Large-scale proteomics reveals precise biomarkers for detection of ovarian cancer in symptomatic women.

Ovarian cancer is the 8th most common cancer among women and has a 5-year survival of only 30-50%. While the survival is close to 90% for stage I tumours it is only 20% for stage IV. Current biomarkers are not sensitive nor specific enough, and novel biomarkers are urgently needed. We used the Explore PEA technology for large-scale analysis of 2943 plasma proteins to search for new biomarkers using two independent clinical cohorts. The discovery analysis using the first cohort identified 296 proteins that had significantly different levels in malign tumours as compared to benign and for 269 (91%) of these, the association was replicated in the second cohort. Multivariate modelling, including all proteins independent of their association in the univariate analysis, identified a model for separating benign conditions from malign tumours (stage I-IV) consisting of three proteins; WFDC2, KRT19 and RBFOX3. This model achieved an AUC of 0.92 in the replication cohort and a sensitivity and specificity of 0.93 and 0.77 at a cut-off developed in the discovery cohort. There was no statistical difference of the performance in the replication cohort compared to the discovery cohort. WFDC2 and KRT19 have previously been associated with ovarian cancer but RBFOX3 has not previously been identified as a potential biomarker. Our results demonstrate the ability of using high-throughput precision proteomics for identification of novel plasma protein biomarker for ovarian cancer detection.

Parenting under pressure: a cross-sectional questionnaire study of psychological distress, parenting concerns, self-efficacy, and emotion regulation in parents with cancer.

BACKGROUND AND PURPOSE: As many as one in four adults with cancer have children under 18 years. Balancing parenting and cancer is challenging and can be a source of psychological distress. This study aimed to examine psychological distress in parents with cancer and its associations with parenting concerns, self-efficacy, and emotion regulation. MATERIALS AND METHODS: This was a cross-sectional questionnaire study of 406 parents (aged 25-60 years) diagnosed with cancer within the last 5 years, with at least one dependent child (≤ 18 years). Parents completed questionnaires on psychological distress (DASS-21), parenting concerns (PCQ), self-efficacy (GSE), emotion regulation (ERQ), mental and physical health, and sociodemographics. Data were analysed using multiple logistic regressions on depression (yes/no), anxiety (yes/no), and stress (yes/no). RESULTS: Higher parenting concerns were associated with greater odds of depression (OR = 2.33, 95% CI: 1.64-3.31), anxiety (OR = 2.30, 95% CI: 1.64-3.20), and stress (OR = 3.21, 95% CI: 2.20-4.69) when adjusting for health and sociodemographic factors. Poorer self-efficacy was associated with increased odds of anxiety (OR = 0.94, 95% CI: 0.89-0.99, p < 0.05), whereas lower use of cognitive reappraisal and higher use of expressive suppression increased the odds of depression (OR = 0.76, 95% CI: 0.59-0.98 | OR = 1.46, 95% CI: 1.18-1.80). INTERPRETATION: The findings highlight the complexity of parental well-being in relation to parenthood and cancer, stressing the need for interventions that address relevant psychological factors to improve overall mental health in this population.

Compositional and functional differences of the vaginal microbiota of women with and without cervical dysplasia.

Alterations in the vaginal microbiota, including both species composition and functional pathways, have been associated with HPV infection and progression of dysplasia to cervical cancer. To further explore this, shotgun metagenomic sequencing was used to taxonomically and functionally characterize the vaginal microbiota of women with and without cervical dysplasia. Women with histologically verified dysplasia (n = 177; low grade dysplasia (LSIL) n = 81, high-grade dysplasia (HSIL) n = 94, cancer n = 2) were compared with healthy controls recruited from the cervical screening programme (n = 177). Women with dysplasia had a higher vaginal microbial diversity, and higher abundances of Gardnerella vaginalis, Aerococcus christensenii, Peptoniphilus lacrimalis and Fannyhessea vaginae, while healthy controls had higher relative abundance of Lactobacillus crispatus. Genes involved in e.g. nucleotide biosynthesis and peptidoglycan biosynthesis were more abundant in women with dysplasia. Healthy controls showed higher abundance of genes important for e.g. amino acid biosynthesis, (especially L-lysine) and sugar degradation. These findings suggest that the microbiota may have a role in creating a pro-oncogenic environment in women with dysplasia. Its role and potential interactions with other components in the microenvironment deserve further exploration.

Has time to chemotherapy from primary debulking surgery in advanced ovarian cancer an impact on survival? - A population-based nationwide SweGCG study.

OBJECTIVE: The aim of the study was to investigate if time to start chemotherapy (TTC) after primary debulking surgery (PDS) impacted relative survival (RS) in advanced epithelial ovarian/fallopian tube/primary peritoneal cancer (EOC). METHODS: Nationwide population-based study of women with EOC FIGO stages IIIC-IV, registered 2008-2018 in the Swedish Quality Register for Gynecologic Cancer, treated with PDS and chemotherapy. TTC was categorized into; ≤21 days, 22-28 days, 29-35 days, 36-42 days and > 42 days. Relative survival (RS) was estimated using the Pohar-Perme estimate of net survival. Multivariable analyses of excess mortality rate ratios (EMRRs) were estimated by Poisson regression models. RESULTS: In total, 1694 women were included. The median age was 65.0 years. Older age and no residual disease were more common in TTC >42 days than 0-21 days. The RS at 5-years was 37.9% and did not differ between TTC groups. In the R0 (no residual disease) cohort (n = 806), 2-year RS was higher in TTC ≤21 days (91.6%) and 22-28 days (91.4%) than TTC >42 days (79.1%). TTC >42 days (EMRR 2.33, p = 0.026), FIGO stage IV (EMRR 1.83, p = 0.007) and non-serous histology (EMRR 4.20, p < 0.001) were associated with 2-year worse excess mortality compared to TTC 0-21 days, in the R0 cohort. TTC was associated with 2-year survival in the R0 cohort in FIGO stage IV but not in stage IIIC. TTC was not associated with RS in patients with residual disease. CONCLUSIONS: For the entire cohort, stage IV, non-serous morphology and residual disease, but not TTC, influenced 5-year relative survival. However, longer TTC was associated with a poorer 2-year survival for those without residual disease after PDS.

Application of PET/MRI in Gynecologic Malignancies.

The diagnosis, treatment, and management of gynecologic malignancies benefit from both positron emission tomography/computed tomography (PET/CT) and MRI. PET/CT provides important information on the local extent of disease as well as diffuse metastatic involvement. MRI offers soft tissue delineation and loco-regional disease involvement. The combination of these two technologies is key in diagnosis, treatment planning, and evaluating treatment response in gynecological malignancies. This review aims to assess the performance of PET/MRI in gynecologic cancer patients and outlines the technical challenges and clinical advantages of PET/MR systems when specifically applied to gynecologic malignancies.

Association between parity and pregnancy-associated tumor features in high-grade serous ovarian cancer.

PURPOSE: High-grade serous ovarian cancer (HGSC) is the most common ovarian cancer subtype. Parity is an important risk-reducing factor, but the underlying mechanism behind the protective effect is unclear. Our aim was to study if the expression of hormones and proteins involved in pregnancy were affected by the woman's parity status, and if they may be associated with tumor stage and survival. METHODS: We evaluated expression of progesterone receptor (PR), progesterone receptor membrane component 1 (PGRMC1), relaxin-2, and transforming growth factor beta 1 (TGFß1) in tumor tissue from 92 women with HGSC parous (n = 73) and nulliparous (n = 19). Key findings were then evaluated in an independent expansion cohort of 49 patients. Survival rates by hormone/protein expression were illustrated using the Kaplan-Meier method. The independent prognostic value was tested by Cox regression, using models adjusted for established poor-prognostic factors (age at diagnosis, FIGO stage, type of surgery, and macroscopic residual tumor after surgery). RESULTS: HGSC tumors from parous women were PR positive (≥ 1% PR expression in tumor cells) more often than tumors from nulliparous women (42% vs. 16%; p-value 0.04), and having more children was associated with developing PR positive tumors [i.e., ≥ 3 children versus nulliparity, adjusted for age at diagnosis and stage: OR 4.31 (95% CI 1.12-19.69)]. A similar result was seen in the expansion cohort. Parity status had no impact on expression of PGRMC1, relaxin-2 and TGFß1. No associations were seen with tumor stage or survival. CONCLUSION: Tumors from parous women with HGSC expressed PR more often than tumors from nulliparous women, indicating that pregnancies might possibly have a long-lasting impact on ovarian cancer development.

Toward ovarian cancer screening with protein biomarkers using dried, self-sampled cervico-vaginal fluid.

Early detection is key for increased survival in ovarian cancer, but no general screening program exists today due to lack of biomarkers and overall cost versus benefit over traditional clinical methods. Here, we used dried cervico-vaginal fluid (CVF) as sampling matrix coupled with mass spectrometry for detection of protein biomarkers. We find that self-collected CVF on paper cards yields robust results and is suitable for high-throughput proteomics. Artificial intelligence-based methods were used to identify an 11-protein panel that separates cases from controls. In validation data, the panel achieved a sensitivity of 0.97 (95% CI 0.91-1.00) at a specificity of 0.67 (0.40-0.87). Analyses of samples collected prior to development of symptoms indicate that the panel is informative also of future risk of disease. Dried CVF is used in cervical cancer screening, and our results opens the possibility for a screening program also for ovarian cancer, based on self-collected CVF samples.

The Complexity of Being a Parent in the Hospital and a Patient at Home: A Qualitative Study on Parenting Concerns and Challenges Among Parents With Cancer.

BACKGROUND: Parents given a diagnosis of cancer must balance the demands of their illness and caregiving responsibilities. This can result in parental stress and have a negative impact on the well-being of the whole family. A greater understanding of the experiences of parents with cancer is necessary to provide adequate support. OBJECTIVE: The aim of this study was to explore parenting concerns and challenges among parents with cancer who were caring for dependent children younger than 18 years. METHODS: Semistructured interviews were carried out with 22 parents with cancer. Interviews were audio-recorded, transcribed, and analyzed using thematic analysis. RESULTS: Parental concerns and challenges affected parents in their parental role and their everyday family life. Three overarching themes described the struggles in balancing life as a parent and as a patient: navigating dual roles as a parent with cancer, impact of cancer on parenting, and impact on family life. Parents' primary focus was on their children's well-being, and they struggled to manage their own expectations of parenting and the demands on their role in the family. CONCLUSION: The results highlight the complexity of being a parent with cancer while caring for dependent children. To support parents during the cancer journey, it is important to understand the consequences of their illness on their parental role and the family. IMPLICATIONS FOR PRACTICE: Supporting parents to feel secure in their parental role and providing support to them during their cancer journey should be integrated into routine cancer care, where parenting concerns and challenges are addressed.

Psychosocial interventions targeting parenting distress among parents with cancer - A systematic review and narrative synthesis of available interventions.

BACKGROUND: Balancing having cancer and parenting a major stressor, and may result in parenting distress, negatively affecting the whole family. To provide adequate support, knowledge of existing psychosocial interventions are crucial to guide future interventions. This study aimed to describe available psychosocial interventions for parents with cancer and dependent children (<18 years). METHOD: We conducted a systematic review, and four databases were searched from January 2000 to March 2023. RESULTS: Thirty studies were included, reporting on 22 psychosocial interventions for parents with cancer. They aimed to improve different aspects of parenting distress, and included psychoeducation and communication strategies. Interventions were beneficial to and acceptable among parents, but only a few had been evaluated. The study quality was, overall, assessed as moderate. CONCLUSIONS: The results of this review highlight the diversity of available psychosocial interventions for parents with cancer and the outcomes on parenting distress, as well as methodological challenges.

Next generation pan-cancer blood proteome profiling using proximity extension assay.

A comprehensive characterization of blood proteome profiles in cancer patients can contribute to a better understanding of the disease etiology, resulting in earlier diagnosis, risk stratification and better monitoring of the different cancer subtypes. Here, we describe the use of next generation protein profiling to explore the proteome signature in blood across patients representing many of the major cancer types. Plasma profiles of 1463 proteins from more than 1400 cancer patients are measured in minute amounts of blood collected at the time of diagnosis and before treatment. An open access Disease Blood Atlas resource allows the exploration of the individual protein profiles in blood collected from the individual cancer patients. We also present studies in which classification models based on machine learning have been used for the identification of a set of proteins associated with each of the analyzed cancers. The implication for cancer precision medicine of next generation plasma profiling is discussed.

Advanced gynecological cancer: Quality of life one year after diagnosis.

OBJECTIVE: Gynaecological cancer treatment impacts women's physical and psychological health. Our objective was to examine quality of life (QoL) in women with advanced gynaecological cancer at diagnosis and one year later, and to identify sociodemographic and clinical characteristics associated with QoL. METHODS: Women with endometrial, ovarian or cervical cancer treated in Uppsala, Sweden 2012-2019 were included. FIGO stage ≥II was considered advanced gynaecological cancer, whereas women in FIGO stage I were used as a control group. QoL was assessed with SF-36. We obtained information on sociodemographic and clinical characteristics from medical records and health questionnaires. Differences in QoL domains were tested with t-tests, a mixed model ANOVA and multiple linear regression analyses. RESULTS: The study population (n = 372) included 150 (40.3%) women with advanced gynaecological cancer. At diagnosis, women with advanced cancer reported lower physical (71.6 vs 81.8 (mean) p<0.05) and role functioning/physical scores (62.6 vs 77.2 (mean) p<0.05) than women in FIGO stage I. One year later, women with advanced cancer reported higher scores in the mental health domain (78.3 vs 73.2 (mean) p<0.05) than women in FIGO stage I. However, no difference was found in the QoL scores of women with advanced disease one year after diagnoses when stratified by diagnosis. Women with a history of psychiatric illness and higher BMI reported poorer physical and mental QoL at follow-up, while advanced stage, level of education and smoking were not associated with QoL. CONCLUSION: Women with advanced gynaecological cancer have equally good QoL one year after diagnosis as women with limited disease. Women with previous psychiatric illness and high BMI, are at risk of impaired physical and mental health.

Noninvasive detection of any-stage cancer using free glycosaminoglycans.

Cancer mortality is exacerbated by late-stage diagnosis. Liquid biopsies based on genomic biomarkers can noninvasively diagnose cancers. However, validation studies have reported ~10% sensitivity to detect stage I cancer in a screening population and specific types, such as brain or genitourinary tumors, remain undetectable. We investigated urine and plasma free glycosaminoglycan profiles (GAGomes) as tumor metabolism biomarkers for multi-cancer early detection (MCED) of 14 cancer types using 2,064 samples from 1,260 cancer or healthy subjects. We observed widespread cancer-specific changes in biofluidic GAGomes recapitulated in an in vivo cancer progression model. We developed three machine learning models based on urine (Nurine = 220 cancer vs. 360 healthy) and plasma (Nplasma = 517 vs. 425) GAGomes that can detect any cancer with an area under the receiver operating characteristic curve of 0.83-0.93 with up to 62% sensitivity to stage I disease at 95% specificity. Undetected patients had a 39 to 50% lower risk of death. GAGomes predicted the putative cancer location with 89% accuracy. In a validation study on a screening-like population requiring ≥ 99% specificity, combined GAGomes predicted any cancer type with poor prognosis within 18 months with 43% sensitivity (21% in stage I; N = 121 and 49 cases). Overall, GAGomes appeared to be powerful MCED metabolic biomarkers, potentially doubling the number of stage I cancers detectable using genomic biomarkers.

Data-driven analysis of a validated risk score for ovarian cancer identifies clinically distinct patterns during follow-up and treatment.

Background: Ovarian cancer is the eighth most common cancer among women and due to late detection prognosis is poor with an overall 5-year survival of 30-50%. Novel biomarkers are needed to reduce diagnostic surgery and enable detection of early-stage cancer by population screening. We have previously developed a risk score based on an 11-biomarker plasma protein assay to distinguish benign tumors (cysts) from malignant ovarian cancer in women with adnexal ovarian mass. Methods: Protein concentrations of 11 proteins were characterized in plasma from 1120 clinical samples with a custom version of the proximity extension assay. The performance of the assay was evaluated in terms of prediction accuracy based on receiver operating characteristics (ROC) and multiple hypothesis adjusted Fisher's Exact tests on achieved sensitivity and specificity. Results: The assay's performance is validated in two independent clinical cohorts with a sensitivity of 0.83/0.91 and specificity of 0.88/0.92. We also show that the risk score follows the clinical development and is reduced upon treatment, and increased with relapse and cancer progression. Data-driven modeling of the risk score patterns during a 2-year follow-up after diagnosis identifies four separate risk score trajectories linked to clinical development and survival. A Cox proportional hazard regression analysis of 5-year survival shows that at time of diagnosis the risk score is the second-strongest predictive variable for survival after tumor stage, whereas MUCIN-16 (CA-125) alone is not significantly predictive. Conclusion: The robust performance of the biomarker assay across clinical cohorts and the correlation with clinical development indicates its usefulness both in the diagnostic work-up of women with adnexal ovarian mass and for predicting their clinical course.

Ex vivo assessment of cancer drug sensitivity in epithelial ovarian cancer and its association with histopathological type, treatment history and clinical outcome.

Epithelial ovarian cancer (EOC) is divided into type I and type II based on histopathological features. Type I is clinically more indolent, but also less sensitive to chemotherapy, compared with type II. The basis for this difference is not fully clarified. The present study investigated the pattern of drug activity in type I and type II EOC for standard cytotoxic drugs and recently introduced tyrosine kinase inhibitors (TKIs), and assessed the association with treatment history and clinical outcome. Isolated EOC tumor cells obtained at surgery were investigated for their sensitivity to seven standard cytotoxic drugs and nine TKIs using a short­term fluorescent microculture cytotoxicity assay (FMCA). Drug activity was compared with respect to EOC subtype, preoperative chemotherapy, cross­resistance and association with progression­free survival (PFS). Out of 128 EOC samples, 120 samples, including 21 type I and 99 type II, were successfully analyzed using FMCA. Patients with EOC type I had a significantly longer PFS time than patients with EOC type II (P=0.01). In line with clinical experience, EOC type I samples were generally more resistant than type II samples to both standard cytotoxic drugs and the TKIs, reaching statistical significance for cisplatin (P=0.03) and dasatinib (P=0.002). A similar pattern was noted in samples from patients treated with chemotherapy prior to surgery compared with treatment­naive samples, reaching statistical significance for fluorouracil, irinotecan, dasatinib and nintedanib (all P<0.05). PFS time gradually shortened with increasing degree of drug resistance. Cross­resistance between drugs was in most cases statistically significant yet moderate in degree (r<0.5). The clinically observed relative drug resistance of EOC type I, as well as in patients previously treated, is at least partly due to mechanisms in the tumor cells. These mechanisms seemingly also encompass kinase inhibitors. Ex vivo assessment of drug activity is suggested to have a role in the optimization of drug therapy in EOC.

Long-term incidence of endometrial cancer after endometrial resection and ablation: A population based Swedish gynecologic cancer group (SweGCG) study.

INTRODUCTION: Minimally invasive methods to reduce menorrhagia were introduced in the 1980s and 1990s. Transcervical endometrial resection (TCRE) and endometrial ablation (EA) are two of the most frequently used methods. As none of them can guarantee a complete removal of the endometrium, there are concerns that the remaining endometrium may develop to endometrial cancer (EC) later in life. The primary aim was to analyze the long-term incidence of EC after TCRE and EA in a nationwide population. The secondary aim was to assess the two treatment modalities separately. MATERIAL AND METHODS: The Swedish National Patient Registry and National Quality Registry for Gynecological Surgery were used for identification of women who had TCRE or EA performed between 1997-2017. The cohort was followed from the first TCRE or EA until hysterectomy, diagnosis of EC, or death. Follow-up data were retrieved from the National Cancer Registry and the National Death Registry. Expected incidence for EC in Swedish women was calculated using Swedish data retrieved from the NORDCAN project after having taken into account differences of age and follow-up time. Cumulative incidence of EC after TCRE and EA, was calculated. A standardized incidence ratio was calculated based on the expected and observed incidence, stratified by age and year of diagnosis. RESULTS: In total, 17 296 women (mean age 45.1 years) underwent TCRE (n = 8626) or EA (n = 8670). Excluded were 3121 who had a hysterectomy for benign causes during follow up. During a median follow-up time of 7.1 years (interquartile range 3.1-13.3 years) the numbers of EC were 25 (0.3%) after TCRE and 2 (0.02%) after EA, respectively. The observed incidence was significantly lower than expected (population-based estimate) after EA but not after TCRE, giving a standardized incidence ratio of 0.13 (95% confidence interval [CI] 0.03-0.53) after EA and 1.27 (95% CI 0.86-1.88) after TCRE. Median times to EC were 3.0 and 8.3 years after TCRE and EA, respectively. CONCLUSIONS: There was a significant reduction of EC after EA, suggesting a protective effect, whereas endometrial resection showed an incidence within the expected rate.

Next Generation Plasma Proteomics Identifies High-Precision Biomarker Candidates for Ovarian Cancer.

BACKGROUND: Ovarian cancer is the eighth most common cancer among women and has a 5-year survival of only 30-50%. The survival is close to 90% for patients in stage I but only 20% for patients in stage IV. The presently available biomarkers have insufficient sensitivity and specificity for early detection and there is an urgent need to identify novel biomarkers. METHODS: We employed the Explore PEA technology for high-precision analysis of 1463 plasma proteins and conducted a discovery and replication study using two clinical cohorts of previously untreated patients with benign or malignant ovarian tumours (N = 111 and N = 37). RESULTS: The discovery analysis identified 32 proteins that had significantly higher levels in malignant cases as compared to benign diagnoses, and for 28 of these, the association was replicated in the second cohort. Multivariate modelling identified three highly accurate models based on 4 to 7 proteins each for separating benign tumours from early-stage and/or late-stage ovarian cancers, all with AUCs above 0.96 in the replication cohort. We also developed a model for separating the early-stage from the late-stage achieving an AUC of 0.81 in the replication cohort. These models were based on eleven proteins in total (ALPP, CXCL8, DPY30, IL6, IL12, KRT19, PAEP, TSPAN1, SIGLEC5, VTCN1, and WFDC2), notably without MUCIN-16. The majority of the associated proteins have been connected to ovarian cancer but not identified as potential biomarkers. CONCLUSIONS: The results show the ability of using high-precision proteomics for the identification of novel plasma protein biomarker candidates for the early detection of ovarian cancer.

Parity is associated with better prognosis in ovarian germ cell tumors, but not in other ovarian cancer subtypes.

Ovarian cancer is influenced by reproductive factors, with a reduced risk of epithelial ovarian cancer in parous women. Nonepithelial ovarian cancer frequently affects young women and often precedes or occurs during the childbearing years. However, the impact of reproductive factors on ovarian cancer survival remains unclear: in epithelial ovarian cancer, data are conflicting, and subtype-specific associations have not been examined, and in nonepithelial ovarian cancer, it has not been studied. Using Swedish registers, we evaluated associations between women's reproductive history and cancer-specific mortality by subtype of epithelial and nonepithelial ovarian cancer in 3791 women born 1953 and later, diagnosed from 1990 to 2018. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated using Cox-proportional hazard models. Parity was associated with a 78% decreased risk of cause-specific mortality in 243 women with germ cell tumors (GCTs) (parous vs nulliparous, adjusted for age at diagnosis: HR: 0.22 [95% CI 0.07-0.62]), with a decreased risk with increasing number of births (per birth: HR: 0.60 [95% CI 0.38-0.95]). We found no evidence of associations between parity and cause-specific mortality among the 334 patients with sex-cord stromal tumors, nor among the 3214 patients with epithelial ovarian cancer; neither overall, nor by subtype. In conclusion, in our large, population-based study, parity was associated with a clearly better prognosis in GCTs but not in the other ovarian cancer subtypes. Future research on how hormone exposure impacts GCT development may lead to a better understanding of mechanisms affecting survival.

The wait time to primary surgery in endometrial cancer - impact on survival and predictive factors: a population-based SweGCG study.

BACKGROUND: Poor survival rates in different cancer types are sometimes blamed on diagnostic and treatment delays, and it has been suggested that such delays might be related to sociodemographic factors such as education and ethnicity. We examined associations of the wait time from diagnosis to surgery and survival in endometrial cancer (EC) and explored patient and tumour factors influencing the wait time. MATERIAL AND METHODS: In this historical population-based cohort study, The Swedish Quality Registry for Gynaecologic Cancer (SQRGC) was used to identify EC patients who underwent primary surgery between 2010 and 2018. Factors associated with a wait time > 32 d were analysed with logistic regression. The 32-d time point was defined in accordance with the Swedish Standardisation Cancer Care programme. Adjusted Poisson regression analyses were used to analyse excess mortality rate ratio (EMRR). RESULTS: Out of 7366 women, 5535 waited > 32 d for surgery and 1098 > 70 d. The overall median wait time was 44 d. The factors most strongly associated with a wait time > 32 d were surgery at a university hospital (adjusted odds ratio [OR] 1.34, 95% confidence interval [CI] 1.08-1.66) followed by country of birth (OR 1.31, 95% CI 1.10-1.55) and year of diagnosis. There were no associations between wait time and histology or age. A wait time < 15 d was associated with higher mortality (adjusted EMRR 2.29,95% CI 1.36-3.84) whereas no negative survival impact was seen with a wait time of 70 d. Age, tumour stage, histology and risk group were highly associated with survival, whereas education, country of origin and hospital level did not have any impact on survival. CONCLUSIONS: Surgery within the first two weeks after EC diagnosis was associated with worsened survival. A prolonged wait time did not seem to have any significant adverse effect on prognosis.HighlightsSurgery within the first two weeks after diagnosis of endometrial cancer (EC) was associated with poorer survival.A prolonged wait time to surgery did not worsen prognosis.Delay in time to surgery was associated with sociodemographic factors.

Risk factors for lymphedema and method of assessment in endometrial cancer: a prospective longitudinal multicenter study.

OBJECTIVE: The aim of the study was to determine risk factors for lymphedema of the lower limbs, assessed by four methods, 1 year after surgery for endometrial cancer. METHODS: A prospective longitudinal multicenter study was conducted in 14 Swedish hospitals. 235 women with endometrial cancer were included; 116 underwent surgery including lymphadenectomy, and 119 had surgery without lymphadenectomy. Lymphedema was assessed preoperatively and 1 year postoperatively objectively by systematic circumferential measurements of the legs, enabling volume estimation addressed as (1) crude volume and (2) body mass index-standardized volume, or (3) clinical grading, and (4) subjectively by patient-reported perception of leg swelling. In volume estimation, lymphedema was defined as a volume increase ≥10%. Risk factors were analyzed using forward stepwise logistic regression models and presented as adjusted odds ratio (aOR) and 95% confidence interval (95% CI). RESULTS: Risk factors varied substantially, depending on the method of determining lymphedema. Lymphadenectomy was a risk factor for lymphedema when assessed by body mass index-standardized volume (aOR 14.42, 95% CI 3.49 to 59.62), clinical grading (aOR 2.11, 95% CI 1.04 to 4.29), and patient-perceived swelling (aOR 2.51, 95% CI 1.33 to 4.73), but not when evaluated by crude volume. Adjuvant radiotherapy was only a risk factor for lymphedema when assessed by body mass index-standardized volume (aOR 15.02, 95% CI 2.34 to 96.57). Aging was a risk factor for lymphedema when assessed by body mass index-standardized volume (aOR 1.07, 95% CI 1.00 to 1.15) and patient-perceived swelling (aOR 1.06, 95% CI 1.02 to 1.10), but not when assessed by crude volume or clinical grading. Increase in body mass index was a risk factor for lymphedema when estimated by crude volume (aOR 1.92, 95% CI 1.36 to 2.71) and patient-perceived swelling (aOR 1.36, 95% CI 1.11 to 1.66), but not by body mass index-standardized volume or clinical grading. The extent of lymphadenectomy was strongly predictive for the development of lymphedema when assessed by body mass index-standardized volume and patient-perceived swelling, but not by crude volume or clinical grading. CONCLUSION: Apparent risk factors for lymphedema differed considerably depending on the method used to determine lymphedema. This highlights the need for a 'gold standard' method when addressing lymphedema for determining risk factors.

Survival in endometrial cancer in relation to minimally invasive surgery or open surgery - a Swedish Gynecologic Cancer Group (SweGCG) study.

BACKGROUND: The aim of this study was to analyze overall survival in endometrial cancer patients' FIGO stages I-III in relation to surgical approach; minimally invasive (MIS) or open surgery (laparotomy). METHODS: A population-based retrospective study of 7275 endometrial cancer patients included in the Swedish Quality Registry for Gynecologic Cancer diagnosed from 2010 to 2018. Cox proportional hazard models were used in univariable and multivariable survival analyses. RESULTS: In univariable analysis open surgery was associated with worse overall survival compared with MIS hazard ratio, HR, 1.39 (95% CI 1.18-1.63) while in the multivariable analysis, surgical approach (MIS vs open surgery) was not associated with overall survival after adjustment for known risk factors (HR 1.12, 95% CI 0.95-1.32). Higher FIGO stage, non-endometrioid histology, non-diploid tumors, lymphovascular space invasion and increasing age were independent risk factors for overall survival. CONCLUSION: The minimal invasive or open surgical approach did not show any impact on survival for patients with endometrial cancer stages I-III when known prognostic risk factors were included in the multivariable analyses.