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.
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 (
= 111 and
= 37).
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.
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.
prediction and importance of severe postoperative complications after ovarian cancer surgery is a strong issue in patient selection and evaluation. Pre- and early peroperative predictors of severe ...30-days postoperative complications (Clavien-Dindo class ≥3) after surgery for primary ovarian cancer are not fully established, neither their impact on patients’ survival.
A prospective observational study included 256 patients with primary ovarian cancer FIGO stages IIB-IV, operated during 2009–2018 in a primary or interval debulking surgery setting. Patient variables were analysed in relation to severe postoperative complications (Clavien-Dindo class ≥3) and overall survival.
High-grade postoperative complications occurred in 24.2% patients. Class 3a complications were observed in 12.5% cases. High-grade complications class ≥3 were observed in 31.6% after primary debulking surgery compared to 12.2% after interval debulking surgery (p = 0.0004). Peritoneal cancer index ≥21 and preoperative albumin concentration ≤33 g/L were independent predictors of high-grade complications. Peritoneal cancer index correlated with the surgical complexity score and completeness of cytoreduction. Increased peritoneal cancer index was a negative predictor of overall survival, but high-grade complications did not influence survival negatively.
Peritoneal cancer index ≥21 was an independent predictor of high-grade complications after ovarian cancer surgery. Increased peritoneal cancer index also impacted overall survival negatively, but high-grade complications did not influence overall survival.
•Peritoneal cancer index predicted high-grade postoperative complications.•High-grade postoperative complications did not impact overall survival negatively.•Peritoneal cancer index and surgical complexity score correlated positively.•High peritoneal cancer index correlated with incomplete cytoreduction.
Ovarian cancer is usually detected at a late stage and the overall 5-year survival is only 30-40%. Additional means for early detection and improved diagnosis are acutely needed. To search for novel ...biomarkers, we compared circulating plasma levels of 593 proteins in three cohorts of patients with ovarian cancer and benign tumors, using the proximity extension assay (PEA). A combinatorial strategy was developed for identification of different multivariate biomarker signatures. A final model consisting of 11 biomarkers plus age was developed into a multiplex PEA test reporting in absolute concentrations. The final model was evaluated in a fourth independent cohort and has an AUC = 0.94, PPV = 0.92, sensitivity = 0.85 and specificity = 0.93 for detection of ovarian cancer stages I-IV. The novel plasma protein signature could be used to improve the diagnosis of women with adnexal ovarian mass or in screening to identify women that should be referred to specialized examination.
Vulvar cancer affects mainly elderly women and with an ageing population the incidence has increased. We explored the primary treatment patterns and relative survival of patients with vulvar squamous ...cell carcinoma (VSCC) by stage and age-group.
A population-based nationwide study on women diagnosed with VSCC between 2012 and 2016 and registered in the Swedish Quality Registry for Gynecologic Cancer (SQRGC). Main outcome was 5-year relative survival (RS) estimated by the Pohar Perme method. The relative risk of excess mortality (EMRR) between different groups was analyzed by Poisson regression. The age-standardized relative survival (AS-RS) was estimated for the total cohort.
Median follow-up time was 41 months. The study population included 657 women; 33% were ≥ 80 years old. FIGO stage I was most common (55%). Primary surgery was performed in 96% stage I, 65% stage II, 80% stage III and 28% stage IV. In women ≥80 years, exploration of the groins and chemoradiotherapy was less often performed. They also received lower mean doses of radiation than younger women. The 5-year AS-RS was 74%. 5-year RS was 84% for stage I, 60% for stage II, 54% for stage III and 35% for stage IV. The EMRR for women ≥80 years compared with women <60 years was 4.3 (p < 0.001); 4.9 (p < 0.001) for stages I-II and 3.5(p = 0.007) for stage III.
In general, primary treatment of patients with vulvar squamous cell carcinoma in Sweden adhered to guidelines. Areas of improvement include treatment for stage II and for the very old.
•The estimated age-standardized 5-year relative survival was 74% for vulvar squamous cell carcinoma diagnosed 2012–2016.•Primary treatment adhered well to evidence-based guidelines, except for stage II and the age-group ≥80 years old.•Surgery was the mainstay of primary treatment, but in women ≥80 years old a complete staging procedure was often omitted.•Survival was excellent for stage I disease, but women≥80 years old had a 5-fold increased risk for excess mortality.•In stage II there was a 3-fold excess mortality rate compared with stage I.
•Gynaecological cancer poses great stress on young women even after end of treatment.•Health care needs adequate resources for long-term psychosocial follow-up.•Multi-professional teams are warranted ...in gynaecologic oncology care.•Young survivors' family life and work participation need further attention.
To investigate the prevalence and predictors of cancer-related distress in younger women treated for gynaecological cancer, and to explore women's needs and experiences of psychosocial support following end-of-treatment.
Data were collected from 337 gynaecological cancer survivors, 19–39years at diagnosis, using a study-specific questionnaire and the Swedish Quality Register of Gynaecologic Cancer. Predictors of distress were investigated with multivariable logistic regression analysis. Open-ended questions were analysed with content analysis.
The prevalence of cancer-related distress was 85% (n=286) including fear of cancer-recurrence (n=175, 61%), anxiety (n=152, 53%), depression (n=145, 51%), fear of death (n=91, 32%), concerns regarding sexuality (n=87, 34%) and fertility (n=78, 27%), and changed body image (n=78, 27%). Multi-modal treatment (OR 2.25, 95% CI 1.13–4.49) and a history of psychological distress (OR 3.44, 95% CI 1.41–8.39) predicted cancer-related distress. The majority of women experiencing distress also reported a need for support after end-of-treatment (n=205, 71%). One-third of those receiving support reported the received support as inadequate (n=55, 34%). Eight categories described reasons for not seeking support, e.g., lacked strength to seek professional support and too busy managing every-day life and, wanted help but did not know who to turn to. Four categories described reasons for not receiving sought support e.g., found it difficult to openly express feelings, psychosocial care was under-dimensioned, insufficient and unprofessional.
Results identify the importance of support and longer-term follow-up for young survivors of gynaecological cancer. The support needs to be organised to meet this group's specific needs.
Introduction
Deep myometrial invasion (≥50%) is a prognostic factor for lymph node metastases and decreased survival in endometrial cancer. There is no consensus regarding which pre/intraoperative ...diagnostic method should be preferred. Our aim was to explore the pattern of diagnostic methods for myometrial invasion assessment in Sweden and to evaluate differences among magnetic resonance imaging (MRI), transvaginal sonography, frozen section, and gross examination in clinical practice.
Material and methods
This is a nationwide historical cohort study; women with endometrial cancer with data on assessment of myometrial invasion and FIGO stage I‐III registered in the Swedish Quality Registry for Gynecologic Cancer (SQRGC) between 2017 and 2019 were eligible. Data on age, histology, FIGO stage, method, and results of myometrial invasion assessment, pathology results, and hospital level were collected from the SQRGC. The final assessment by the pathologist was considered the reference standard.
Results
In the study population of 1401 women, 32% (n = 448) had myometrial invasion of 50% of more. The methods reported for myometrial invasion assessment were transvaginal sonography in 59%, MRI in 28%, gross examination in 8% and frozen section in 5% of cases. Only minor differences were found for age and FIGO stage when comparing methods applied for myometrial invasion assessment. The sensitivity, specificity, and accuracy to find myometrial invasion of 50% or more with transvaginal sonography were 65.6%, 80.3%, and 75.8%, for MRI they were 76.9%, 71.9%, and 73.8%, for gross examination they were 71.9%, 93.6%, and 87.3%, and for frozen section they were 90.0%, 92.7%, and 92.0%, respectively.
Conclusions
In Sweden, the assessment of deep myometrial invasion is most often performed with transvaginal sonography, but the sensitivity is lower than for the other diagnostic methods. In clinical practice, the accuracy is moderate for transvaginal sonography and MRI.
Over 500,000 women worldwide are diagnosed with ovarian or endometrial cancer each year. We have used a two-step strategy to identify plasma proteins that could be used to improve the diagnosis of ...women with an indication of gynecologic tumor and in population screening.
In the discovery step we screened 441 proteins in plasma using the proximity extension assay (PEA) and five Olink Multiplex assays (CVD II, CVD III, INF I, ONC II, NEU I) in women with ovarian cancer (n = 106), endometrial cancer (n = 74), benign ovarian tumors (n = 150) and healthy population controls (n = 399). Based on the discovery analyses a set of 27 proteins were selected and two focused multiplex PEA assays were developed. In a replication step the focused assays were used to study an independent set of cases with ovarian cancer (n = 280), endometrial cancer (n = 228), women with benign ovarian tumors (n = 76) and healthy controls (n = 57).
In the discovery step, 27 proteins that showed an association to cancer status were identified. In the replication analyses, the focused assays distinguished benign tumors from ovarian cancer stage III-IV with a sensitivity of 0.88 and specificity of 0.92 (AUC = 0.92). The assays had a significantly higher AUC for distinguishing benign tumors from late stage ovarian cancer than using CA125 and HE4 (
= 9.56e-22). Also, population controls could be distinguished from ovarian cancer stage III-IV with a sensitivity of 0.85 and a specificity of 0.92 (AUC = 0.89).
The PEA assays represent useful tools for identification of new biomarkers for gynecologic cancers. The selected protein assays could be used to distinguish benign tumors from ovarian and endometrial cancer in women diagnosed with an unknown suspicious pelvic mass. The panels could also be used in population screening, for identification of women in need of specialized gynecologic transvaginal ultrasound examination.
The Swedish Cancer Foundation, Vinnova (SWELIFE), The Foundation for Strategic Research (SSF), Assar Gabrielsson Foundation.
The aim of this study is to evaluate the quality of data on endometrial (EC) and ovarian, fallopian tube, peritoneal, abdominal or pelvic cancers (OC) registered in the Swedish Quality Register of ...Gynecologic Cancer (SQRGC).
A random sample of 500 patients was identified in the SQRGC and their medical charts were reviewed for re-abstraction of 31 selected core variables by an independent validator. The data in the SQRGC and the re-abstracted data were compared. The data were collected from 25 hospitals evenly distributed throughout Sweden. The main outcomes were comparability, timeliness, completeness and validity. Coverage was compared with the National Cancer Register (NCR). Timeliness was defined as the speed of registration i.e. when patients were registered in the SQRGC relative to date of diagnosis. Internationally accepted coding systems for stage, grading and histologic type were used ensuring a high degree of comparability. Correlations were estimated using Pearson's correlation coefficient and Cohen´s kappa coefficient.
The completeness was 95%. The timeliness was 88-91% within 12 months of diagnosis. The median degree of agreement between re-abstracted data and data in the SQRGC was 82.1%, with a median kappa value of 0.73 for ordinate variables and a median Pearson's correlation coefficient of 0.96. The agreements for the type of surgery were 76% (95% CI 70-81%; kappa 0.49) and type of primary treatment 90% (95% CI 87-94%; kappa 0.85) in OC and in EC 88% (95% CI 84-93%; kappa 0.84). The agreements for the FIGO stage were in OC and EC 74% (95% CI 68-80%; kappa 0.69) and 87% (95% CI 82-91%; kappa 0.79), respectively.
The data in the Swedish Quality Register for Gynecologic Cancer are of adequate quality in order to be used as a basis for research and to evaluate possible differences in treatment, lead times and treatment results.
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