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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.

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.

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.

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 & GE;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.

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, r

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.

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.

Objective: To assess the impact of lymphadenectomy and lymphoedema of the lower limbs (LLL) on health-related quality of life (HRQoL) 1 year after surgery for endometrial cancer (EC). Design: Prospective longitudinal cohort multicentre study. Setting: Departments of obstetrics and gynaecology at four university hospitals, six central hospitals and four county hospitals in Sweden. Population: Two-hundred-and-thirty-five women with early stage EC were included; 116 with high-risk EC underwent surgery including lymphadenectomy (+LA), and 119 with low-risk EC had surgery without lymphadenectomy (-LA). Methods: The generic SF-36 and EQ-5D-3L and the lymphoedema-specific LYMQOL questionnaire were used to assess HRQoL. LLL was assessed by systematic circumferential measurements of the legs enabling volume estimation, clinical evaluation and patient-reported perception of leg swelling. All assessments were carried out on four occasions; preoperatively, and 4-6 weeks, 6 months and 1 year postoperatively. Main outcome measure: HRQoL scores. Results: No significant differences were seen in HRQoL between the +LA and -LA groups 1 year postoperatively. Irrespective of method of determining LLL, women with LLL were significantly more affected in the LYMQOL domains Function, Appearance/body image and Physical symptoms, but not in the domain Emotion/mood, than women without LLL. No such differences were seen in the generic HRQoL or in the LYMQOL global score between the groups with and without LLL. Conclusions: Lymphadenectomy did not seem to affect generic HRQoL adversely. Irrespective of the method of measuring, LLL affected the lymphoedema-specific HRQoL negatively, mainly in physical domains, but had no impact on the generic HRQoL.

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. What's new? While risk of epithelial ovarian cancer is known to be influenced by pregnancy, the mechanisms underlying this association remain unclear. In this population-based study, the impact of reproductive history on ovarian cancer prognosis was evaluated by ovarian cancer subtype. Among women with germ cell tumors, par

Cancer mortality is exacerbated by late-stage diagnosis. Liquid biopsies based on genomic biomarkers can noninvasively diagnose cancers. However, validation studies have reported similar to 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 (N-urine = 220 cancer vs. 360 healthy) and plasma (N-plasma = 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.

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 short-term fluorescent microculture cytotoxicity assay (FMCA). Drug activity was compared with respect to EOC subtype, preoperative chemotherapy, cross-resistance and association with progression-free 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 treatment-naive samples, reaching statistical significance for fluorouracil, irinotecan, dasatinib and nintedanib (all P<0.05). PFS time gradually shortened with increasing degree of drug resistance. Cross-resistance 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 su

Background: Research focusing on patients’ perceptions of the quality of gynecological cancer care is needed. Objective: To adapt the Quality from the Patient’s Perspective instrument for use in gynecological cancer care (QPP-GynCa) and describe patients’ perceptions of their quality of care in terms of the care received and the subjective importance of the aspects of care. Methods: A cross-sectional study 6–8 months after diagnosis was conducted, involving 1511 patients (response rate of 50.4%) included in the Swedish quality registry for gynecologic cancer. Results: The exploratory factor analysis (n = 1431) resulted in the QPP-GynCa with a 5-factor structure and an eigenvalue of ≥1, explaining 73.1% of the total scale variance. The final 27-item version of the QPP-GynCa consisted of 18 items with 8 additional single items and 1 global single item. The Cronbach’s alpha was acceptable for most factors (>.80). Subjective importance scores were higher than corresponding quality of care scores for care received (P ≤ .01)in all dimensions, factors, and items. Conclusions: The QPP-GynCa instrument reflects all 4 dimensions of the theoretical model of quality of care and achieved good validity as a reliable instrument in assessing the quality of gynecological cancer care. Implication for Practice: Information related to self-care, aspects of sexuality, and reducing patient waiting times need improvement. What Is Foundational: This study contributes to a better understanding of quality of gynecological cancer treatment and care. The validated QPP-GynCa instrument will be a platform for more research on how this group of patients experience their received care, as well as importance of each aspect of care.