pharmaceuticals, OncoQuest, PRA International, Regeneron Pharmaceuticals, Seattle Genetics, Serono, Sutro Biopharm, Tesaro (GSK), Arcus Biosciences, Inc., Sumitomo Dainippon Pharma Oncology, Cerulean Pharma, Karyopharm, BeiGene USA, Inc., Ovagene, Pfizer Inc., PharmaMar USA Inc.,Precision Therapeutics, Inc., Sanofi, Stemcentrx, Inc., TRACON Pharm, Verastem, Inc.). Yvette He: Employee contracted to provide statistical support to Roche (Parexel). Luciana Molinero, Sheetal Patel, and Victor K. Khor: Employees (Roche/Genentech); Share holders (Roche). Yvonne G. Lin: Employee (Roche/Genentech); Participation on Advisory Board (Intervenn Biosciences, unpaid); Leadership position/committee member (SGO Membership Committee); Share holder (Roche). Kathleen N. Moore: Research funding to institution (PTC Therapeutics, Lilly, Clovis, Genentech, GSK, Verastem), Personal royalties (UptoDate), Personal consulting fees for advisory boards (Aadi, Alkemeres, Aravive, AstraZeneca, Blueprint pharma, Caris, Clovis, Eisai, Genentech/Roche, GSK, Hengrui, Immunogen, Inxmed, IMab, Iovance, Lilly, Merck, Mereo, Mersana, Myriad, Novartis, Novocure, Onconova, OncXerna, Pannavance, Tarveda, VBL Therapeutics, Verastem); Personal honoraria for lectures/presentations/speaker bureau (AstraZeneca, GSK, Immunogen, PRIME, RTP, Medscape, Great Debates and Updates); Support for attending meetings and/or travel (AstraZeneca); Leadership role (GOG Partners Associate director). All authors: Medical writing and article processing charges (F. Hoffmann-La Roche)., (Copyright © 2023. Published by Elsevier Inc.)

Objective: Recent theories propose that most epithelial ovarian cancer (EOC), depending on histological type, originate from other gynecological tissues and involve the ovary secondarily. According to these theories, any protective effect of salpingectomy and tubal ligation may vary by histological type. The study aim was to examine the association between salpingectomy and tubal ligation, respectively, and risk of EOC, with a focus on associations specific for histological types., Methods: We identified EOC cases and matching controls in national registries and gathered information on surgical procedures and potential confounders. Conditional logistic regression was used to estimate odds ratio (OR) with 95% confidence interval (CI) of EOC related to salpingectomy and tubal ligation, respectively, overall and stratified by histological type. Furthermore, we investigated the association according to timing of the procedures., Results: Our study comprised 16,822 EOC cases. Each case was matched with 40 controls. There was an overall EOC risk reduction after unilateral (OR = 0.73; 95% CI: 0.60-0.87) and bilateral salpingectomy (OR = 0.46; 95% CI: 0.31-0.67). A slight risk reduction was seen among women with previous tubal ligation (OR = 0.91; 95% CI: 0.83-0.99). For salpingectomy, the risk reduction increased with increasing time since the surgical procedure and was only present among women younger than 50 years at salpingectomy. Unilateral and bilateral salpingectomy was associated with a risk reduction for most histological types., Conclusion: The association between previous salpingectomy and reduced risk of several histological subtypes of EOC supports the suggested theories about the site of origin of EOC and may be of clinical importance., Competing Interests: Declaration of Competing Interest The authors declare no potential conflict of interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

An association between polycystic ovary syndrome (PCOS) and epithelial ovarian tumors is biologically plausible as conditions inherent to PCOS such as excessive androgenic hormones, reproductive factors and obesity are also risk factors for these hormone-sensitive tumors. However, previous studies have showed conflicting results and have various methodological limitations. This population-based cohort study investigates the association between PCOS and epithelial ovarian tumors and includes all women born in Denmark between January 1, 1940 and December 31, 1993 (n = 1 719 304). PCOS diagnoses, ovarian cancer and borderline ovarian tumor diagnoses, covariates, migration and vital status were obtained from the Danish national registers. Adjusted cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CI) for epithelial ovarian cancer and for borderline ovarian tumors overall as well as for histological subtypes separately. During median 26 years of follow-up we identified 6490 women with ovarian cancer and 2990 women with borderline ovarian tumors. Overall, we observed no marked associations between a diagnosis of PCOS and overall epithelial ovarian cancer or overall epithelial borderline ovarian tumors, irrespective of time since diagnosis. However, we found an increased risk of ovarian cancer among postmenopausal women with PCOS (HR 2.28 95% CI 1.02-5.09) and an increased risk of serous borderline ovarian tumors (HR 2.34 95% CI 1.21-4.53) in women with PCOS compared with women without PCOS. Importantly, low statistical precision is a crucial limitation of our study and in previous studies and larger studies with longer follow-up are therefore warranted., (© 2023 UICC.)

Objectives: To investigate employment in an occupation or industry and specific occupational exposures in relation to ovarian cancer risk., Methods: In a population-based case-control study conducted in Montreal, Canada (2011-2016), lifetime occupational histories were collected for 491 cases of ovarian cancer and 897 controls. An industrial hygienist coded the occupation and industry of each participant's job. Associations with ovarian cancer risk were estimated for each of several occupations and industries. Job codes were linked to the Canadian job-exposure matrix, thereby generating exposure histories to many agents. The relationship between exposure to each of the 29 most prevalent agents and ovarian cancer risk was assessed. Odds ratios and 95% confidence intervals (OR (95% CI)) for associations with ovarian cancer risk were estimated using logistic regression and controlling for multiple covariates., Results: Elevated ORs (95% CI) were observed for employment ≥10 years as Accountants (2.05 (1.10 to 3.79)); Hairdressers, Barbers, Beauticians and Related Workers (3.22 (1.25 to 8.27)); Sewers and Embroiderers (1.85 (0.77 to 4.45)); and Salespeople, Shop Assistants and Demonstrators (1.45 (0.71 to 2.96)); and in the industries of Retail Trade (1.59 (1.05 to 2.39)) and Construction (2.79 (0.52 to 4.83)). Positive associations with ORs above 1.42 were seen for high cumulative exposure versus never exposure to 18 agents: cosmetic talc, ammonia, hydrogen peroxide, hair dust, synthetic fibres, polyester fibres, organic dyes and pigments, cellulose, formaldehyde, propellant gases, aliphatic alcohols, ethanol, isopropanol, fluorocarbons, alkanes (C5-C17), mononuclear aromatic hydrocarbons, polycyclic aromatic hydrocarbons from petroleum and bleaches., Conclusions: Certain occupations, industries and specific occupational exposures may be associated with ovarian cancer risk. Further research is needed to provide a more solid grounding for any inferences in this regard., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: MetS is associated with greater morbidity and mortality in relation to a number of malignancies, but its association with ovarian cancer remains contested. The present study was a systematic review and meta-analysis of case-control and cohort studies examining the association between MetS and ovarian cancer risk., Methods: The study was registered on the PROSPERO platform in January 2023 (CRD42023391830). Up until February 13, 2023, a complete search was undertaken in PubMed, EMBASE, Web of Science, the Cochrane Library, and ClinicalTrials. On the basis of inclusion and exclusion criteria, eligible studies for meta-analysis were screened to determine the association between MetS and ovarian cancer risk., Results: Five studies were included in total, including three cohort studies and two case-control studies. Meta-analysis showed no significant correlation between metabolic syndrome and ovarian cancer (OR=1.29, 95% CI: 0.90-1.84). Significant heterogeneity (I 2 = 92.6, P<0.05) existed between the included studies. We performed a subgroup analysis of the risk of bias and showed that only unadjusted stratification of risk of bias for smoking (OR= 3.19, 95% CI: 2.14-4.76) and hysterectomy (OR= 3.19, 95% CI: 2.14-4.76) demonstrated a relationship between metabolic syndrome and ovarian cancer risk. The meta-regression analysis revealed that smoking and hysterectomy excision were substantially linked with heterogeneity (p < 0.05)., Conclusion: Our research revealed no statistically significant association between MetS and ovarian cancer risk. The prevalence of metabolic syndrome has highlighted the need of enhancing and controlling women's metabolic health. However, the evaluation of metabolic syndrome as a cancer risk factor may be deceptive and etiologically uninformative., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Liu, Yang, Liu and Kong.)

Objective: Mode of delivery has long-term implications on the mother, including recent data regarding the level of transmission of fetal microchimeric cells (FMc) and their possible effect on cancer development. We aimed to evaluate the association between cesarean section (CS) and future risk for neoplasms., Study Design: A population-based cohort analysis comparing the long-term risk for neoplasms between patients that delivered only by CS to those that delivered only vaginally (VD). Neoplasms were pre-defined based on ICD-9 codes. Deliveries occurred between the years 1991-2017 in a tertiary medical center. Kaplan-Meier survival curves were used to compare the cumulative incidence of neoplasms and Cox proportional hazards models were constructed to control for confounders., Results: During the study period 105,992 patients met the inclusion criteria; 14150 (13.4%) of patients had only CS and 91842 (86.6%) had VD (comparison group). The CS group had significantly higher incidence of benign and malignant neoplasms (4.73 per 1000 patient-years versus 3.88 per 1000 patient-years, OR = 1.26, 95% CI 1.16-1.37; p = 0.001; 2.19 per 1000 patient-years of follow up versus 1.93 per 1000 patient-years, OR = 1.16, 95% CI 1.03-1.31; p = 0.013). Specifically, the CS group had higher incidence of uterine cancer (1.2 versus 0.06 per 1000 patient-years, OR = 1.97, 95% CI 1.14-3.39; p = 0.013). The cumulative incidence of benign, malignant and uterine neoplasms was significantly higher in the CS group (Log rank test p = 0.001; 0.036 and 0.014; respectively). Importantly, no significant association was found with breast and ovarian malignancies." When performing a Cox regression model controlling for confounders, the risk for malignancy-related hospitalizations remained significant (adjusted HR = 1.22, 95% CI 1.01-1.48; p = 0.031) but not for uterine cancer (adjusted HR = 1.6, 95% CI 0.9-2.8; p = 0.103)., Conclusion: Our findings provide support to linkage between delivery by cesarean section and future maternal malignancy., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Although folate intake has not been associated with an increased risk of ovarian cancer overall, studies of other cancer types have suggested that high folate intake may promote carcinogenesis in precancerous lesions. Women with endometriosis (a potential precancerous lesion) have an increased risk of developing ovarian cancer; however, whether high folate intake increases risk in this group is unknown., Methods: We conducted a pooled analysis of six case-control studies from the Ovarian Cancer Association Consortium to investigate the association between folate intake and risk of ovarian cancer among women with and without self-reported endometriosis. We included 570 cases/558 controls with and 5,171/7,559 without endometriosis. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals for the association between folate intake (dietary, supplemental, and total) and ovarian cancer risk. Finally, we used Mendelian randomization (MR) to evaluate our results using genetic markers as a proxy for folate status., Results: Higher dietary folate intake was associated with an increased risk of ovarian cancer for women with endometriosis [OR, 1.37 (1.01-1.86)] but not for women without endometriosis. There was no association between supplemental folate intake and ovarian cancer risk for women with or without endometriosis. A similar pattern was seen using MR., Conclusions: High dietary folate intake may be associated with an increased risk of ovarian cancer among women with endometriosis., Impact: Women with endometriosis with high folate diets may be at increased risk of ovarian cancer. Further research is needed on the potential cancer-promoting effects of folate in this group., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background: Observational investigations examining cancer risk among multiple sclerosis (MS) patients have produced contradictory findings. Herein, we performed an extensive review and meta-analysis to evaluate the correlation and causation between MS and cancer incidence., Methods: We systematically screened for published articles examining cancer incidences among MS patients within the Cochrane Library, PubMed, and Embase databases. Next, we employed STATA v.16.0 for data analysis. Following meta-analysis, we performed a two-sample Mendelian randomization (MR) analysis to uncover the underlying mechanism behind the MS-mediated regulation of certain cancers., Results: Overall, we selected 18 articles encompassing 14 individual cancers incidences and a total of 368,952 patients for meta-analysis. Based on our analysis, there was reduced pancreatic (ES = 0.68; 95% CI: 0.49-0.93; I 2 = 0%) and ovarian cancer (ES = 0.65; 95% CI: 0.53-0.80; I 2 = 86.7%) co-occurrences among MS patients. Meanwhile, the incidences of breast (ES = 1.10; 95% CI: 1.01-1.21; I 2 = 60.9%) and brain cancers (ES = 1.94; 95% CI: 1.12-3.37; I 2 = 56.1%) were elevated among the same population. However, MR analysis revealed the opposite relation between MS and breast cancer risk (OR = 0.94392; 95% CI: 0.91011-0.97900, P = 0.002). Moreover, it revealed strong incidence of lung cancer (OR = 1.0004; 95% CI: 1.0001-1.0083, P = 0.001) among MS patients, as evidenced by the inverse variance weighting estimator. Lastly, MR found that other forms of cancers were not significantly related to MS., Conclusions: Using meta-analysis, we demonstrated that MS patients exhibited enhanced pancreatic and ovarian cancer risk, and diminished breast and brain cancer risk. However, using MR analysis, we discovered an inverse relation between MS and breast cancer risk, and additionally saw an uptick in lung cancer co-occurrence among MS patients., Competing Interests: Declaration of Competing Interest None of the authors declare any potential conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Purpose: Patients with platinum-resistant ovarian cancer respond poorly to existing therapies. Hence there is a need for more effective treatments., Patients and Methods: The DeCidE1 trial is a multicenter, randomized, open-label, single-arm phase II study to evaluate the safety and effectiveness of maveropepimut-S with cyclophosphamide in patients with recurrent ovarian cancer. Median follow-up for evaluable subjects was 4.4 months. Data were collected from March 2019 to June 2021. Subjects received two injections of 0.25 mL maveropepimut-S 3 weeks apart, followed by one 0.1-mL doses, every 8 weeks up to progression. Oral cyclophosphamide, 50 mg twice daily, was administered in repeating weekly on and off cycles., Results: Twenty-two patients were enrolled. Median age was 58 years (38-78 years). Among the evaluable population, the objective response rate (ORR) was 21% [90% confidence interval (CI), 7.5%-41.9%], with a disease control rate (DCR) of 63% (90% CI, 41.8%-81.3%), including 4 (21%) patients with partial responses, 8 (42%) stable disease, and 7 (37%) progressive disease. The ORRs were consistent across subgroups based on platinum sensitivity, and DCR was higher in the platinum-resistant subpopulation. Four SD patients maintained clinical benefit up to 25 months. Most treatment-related adverse events (TRAE) were grade 1 and 2 (87% of unique events). Most common AEs were injection site reactions. Eight subjects reported grade 3 and no grade 4 AEs. Survivin-specific T-cell responses were observed in treated patients with clinical benefit., Conclusions: Maveropepimut-S with intermittent low-dose cyclophosphamide is well-tolerated, with clinical benefit for patients with recurrent ovarian cancer. Observed responses are irrespective of the platinum status., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background: Few modifiable risk factors for epithelial ovarian cancer have been identified. We and other investigators have found that individual psychosocial factors related to distress are associated with higher risk of ovarian cancer. The present study examined whether co-occurring distress-related factors are associated with ovarian cancer risk., Methods: Five distress-related factors were measured repeatedly over 21 years of follow-up: depression, anxiety, social isolation, widowhood, and, in a subset or women, posttraumatic stress disorder (PTSD). Cox proportional hazards models estimate relative risks (RR) and 95% confidence intervals (CI) of ovarian cancer for a time-updated count of distress-related factors, in age-adjusted models, then further adjusted for ovarian cancer risk factors and behavior-related health risk factors., Results: Across 1,193,927 person-years of follow-up, 526 incident ovarian cancers occurred. Women with ≥3 versus no distress-related psychosocial factors demonstrated increased ovarian cancer risk (HR age-adjusted  = 1.71; 95% CI = 1.16, 2.52). No significant difference in ovarian cancer risk was observed in women with one or two versus no distress-related psychosocial factors. In the subsample with PTSD assessed, ≥3 versus no distress-related psychosocial factors was associated with twofold greater ovarian cancer risk (HR age-adjusted  = 2.08, 95% CI = 1.01, 4.29). Further analysis suggested that women at highest ovarian cancer risk had PTSD co-occurring with any other distress-related factor (HR = 2.19, 95% CI = 1.20, 4.01). Adjusting for cancer risk factors and health behaviors minimally impacted risk estimates., Conclusions: Presence of multiple indicators of distress was associated with risk of ovarian cancer. When including PTSD as an indicator of distress, the association was strengthened., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: To evaluate the effectiveness and safety of nab-paclitaxel plus platinum as first-line chemotherapy for ovarian cancer (OC)., Methods: Patients administered platinum combined with nab-paclitaxel as first-line chemotherapy for epithelial OC, fallopian tube cancer, or primary peritoneal cancer from July 2018 to December 2021 were retrospectively evaluated. The primary outcome was progression-free survival (PFS). Adverse events (AEs) were examined. Subgroup analysis was performed., Results: Seventy-two patients (median age, 54.5 years; range, 20.0-79.0 years) were evaluated, including 12 and 60 administered neoadjuvant therapy and primary surgery with subsequent chemotherapy, respectively. The median follow-up duration was 25.6 months, and the median PFS was 26.7 (95% confidence interval [CI]=24.0-29.3) months in the whole patient population. In the neoadjuvant subgroup, the median PFS was 26.7 (95% CI=22.9-30.5) months vs. 30.1 (95% CI=23.1-37.1) months in the primary surgery subgroup. Twenty-seven patients were administered nab-paclitaxel plus carboplatin and had a median PFS of 30.3 (95% CI=not available [NA]-NA) months. The commonest grade 3-4 AEs included anemia (15.3%), white blood cell decreased (11.1%), and neutrophil count decreased (20.8%). No drug-related hypersensitivity reactions occurred., Conclusion: Nab-paclitaxel plus platinum as first-line treatment in OC was associated with a favorable prognosis and was tolerable in patients with OC., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2023. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Background: This nationwide, register-based case-control study investigated the association between hysterectomy and risk of epithelial ovarian cancer according to histology and by history of endometriosis and menopausal hormone therapy (MHT) use., Methods: From the Danish Cancer Registry, all women registered with epithelial ovarian cancer at age 40-79 years during 1998-2016 were identified (n = 6738). Each case was sex- and age-matched to 15 population controls using risk-set sampling. Information on previous hysterectomy on benign indication and potential confounders was retrieved from nationwide registers. Conditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for the association between hysterectomy and ovarian cancer according to histology, endometriosis, and use of MHT., Results: Hysterectomy was not associated with risk of epithelial ovarian cancer overall (OR=0.99; 95% CI 0.91 -1.09) but was associated with reduced risk of clear cell ovarian cancer (OR=0.46; 95% CI 0.28-0.78). In stratified analyses, decreased ORs associated with hysterectomy were seen in women with endometriosis (OR=0.74; 95% CI 0.50-1.10) and in non-users of MHT (OR=0.87; 95% CI 0.76-1.01). In contrast, among long-term MHT users, hysterectomy was associated with increased odds for ovarian cancer (OR=1.20; 95% CI 1.03-1.39)., Conclusion: Hysterectomy was not associated with epithelial ovarian cancer overall but with reduced risk of clear cell ovarian cancer. Our findings may suggest a reduced risk of ovarian cancer after hysterectomy in women with endometriosis and in MHT non-users. Interestingly our data pointed to an increased ovarian cancer risk associated with hysterectomy among long-term users of MHT., Competing Interests: Declaration of Competing Interest Lene Mellemkjær has an immediate family member employed at Novo Nordisk, and has an immediate family member who owns stocks in Novo Nordisk. All other authors declare no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: To investigate the association between alcohol intake over the lifetime and the risk of overall, borderline, and invasive ovarian cancer., Methods: In a population-based case-control study of 495 cases and 902 controls, conducted in Montreal, Canada, average alcohol intake over the lifetime and during specific age periods were computed from a detailed assessment of the intake of beer, red wine, white wine and spirits. Multivariable logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the association between alcohol intake and ovarian cancer risk., Results: For each one drink/week increment in average alcohol intake over the lifetime, the adjusted OR (95% CI) was 1.06 (1.01-1.10) for ovarian cancer overall, 1.13 (1.06-1.20) for borderline ovarian cancers and 1.02 (0.97-1.08) for invasive ovarian cancers. This pattern of association was similarly observed for alcohol intake in early (15- < 25 years), mid (25- < 40 years) and late adulthood (≥ 40 years), as well as for the intake of specific alcohol beverages over the lifetime., Conclusions: Our results support the hypothesis that a higher alcohol intake modestly increases the risk of overall ovarian cancer, and more specifically, borderline tumours., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: The role of ovulation in epithelial ovarian cancer (EOC) is supported by the consistent protective effects of parity and oral contraceptive use. Whether these factors protect through anovulation alone remains unclear. We explored the association between lifetime ovulatory years (LOY) and EOC., Methods: LOY was calculated using 12 algorithms. Odds ratios (ORs) and 95% confidence intervals (CIs) estimated the association between LOY or LOY components and EOC among 26 204 control participants and 21 267 case patients from 25 studies. To assess whether LOY components act through ovulation suppression alone, we compared beta coefficients obtained from regression models with expected estimates assuming 1 year of ovulation suppression has the same effect regardless of source., Results: LOY was associated with increased EOC risk (OR per year increase = 1.014, 95% CI = 1.009 to 1.020 to OR per year increase = 1.044, 95% CI = 1.041 to 1.048). Individual LOY components, except age at menarche, also associated with EOC. The estimated model coefficient for oral contraceptive use and pregnancies were 4.45 times and 12- to 15-fold greater than expected, respectively. LOY was associated with high-grade serous, low-grade serous, endometrioid, and clear cell histotypes (ORs per year increase = 1.054, 1.040, 1.065, and 1.098, respectively) but not mucinous tumors. Estimated coefficients of LOY components were close to expected estimates for high-grade serous but larger than expected for low-grade serous, endometrioid, and clear cell histotypes., Conclusions: LOY is positively associated with nonmucinous EOC. Differences between estimated and expected model coefficients for LOY components suggest factors beyond ovulation underlie the associations between LOY components and EOC in general and for non-HGSOC., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aim: Real-world data on treatment patterns and outcomes of advanced ovarian cancer (OC) patients since bevacizumab approval in first-line (1L) OC treatment were assessed. Materials & methods: In this descriptive retrospective study using the ConcertAI Oncology Dataset, patient characteristics, treatment patterns and real-world progression-free survival (rwPFS) from start of 1L were evaluated among patients diagnosed with advanced OC between 2011-2020. Treatment data from structured sources were confirmed and/or supplemented by human review of unstructured data. Results: Median rwPFS for bevacizumab and non bevacizumab cohorts was 17.3 months (95% CI: 14.9, 20.4) and 15.7 months (95% CI: 12.3, 29.1), respectively. Patients with ≥10 doses during 1L had higher median rwPFS compared with patients receiving 3-9 doses. Conclusion: This real-world study suggests benefits of bevacizumab treatment in advanced OC were primarily experienced by patients who received ≥10 doses in 1L.

Objective: This study aimed to evaluate the risk of ovarian cancer associated with hormone therapy regimens using a Korean population-based study., Methods: This retrospective cohort study used national health checkup and insurance data from January 1, 2002, to December 31, 2019, provided by Korea's National Health Insurance Service. Women older than 40 years who recorded "menopause" in the questionnaire from 2002 to 2011 were included in this study. Menopausal hormone therapy (MHT) preparations were classified into tibolone, combined estrogen plus progestin by the manufacturer, combined estrogen plus progestin by physician, estrogen, and topical estrogen groups. The number of participants recorded as menopausal during the national health examination between 2002 and 2011 was 2,506,271. The MHT and non-MHT groups consisted of 373,271 and 1,382,653 patients, respectively. The hazard ratios (HR) of ovarian cancer according to MHT type, age at inclusion, body mass index, region, socioeconomic status, Charlson comorbidity index, age at menarche, age at menopause, parity, smoking, alcohol consumption, physical exercise, and period from menopause to inclusion were evaluated., Results: The risk of ovarian cancer was reduced in the tibolone group (HR, 0.84; 95% confidence interval, 0.75-0.93; P = 0.003) and in patients in rural areas (HR, 0.90; 95% confidence interval, 0.845-0.98; P = 0.013). The risk of ovarian cancer was not related to the other MHT treatments., Conclusion: Tibolone was associated with a lower risk of ovarian cancer. No other MHT was associated with ovarian cancer., Competing Interests: Financial disclosure/conflicts of interest: None reported., (Copyright © 2023 by The North American Menopause Society.)

Introduction: This study aimed to verify the association between ovarian cancer (OC) and reproductive- and lifestyle-related risk factors stratified by the subtype of OC., Methods: In this matched case-control study derived from the Korean epithelial ovarian cancer study (Ko-EVE), we calculated the risk of OC subtypes using odds ratios (ORs) and 95% confidence intervals (95% CIs) in a logistic regression model., Results: As a result of matching, 531 cases and 2,124 controls were selected. Smoking had positive association with high-grade serous (HGS) OC (OR = 2.69, 95% CI = 1.15-6.30), whereas alcohol consumption had positive association with mucinous type (MUC) (OR = 3.63, 95% CI = 1.39-9.49). Obesity (≥30 kg/m 2 ) was associated with clear cell type (CLC) (OR = 4.57, 95% CI = 1.06-19.77). Spontaneous abortion was negatively associated with CLC (OR = 0.34, 95% CI = 0.13-0.90), in contrast to HGS (OR = 1.43, 95% CI = 0.96-2.15). Tubal ligation, hysterectomy, and oophorectomy were associated with decreased risk of HGS (OR = 0.14, 95% CI = 0.05-0.39; OR = 0.23, 95% CI = 0.07-0.73; OR = 0.28, 95% CI = 0.08-0.97, respectively). Early menarche was strongly associated with increased risk of CLC, but not MUC (OR = 6.11, 95% CI = 1.53-24.42; OR = 3.23, 95% CI = 0.98-10.86). Further, childbirth (≥2 times) was negatively associated with endometrioid type OC and CLC (OR = 0.11, 95% CI = 0.04-0.35; OR = 0.12, 95% CI = 0.02-0.37, respectively). Oral contraceptives and hormone replacement therapy were negatively associated with OC (OR = 0.61, 95% CI = 0.40-0.93; OR = 0.51, 95% CI = 0.32-0.80, respectively), and similar negative associations were also observed in HGS (OR = 0.69; OR = 0.60, respectively). Associations between family history of breast cancer and OC, regular exercise (≥5/week), and artificial abortion and OC were similar across all subtypes (OR = 3.92; OR = 0.41; OR = 0.72, respectively)., Conclusion: A heterogeneous association between some risk factors and the incidence of each subtype of epithelial OC was observed, suggesting that the carcinogenic mechanisms of each subtype may be partly different., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: The objective of this study was to evaluate the efficacy of gemcitabine plus nab-paclitaxel in patients with recurrent ovarian cancer., Methods: We performed a single institution retrospective review of patients with recurrent ovarian cancer who were treated with gemcitabine plus nab-paclitaxel from 2012 to 2018 at the Mayo Clinic in Florida., Results: Twenty patients were identified and the median PFS for patients treated with gemcitabine plus nab-paclitaxel was 9 months (95% CI, 5.7-20.7). Overall, 17 of the 20 patients (85%) achieved a clinical benefit (complete response 5%, partial response 55%, or stable disease at 3 months 25%). For platinum-sensitive disease and platinum-resistant disease, the median OS were 38.7 months (95% CI, 5.8-63.1) and 31.2 months (95% CI, 12.8-51.8), respectively (p = 0.4306)., Conclusion: This well-tolerated regimen shows promising activity in recurrent ovarian cancer and is a viable option for patients who are intolerant to paclitaxel or carboplatin because of allergic reactions., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: This trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to extend the platinum-free interval (TFIp) can improve overall survival (OS) in patients with recurrent ovarian cancer (OC)., Methods: Patients with OC (up to two previous platinum-based lines), with a TFIp of 6-12 months, were randomised to receive carboplatin/PLD (CP) or TP followed by platinum therapy at relapse. The primary endpoint was OS (HR: 0.75)., Results: The study enrolled 617 patients. The median TFIp was 8.3 months and 30.3% of patients had received two previous platinum lines. 74% and 73.9% of patients, respectively, received a subsequent therapy (ST) in the CP and TP arm; in the latter TP arm 87.2% of ST was platinum-based, as per protocol. The median OS was 21.4 for CP and 21.9 months for TP (HR 1.13; 95% CI: 0.94-1.35; p = 0.197). Grade 3-5 adverse reactions occurred in 37.1% of patients in the CP arm and 69.7% of patients in the TP arm, and the most frequent were neutropenia (22.8% CP, 39.5% TP), gastrointestinal (7.1% CP, 17.4% TP), hepatic (0.7% CP, 19.1% TP)., Conclusions: This study did not meet the primary endpoint. CP combination remains the standard for patients with recurrent OC and a 6-12 months TFIp; TP is an effective treatment in patients suffering from persistent platinum toxicities., Clinical Trial Registration: ClinicalTrials.gov, number NCT01379989., (© 2023. The Author(s).)

The aim of this study was to assess the therapeutic efficacy of a cisplatin and vinorelbine combination as second- or higher-line palliative chemotherapy in patients with advanced ovarian cancer. We retrospectively reviewed the medical records of patients with advanced ovarian cancer who were treated with cisplatin (60 mg/m2 on day 1) and vinorelbine (25 mg/m2 on days 1 and 8) every 3 weeks between January 2004 and March 2021. Treatment responses, progression-free survival (PFS), and overall survival (OS) were assessed; laboratory data were reviewed to determine toxicity. Thirty-two patients with advanced ovarian cancer were treated with a combination of vinorelbine and cisplatin. The objective response rate (ORR) was 18.8% and the disease control rate was 75.1%. The median PFS was 4.13 months (95% confidence interval [CI], 2.4-5.8 months). The median OS was 56.9 months (95% CI, 50.5-63.7 months). The ORR (42.9% vs 9.1%; P = .035) was higher in the platinum-sensitive group than in the platinum-resistant group. The median PFS tended to be longer in the platinum-sensitive group (5.3 vs 3.8 months; P = .339) and the median OS was significantly longer in the platinum-sensitive group than in the platinum-resistant group (69.6 vs 24 months; P < .001). All patients developed hematological toxicities, with 56% experiencing grade 3 to 4 neutropenia. Two (6.2%) patients developed febrile neutropenia, but no treatment-related death occurred. This combination therapy may be effective in patients with heavily treated advanced ovarian cancer, particularly in platinum-sensitive patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: The aim of this study was to evaluate the indications and management of grade III-IV postoperative complications in patients requiring vacuum-assisted open abdomen after debulking surgery for ovarian carcinomatosis., Methods: Retrospective study of prospectively collected data from patients who underwent a cytoreductive surgery by laparotomy for an epithelial ovarian cancer that required postoperative management of an open abdomen. An abdominal vacuum-assisted wound closure (VAWC) was applied in cases of abdominal compartmental syndrome (ACS) or intra-abdominal hypertension, to prevent ACS. The fascia was closed with a suture or a biologic mesh. The primary aim was to achieve primary fascial closure. Secondary outcomes considered included complications of cytoreductive surgery (CRS) and open abdominal wounds (hernia, fistula)., Results: Two percent of patients who underwent CRS required VAWC during the study's patient inclusion period. VAWC indications included: (i) seven cases of gastro-intestinal perforation, (ii) three necrotic enterocolitis, (iii) two intestinal ischemia, (iv) three anastomotic leakages and (v) four intra-abdominal hemorrhages. VAWC was used to treat indications (i) to (iv) (which represented 73.7% of cases), to prevent compartmental syndrome. Primary fascia closure was achieved in 100% of cases, in four cases (21.0%) a biologic mesh was used. Median hospital stay was 65 days (range: 18-153). Four patients died during hospitalization, three of these within 30 days of VAWC completion., Conclusion: VAWC for managing open abdominal wounds is a reliable technique to treat surgical post-CRS complications in advanced ovarian cancer and reduces the early post-operative mortality in cases presenting with severe complications., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Although cholesterol has been hypothesized to promote cancer development through several potential pathways, its role in the risk of developing hormonally driven cancer is controversial. This literature review summarizes evidence from the highest quality studies to examine the consistency and strength of the relationship between serum cholesterol parameters and incidence of hormonally driven cancer. Articles were identified using EMBASE. Longitudinal observational studies published between January 2000 and December 2020 were considered for inclusion. The endpoint of interest was incident prostate, ovary, breast, endometrium, and uterine cancers. In total, 2732 reports were identified and screened; 41 studies were included in the review. No associations were found for ovarian cancer. Most endometrial cancer studies were null. The majority (76.9%) of studies reported no association between cholesterol and prostate cancer. Data on breast cancer were conflicting, associations limited, and effect sizes modest. Our results do not provide evidence for a clear association between cholesterol and different types of incident, hormonally driven reproductive cancers. Future studies should investigate the impact of lipid-lowering therapy., (© 2022 Regeneron Pharmaceuticals, Inc. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Uptake of risk-reducing surgery has increased among women at high risk of epithelial ovarian cancer. We sought to characterise familial risk of epithelial ovarian cancer histotypes in a population-based study after accounting for gynaecological surgeries, including bilateral oophorectomy., Methods: We compared risk of epithelial ovarian cancer in relatives of 3536 epithelial ovarian cancer cases diagnosed in 1966-2016 and relatives of 35 326 matched controls. We used Cox competing risk models, incorporating bilateral oophorectomy as a competing risk, to estimate the relative risk of ovarian cancer in first-degree (FDR), second-degree (SDR) and third-degree (TDR) relatives from 1966 to 2016. We also estimated relative risks in time periods before (1966-1994, 1995-2004) and after (2005-2016) formal recommendations were made for prophylactic oophorectomy among women with pathogenic variants in BRCA1/2 ., Results: The relative risks of epithelial ovarian cancer in FDRs, SDRs and TDRs of cases versus controls were 1.68 (95% CI 1.39 to 2.04), 1.51 (95% CI 1.30 to 1.75) and 1.34 (95% CI 1.20 to 1.48), respectively. Relative risks were greatest for high-grade serous, mucinous and 'other epithelial' histotypes. Relative risks were attenuated for case FDRs, but not for SDRs or TDRs, from 2005 onwards, consistent with the timing of recommendations for prophylactic surgery., Conclusion: Familial risk of epithelial ovarian cancer extends to TDRs, especially for high-grade serous and mucinous histotypes. Distant relatives share genes but minimal environment, highlighting the importance of germline inherited genetics in ovarian cancer aetiology. Increased ovarian cancer risk in distant relatives has implications for counselling and recommendations for prophylactic surgeries that, from our data, appear only to reach FDRs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)